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Conserved domains on  [gi|1370514551|ref|XP_024303329|]
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atrial natriuretic peptide receptor 2 isoform X2 [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
50-324 0e+00

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


:

Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 537.95  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  50 SLRGSSYGSLMTAHGKY--QIFANTGHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIV 127
Cdd:cd14042     1 SLSSSSYGSLMTAASFDqsQIFTKTGYYKGNLVAIKKVNKKRIDLTREVLKELKHMRDLQHDNLTRFIGACVDPPNICIL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 128 TEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE-P 206
Cdd:cd14042    81 TEYCPKGSLQDILENEDIKLDWMFRYSLIHDIVKGMHYLHDSEIKSHGNLKSSNCVVDSRFVLKITDFGLHSFRSGQEpP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 207 DDSHALYAKKLWTAPELLSGNPLPTTGMQKADVYSFGIILQEIALRSGPFYLEGLDLSPKEIV-QKVRNGQRPYFRPSID 285
Cdd:cd14042   161 DDSHAYYAKLLWTAPELLRDPNPPPPGTQKGDVYSFGIILQEIATRQGPFYEEGPDLSPKEIIkKKVRNGEKPPFRPSLD 240
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1370514551 286 RTQLNEELVLLMERCWAQDPAERPDFGQIKGFIRRFNKE 324
Cdd:cd14042   241 ELECPDEVLSLMQRCWAEDPEERPDFSTLRNKLKKLNKG 279
CYCc smart00044
Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl ...
357-541 4.17e-98

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.


:

Pssm-ID: 214485  Cd Length: 194  Bit Score: 296.48  E-value: 4.17e-98
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  357 EEKRKAEALLYQILPHSVAEQLKRGE-TVQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTLLNDLYTCFDAIIDNFDVY 435
Cdd:smart00044   1 EEKKKTDRLLDQLLPASVAEQLKRGGsPVPAESYDNVTILFSDIVGFTSLCSTSTPEQVVNLLNDLYSRFDQIIDRHGGY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  436 KVETIGDAYMVVSGLPGRNGQRHAPEIARMALALLDAVSSFRIRHRpHDQLRLRIGVHTGPVCAGVVGLKMPRYCLFGDT 515
Cdd:smart00044  81 KVKTIGDAYMVASGLPEEALVDHAELIADEALDMVEELKTVLVQHR-EEGLRVRIGIHTGPVVAGVVGIRMPRYCLFGDT 159
                          170       180
                   ....*....|....*....|....*.
gi 1370514551  516 VNTASRMESNGQALKIHVSSTTKDAL 541
Cdd:smart00044 160 VNLASRMESAGDPGQIQVSEETYSLL 185
HNOBA super family cl06648
Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and ...
330-378 2.08e-06

Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and pfam00211 in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals.


The actual alignment was detected with superfamily member pfam07701:

Pssm-ID: 462234  Cd Length: 214  Bit Score: 48.73  E-value: 2.08e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370514551 330 LDNLLLRMEQYANNLEKLVEErtqayLE-EKRKAEALLYQILPHSVAEQL 378
Cdd:pfam07701 170 LKLALDQLEQKSAELEESMRE-----LEeEKKKTDELLYSMLPKSVADRL 214
 
Name Accession Description Interval E-value
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
50-324 0e+00

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 537.95  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  50 SLRGSSYGSLMTAHGKY--QIFANTGHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIV 127
Cdd:cd14042     1 SLSSSSYGSLMTAASFDqsQIFTKTGYYKGNLVAIKKVNKKRIDLTREVLKELKHMRDLQHDNLTRFIGACVDPPNICIL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 128 TEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE-P 206
Cdd:cd14042    81 TEYCPKGSLQDILENEDIKLDWMFRYSLIHDIVKGMHYLHDSEIKSHGNLKSSNCVVDSRFVLKITDFGLHSFRSGQEpP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 207 DDSHALYAKKLWTAPELLSGNPLPTTGMQKADVYSFGIILQEIALRSGPFYLEGLDLSPKEIV-QKVRNGQRPYFRPSID 285
Cdd:cd14042   161 DDSHAYYAKLLWTAPELLRDPNPPPPGTQKGDVYSFGIILQEIATRQGPFYEEGPDLSPKEIIkKKVRNGEKPPFRPSLD 240
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1370514551 286 RTQLNEELVLLMERCWAQDPAERPDFGQIKGFIRRFNKE 324
Cdd:cd14042   241 ELECPDEVLSLMQRCWAEDPEERPDFSTLRNKLKKLNKG 279
CYCc smart00044
Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl ...
357-541 4.17e-98

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.


Pssm-ID: 214485  Cd Length: 194  Bit Score: 296.48  E-value: 4.17e-98
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  357 EEKRKAEALLYQILPHSVAEQLKRGE-TVQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTLLNDLYTCFDAIIDNFDVY 435
Cdd:smart00044   1 EEKKKTDRLLDQLLPASVAEQLKRGGsPVPAESYDNVTILFSDIVGFTSLCSTSTPEQVVNLLNDLYSRFDQIIDRHGGY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  436 KVETIGDAYMVVSGLPGRNGQRHAPEIARMALALLDAVSSFRIRHRpHDQLRLRIGVHTGPVCAGVVGLKMPRYCLFGDT 515
Cdd:smart00044  81 KVKTIGDAYMVASGLPEEALVDHAELIADEALDMVEELKTVLVQHR-EEGLRVRIGIHTGPVVAGVVGIRMPRYCLFGDT 159
                          170       180
                   ....*....|....*....|....*.
gi 1370514551  516 VNTASRMESNGQALKIHVSSTTKDAL 541
Cdd:smart00044 160 VNLASRMESAGDPGQIQVSEETYSLL 185
Guanylate_cyc pfam00211
Adenylate and Guanylate cyclase catalytic domain;
384-570 6.73e-94

Adenylate and Guanylate cyclase catalytic domain;


Pssm-ID: 425528  Cd Length: 183  Bit Score: 285.29  E-value: 6.73e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 384 VQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTLLNDLYTCFDAIIDNFDVYKVETIGDAYMVVSGLPgRNGQRHAPEIA 463
Cdd:pfam00211   1 VYAQPYDNVTILFADIVGFTALSSRHSPEQVVRLLNELYTRFDRLLDKHKVYKVKTIGDAYMVVSGLP-EPSPAHARKIA 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 464 RMALALLDAVSSFRIRHRPhdQLRLRIGVHTGPVCAGVVGLKMPRYCLFGDTVNTASRMESNGQALKIHVSSTTKDALDE 543
Cdd:pfam00211  80 EMALDMLEAIGEVNVESSE--GLRVRVGIHTGPVVAGVIGARMPRYDLWGNTVNLASRMESTGVPGKIHVSEETYRLLKT 157
                         170       180
                  ....*....|....*....|....*..
gi 1370514551 544 LGcFQLELRGDVEMKGKGKMRTYWLLG 570
Cdd:pfam00211 158 EG-FEFTERGEIEVKGKGKMKTYFLNG 183
CHD cd07302
cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also ...
392-568 2.05e-73

cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also called cyclase homology domains (CHDs), are part of the class III nucleotidyl cyclases. This class includes eukaryotic and prokaryotic adenylate cyclases (AC's) and guanylate cyclases (GC's). They seem to share a common catalytic mechanism in their requirement for two magnesium ions to bind the polyphosphate moiety of the nucleotide.


Pssm-ID: 143636 [Multi-domain]  Cd Length: 177  Bit Score: 232.08  E-value: 2.05e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 392 VTIYFSDIVGFTALSAESTPMQVVTLLNDLYTCFDAIIDNFDVYKVETIGDAYMVVSGLPGRNgQRHAPEIARMALALLD 471
Cdd:cd07302     2 VTVLFADIVGFTALSERLGPEELVELLNEYFSAFDEIIERHGGTVDKTIGDAVMAVFGLPGAH-EDHAERAVRAALEMQE 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 472 AVSSFRIRHRPHDQLRLRIGVHTGPVCAGVVGLKMPRYCLFGDTVNTASRMESNGQALKIHVSSTTKDALDELGcFQLEL 551
Cdd:cd07302    81 ALAELNAEREGGPPLRLRIGIHTGPVVAGVVGSERPEYTVIGDTVNLAARLESLAKPGQILVSEATYELLGDAG-FEFEE 159
                         170
                  ....*....|....*...
gi 1370514551 552 RGDVEMKGK-GKMRTYWL 568
Cdd:cd07302   160 LGEVELKGKsGPVRVYRL 177
AcyC COG2114
Adenylate cyclase, class 3 [Signal transduction mechanisms];
347-575 1.60e-52

Adenylate cyclase, class 3 [Signal transduction mechanisms];


Pssm-ID: 441717 [Multi-domain]  Cd Length: 407  Bit Score: 184.62  E-value: 1.60e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 347 LVEERTQAYLEEKRKAEALLYQILPHSVAEQLKRG--ETVQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTLLNDLYTC 424
Cdd:COG2114   176 ALLLLLLLALRERERLRDLLGRYLPPEVAERLLAGgeELRLGGERREVTVLFADIVGFTALSERLGPEELVELLNRYFSA 255
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 425 FDAIIDNFDVYKVETIGDAYMVVSGLPGRNGQrHAPEIARMALALLDAVSSFRIRHRPH--DQLRLRIGVHTGPVCAGVV 502
Cdd:COG2114   256 MVEIIERHGGTVDKFIGDGVMAVFGAPVARED-HAERAVRAALAMQEALAELNAELPAEggPPLRVRIGIHTGEVVVGNI 334
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 503 G-LKMPRYCLFGDTVNTASRMESNGQALKIHVSSTTKDALDELgcFQLELRGDVEMKGKGK-MRTYWLLGERKGP 575
Cdd:COG2114   335 GsEDRLDYTVIGDTVNLAARLESLAKPGEILVSEATYDLLRDR--FEFRELGEVRLKGKAEpVEVYELLGAKEAA 407
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
80-318 9.99e-42

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 151.14  E-value: 9.99e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551   80 VAIK-----HVNKKRIELTRqvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN--DSINLDWMFR 152
Cdd:smart00219  31 VAVKtlkedASEQQIEEFLR----EARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYMEGGDLLSYLRKnrPKLSLSDLLS 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  153 YSLinDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEpDDSHALYAKKL---WTAPELLSgnp 228
Cdd:smart00219 107 FAL--QIARGMEYLEsKNFI--HRDLAARNCLVGENLVVKISDFGLS--RDLYD-DDYYRKRGGKLpirWMAPESLK--- 176
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  229 lptTGM--QKADVYSFGIILQEIALRSGPFYlegLDLSPKEIVQKVRNGQRPYfRPSIDRtqlnEELVLLMERCWAQDPA 306
Cdd:smart00219 177 ---EGKftSKSDVWSFGVLLWEIFTLGEQPY---PGMSNEEVLEYLKNGYRLP-QPPNCP----PELYDLMLQCWAEDPE 245
                          250
                   ....*....|..
gi 1370514551  307 ERPDFGQIKGFI 318
Cdd:smart00219 246 DRPTFSELVEIL 257
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
80-318 2.73e-41

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 149.95  E-value: 2.73e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL--ENDSINLDWMFRYSLi 156
Cdd:pfam07714  31 VAVKTLKEGADEEEREDFLeEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEYMPGGDLLDFLrkHKRKLTLKDLLSMAL- 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 nDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKKL---WTAPELLSGNPLpTT 232
Cdd:pfam07714 110 -QIAKGMEYLEsKNFV--HRDLAARNCLVSENLVVKISDFGLS--RDIYDDDYYRKRGGGKLpikWMAPESLKDGKF-TS 183
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 233 gmqKADVYSFGIILQEIALRSG-PFYleglDLSPKEIVQKVRNGQRPYfRPSIDRTQLNEelvlLMERCWAQDPAERPDF 311
Cdd:pfam07714 184 ---KSDVWSFGVLLWEIFTLGEqPYP----GMSNEEVLEFLEDGYRLP-QPENCPDELYD----LMKQCWAYDPEDRPTF 251

                  ....*..
gi 1370514551 312 GQIKGFI 318
Cdd:pfam07714 252 SELVEDL 258
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
88-309 1.64e-17

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 85.45  E-value: 1.64e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  88 KRIELTRQVLfeLKHMRDVQFNH---LTRF-----IGACIDPPNI-------------CIVTEYCPRGSLQDILENDSiN 146
Cdd:COG0515    27 RDLRLGRPVA--LKVLRPELAADpeaRERFrrearALARLNHPNIvrvydvgeedgrpYLVMEYVEGESLADLLRRRG-P 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLS 225
Cdd:COG0515   104 LPPAEALRILAQLAEALAAAHaAGIV--HRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGTVVGTPGYMAPEQAR 181
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 226 GNPLpttgMQKADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNGQRPyfRPSIDRTQLNEELVLLMERCWAQDP 305
Cdd:COG0515   182 GEPV----DPRSDVYSLGVTLYELLTGRPPFDGD----SPAELLRAHLREPPP--PPSELRPDLPPALDAIVLRALAKDP 251

                  ....
gi 1370514551 306 AERP 309
Cdd:COG0515   252 EERY 255
PHA02988 PHA02988
hypothetical protein; Provisional
67-321 2.23e-16

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 79.79  E-value: 2.23e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  67 QIFANTGHFKGNVVAIK-----HVN-KKRIELTRQvlfELKHMRDVQFNHLTR----FIGACIDPPNICIVTEYCPRGSL 136
Cdd:PHA02988   33 QNSIYKGIFNNKEVIIRtfkkfHKGhKVLIDITEN---EIKNLRRIDSNNILKiygfIIDIVDDLPRLSLILEYCTRGYL 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 137 QDILENDSiNLDWMFRYSLINDLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALyakk 216
Cdd:PHA02988  110 REVLDKEK-DLSFKTKLDMAIDCCKGLYNLYKYTNKPYKNLTSVSFLVTENYKLKIICHGLEKILSSPPFKNVNFM---- 184
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 217 LWTAPELLSGNPLPTTgmQKADVYSFGIILQEIALRSGPFylEGLDLspKEIVQKVRNGQRPYFRPsidrTQLNEELVLL 296
Cdd:PHA02988  185 VYFSYKMLNDIFSEYT--IKDDIYSLGVVLWEIFTGKIPF--ENLTT--KEIYDLIINKNNSLKLP----LDCPLEIKCI 254
                         250       260
                  ....*....|....*....|....*
gi 1370514551 297 MERCWAQDPAERPDFGQIKGFIRRF 321
Cdd:PHA02988  255 VEACTSHDSIKRPNIKEILYNLSLY 279
HNOBA pfam07701
Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and ...
330-378 2.08e-06

Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and pfam00211 in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals.


Pssm-ID: 462234  Cd Length: 214  Bit Score: 48.73  E-value: 2.08e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370514551 330 LDNLLLRMEQYANNLEKLVEErtqayLE-EKRKAEALLYQILPHSVAEQL 378
Cdd:pfam07701 170 LKLALDQLEQKSAELEESMRE-----LEeEKKKTDELLYSMLPKSVADRL 214
 
Name Accession Description Interval E-value
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
50-324 0e+00

Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-A binds and is activated by the atrial and B-type natriuretic peptides, ANP and BNP, which are important in blood pressure regulation and cardiac pathophysiology. GC-B binds the C-type natriuretic peptide, CNP, which is a potent vasorelaxant and functions in vascular remodeling and bone growth regulation. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-A/B subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 537.95  E-value: 0e+00
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  50 SLRGSSYGSLMTAHGKY--QIFANTGHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIV 127
Cdd:cd14042     1 SLSSSSYGSLMTAASFDqsQIFTKTGYYKGNLVAIKKVNKKRIDLTREVLKELKHMRDLQHDNLTRFIGACVDPPNICIL 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 128 TEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE-P 206
Cdd:cd14042    81 TEYCPKGSLQDILENEDIKLDWMFRYSLIHDIVKGMHYLHDSEIKSHGNLKSSNCVVDSRFVLKITDFGLHSFRSGQEpP 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 207 DDSHALYAKKLWTAPELLSGNPLPTTGMQKADVYSFGIILQEIALRSGPFYLEGLDLSPKEIV-QKVRNGQRPYFRPSID 285
Cdd:cd14042   161 DDSHAYYAKLLWTAPELLRDPNPPPPGTQKGDVYSFGIILQEIATRQGPFYEEGPDLSPKEIIkKKVRNGEKPPFRPSLD 240
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1370514551 286 RTQLNEELVLLMERCWAQDPAERPDFGQIKGFIRRFNKE 324
Cdd:cd14042   241 ELECPDEVLSLMQRCWAEDPEERPDFSTLRNKLKKLNKG 279
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
52-321 1.47e-135

Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270894 [Multi-domain]  Cd Length: 268  Bit Score: 395.22  E-value: 1.47e-135
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  52 RGSSYGSLMTAHGKYQIFAntGHFKGNVVAIKHVNKKRIElTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYC 131
Cdd:cd13992     2 SCGSGASSHTGEPKYVKKV--GVYGGRTVAIKHITFSRTE-KRTILQELNQLKELVHDNLNKFIGICINPPNIAVVTEYC 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 132 PRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE--PDDS 209
Cdd:cd13992    79 TRGSLQDVLLNREIKMDWMFKSSFIKDIVKGMNYLHSSSIGYHGRLKSSNCLVDSRWVVKLTDFGLRNLLEEQTnhQLDE 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 210 HALYAKKLWTAPELLSGNPLPTTGMQKADVYSFGIILQEIALRSGPFYLEGldlsPKEIVQKVRNGQRPYFRPSIDR--T 287
Cdd:cd13992   159 DAQHKKLLWTAPELLRGSLLEVRGTQKGDVYSFAIILYEILFRSDPFALER----EVAIVEKVISGGNKPFRPELAVllD 234
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1370514551 288 QLNEELVLLMERCWAQDPAERPDFGQIKGFIRRF 321
Cdd:cd13992   235 EFPPRLVLLVKQCWAENPEKRPSFKQIKKTLTEN 268
CYCc smart00044
Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl ...
357-541 4.17e-98

Adenylyl- / guanylyl cyclase, catalytic domain; Present in two copies in mammalian adenylyl cyclases. Eubacterial homologues are known. Two residues (Asn, Arg) are thought to be involved in catalysis. These cyclases have important roles in a diverse range of cellular processes.


Pssm-ID: 214485  Cd Length: 194  Bit Score: 296.48  E-value: 4.17e-98
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  357 EEKRKAEALLYQILPHSVAEQLKRGE-TVQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTLLNDLYTCFDAIIDNFDVY 435
Cdd:smart00044   1 EEKKKTDRLLDQLLPASVAEQLKRGGsPVPAESYDNVTILFSDIVGFTSLCSTSTPEQVVNLLNDLYSRFDQIIDRHGGY 80
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  436 KVETIGDAYMVVSGLPGRNGQRHAPEIARMALALLDAVSSFRIRHRpHDQLRLRIGVHTGPVCAGVVGLKMPRYCLFGDT 515
Cdd:smart00044  81 KVKTIGDAYMVASGLPEEALVDHAELIADEALDMVEELKTVLVQHR-EEGLRVRIGIHTGPVVAGVVGIRMPRYCLFGDT 159
                          170       180
                   ....*....|....*....|....*.
gi 1370514551  516 VNTASRMESNGQALKIHVSSTTKDAL 541
Cdd:smart00044 160 VNLASRMESAGDPGQIQVSEETYSLL 185
Guanylate_cyc pfam00211
Adenylate and Guanylate cyclase catalytic domain;
384-570 6.73e-94

Adenylate and Guanylate cyclase catalytic domain;


Pssm-ID: 425528  Cd Length: 183  Bit Score: 285.29  E-value: 6.73e-94
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 384 VQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTLLNDLYTCFDAIIDNFDVYKVETIGDAYMVVSGLPgRNGQRHAPEIA 463
Cdd:pfam00211   1 VYAQPYDNVTILFADIVGFTALSSRHSPEQVVRLLNELYTRFDRLLDKHKVYKVKTIGDAYMVVSGLP-EPSPAHARKIA 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 464 RMALALLDAVSSFRIRHRPhdQLRLRIGVHTGPVCAGVVGLKMPRYCLFGDTVNTASRMESNGQALKIHVSSTTKDALDE 543
Cdd:pfam00211  80 EMALDMLEAIGEVNVESSE--GLRVRVGIHTGPVVAGVIGARMPRYDLWGNTVNLASRMESTGVPGKIHVSEETYRLLKT 157
                         170       180
                  ....*....|....*....|....*..
gi 1370514551 544 LGcFQLELRGDVEMKGKGKMRTYWLLG 570
Cdd:pfam00211 158 EG-FEFTERGEIEVKGKGKMKTYFLNG 183
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
69-323 1.24e-73

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-2D is allso called Retinal Guanylyl Cyclase 1 (RETGC-1) or Rod Outer Segment membrane Guanylate Cyclase (ROS-GC). It is found in the photoreceptors of the retina where it anchors the reciprocal feedback loop between calcium and cGMP, which regulates the dark, light, and recovery phases in phototransduction. It is also found in other sensory neurons and may be a universal transduction component that plays a role in the perception of all senses. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-2D subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270945 [Multi-domain]  Cd Length: 267  Bit Score: 236.15  E-value: 1.24e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  69 FANTG-HFKGNVVAIKHV-NKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSIN 146
Cdd:cd14043    14 SSNTGvAYEGDWVWLKKFpGGSHTELRPSTKNVFSKLRELRHENVNLFLGLFVDCGILAIVSEHCSRGSLEDLLRNDDMK 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYSLINDLVKGMAFLHNSIIsSHGSLKSSNCVVDSRFVLKITDYGLASF----RSTAEPDDSHALyakkLWTAPE 222
Cdd:cd14043    94 LDWMFKSSLLLDLIKGMRYLHHRGI-VHGRLKSRNCVVDGRFVLKITDYGYNEIleaqNLPLPEPAPEEL----LWTAPE 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 223 LLSGNPLPTTGMQKADVYSFGIILQEIALRSGPFYLegLDLSPKEIVQKVRNgQRPYFRPSIDRTQLNEELVLLMERCWA 302
Cdd:cd14043   169 LLRDPRLERRGTFPGDVFSFAIIMQEVIVRGAPYCM--LGLSPEEIIEKVRS-PPPLCRPSVSMDQAPLECIQLMKQCWS 245
                         250       260
                  ....*....|....*....|.
gi 1370514551 303 QDPAERPDFGQIKGFIRRFNK 323
Cdd:cd14043   246 EAPERRPTFDQIFDQFKSINK 266
CHD cd07302
cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also ...
392-568 2.05e-73

cyclase homology domain; Catalytic domains of the mononucleotidyl cyclases (MNC's), also called cyclase homology domains (CHDs), are part of the class III nucleotidyl cyclases. This class includes eukaryotic and prokaryotic adenylate cyclases (AC's) and guanylate cyclases (GC's). They seem to share a common catalytic mechanism in their requirement for two magnesium ions to bind the polyphosphate moiety of the nucleotide.


Pssm-ID: 143636 [Multi-domain]  Cd Length: 177  Bit Score: 232.08  E-value: 2.05e-73
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 392 VTIYFSDIVGFTALSAESTPMQVVTLLNDLYTCFDAIIDNFDVYKVETIGDAYMVVSGLPGRNgQRHAPEIARMALALLD 471
Cdd:cd07302     2 VTVLFADIVGFTALSERLGPEELVELLNEYFSAFDEIIERHGGTVDKTIGDAVMAVFGLPGAH-EDHAERAVRAALEMQE 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 472 AVSSFRIRHRPHDQLRLRIGVHTGPVCAGVVGLKMPRYCLFGDTVNTASRMESNGQALKIHVSSTTKDALDELGcFQLEL 551
Cdd:cd07302    81 ALAELNAEREGGPPLRLRIGIHTGPVVAGVVGSERPEYTVIGDTVNLAARLESLAKPGQILVSEATYELLGDAG-FEFEE 159
                         170
                  ....*....|....*...
gi 1370514551 552 RGDVEMKGK-GKMRTYWL 568
Cdd:cd07302   160 LGEVELKGKsGPVRVYRL 177
PK_GC_unk cd14045
Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The ...
54-320 1.21e-66

Pseudokinase domain of the unknown subfamily of membrane Guanylate Cyclase receptors; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs lack a critical aspartate involved in ATP binding and does not exhibit kinase activity. It functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270947 [Multi-domain]  Cd Length: 269  Bit Score: 217.80  E-value: 1.21e-66
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  54 SSYGSLMTAHGKYQI-FANTGHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCP 132
Cdd:cd14045     6 TVLSSCTTAHNAQKKpFTQTGIYDGRTVAIKKIAKKSFTLSKRIRKEVKQVRELDHPNLCKFIGGCIEVPNVAIITEYCP 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 133 RGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIIsSHGSLKSSNCVVDSRFVLKITDYGLASFRS--TAEPDDSH 210
Cdd:cd14045    86 KGSLNDVLLNEDIPLNWGFRFSFATDIARGMAYLHQHKI-YHGRLKSSNCVIDDRWVCKIADYGLTTYRKedGSENASGY 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 211 ALYAKKLWTAPELLSGN-PLPTtgmQKADVYSFGIILQEIALRSGPFYLE--GLDLSPKEIVQKVRNGQrpyfrpSIDRT 287
Cdd:cd14045   165 QQRLMQVYLPPENHSNTdTEPT---QATDVYSYAIILLEIATRNDPVPEDdySLDEAWCPPLPELISGK------TENSC 235
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1370514551 288 QLNEELVLLMERCWAQDPAERPDFGQIKGFIRR 320
Cdd:cd14045   236 PCPADYVELIRRCRKNNPAQRPTFEQIKKTLHK 268
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
73-314 1.15e-65

Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed mainly of MAP3Ks and similar proteins, including TGF-beta Activated Kinase-1 (TAK1, also called MAP3K7), MAP3K12, MAP3K13, Mixed lineage kinase (MLK), MLK-Like mitogen-activated protein Triple Kinase (MLTK), and Raf (Rapidly Accelerated Fibrosarcoma) kinases. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Also included in this subfamily is the pseudokinase Kinase Suppressor of Ras (KSR), which is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway.


Pssm-ID: 270901 [Multi-domain]  Cd Length: 245  Bit Score: 214.32  E-value: 1.15e-65
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIK--HVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWM 150
Cdd:cd13999    12 GKWRGTDVAIKklKVEDDNDELLKEFRREVSILSKLRHPNIVQFIGACLSPPPLCIVTEYMPGGSLYDLLHKKKIPLSWS 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 151 FRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKlWTAPELLSGNPL 229
Cdd:cd13999    92 LRLKIALDIARGMNYLHsPPII--HRDLKSLNILLDENFTVKIADFGLSRIKNSTTEKMTGVVGTPR-WMAPEVLRGEPY 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 230 PttgmQKADVYSFGIILQEIALRSGPFylEGLDlSPKEIVQKVRNGQRPYFRPSIDrtqlnEELVLLMERCWAQDPAERP 309
Cdd:cd13999   169 T----EKADVYSFGIVLWELLTGEVPF--KELS-PIQIAAAVVQKGLRPPIPPDCP-----PELSKLIKRCWNEDPEKRP 236

                  ....*
gi 1370514551 310 DFGQI 314
Cdd:cd13999   237 SFSEI 241
AcyC COG2114
Adenylate cyclase, class 3 [Signal transduction mechanisms];
347-575 1.60e-52

Adenylate cyclase, class 3 [Signal transduction mechanisms];


Pssm-ID: 441717 [Multi-domain]  Cd Length: 407  Bit Score: 184.62  E-value: 1.60e-52
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 347 LVEERTQAYLEEKRKAEALLYQILPHSVAEQLKRG--ETVQAEAFDSVTIYFSDIVGFTALSAESTPMQVVTLLNDLYTC 424
Cdd:COG2114   176 ALLLLLLLALRERERLRDLLGRYLPPEVAERLLAGgeELRLGGERREVTVLFADIVGFTALSERLGPEELVELLNRYFSA 255
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 425 FDAIIDNFDVYKVETIGDAYMVVSGLPGRNGQrHAPEIARMALALLDAVSSFRIRHRPH--DQLRLRIGVHTGPVCAGVV 502
Cdd:COG2114   256 MVEIIERHGGTVDKFIGDGVMAVFGAPVARED-HAERAVRAALAMQEALAELNAELPAEggPPLRVRIGIHTGEVVVGNI 334
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 503 G-LKMPRYCLFGDTVNTASRMESNGQALKIHVSSTTKDALDELgcFQLELRGDVEMKGKGK-MRTYWLLGERKGP 575
Cdd:COG2114   335 GsEDRLDYTVIGDTVNLAARLESLAKPGEILVSEATYDLLRDR--FEFRELGEVRLKGKAEpVEVYELLGAKEAA 407
PK_GC-C cd14044
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain ...
73-315 1.99e-50

Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-C; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity and/or ATP binding. GC-C binds and is activated by the intestinal hormones, guanylin (GN) and uroguanylin (UGN), which are secreted after salty meals to inhibit sodium absorption and induce the secretion of chloride, bicarbonate, and water. GN and UGN are also present in the kidney, where they induce increased salt and water secretion. This prevents the development of hypernatremia and hypervolemia after ingestion of high amounts of salt. Membrane (or particulate) GCs consist of an extracellular ligand-binding domain, a single transmembrane region, and an intracellular tail that contains a PK-like domain, an amphiphatic region and a catalytic GC domain that catalyzes the conversion of GTP into cGMP and pyrophosphate. Membrane GCs act as receptors that transduce an extracellular signal to the intracellular production of cGMP, which has been implicated in many processes including cell proliferation, phototransduction, and muscle contractility, through its downstream effectors such as PKG. The PK-like domain of GCs functions as a negative regulator of the catalytic GC domain and may also act as a docking site for interacting proteins such as GC-activating proteins. The GC-C subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270946 [Multi-domain]  Cd Length: 271  Bit Score: 175.07  E-value: 1.99e-50
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILeNDSIN------ 146
Cdd:cd14044    27 GKYDKKVVILKDLKNNEGNFTEKQKIELNKLLQIDYYNLTKFYGTVKLDTMIFGVIEYCERGSLRDVL-NDKISypdgtf 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYSLINDLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTaepddshalyAKKLWTAPELLSG 226
Cdd:cd14044   106 MDWEFKISVMYDIAKGMSYLHSSKTEVHGRLKSTNCVVDSRMVVKITDFGCNSILPP----------SKDLWTAPEHLRQ 175
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPttgmQKADVYSFGIILQEIALRSGPFYLEGLDlSPKEIVQKVRN--GQRPyFRPSIDRTQLNE---ELVLLMERCW 301
Cdd:cd14044   176 AGTS----QKGDVYSYGIIAQEIILRKETFYTAACS-DRKEKIYRVQNpkGMKP-FRPDLNLESAGErerEVYGLVKNCW 249
                         250
                  ....*....|....
gi 1370514551 302 AQDPAERPDFGQIK 315
Cdd:cd14044   250 EEDPEKRPDFKKIE 263
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
80-318 9.99e-42

Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 151.14  E-value: 9.99e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551   80 VAIK-----HVNKKRIELTRqvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN--DSINLDWMFR 152
Cdd:smart00219  31 VAVKtlkedASEQQIEEFLR----EARIMRKLDHPNVVKLLGVCTEEEPLYIVMEYMEGGDLLSYLRKnrPKLSLSDLLS 106
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  153 YSLinDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEpDDSHALYAKKL---WTAPELLSgnp 228
Cdd:smart00219 107 FAL--QIARGMEYLEsKNFI--HRDLAARNCLVGENLVVKISDFGLS--RDLYD-DDYYRKRGGKLpirWMAPESLK--- 176
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  229 lptTGM--QKADVYSFGIILQEIALRSGPFYlegLDLSPKEIVQKVRNGQRPYfRPSIDRtqlnEELVLLMERCWAQDPA 306
Cdd:smart00219 177 ---EGKftSKSDVWSFGVLLWEIFTLGEQPY---PGMSNEEVLEYLKNGYRLP-QPPNCP----PELYDLMLQCWAEDPE 245
                          250
                   ....*....|..
gi 1370514551  307 ERPDFGQIKGFI 318
Cdd:smart00219 246 DRPTFSELVEIL 257
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
80-315 1.04e-41

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP kinases serve as essential sensors of cellular stress. They are involved in regulating NF-kappaB and MAPK signaling, and are implicated in mediating cellular processes such as apoptosis, necroptosis, differentiation, and survival. RIP kinases contain a homologous N-terminal kinase domain and varying C-terminal domains. Higher vertebrates contain multiple RIP kinases, with mammals harboring at least five members. RIP1 and RIP2 harbor C-terminal domains from the Death domain (DD) superfamily while RIP4 contains ankyrin (ANK) repeats. RIP3 contain a RIP homotypic interaction motif (RHIM) that facilitates binding to RIP1. RIP1 and RIP3 are important in apoptosis and necroptosis, while RIP2 and RIP4 play roles in keratinocyte differentiation and inflammatory immune responses. The RIP subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270880 [Multi-domain]  Cd Length: 263  Bit Score: 151.07  E-value: 1.04e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKR--IELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLIN 157
Cdd:cd13978    21 VAIKCLHSSPncIEERKALLKEAEKMERARHSYVLPLLGVCVERRSLGLVMEYMENGSLKSLLEREIQDVPWSLRFRIIH 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLHNS---IIssHGSLKSSNCVVDSRFVLKITDYGLASFR----STAEPDDSHALYAKKLWTAPELL-SGNPL 229
Cdd:cd13978   101 EIALGMNFLHNMdppLL--HHDLKPENILLDNHFHVKISDFGLSKLGmksiSANRRRGTENLGGTPIYMAPEAFdDFNKK 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 230 PTTgmqKADVYSFGIILQEIALRSGPFYLEgldLSPKEIVQKVRNGQRPYFrPSIDRTQLNE---ELVLLMERCWAQDPA 306
Cdd:cd13978   179 PTS---KSDVYSFAIVIWAVLTRKEPFENA---INPLLIMQIVSKGDRPSL-DDIGRLKQIEnvqELISLMIRCWDGNPD 251

                  ....*....
gi 1370514551 307 ERPDFGQIK 315
Cdd:cd13978   252 ARPTFLECL 260
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
80-318 2.72e-41

Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class of kinases can not be predicted. Possible dual-specificity Ser/Thr/Tyr kinase.


Pssm-ID: 214568 [Multi-domain]  Cd Length: 258  Bit Score: 150.01  E-value: 2.72e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551   80 VAIKHVNKKRIELTRQ-VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL---ENDSINLDWMFRYSL 155
Cdd:smart00221  31 VAVKTLKEDASEQQIEeFLREARIMRKLDHPNIVKLLGVCTEEEPLMIVMEYMPGGDLLDYLrknRPKELSLSDLLSFAL 110
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  156 inDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRsTAEPDDSHALYAKKL---WTAPELLSgnplpt 231
Cdd:smart00221 111 --QIARGMEYLEsKNFI--HRDLAARNCLVGENLVVKISDFGLS--R-DLYDDDYYKVKGGKLpirWMAPESLK------ 177
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  232 TGM--QKADVYSFGIILQEIALRSGPFYLEgldLSPKEIVQKVRNGQRPYFRPSIdrtqlNEELVLLMERCWAQDPAERP 309
Cdd:smart00221 178 EGKftSKSDVWSFGVLLWEIFTLGEEPYPG---MSNAEVLEYLKKGYRLPKPPNC-----PPELYKLMLQCWAEDPEDRP 249

                   ....*....
gi 1370514551  310 DFGQIKGFI 318
Cdd:smart00221 250 TFSELVEIL 258
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
80-318 2.73e-41

Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. Protein kinases catalyze the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. Phosphoprotein phosphatases catalyze the reverse process. Protein kinases fall into three broad classes, characterized with respect to substrate specificity; Serine/threonine-protein kinases, tyrosine-protein kinases, and dual specificity protein kinases (e.g. MEK - phosphorylates both Thr and Tyr on target proteins). This entry represents the catalytic domain found in a number of serine/threonine- and tyrosine-protein kinases. It does not include the catalytic domain of dual specificity kinases.


Pssm-ID: 462242 [Multi-domain]  Cd Length: 258  Bit Score: 149.95  E-value: 2.73e-41
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL--ENDSINLDWMFRYSLi 156
Cdd:pfam07714  31 VAVKTLKEGADEEEREDFLeEASIMKKLDHPNIVKLLGVCTQGEPLYIVTEYMPGGDLLDFLrkHKRKLTLKDLLSMAL- 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 nDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKKL---WTAPELLSGNPLpTT 232
Cdd:pfam07714 110 -QIAKGMEYLEsKNFV--HRDLAARNCLVSENLVVKISDFGLS--RDIYDDDYYRKRGGGKLpikWMAPESLKDGKF-TS 183
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 233 gmqKADVYSFGIILQEIALRSG-PFYleglDLSPKEIVQKVRNGQRPYfRPSIDRTQLNEelvlLMERCWAQDPAERPDF 311
Cdd:pfam07714 184 ---KSDVWSFGVLLWEIFTLGEqPYP----GMSNEEVLEFLEDGYRLP-QPENCPDELYD----LMKQCWAYDPEDRPTF 251

                  ....*..
gi 1370514551 312 GQIKGFI 318
Cdd:pfam07714 252 SELVEDL 258
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
76-315 2.58e-40

Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. PKs make up a large family of serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins. Majority of protein phosphorylation occurs on serine residues while only 1% occurs on tyrosine residues. Protein phosphorylation is a mechanism by which a wide variety of cellular proteins, such as enzymes and membrane channels, are reversibly regulated in response to certain stimuli. PKs often function as components of signal transduction pathways in which one kinase activates a second kinase, which in turn, may act on other kinases; this sequential action transmits a signal from the cell surface to target proteins, which results in cellular responses. The PK family is one of the largest known protein families with more than 100 homologous yeast enzymes and more than 500 human proteins. A fraction of PK family members are pseudokinases that lack crucial residues for catalytic activity. The mutiplicity of kinases allows for specific regulation according to substrate, tissue distribution, and cellular localization. PKs regulate many cellular processes including proliferation, division, differentiation, motility, survival, metabolism, cell-cycle progression, cytoskeletal rearrangement, immunity, and neuronal functions. Many kinases are implicated in the development of various human diseases including different types of cancer. The PK family is part of a larger superfamily that includes the catalytic domains of RIO kinases, aminoglycoside phosphotransferase, choline kinase, phosphoinositide 3-kinase (PI3K), and actin-fragmin kinase.


Pssm-ID: 270622 [Multi-domain]  Cd Length: 215  Bit Score: 145.88  E-value: 2.58e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  76 KGNVVAIKHVNKKRIELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYS 154
Cdd:cd00180    17 TGKKVAVKVIPKEKLKKLLEELLrEIEILKKLNHPNIVKLYDVFETENFLYLVMEYCEGGSLKDLLKENKGPLSEEEALS 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGNPlptTG 233
Cdd:cd00180    97 ILRQLLSALEYLHsNGII--HRDLKPENILLDSDGTVKLADFGLAKDLDSDDSLLKTTGGTTPPYYAPPELLGGR---YY 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 234 MQKADVYSFGIILQEIalrsgpfylegldlspkeivqkvrngqrpyfrpsidrtqlnEELVLLMERCWAQDPAERPDFGQ 313
Cdd:cd00180   172 GPKVDIWSLGVILYEL-----------------------------------------EELKDLIRRMLQYDPKKRPSAKE 210

                  ..
gi 1370514551 314 IK 315
Cdd:cd00180   211 LL 212
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
64-319 6.87e-40

Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. They can be classified into receptor and non-receptor tyr kinases. PTKs play important roles in many cellular processes including, lymphocyte activation, epithelium growth and maintenance, metabolism control, organogenesis regulation, survival, proliferation, differentiation, migration, adhesion, motility, and morphogenesis. Receptor tyr kinases (RTKs) are integral membrane proteins which contain an extracellular ligand-binding region, a transmembrane segment, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain, leading to intracellular signaling. Some RTKs are orphan receptors with no known ligands. Non-receptor (or cytoplasmic) tyr kinases are distributed in different intracellular compartments and are usually multi-domain proteins containing a catalytic tyr kinase domain as well as various regulatory domains such as SH3 and SH2. PTKs are usually autoinhibited and require a mechanism for activation. In many PTKs, the phosphorylation of tyr residues in the activation loop is essential for optimal activity. Aberrant expression of PTKs is associated with many development abnormalities and cancers.The PTK family is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270623 [Multi-domain]  Cd Length: 262  Bit Score: 146.14  E-value: 6.87e-40
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  64 GKYQIFANTGHfkgnVVAIK-----HVNKKRIELTRqvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQD 138
Cdd:cd00192    14 GKLKGGDGKTV----DVAVKtlkedASESERKDFLK----EARVMKKLGHPNVVRLLGVCTEEEPLYLVMEYMEGGDLLD 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 139 ILENDSINLDWMFRYSL-INDLV-------KGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDS 209
Cdd:cd00192    86 FLRKSRPVFPSPEPSTLsLKDLLsfaiqiaKGMEYLAsKKFV--HRDLAARNCLVGEDLVVKISDFGLS--RDIYDDDYY 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 210 HALYAKKL---WTAPELLSGNpLPTTgmqKADVYSFGIILQEIALRSG-PFYleglDLSPKEIVQKVRNGQRPYfRPSId 285
Cdd:cd00192   162 RKKTGGKLpirWMAPESLKDG-IFTS---KSDVWSFGVLLWEIFTLGAtPYP----GLSNEEVLEYLRKGYRLP-KPEN- 231
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1370514551 286 rtqLNEELVLLMERCWAQDPAERPDFGQIKGFIR 319
Cdd:cd00192   232 ---CPDELYELMLSCWQLDPEDRPTFSELVERLE 262
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
53-316 1.40e-39

Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated protein Triple Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLTK, also called zipper sterile-alpha-motif kinase (ZAK), contains a catalytic kinase domain and a leucine zipper. There are two alternatively-spliced variants, MLTK-alpha and MLTK-beta. MLTK-alpha contains a sterile-alpha-motif (SAM) at the C-terminus. MLTK regulates the c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 MAPK, and NF-kB pathways. ZAK is the MAP3K involved in the signaling cascade that leads to the ribotoxic stress response initiated by cellular damage due to Shiga toxins and ricin. It may also play a role in cell transformation and cancer development. MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals.The MLTK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270962 [Multi-domain]  Cd Length: 242  Bit Score: 144.71  E-value: 1.40e-39
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  53 GSSYGSLMTAHGKYQifantghfkGNVVAIKHVNKkrIELTRQVLFELKHMRDVQFnhltrfIGACIDPPNICIVTEYCP 132
Cdd:cd14060     3 GGSFGSVYRAIWVSQ---------DKEVAVKKLLK--IEKEAEILSVLSHRNIIQF------YGAILEAPNYGIVTEYAS 65
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 133 RGSLQDIL-ENDSINLDWMFRYSLINDLVKGMAFLHNS--IISSHGSLKSSNCVVDSRFVLKITDYGLASFRStaepDDS 209
Cdd:cd14060    66 YGSLFDYLnSNESEEMDMDQIMTWATDIAKGMHYLHMEapVKVIHRDLKSRNVVIAADGVLKICDFGASRFHS----HTT 141
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 210 H-ALYAKKLWTAPELLSGnpLPTTgmQKADVYSFGIILQEIALRSGPFY-LEGLDLSpkEIVqkVRNGQRPYFRPSIDRT 287
Cdd:cd14060   142 HmSLVGTFPWMAPEVIQS--LPVS--ETCDTYSYGVVLWEMLTREVPFKgLEGLQVA--WLV--VEKNERPTIPSSCPRS 213
                         250       260
                  ....*....|....*....|....*....
gi 1370514551 288 qlneeLVLLMERCWAQDPAERPDFGQIKG 316
Cdd:cd14060   214 -----FAELMRRCWEADVKERPSFKQIIG 237
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
77-315 8.10e-36

Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or threonine-specific kinase subfamily.


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 134.58  E-value: 8.10e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551   77 GNVVAIKHVNKKRIELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-ENDSINLDWMFRYS 154
Cdd:smart00220  24 GKLVAIKVIKKKKIKKDRERILrEIKILKKLKHPNIVRLYDVFEDEDKLYLVMEYCEGGDLFDLLkKRGRLSEDEARFYL 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  155 LinDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDS--HALYakklWTAPELLSGNPLPT 231
Cdd:smart00220 104 R--QILSALEYLHsKGIV--HRDLKPENILLDEDGHVKLADFGLARQLDPGEKLTTfvGTPE----YMAPEVLLGKGYGK 175
                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  232 tgmqKADVYSFGIILQEIALRSGPFYleGlDLSPKEIVQKVRNGQRPYFRPSIDrtqLNEELVLLMERCWAQDPAERPDF 311
Cdd:smart00220 176 ----AVDIWSLGVILYELLTGKPPFP--G-DDQLLELFKKIGKPKPPFPPPEWD---ISPEAKDLIRKLLVKDPEKRLTA 245

                   ....
gi 1370514551  312 GQIK 315
Cdd:smart00220 246 EEAL 249
Nucleotidyl_cyc_III cd07556
Class III nucleotidyl cyclases; Class III nucleotidyl cyclases are the largest, most diverse ...
392-532 3.48e-35

Class III nucleotidyl cyclases; Class III nucleotidyl cyclases are the largest, most diverse group of nucleotidyl cyclases (NC's) containing prokaryotic and eukaryotic proteins. They can be divided into two major groups; the mononucleotidyl cyclases (MNC's) and the diguanylate cyclases (DGC's). The MNC's, which include the adenylate cyclases (AC's) and the guanylate cyclases (GC's), have a conserved cyclase homology domain (CHD), while the DGC's have a conserved GGDEF domain, named after a conserved motif within this subgroup. Their products, cyclic guanylyl and adenylyl nucleotides, are second messengers that play important roles in eukaryotic signal transduction and prokaryotic sensory pathways.


Pssm-ID: 143637 [Multi-domain]  Cd Length: 133  Bit Score: 129.01  E-value: 3.48e-35
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 392 VTIYFSDIVGFTALSAESTPMQVVTLLNDLYTCFDAIIDNFDVYKVETIGDAYMVVSGLPgrngqrHAPEIARMALALLD 471
Cdd:cd07556     2 VTILFADIVGFTSLADALGPDEGDELLNELAGRFDSLIRRSGDLKIKTIGDEFMVVSGLD------HPAAAVAFAEDMRE 75
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370514551 472 AVSSFRIRHRPHdqLRLRIGVHTGPVCAGVVGLKmPRYCLFGDTVNTASRMESNGQALKIH 532
Cdd:cd07556    76 AVSALNQSEGNP--VRVRIGIHTGPVVVGVIGSR-PQYDVWGALVNLASRMESQAKAGQVL 133
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
73-314 1.34e-32

Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. Some IRAKs may also play roles in T- and B-cell signaling, and adaptive immunity. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK-1, -2, and -4 are ubiquitously expressed and are active kinases, while IRAK-M is only induced in monocytes and macrophages and is an inactive kinase. Variations in IRAK genes are linked to diverse diseases including infection, sepsis, cancer, and autoimmune diseases. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase domain in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. This subfamily includes plant receptor-like kinases (RLKs) including Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1). BAK1 functions in BR (brassinosteroid)-regulated plant development and in pathways involved in plant resistance to pathogen infection and herbivore attack. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The IRAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270968 [Multi-domain]  Cd Length: 272  Bit Score: 126.23  E-value: 1.34e-32
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGN-VVAIKHVNKKRI-ELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-ENDSIN-LD 148
Cdd:cd14066    12 GVLENGtVVAVKRLNEMNCaASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKLLVYEYMPNGSLEDRLhCHKGSPpLP 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLINDLVKGMAFLHNS----IIssHGSLKSSNCVVDSRFVLKITDYGLA----SFRSTAEPDDSHALYAkklWTA 220
Cdd:cd14066    92 WPQRLKIAKGIARGLEYLHEEcpppII--HGDIKSSNILLDEDFEPKLTDFGLArlipPSESVSKTSAVKGTIG---YLA 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 221 PELLSGNpLPTTgmqKADVYSFGIILQEIALRSGPFYLEGLDLSPKEIVQKVRNGQRPYFRPSIDR------TQLNEELV 294
Cdd:cd14066   167 PEYIRTG-RVST---KSDVYSFGVVLLELLTGKPAVDENRENASRKDLVEWVESKGKEELEDILDKrlvdddGVEEEEVE 242
                         250       260
                  ....*....|....*....|...
gi 1370514551 295 LLME---RCWAQDPAERPDFGQI 314
Cdd:cd14066   243 ALLRlalLCTRSDPSLRPSMKEV 265
STKc_RIP4_like cd14025
Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar ...
81-315 7.86e-29

Catalytic domain of the Serine/Threonine kinases, Receptor Interacting Protein 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of RIP4, ankyrin (ANK) repeat and kinase domain containing 1 (ANKK1), and similar proteins, all of which harbor C-terminal ANK repeats. RIP4, also called Protein Kinase C-associated kinase (PKK), regulates keratinocyte differentiation and cutaneous inflammation. It activates NF-kappaB and is important in the survival of diffuse large B-cell lymphoma cells. The ANKK1 protein, also called PKK2, has not been studied extensively. The ANKK1 gene, located less than 10kb downstream of the D2 dopamine receptor (DRD2) locus, is altered in the Taq1 A1 polymorphism, which is related to a reduced DRD2 binding affinity and consequently, to mental disorders. The RIP4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270927 [Multi-domain]  Cd Length: 267  Bit Score: 115.67  E-value: 7.86e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  81 AIK-----HVNKK-RIELtrqvLFELKHMRDVQFNHLTRFIGACIDPpnICIVTEYCPRGSLQDILENDSinLDWMFRYS 154
Cdd:cd14025    25 AIKcppslHVDDSeRMEL----LEEAKKMEMAKFRHILPVYGICSEP--VGLVMEYMETGSLEKLLASEP--LPWELRFR 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHnSIISS--HGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDD--SHALYAKKLWTAPE-LLSGNPL 229
Cdd:cd14025    97 IIHETAVGMNFLH-CMKPPllHLDLKPANILLDAHYHVKISDFGLAKWNGLSHSHDlsRDGLRGTIAYLPPErFKEKNRC 175
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 230 PTTgmqKADVYSFGIILQEIALRSGPFYLEGLDLSpkeIVQKVRNGQRPYFRP-SIDRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd14025   176 PDT---KHDVYSFAIVIWGILTQKKPFAGENNILH---IMVKVVKGHRPSLSPiPRQRPSECQQMICLMKRCWDQDPRKR 249

                  ....*..
gi 1370514551 309 PDFGQIK 315
Cdd:cd14025   250 PTFQDIT 256
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
73-323 8.79e-29

Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR is a scaffold protein that functions downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases, but there is some debate in this designation as a few groups have reported detecting kinase catalytic activity for KSRs, specifically KSR1. Vertebrates contain two KSR proteins, KSR1 and KSR2. The KSR subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270965 [Multi-domain]  Cd Length: 271  Bit Score: 115.52  E-value: 8.79e-29
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVvAIKHVNKKRIELTRQVLFELKHM--RDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN--DSINLD 148
Cdd:cd14063    19 GRWHGDV-AIKLLNIDYLNEEQLEAFKEEVAayKNTRHDNLVLFMGACMDPPHLAIVTSLCKGRTLYSLIHErkEKFDFN 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLinDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLkITDYGLASF-RSTAEPDDSHALYAKKLWT---APEL 223
Cdd:cd14063    98 KTVQIAQ--QICQGMGYLHaKGII--HKDLKSKNIFLENGRVV-ITDFGLFSLsGLLQPGRREDTLVIPNGWLcylAPEI 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 224 L--------SGNPLPTTgmQKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQRPyfrpSIDRTQLNEELVL 295
Cdd:cd14063   173 IralspdldFEESLPFT--KASDVYAFGTVWYELLAGRWPFK----EQPAESIIWQVGCGKKQ----SLSQLDIGREVKD 242
                         250       260
                  ....*....|....*....|....*...
gi 1370514551 296 LMERCWAQDPAERPDFGQIKGFIRRFNK 323
Cdd:cd14063   243 ILMQCWAYDPEKRPTFSDLLRMLERLPK 270
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
80-323 1.76e-28

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP2, also called RICK or CARDIAK, harbors a C-terminal Caspase Activation and Recruitment domain (CARD) belonging to the Death domain (DD) superfamily. It functions as an effector kinase downstream of the pattern recognition receptors from the Nod-like (NLR) family, Nod1 and Nod2, which recognizes bacterial peptidoglycans released upon infection. RIP2 may also be involved in regulating wound healing and keratinocyte proliferation. RIP kinases serve as essential sensors of cellular stress. The RIP2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270928 [Multi-domain]  Cd Length: 284  Bit Score: 115.02  E-value: 1.76e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIELTRQ---VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLD--WMFRYS 154
Cdd:cd14026    25 VAIKCLKLDSPVGDSErncLLKEAEILHKARFSYILPILGICNEPEFLGIVTEYMTNGSLNELLHEKDIYPDvaWPLRLR 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHN-SIISSHGSLKSSNCVVDSRFVLKITDYGLASFR----STAEPDDSHALYAKKLWTAPEllSGNPL 229
Cdd:cd14026   105 ILYEIALGVNYLHNmSPPLLHHDLKTQNILLDGEFHVKIADFGLSKWRqlsiSQSRSSKSAPEGGTIIYMPPE--EYEPS 182
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 230 PTTGMQ-KADVYSFGIILQEIALRSGPFylEGLdLSPKEIVQKVRNGQrpyfRPSIDRTQL------NEELVLLMERCWA 302
Cdd:cd14026   183 QKRRASvKHDIYSYAIIMWEVLSRKIPF--EEV-TNPLQIMYSVSQGH----RPDTGEDSLpvdiphRATLINLIESGWA 255
                         250       260
                  ....*....|....*....|....*
gi 1370514551 303 QDPAERPDFG----QIKGFIRRFNK 323
Cdd:cd14026   256 QNPDERPSFLkcliELEPVLRTFDE 280
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
73-314 3.63e-28

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase Kinases 12 and 13; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K12 is also called MAPK upstream kinase (MUK), dual leucine zipper-bearing kinase (DLK) or leucine-zipper protein kinase (ZPK). It is involved in the c-Jun N-terminal kinase (JNK) pathway that directly regulates axonal regulation through the phosphorylation of microtubule-associated protein 1B (MAP1B). It also regulates the differentiation of many cell types including adipocytes and may play a role in adipogenesis. MAP3K13, also called leucine zipper-bearing kinase (LZK), directly phosphorylates and activates MKK7, which in turn activates the JNK pathway. It also activates NF-kB through IKK activation and this activity is enhanced by antioxidant protein-1 (AOP-1). MAP3Ks (MKKKs or MAPKKKs) phosphorylate and activate MAP2Ks (MAPKKs or MKKs), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The MAP3K12/13 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270961 [Multi-domain]  Cd Length: 237  Bit Score: 112.97  E-value: 3.63e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVNKKRIEltrqvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEND-----SINL 147
Cdd:cd14059    12 GKFRGEEVAVKKVRDEKET-------DIKHLRKLNHPNIIKFKGVCTQAPCYCILMEYCPYGQLYEVLRAGreitpSLLV 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 148 DWmfryslINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGlaSFRSTAEPDDSHALYAKKLWTAPELLSG 226
Cdd:cd14059    85 DW------SKQIASGMNYLHlHKII--HRDLKSPNVLVTYNDVLKISDFG--TSKELSEKSTKMSFAGTVAWMAPEVIRN 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPttgmQKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQRPYFRPSidrtQLNEELVLLMERCWAQDPA 306
Cdd:cd14059   155 EPCS----EKVDIWSFGVVLWELLTGEIPYK----DVDSSAIIWGVGSNSLQLPVPS----TCPDGFKLLMKQCWNSKPR 222

                  ....*...
gi 1370514551 307 ERPDFGQI 314
Cdd:cd14059   223 NRPSFRQI 230
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
75-318 4.66e-28

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated Kinase-1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAK1 is also known as mitogen-activated protein kinase kinase kinase 7 (MAPKKK7 or MAP3K7), TAK, or MEKK7. As a MAPKKK, it is an important mediator of cellular responses to extracellular signals. It regulates both the c-Jun N-terminal kinase and p38 MAPK cascades by activating the MAPK kinases, MKK4 and MKK3/6. In addition, TAK1 plays diverse roles in immunity and development, in different biological contexts, through many signaling pathways including TGFbeta/BMP, Wnt/Fz, and NF-kB. It is also implicated in the activation of the tumor suppressor kinase, LKB1. The TAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270960 [Multi-domain]  Cd Length: 253  Bit Score: 112.92  E-value: 4.66e-28
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  75 FKGNVVAIKHV----NKKRIELtrqvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSIN---- 146
Cdd:cd14058    14 WRNQIVAVKIIesesEKKAFEV------EVRQLSRVDHPNIIKLYGACSNQKPVCLVMEYAEGGSLYNVLHGKEPKpiyt 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 ----LDWMFRYSlindlvKGMAFLHN----SIIssHGSLKSSN-CVVDSRFVLKITDYGLASFRSTAEPDDSHALyakkL 217
Cdd:cd14058    88 aahaMSWALQCA------KGVAYLHSmkpkALI--HRDLKPPNlLLTNGGTVLKICDFGTACDISTHMTNNKGSA----A 155
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 218 WTAPELLSGNPLPttgmQKADVYSFGIILQEIALRSGPFylEGLDLSPKEIVQKVRNGQRPyfrPSIdrTQLNEELVLLM 297
Cdd:cd14058   156 WMAPEVFEGSKYS----EKCDVFSWGIILWEVITRRKPF--DHIGGPAFRIMWAVHNGERP---PLI--KNCPKPIESLM 224
                         250       260
                  ....*....|....*....|.
gi 1370514551 298 ERCWAQDPAERPDFGQIKGFI 318
Cdd:cd14058   225 TRCWSKDPEKRPSMKEIVKIM 245
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
73-315 2.46e-26

Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of Csk, Chk, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. They negatively regulate the activity of Src kinases that are anchored to the plasma membrane. To inhibit Src kinases, Csk and Chk are translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Chk inhibit Src kinases using a noncatalytic mechanism by simply binding to them. As negative regulators of Src kinases, Csk and Chk play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. The Csk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270635 [Multi-domain]  Cd Length: 256  Bit Score: 108.21  E-value: 2.46e-26
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVnKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL---ENDSINLDW 149
Cdd:cd05039    25 GDYRGQKVAVKCL-KDDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGNGLYIVTEYMAKGSLVDYLrsrGRAVITRKD 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 150 MFRYSLinDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASfrstaepDDSHALYAKKL---WTAPELLS 225
Cdd:cd05039   104 QLGFAL--DVCEGMEYLEsKKFV--HRDLAARNVLVSEDNVAKVSDFGLAK-------EASSNQDGGKLpikWTAPEALR 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 226 GNPLPTtgmqKADVYSFGIILQEI-ALRSGPFYLEGLdlspKEIVQKVRNGQR---PYFRPSidrtqlneELVLLMERCW 301
Cdd:cd05039   173 EKKFST----KSDVWSFGILLWEIySFGRVPYPRIPL----KDVVPHVEKGYRmeaPEGCPP--------EVYKVMKNCW 236
                         250
                  ....*....|....
gi 1370514551 302 AQDPAERPDFGQIK 315
Cdd:cd05039   237 ELDPAKRPTFKQLR 250
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
73-314 4.93e-25

Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLKs act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Mammals have four MLKs (MLK1-4), mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270963 [Multi-domain]  Cd Length: 258  Bit Score: 104.40  E-value: 4.93e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIK---HVNKKRIELTRQ-------VLFELKHMRDVQFNhltrfiGACIDPPNICIVTEYCPRGSLQDILEN 142
Cdd:cd14061    13 GIWRGEEVAVKaarQDPDEDISVTLEnvrqearLFWMLRHPNIIALR------GVCLQPPNLCLVMEYARGGALNRVLAG 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 143 DSINLDWMFRYSLIndLVKGMAFLHN----SIIssHGSLKSSNCVVDSRF--------VLKITDYGLAS--FRSTAEpdD 208
Cdd:cd14061    87 RKIPPHVLVDWAIQ--IARGMNYLHNeapvPII--HRDLKSSNILILEAIenedlenkTLKITDFGLARewHKTTRM--S 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 209 SHALYAkklWTAPELLSGNplptTGMQKADVYSFGIILQEIALRSGPFylEGLDlsPKEIVQKVRNGQRPYFRPSidrtQ 288
Cdd:cd14061   161 AAGTYA---WMAPEVIKSS----TFSKASDVWSYGVLLWELLTGEVPY--KGID--GLAVAYGVAVNKLTLPIPS----T 225
                         250       260
                  ....*....|....*....|....*.
gi 1370514551 289 LNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14061   226 CPEPFAQLMKDCWQPDPHDRPSFADI 251
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
77-309 8.94e-25

Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. This family is composed of STKs, and some dual-specificity PKs that phosphorylate both threonine and tyrosine residues of target proteins. Most members are kinases involved in mitogen-activated protein kinase (MAPK) signaling cascades, acting as MAPK kinases (MAPKKs), MAPKK kinases (MAPKKKs), or MAPKKK kinases (MAP4Ks). The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPKK, which itself is phosphorylated and activated by a MAPKKK. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAPKKK to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Other STE family members include p21-activated kinases (PAKs) and class III myosins, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. Class III myosins are motor proteins containing an N-terminal kinase catalytic domain and a C-terminal actin-binding domain, which can phosphorylate several cytoskeletal proteins, conventional myosin regulatory light chains, as well as autophosphorylate the C-terminal motor domain. They play an important role in maintaining the structural integrity of photoreceptor cell microvilli. The STE family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270692 [Multi-domain]  Cd Length: 254  Bit Score: 103.44  E-value: 8.94e-25
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN--DSINLDWmfRYS 154
Cdd:cd05122    25 GQIVAIKKINLESKEKKESILNEIAILKKCKHPNIVKYYGSYLKKDELWIVMEFCSGGSLKDLLKNtnKTLTEQQ--IAY 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDShaLYAKKLWTAPELLSGNPLPTtg 233
Cdd:cd05122   103 VCKEVLKGLEYLHsHGII--HRDIKAANILLTSDGEVKLIDFGLSAQLSDGKTRNT--FVGTPYWMAPEVIQGKPYGF-- 176
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370514551 234 mqKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQRPYFRpsiDRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd05122   177 --KADIWSLGITAIEMAEGKPPYS----ELPPMKALFLIATNGPPGLR---NPKKWSKEFKDFLKKCLQKDPEKRP 243
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
67-314 4.32e-24

Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. Members of this subfamily include LIMK, Testicular or testis-specific protein kinase (TESK), and similar proteins. LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270967 [Multi-domain]  Cd Length: 252  Bit Score: 101.41  E-value: 4.32e-24
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  67 QIFANTGHFKGNVVAIKHvnKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSIN 146
Cdd:cd14065     8 EVYKVTHRETGKVMVMKE--LKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKDNKLNFITEYVNGGTLEELLKSMDEQ 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYSLINDLVKGMAFLHNSIIsSHGSLKSSNCVV---DSRFVLKITDYGLASF---RSTAEPD--DSHALYAKKLW 218
Cdd:cd14065    86 LPWSQRVSLAKDIASGMAYLHSKNI-IHRDLNSKNCLVreaNRGRNAVVADFGLAREmpdEKTKKPDrkKRLTVVGSPYW 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 219 TAPELLSGNPLPttgmQKADVYSFGIILQEIALR--SGPFYLE-----GLDlspkeiVQKVRNGQRPyfrpsidrtQLNE 291
Cdd:cd14065   165 MAPEMLRGESYD----EKVDVFSFGIVLCEIIGRvpADPDYLPrtmdfGLD------VRAFRTLYVP---------DCPP 225
                         250       260
                  ....*....|....*....|...
gi 1370514551 292 ELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14065   226 SFLPLAIRCCQLDPEKRPSFVEL 248
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
89-321 2.80e-23

Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RIP1 harbors a C-terminal Death domain (DD), which binds death receptors (DRs) including TNF receptor 1, Fas, TNF-related apoptosis-inducing ligand receptor 1 (TRAILR1), and TRAILR2. It also interacts with other DD-containing adaptor proteins such as TRADD and FADD. RIP1 can also recruit other kinases including MEKK1, MEKK3, and RIP3 through an intermediate domain (ID) that bears a RIP homotypic interaction motif (RHIM). RIP1 plays a crucial role in determining a cell's fate, between survival or death, following exposure to stress signals. It is important in the signaling of NF-kappaB and MAPKs, and it links DR-associated signaling to reactive oxygen species (ROS) production. Abnormal RIP1 function may result in ROS accummulation affecting inflammatory responses, innate immunity, stress responses, and cell survival. RIP kinases serve as essential sensors of cellular stress. The RIP1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270929 [Multi-domain]  Cd Length: 267  Bit Score: 99.50  E-value: 2.80e-23
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  89 RIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLinDLVKGMAFLH- 167
Cdd:cd14027    31 CIEHNEALLEEGKMMNRLRHSRVVKLLGVILEEGKYSLVMEYMEKGNLMHVLKKVSVPLSVKGRIIL--EIIEGMAYLHg 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 168 NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKL------------WTAPELLsgNPLPTTGMQ 235
Cdd:cd14027   109 KGVI--HKDLKPENILVDNDFHIKIADLGLASFKMWSKLTKEEHNEQREVdgtakknagtlyYMAPEHL--NDVNAKPTE 184
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 236 KADVYSFGIILQEIALRSGPFylEGLdLSPKEIVQKVRNGQRPYFRPSIDRTQlnEELVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd14027   185 KSDVYSFAIVLWAIFANKEPY--ENA-INEDQIIMCIKSGNRPDVDDITEYCP--REIIDLMKLCWEANPEARPTFPGIE 259

                  ....*.
gi 1370514551 316 GFIRRF 321
Cdd:cd14027   260 EKFRPF 265
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
77-311 1.41e-22

Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are PTKs, catalyzing the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jaks are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270634 [Multi-domain]  Cd Length: 284  Bit Score: 97.84  E-value: 1.41e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLF-ELKHMRDVQFNHLTRFIGACIDP--PNICIVTEYCPRGSLQDILEN--DSINLDWMF 151
Cdd:cd05038    33 GEQVAVKSLQPSGEEQHMSDFKrEIEILRTLDHEYIVKYKGVCESPgrRSLRLIMEYLPSGSLRDYLQRhrDQIDLKRLL 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLinDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTA-------EPDDSHAlyakkLWTAPEL 223
Cdd:cd05038   113 LFAS--QICKGMEYLGSqRYI--HRDLAARNILVESEDLVKISDFGLAKVLPEDkeyyyvkEPGESPI-----FWYAPEC 183
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 224 LSGNplptTGMQKADVYSFGIILQEIALRSGPFYlegldlSPK-EIVQKVRN--GQRPYFRpSIDRTQLNE--------- 291
Cdd:cd05038   184 LRES----RFSSASDVWSFGVTLYELFTYGDPSQ------SPPaLFLRMIGIaqGQMIVTR-LLELLKSGErlprppscp 252
                         250       260
                  ....*....|....*....|.
gi 1370514551 292 -ELVLLMERCWAQDPAERPDF 311
Cdd:cd05038   253 dEVYDLMKECWEYEPQDRPSF 273
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
107-314 1.52e-22

Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; Fes subfamily; catalytic (c) domain. Fes subfamily members include Fes (or Fps), Fer, and similar proteins. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes subfamily proteins are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated tyr kinase activity. Fes and Fer kinases play roles in haematopoiesis, inflammation and immunity, growth factor signaling, cytoskeletal regulation, cell migration and adhesion, and the regulation of cell-cell interactions. Fes and Fer show redundancy in their biological functions.


Pssm-ID: 270637 [Multi-domain]  Cd Length: 251  Bit Score: 97.13  E-value: 1.52e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 107 QFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLH--NSIissHGSLKSSNC 182
Cdd:cd05041    49 QYDHpnIVKLIGVCVQKQPIMIVMELVPGGSLLTFLRKKGARLTVKQLLQMCLDAAAGMEYLEskNCI---HRDLAARNC 125
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 183 VVDSRFVLKITDYGLASfrstaEPDDSHALYAKKL------WTAPELLSgnplptTG--MQKADVYSFGIILQEI-ALRS 253
Cdd:cd05041   126 LVGENNVLKISDFGMSR-----EEEDGEYTVSDGLkqipikWTAPEALN------YGryTSESDVWSFGILLWEIfSLGA 194
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370514551 254 GPFYleglDLSPKEIVQKVRNGQRpyfRPSIDRTQlnEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05041   195 TPYP----GMSNQQTREQIESGYR---MPAPELCP--EAVYRLMLQCWAYDPENRPSFSEI 246
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
73-315 1.71e-22

Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Csk catalyzes the tyr phosphorylation of the regulatory C-terminal tail of Src kinases, resulting in their inactivation. Csk is expressed in a wide variety of tissues. As a negative regulator of Src, Csk plays a role in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Csk is a cytoplasmic (or nonreceptor) PTK containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases, Csk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. In addition, Csk also shows Src-independent functions. It is a critical component in G-protein signaling, and plays a role in cytoskeletal reorganization and cell migration. The Csk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133213 [Multi-domain]  Cd Length: 256  Bit Score: 96.97  E-value: 1.71e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVnkKRIELTRQVLFELKHMRDVQFNHLTRFIGACI-DPPNICIVTEYCPRGSLQDILENDS---INLD 148
Cdd:cd05082    25 GDYRGNKVAVKCI--KNDATAQAFLAEASVMTQLRHSNLVQLLGVIVeEKGGLYIVTEYMAKGSLVDYLRSRGrsvLGGD 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLinDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEpdDSHALYAKklWTAPELLSGN 227
Cdd:cd05082   103 CLLKFSL--DVCEAMEYLEgNNFV--HRDLAARNVLVSEDNVAKVSDFGLTKEASSTQ--DTGKLPVK--WTAPEALREK 174
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 228 PLPTtgmqKADVYSFGIILQEI-ALRSGPFYLEGLdlspKEIVQKVRNGQRpyfrpsIDRTQLNEELVL-LMERCWAQDP 305
Cdd:cd05082   175 KFST----KSDVWSFGILLWEIySFGRVPYPRIPL----KDVVPRVEKGYK------MDAPDGCPPAVYdVMKNCWHLDA 240
                         250
                  ....*....|
gi 1370514551 306 AERPDFGQIK 315
Cdd:cd05082   241 AMRPSFLQLR 250
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
73-314 2.23e-22

Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. ILK contains N-terminal ankyrin repeats, a Pleckstrin Homology (PH) domain, and a C-terminal pseudokinase domain. It is a component of the IPP (ILK/PINCH/Parvin) complex that couples beta integrins to the actin cytoskeleton, and plays important roles in cell adhesion, spreading, invasion, and migration. ILK was initially thought to be an active kinase despite the lack of key conserved residues because of in vitro studies showing that it can phosphorylate certain protein substrates. However, in vivo experiments in Caenorhabditis elegans, Drosophila melanogaster, and mice (ILK-null and knock-in) proved that ILK is not an active kinase. In addition to actin cytoskeleton regulation, ILK also influences the microtubule network and mitotic spindle orientation. The pseudokinase domain of ILK binds several adaptor proteins including the parvins and paxillin. The ILK subfamily is part of a larger superfamily that includes the catalytic domains of protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270959 [Multi-domain]  Cd Length: 251  Bit Score: 96.40  E-value: 2.23e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDIL-ENDSINLDW 149
Cdd:cd14057    14 GRWQGNDIVAKILKVRDVTTRISRDFNEEYPRLRIFSHpnVLPVLGACNSPPNLVVISQYMPYGSLYNVLhEGTGVVVDQ 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 150 MFRYSLINDLVKGMAFLH--NSIISSHgSLKSSNCVVDSRFVLKITdygLASFR-STAEPDDSHAlyakKLWTAPELLSG 226
Cdd:cd14057    94 SQAVKFALDIARGMAFLHtlEPLIPRH-HLNSKHVMIDEDMTARIN---MADVKfSFQEPGKMYN----PAWMAPEALQK 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPlPTTGMQKADVYSFGIILQEIALRSGPFylegLDLSPKEIVQKVR-NGQRPYFRPSIDRtqlneELVLLMERCWAQDP 305
Cdd:cd14057   166 KP-EDINRRSADMWSFAILLWELVTREVPF----ADLSNMEIGMKIAlEGLRVTIPPGISP-----HMCKLMKICMNEDP 235

                  ....*....
gi 1370514551 306 AERPDFGQI 314
Cdd:cd14057   236 GKRPKFDMI 244
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
77-314 3.85e-22

Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Abl (or c-Abl) is a ubiquitously-expressed cytoplasmic (or nonreceptor) PTK that contains SH3, SH2, and tyr kinase domains in its N-terminal region, as well as nuclear localization motifs, a putative DNA-binding domain, and F- and G-actin binding domains in its C-terminal tail. It also contains a short autoinhibitory cap region in its N-terminus. Abl function depends on its subcellular localization. In the cytoplasm, Abl plays a role in cell proliferation and survival. In response to DNA damage or oxidative stress, Abl is transported to the nucleus where it induces apoptosis. In chronic myelogenous leukemia (CML) patients, an aberrant translocation results in the replacement of the first exon of Abl with the BCR (breakpoint cluster region) gene. The resulting BCR-Abl fusion protein is constitutively active and associates into tetramers, resulting in a hyperactive kinase sending a continuous signal. This leads to uncontrolled proliferation, morphological transformation and anti-apoptotic effects. BCR-Abl is the target of selective inhibitors, such as imatinib (Gleevec), used in the treatment of CML. Abl2, also known as ARG (Abelson-related gene), is thought to play a cooperative role with Abl in the proper development of the nervous system. The Tel-ARG fusion protein, resulting from reciprocal translocation between chromosomes 1 and 12, is associated with acute myeloid leukemia (AML). The TEL gene is a frequent fusion partner of other tyr kinase oncogenes, including Tel/Abl, Tel/PDGFRbeta, and Tel/Jak2, found in patients with leukemia and myeloproliferative disorders. The Abl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270645 [Multi-domain]  Cd Length: 263  Bit Score: 96.34  E-value: 3.85e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELtRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-ENDSINLDWMFRYSL 155
Cdd:cd05052    31 NLTVAVKTLKEDTMEV-EEFLKEAAVMKEIKHPNLVQLLGVCTREPPFYIITEFMPYGNLLDYLrECNREELNAVVLLYM 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 INDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRStaepDDSHALYA-KKL---WTAPELLSGNPLP 230
Cdd:cd05052   110 ATQIASAMEYLEkKNFI--HRDLAARNCLVGENHLVKVADFGLSRLMT----GDTYTAHAgAKFpikWTAPESLAYNKFS 183
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 231 TtgmqKADVYSFGIILQEIALRSGPFYlEGLDLSpkEIVQKVRNGQRpyfrpsIDRTQ-LNEELVLLMERCWAQDPAERP 309
Cdd:cd05052   184 I----KSDVWAFGVLLWEIATYGMSPY-PGIDLS--QVYELLEKGYR------MERPEgCPPKVYELMRACWQWNPSDRP 250

                  ....*
gi 1370514551 310 DFGQI 314
Cdd:cd05052   251 SFAEI 255
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
75-309 4.69e-22

Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mos (or c-Mos) is a germ-cell specific kinase that plays roles in both the release of primary arrest and the induction of secondary arrest in oocytes. It is expressed towards the end of meiosis I and is quickly degraded upon fertilization. It is a component of the cytostatic factor (CSF), which is responsible for metaphase II arrest. In addition, Mos activates a phoshorylation cascade that leads to the activation of the p34 subunit of MPF (mitosis-promoting factor or maturation promoting factor), a cyclin-dependent kinase that is responsible for the release of primary arrest in meiosis I. The Mos subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270881 [Multi-domain]  Cd Length: 265  Bit Score: 95.91  E-value: 4.69e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  75 FKGNVVAIKHVNKKRIEL-TRQVLFELKHMRDVQFNHLTRFIGA--CIDPPNI-CIVTEYCPRGSLQDILENDSINLDWM 150
Cdd:cd13979    24 YKGETVAVKIVRRRRKNRaSRQSFWAELNAARLRHENIVRVLAAetGTDFASLgLIIMEYCGNGTLQQLIYEGSEPLPLA 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 151 FRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYG----LASFRSTAEPddSHALYAKKLWTAPELLSG 226
Cdd:cd13979   104 HRILISLDIARALRFCHSHGIV-HLDVKPANILISEQGVCKLCDFGcsvkLGEGNEVGTP--RSHIGGTYTYRAPELLKG 180
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPlPTTgmqKADVYSFGIILQEIALRSGPFylEGldLSPKEIVQKVRNGQRPYFRPSIDRTqLNEELVLLMERCWAQDPA 306
Cdd:cd13979   181 ER-VTP---KADIYSFGITLWQMLTRELPY--AG--LRQHVLYAVVAKDLRPDLSGLEDSE-FGQRLRSLISRCWSAQPA 251

                  ...
gi 1370514551 307 ERP 309
Cdd:cd13979   252 ERP 254
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
97-317 5.89e-22

Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src subfamily members include Src, Lck, Hck, Blk, Lyn, Fgr, Fyn, Yrk, and Yes. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Src kinases are overexpressed in a variety of human cancers, making them attractive targets for therapy. They are also implicated in acute inflammatory responses and osteoclast function. Src, Fyn, Yes, and Yrk are widely expressed, while Blk, Lck, Hck, Fgr, and Lyn show a limited expression pattern. The Src-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270630 [Multi-domain]  Cd Length: 248  Bit Score: 95.43  E-value: 5.89e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  97 LFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSinldwmFRYSLINDLVK-------GMAFL--H 167
Cdd:cd05034    38 LQEAQIMKKLRHDKLVQLYAVCSDEEPIYIVTELMSKGSLLDYLRTGE------GRALRLPQLIDmaaqiasGMAYLesR 111
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 168 NSIissHGSLKSSNCVVDSRFVLKITDYGLASFrstAEPDDSHALYAKKL---WTAPELLSGNPLpttgMQKADVYSFGI 244
Cdd:cd05034   112 NYI---HRDLAARNILVGENNVCKVADFGLARL---IEDDEYTAREGAKFpikWTAPEAALYGRF----TIKSDVWSFGI 181
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 245 ILQEIaLRSGPFYLEGldLSPKEIVQKVRNGQR-PyfRPsidrTQLNEELVLLMERCWAQDPAERPDFGQIKGF 317
Cdd:cd05034   182 LLYEI-VTYGRVPYPG--MTNREVLEQVERGYRmP--KP----PGCPDELYDIMLQCWKKEPEERPTFEYLQSF 246
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
77-309 5.90e-22

Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes many bacterial eukaryotic-type STKs including Staphylococcus aureus PknB (also called PrkC or Stk1), Bacillus subtilis PrkC, and Mycobacterium tuberculosis Pkn proteins (PknB, PknD, PknE, PknF, PknL, and PknH), among others. S. aureus PknB is the only eukaryotic-type STK present in this species, although many microorganisms encode for several such proteins. It is important for the survival and pathogenesis of S. aureus as it is involved in the regulation of purine and pyrimidine biosynthesis, cell wall metabolism, autolysis, virulence, and antibiotic resistance. M. tuberculosis PknB is essential for growth and it acts on diverse substrates including proteins involved in peptidoglycan synthesis, cell division, transcription, stress responses, and metabolic regulation. B. subtilis PrkC is located at the inner membrane of endospores and functions to trigger spore germination. Bacterial STKs in this subfamily show varied domain architectures. The well-characterized members such as S. aureus and M. tuberculosis PknB, and B. subtilis PrkC, contain an N-terminal cytosolic kinase domain, a transmembrane (TM) segment, and mutliple C-terminal extracellular PASTA domains. The PknB subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270916 [Multi-domain]  Cd Length: 260  Bit Score: 95.73  E-value: 5.90e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIK--HVNKKRIELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-ENDSINLDWMFR 152
Cdd:cd14014    25 GRPVAIKvlRPELAEDEEFRERFLrEARALARLSHPNIVRVYDVGEDDGRPYIVMEYVEGGSLADLLrERGPLPPREALR 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 ysLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGNPLpt 231
Cdd:cd14014   105 --ILAQIADALAAAHrAGIV--HRDIKPANILLTEDGRVKLTDFGIARALGDSGLTQTGSVLGTPAYMAPEQARGGPV-- 178
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 232 tgMQKADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNGQRPyfRPSIDRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd14014   179 --DPRSDIYSLGVVLYELLTGRPPFDGD----SPAAVLAKHLQEAPP--PPSPLNPDVPPALDAIILRALAKDPEERP 248
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
67-315 8.15e-22

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. Vertebrate have two members, LIMK1 and LIMK2. The LIMK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271056 [Multi-domain]  Cd Length: 272  Bit Score: 95.65  E-value: 8.15e-22
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  67 QIFANTGHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSIN 146
Cdd:cd14154     8 QAIKVTHRETGEVMVMKELIRFDEEAQRNFLKEVKVMRSLDHPNVLKFIGVLYKDKKLNLITEYIPGGTLKDVLKDMARP 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYSLINDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLASF----------------RSTAEPDDS 209
Cdd:cd14154    88 LPWAQRVRFAKDIASGMAYLHSmNII--HRDLNSHNCLVREDKTVVVADFGLARLiveerlpsgnmspsetLRHLKSPDR 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 210 HALY---AKKLWTAPELLSGNPLPttgmQKADVYSFGIILQEIALR--SGPFYL---EGLDLSPKEIVQKVRNGQRPYFR 281
Cdd:cd14154   166 KKRYtvvGNPYWMAPEMLNGRSYD----EKVDIFSFGIVLCEIIGRveADPDYLprtKDFGLNVDSFREKFCAGCPPPFF 241
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1370514551 282 PsidrtqlneelvlLMERCWAQDPAERPDFGQIK 315
Cdd:cd14154   242 K-------------LAFLCCDLDPEKRPPFETLE 262
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
77-309 1.01e-21

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKKKs (MKKKs or MAP3Ks) are also called MAP/ERK kinase kinases (MEKKs) in some cases. They phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. This subfamily is composed of the Apoptosis Signal-regulating Kinases ASK1 (or MAPKKK5) and ASK2 (or MAPKKK6), MEKK1, MEKK2, MEKK3, MEKK4, as well as plant and fungal MAPKKKs. Also included in this subfamily are the cell division control proteins Schizosaccharomyces pombe Cdc7 and Saccharomyces cerevisiae Cdc15. The MAPKKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270783 [Multi-domain]  Cd Length: 258  Bit Score: 94.89  E-value: 1.01e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRI--ELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSInldwmFRYS 154
Cdd:cd06606    25 GELMAVKEVELSGDseEELEALEREIRILSSLKHPNIVRYLGTERTENTLNIFLEYVPGGSLASLLKKFGK-----LPEP 99
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LI----NDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKK---LWTAPELLSG 226
Cdd:cd06606   100 VVrkytRQILEGLEYLHsNGIV--HRDIKGANILVDSDGVVKLADFGCA--KRLAEIATGEGTKSLRgtpYWMAPEVIRG 175
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPTtgmqKADVYSFGIILQEIALRSGPFYLEGldlSPKEIVQKV-RNGQRPYFRPSidrtqLNEELVLLMERCWAQDP 305
Cdd:cd06606   176 EGYGR----AADIWSLGCTVIEMATGKPPWSELG---NPVAALFKIgSSGEPPPIPEH-----LSEEAKDFLRKCLQRDP 243

                  ....
gi 1370514551 306 AERP 309
Cdd:cd06606   244 KKRP 247
STKc_ACVR2 cd14053
Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the ...
78-308 1.12e-21

Catalytic domain of the Serine/Threonine Kinase, Activin Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as ACVR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. Vertebrates contain two ACVR2 proteins, ACVR2a (or ActRIIA) and ACVR2b (or ActRIIB). The ACVR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270955 [Multi-domain]  Cd Length: 290  Bit Score: 95.47  E-value: 1.12e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  78 NVVAIK---HVNKKRIElTRQVLFELKHMRdvqFNHLTRFIGA----CIDPPNICIVTEYCPRGSLQDILENDSINLDWM 150
Cdd:cd14053    19 RLVAVKifpLQEKQSWL-TEREIYSLPGMK---HENILQFIGAekhgESLEAEYWLITEFHERGSLCDYLKGNVISWNEL 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 151 FRysLINDLVKGMAFLHNSIISSHGS---------LKSSNCVVDSRFVLKITDYGLA-SFRSTAEPDDSHALYAKKLWTA 220
Cdd:cd14053    95 CK--IAESMARGLAYLHEDIPATNGGhkpsiahrdFKSKNVLLKSDLTACIADFGLAlKFEPGKSCGDTHGQVGTRRYMA 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 221 PELLSGN-PLPTTGMQKADVYSFGIILQEIALRSG-----------PFYLEGLDLSPKEIVQK--VRNGQRPYFRPSIDR 286
Cdd:cd14053   173 PEVLEGAiNFTRDAFLRIDMYAMGLVLWELLSRCSvhdgpvdeyqlPFEEEVGQHPTLEDMQEcvVHKKLRPQIRDEWRK 252
                         250       260
                  ....*....|....*....|..
gi 1370514551 287 TQLNEELVLLMERCWAQDPAER 308
Cdd:cd14053   253 HPGLAQLCETIEECWDHDAEAR 274
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
99-311 1.56e-21

Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Tec-like subfamily is composed of Tec, Btk, Bmx (Etk), Itk (Tsk, Emt), Rlk (Txk), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, some members contain the Tec homology (TH) domain, which contains proline-rich and zinc-binding regions. Tec kinases form the second largest subfamily of nonreceptor PTKs and are expressed mainly by haematopoietic cells, although Tec and Bmx are also found in endothelial cells. B-cells express Btk and Tec, while T-cells express Itk, Txk, and Tec. Collectively, Tec kinases are expressed in a variety of myeloid cells such as mast cells, platelets, macrophages, and dendritic cells. Each Tec kinase shows a distinct cell-type pattern of expression. Tec kinases play important roles in the development, differentiation, maturation, regulation, survival, and function of B-cells and T-cells. Mutations in Btk cause the severe B-cell immunodeficiency, X-linked agammaglobulinaemia (XLA). The Tec-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173637 [Multi-domain]  Cd Length: 256  Bit Score: 94.44  E-value: 1.56e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-ENDSI-NLDWMFrySLINDLVKGMAFLH-NSIIssHG 175
Cdd:cd05059    49 EAKVMMKLSHPKLVQLYGVCTKQRPIFIVTEYMANGCLLNYLrERRGKfQTEQLL--EMCKDVCEAMEYLEsNGFI--HR 124
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 176 SLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGNPLPTtgmqKADVYSFGIILQEIalrsgp 255
Cdd:cd05059   125 DLAARNCLVGEQNVVKVSDFGLARYVLDDEYTSSVGTKFPVKWSPPEVFMYSKFSS----KSDVWSFGVLMWEV------ 194
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 256 fYLEGL----DLSPKEIVQKVRNGQRPYfRPsidrTQLNEELVLLMERCWAQDPAERPDF 311
Cdd:cd05059   195 -FSEGKmpyeRFSNSEVVEHISQGYRLY-RP----HLAPTEVYTIMYSCWHEKPEERPTF 248
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
75-249 2.05e-21

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK4 plays a critical role in NFkB activation by its interaction with MyD88, which acts as a scaffold that enables IRAK4 to phosphorylate and activate IRAK1 and/or IRAK2. It also plays an important role in type I IFN production induced by TLR7/8/9. The IRAK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271060 [Multi-domain]  Cd Length: 288  Bit Score: 94.49  E-value: 2.05e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  75 FKGnVVAIKHVNKKRI---------ELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE--ND 143
Cdd:cd14158    32 FKG-YINDKNVAVKKLaamvdisteDLTKQFEQEIQVMAKCQHENLVELLGYSCDGPQLCLVYTYMPNGSLLDRLAclND 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 144 SINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASfrstAEPDDSHALYAKKL----- 217
Cdd:cd14158   111 TPPLSWHMRCKIAQGTANGINYLHeNNHI--HRDIKSANILLDETFVPKISDFGLAR----ASEKFSQTIMTERIvgtta 184
                         170       180       190
                  ....*....|....*....|....*....|..
gi 1370514551 218 WTAPELLSGNPLPttgmqKADVYSFGIILQEI 249
Cdd:cd14158   185 YMAPEALRGEITP-----KSDIFSFGVVLLEI 211
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
77-314 3.73e-21

Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes three leucine-rich repeat receptor-like kinases (LRR-RLKs): Arabidopsis thaliana BAK1 and CLAVATA1 (CLV1), and Physcomitrella patens CLL1B clavata1-like receptor S/T protein kinase. BAK1 functions in various signaling pathways. It plays a role in BR (brassinosteroid)-regulated plant development as a co-receptor of BRASSINOSTEROID (BR) INSENSITIVE 1 (BRI1), the receptor for BRs, and is required for full activation of BR signaling. It also modulates pathways involved in plant resistance to pathogen infection (pattern-triggered immunity, PTI) and herbivore attack (wound- or herbivore feeding-induced accumulation of jasmonic acid (JA) and JA-isoleucine. CLV1, directly binds small signaling peptides, CLAVATA3 (CLV3) and CLAVATA3/EMBRYO SURROUNDING REGI0N (CLE), to restrict stem cell proliferation: the CLV3-CLV1-WUS (WUSCHEL) module influences stem cell maintenance in the shoot apical meristem, and the CLE40 (CLAVATA3/EMBRYO SURROUNDING REGION40) -ACR4 (CRINKLY4) -CLV1- WOX5 (WUSCHEL-RELATED HOMEOBOX5) module at the root apical meristem. The STK_BAK1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271134 [Multi-domain]  Cd Length: 270  Bit Score: 93.33  E-value: 3.73e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKR-IELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSIN---LDWMFR 152
Cdd:cd14664    17 GTLVAVKRLKGEGtQGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNLLVYEYMPNGSLGELLHSRPESqppLDWETR 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 YSLINDLVKGMAFLHNSIISS--HGSLKSSNCVVDSRFVLKITDYGLASFrstAEPDDSHALYAKK---LWTAPELLSgn 227
Cdd:cd14664    97 QRIALGSARGLAYLHHDCSPLiiHRDVKSNNILLDEEFEAHVADFGLAKL---MDDKDSHVMSSVAgsyGYIAPEYAY-- 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 228 plptTGM--QKADVYSFGIILQEIALRSGPFYLEGLDlSPKEIVQKVRN-----GQRPYFRPSIDRTQLNEELVLLME-- 298
Cdd:cd14664   172 ----TGKvsEKSDVYSYGVVLLELITGKRPFDEAFLD-DGVDIVDWVRGlleekKVEALVDPDLQGVYKLEEVEQVFQva 246
                         250
                  ....*....|....*..
gi 1370514551 299 -RCWAQDPAERPDFGQI 314
Cdd:cd14664   247 lLCTQSSPMERPTMREV 263
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
77-258 5.55e-21

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK1 activation is induced by bone morphogenic protein, vascular endothelial growth factor, and thrombin. It plays roles in microtubule disassembly and cell cycle progression, and is critical in the regulation of neurite outgrowth. LIMK1 knockout mice show abnormalities in dendritic spine morphology and synaptic function. LIMK1 is one of the genes deleted in patients with Williams Syndrome, which is characterized by distinct craniofacial features, cardiovascular problems, as well as behavioral and neurological abnormalities. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271123 [Multi-domain]  Cd Length: 267  Bit Score: 93.10  E-value: 5.55e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLI 156
Cdd:cd14221    18 GEVMVMKELIRFDEETQRTFLKEVKVMRCLEHPNVLKFIGVLYKDKRLNFITEYIKGGTLRGIIKSMDSHYPWSQRVSFA 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLA-----------SFRSTAEPD--DSHALYAKKLWTAPE 222
Cdd:cd14221    98 KDIASGMAYLHSmNII--HRDLNSHNCLVRENKSVVVADFGLArlmvdektqpeGLRSLKKPDrkKRYTVVGNPYWMAPE 175
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 1370514551 223 LLSGNPLPttgmQKADVYSFGIILQEIALR--SGPFYL 258
Cdd:cd14221   176 MINGRSYD----EKVDVFSFGIVLCEIIGRvnADPDYL 209
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
73-321 6.17e-21

Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lck and Blk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lck is expressed in T-cells and natural killer cells. It plays a critical role in T-cell maturation, activation, and T-cell receptor (TCR) signaling. Lck phosphorylates ITAM (immunoreceptor tyr activation motif) sequences on several subunits of TCRs, leading to the activation of different second messenger cascades. Phosphorylated ITAMs serve as binding sites for other signaling factor such as Syk and ZAP-70, leading to their activation and propagation of downstream events. In addition, Lck regulates drug-induced apoptosis by interfering with the mitochondrial death pathway. The apototic role of Lck is independent of its primary function in T-cell signaling. Blk is expressed specifically in B-cells. It is involved in pre-BCR (B-cell receptor) signaling. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lck/Blk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270652 [Multi-domain]  Cd Length: 264  Bit Score: 92.64  E-value: 6.17e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNV-VAIKHVNKKRIELTrQVLFELKHMRDVQFNHLTRFIGACIDPPnICIVTEYCPRGSLQDILENDS-INLDWM 150
Cdd:cd05067    26 GYYNGHTkVAIKSLKQGSMSPD-AFLAEANLMKQLQHQRLVRLYAVVTQEP-IYIITEYMENGSLVDFLKTPSgIKLTIN 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 151 FRYSLINDLVKGMAFLH--NSIissHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGNp 228
Cdd:cd05067   104 KLLDMAAQIAEGMAFIEerNYI---HRDLRAANILVSDTLSCKIADFGLARLIEDNEYTAREGAKFPIKWTAPEAINYG- 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 lptTGMQKADVYSFGIILQEIaLRSGPFYLEGLDlSPKEIvqkvRNGQRPYFRPSIDRTQlnEELVLLMERCWAQDPAER 308
Cdd:cd05067   180 ---TFTIKSDVWSFGILLTEI-VTHGRIPYPGMT-NPEVI----QNLERGYRMPRPDNCP--EELYQLMRLCWKERPEDR 248
                         250
                  ....*....|...
gi 1370514551 309 PDFGQIKGFIRRF 321
Cdd:cd05067   249 PTFEYLRSVLEDF 261
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
95-311 6.31e-21

Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Itk, also known as Tsk or Emt, is a member of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Itk contains the Tec homology (TH) domain containing one proline-rich region and a zinc-binding region. Itk is expressed in T-cells and mast cells, and is important in their development and differentiation. Of the three Tec kinases expressed in T-cells, Itk plays the predominant role in T-cell receptor (TCR) signaling. It is activated by phosphorylation upon TCR crosslinking and is involved in the pathway resulting in phospholipase C-gamma1 activation and actin polymerization. It also plays a role in the downstream signaling of the T-cell costimulatory receptor CD28, the T-cell surface receptor CD2, and the chemokine receptor CXCR4. In addition, Itk is crucial for the development of T-helper(Th)2 effector responses. The Itk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133243 [Multi-domain]  Cd Length: 256  Bit Score: 92.32  E-value: 6.31e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVQFnhltrfIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLH-NSIIss 173
Cdd:cd05112    51 EVMMKLSHPKLVQL------YGVCLEQAPICLVFEFMEHGCLSDYLRTQRGLFSAETLLGMCLDVCEGMAYLEeASVI-- 122
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 174 HGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGNPLPTtgmqKADVYSFGIILQEIalrs 253
Cdd:cd05112   123 HRDLAARNCLVGENQVVKVSDFGMTRFVLDDQYTSSTGTKFPVKWSSPEVFSFSRYSS----KSDVWSFGVLMWEV---- 194
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370514551 254 gpfYLEGL----DLSPKEIVQKVRNGQRPYfRPSIDRTQLNEelvlLMERCWAQDPAERPDF 311
Cdd:cd05112   195 ---FSEGKipyeNRSNSEVVEDINAGFRLY-KPRLASTHVYE----IMNHCWKERPEDRPSF 248
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
91-315 1.56e-20

Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fes (or Fps) is a cytoplasmic (or nonreceptor) PTK containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. The genes for Fes (feline sarcoma) and Fps (Fujinami poultry sarcoma) were first isolated from tumor-causing retroviruses. The viral oncogenes encode chimeric Fes proteins consisting of Gag sequences at the N-termini, resulting in unregulated PTK activity. Fes kinase is expressed in myeloid, vascular endothelial, epithelial, and neuronal cells. It plays important roles in cell growth and differentiation, angiogenesis, inflammation and immunity, and cytoskeletal regulation. A recent study implicates Fes kinase as a tumor suppressor in colorectal cancer. The Fes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270667 [Multi-domain]  Cd Length: 252  Bit Score: 91.15  E-value: 1.56e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  91 ELTRQVLFELKHMRdvQFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHn 168
Cdd:cd05084    36 DLKAKFLQEARILK--QYSHpnIVRLIGVCTQKQPIYIVMELVQGGDFLTFLRTEGPRLKVKELIRMVENAAAGMEYLE- 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 169 SIISSHGSLKSSNCVVDSRFVLKITDYGLasfrSTAEPDDSHALYA--KKL---WTAPELLSGNPLPTtgmqKADVYSFG 243
Cdd:cd05084   113 SKHCIHRDLAARNCLVTEKNVLKISDFGM----SREEEDGVYAATGgmKQIpvkWTAPEALNYGRYSS----ESDVWSFG 184
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 244 IILQE-IALRSGPFylegLDLSPKEIVQKVRNGQRpyfRPSIDrtQLNEELVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd05084   185 ILLWEtFSLGAVPY----ANLSNQQTREAVEQGVR---LPCPE--NCPDEVYRLMEQCWEYDPRKRPSFSTVH 248
Pkinase pfam00069
Protein kinase domain;
77-315 2.04e-20

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 90.00  E-value: 2.04e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRI--ELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENdsinldwMFRYS 154
Cdd:pfam00069  24 GKIVAIKKIKKEKIkkKKDKNILREIKILKKLNHPNIVRLYDAFEDKDNLYLVLEYVEGGSLFDLLSE-------KGAFS 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 ------LINDLVKGMAflhnsiissHGSLKSSNCVvdSRFvlkitdyglasfrstaepddshalyakklWTAPELLSGNP 228
Cdd:pfam00069  97 ereakfIMKQILEGLE---------SGSSLTTFVG--TPW-----------------------------YMAPEVLGGNP 136
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 LPTtgmqKADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNGqrPYFRPSIDRTqLNEELVLLMERCWAQDPAER 308
Cdd:pfam00069 137 YGP----KVDVWSLGCILYELLTGKPPFPGI----NGNEIYELIIDQ--PYAFPELPSN-LSEEAKDLLKKLLKKDPSKR 205

                  ....*..
gi 1370514551 309 PDFGQIK 315
Cdd:pfam00069 206 LTATQAL 212
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
96-327 2.17e-20

Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This group is composed of uncharacterized proteins with similarity to LIMK and Testicular or testis-specific protein kinase (TESK). LIMKs are characterized as serine/threonine kinases (STKs) while TESKs are dual-specificity protein kinases. Both LIMK and TESK phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They are implicated in many cellular functions including cell spreading, motility, morphogenesis, meiosis, mitosis, and spermatogenesis. The LIMK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271058 [Multi-domain]  Cd Length: 256  Bit Score: 91.04  E-value: 2.17e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  96 VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIIsSHG 175
Cdd:cd14156    35 IVREISLLQKLSHPNIVRYLGICVKDEKLHPILEYVSGGCLEELLAREELPLSWREKVELACDISRGMVYLHSKNI-YHR 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 176 SLKSSNCVV--DSRFVLKI-TDYGLAsfRSTAE-----PDDSHALYAKKLWTAPELLSGNPLPttgmQKADVYSFGIILQ 247
Cdd:cd14156   114 DLNSKNCLIrvTPRGREAVvTDFGLA--REVGEmpandPERKLSLVGSAFWMAPEMLRGEPYD----RKVDVFSFGIVLC 187
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 248 EIALR--SGPFYLE-----GLDLSP-KEIVQKVrngqrpyfrpsidrtqlNEELVLLMERCWAQDPAERPDFGQIkgfIR 319
Cdd:cd14156   188 EILARipADPEVLPrtgdfGLDVQAfKEMVPGC-----------------PEPFLDLAASCCRMDAFKRPSFAEL---LD 247

                  ....*...
gi 1370514551 320 RFNKEGGT 327
Cdd:cd14156   248 ELEDIAET 255
STKc_KSR1 cd14152
Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the ...
86-323 2.41e-20

Catalytic domain of the Serine/Threonine Kinase, Kinase Suppressor of Ras 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. KSR1 functions as a transducer of TNFalpha-stimulated C-Raf activation of ERK1/2 and NF-kB. Detected activity of KSR1 is cell type specific and context dependent. It is inactive in normal colon epithelial cells and becomes activated at the onset of inflammatory bowel disease (IBD). Similarly, KSR1 activity is undetectable prior to stimulation by EGF or ceramide in COS-7 or YAMC cells, respectively. KSR proteins are widely regarded as pseudokinases, however, this matter is up for debate as catalytic activity has been detected for KSR1 in some systems. The KSR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271054 [Multi-domain]  Cd Length: 279  Bit Score: 91.18  E-value: 2.41e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  86 NKKRIELTRQvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAF 165
Cdd:cd14152    36 NQDHLKLFKK---EVMNYRQTRHENVVLFMGACMHPPHLAIITSFCKGRTLYSFVRDPKTSLDINKTRQIAQEIIKGMGY 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 166 LHNSIIsSHGSLKSSNCVVDSRFVLkITDYGLASFRSTAEPD-DSHALYAKKLWT---APELLS----GNPLPTTGMQK- 236
Cdd:cd14152   113 LHAKGI-VHKDLKSKNVFYDNGKVV-ITDFGLFGISGVVQEGrRENELKLPHDWLcylAPEIVRemtpGKDEDCLPFSKa 190
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 237 ADVYSFGIILQEIALRSGPFYLEGLDLSPKEIvqkvrnGQRPYFRPSIDRTQLNEELVLLMERCWAQDPAERPDFGQIKG 316
Cdd:cd14152   191 ADVYAFGTIWYELQARDWPLKNQPAEALIWQI------GSGEGMKQVLTTISLGKEVTEILSACWAFDLEERPSFTLLMD 264

                  ....*..
gi 1370514551 317 FIRRFNK 323
Cdd:cd14152   265 MLEKLPK 271
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
77-311 2.67e-20

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak2 is widely expressed in many tissues and is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271107 [Multi-domain]  Cd Length: 284  Bit Score: 91.23  E-value: 2.67e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDP--PNICIVTEYCPRGSLQDILENDSINLDWMFRYS 154
Cdd:cd14205    33 GEVVAVKKLQHSTEEHLRDFEREIEILKSLQHDNIVKYKGVCYSAgrRNLRLIMEYLPYGSLRDYLQKHKERIDHIKLLQ 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLA-------SFRSTAEPDDSHALyakklWTAPELLSGN 227
Cdd:cd14205   113 YTSQICKGMEYLGTKRYI-HRDLATRNILVENENRVKIGDFGLTkvlpqdkEYYKVKEPGESPIF-----WYAPESLTES 186
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 228 PLPTTgmqkADVYSFGIILQEIALrsgpfYLEGLDLSPKEIVQKVRN---GQRPYFRpSIDRTQLN----------EELV 294
Cdd:cd14205   187 KFSVA----SDVWSFGVVLYELFT-----YIEKSKSPPAEFMRMIGNdkqGQMIVFH-LIELLKNNgrlprpdgcpDEIY 256
                         250
                  ....*....|....*..
gi 1370514551 295 LLMERCWAQDPAERPDF 311
Cdd:cd14205   257 MIMTECWNNNVNQRPSF 273
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
80-314 4.53e-20

Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The InsR subfamily is composed of InsR, Insulin-like Growth Factor-1 Receptor (IGF-1R), and similar proteins. InsR and IGF-1R are receptor PTKs (RTKs) composed of two alphabeta heterodimers. Binding of the ligand (insulin, IGF-1, or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR and IGF-1R, which share 84% sequence identity in their kinase domains, display physiologically distinct yet overlapping functions in cell growth, differentiation, and metabolism. InsR activation leads primarily to metabolic effects while IGF-1R activation stimulates mitogenic pathways. In cells expressing both receptors, InsR/IGF-1R hybrids are found together with classical receptors. Both receptors can interact with common adaptor molecules such as IRS-1 and IRS-2. The InsR-like subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173625 [Multi-domain]  Cd Length: 277  Bit Score: 90.48  E-value: 4.53e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVN-----KKRIELtrqvLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN-----------D 143
Cdd:cd05032    39 VAIKTVNenasmRERIEF----LNEASVMKEFNCHHVVRLLGVVSTGQPTLVVMELMAKGDLKSYLRSrrpeaennpglG 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 144 SINLDWMFRYSLinDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDdshalYAKKL------ 217
Cdd:cd05032   115 PPTLQKFIQMAA--EIADGMAYLAAKKFV-HRDLAARNCMVAEDLTVKIGDFGMT--RDIYETD-----YYRKGgkgllp 184
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 218 --WTAPELLSGNPLPTtgmqKADVYSFGIILQEIA-LRSGPFylegLDLSPKEIVQKVRNG---QRPyfrpsidrTQLNE 291
Cdd:cd05032   185 vrWMAPESLKDGVFTT----KSDVWSFGVVLWEMAtLAEQPY----QGLSNEEVLKFVIDGghlDLP--------ENCPD 248
                         250       260
                  ....*....|....*....|...
gi 1370514551 292 ELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05032   249 KLLELMRMCWQYNPKMRPTFLEI 271
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
73-314 4.75e-20

Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Raf kinases act as mitogen-activated protein kinase kinase kinases (MAP3Ks, MKKKs, MAPKKKs), which phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. Aberrant expression or activation of components in this pathway are associated with tumor initiation, progression, and metastasis. Raf proteins contain a Ras binding domain, a zinc finger cysteine-rich domain, and a catalytic kinase domain. Vertebrates have three Raf isoforms (A-, B-, and C-Raf) with different expression profiles, modes of regulation, and abilities to function in the ERK cascade, depending on cellular context and stimuli. They have essential and non-overlapping roles during embryo- and organogenesis. Knockout of each isoform results in a lethal phenotype or abnormality in most mouse strains. The Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270964 [Multi-domain]  Cd Length: 253  Bit Score: 89.76  E-value: 4.75e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGnVVAIKHVNKKRIELTRQVLF--ELKHMRDVQFNHLTRFIGACIDPpNICIVTEYCPRGSLQD---ILENDsinl 147
Cdd:cd14062    12 GRWHG-DVAVKKLNVTDPTPSQLQAFknEVAVLRKTRHVNILLFMGYMTKP-QLAIVTQWCEGSSLYKhlhVLETK---- 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 148 dwmFRYSLINDLVK----GMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASF--RSTAEPdDSHALYAKKLWTA 220
Cdd:cd14062    86 ---FEMLQLIDIARqtaqGMDYLHaKNII--HRDLKSNNIFLHEDLTVKIGDFGLATVktRWSGSQ-QFEQPTGSILWMA 159
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 221 PELL---SGNPLPTtgmqKADVYSFGIILQEIALRSGPFYleglDLSPKE-IVQKVRNGqrpYFRPSID--RTQLNEELV 294
Cdd:cd14062   160 PEVIrmqDENPYSF----QSDVYAFGIVLYELLTGQLPYS----HINNRDqILFMVGRG---YLRPDLSkvRSDTPKALR 228
                         250       260
                  ....*....|....*....|
gi 1370514551 295 LLMERCWAQDPAERPDFGQI 314
Cdd:cd14062   229 RLMEDCIKFQRDERPLFPQI 248
STKc_TGFbR_I cd14056
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type ...
127-309 5.23e-20

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta family Type I Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of type I receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation through trans-phosphorylation by type II receptors, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. They are inhibited by the immunophilin FKBP12, which is thought to control leaky signaling caused by receptor oligomerization in the absence of ligand. The TGFbR-I subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270958 [Multi-domain]  Cd Length: 287  Bit Score: 90.41  E-value: 5.23e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 127 VTEYCPRGSLQDILENDSINLDWMFR--YSLINdlvkGMAFLHNSIISSHGS-------LKSSNCVVDSRFVLKITDYGL 197
Cdd:cd14056    71 ITEYHEHGSLYDYLQRNTLDTEEALRlaYSAAS----GLAHLHTEIVGTQGKpaiahrdLKSKNILVKRDGTCCIADLGL 146
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 198 A----SFRSTAEPDDSHALYAKKlWTAPELLSG--NPLPTTGMQKADVYSFGIILQEIALRSG----------PFYlEGL 261
Cdd:cd14056   147 AvrydSDTNTIDIPPNPRVGTKR-YMAPEVLDDsiNPKSFESFKMADIYSFGLVLWEIARRCEiggiaeeyqlPYF-GMV 224
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 262 DLSP-----KEIVqkVRNGQRPYFRPSIDRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd14056   225 PSDPsfeemRKVV--CVEKLRPPIPNRWKSDPVLRSMVKLMQECWSENPHARL 275
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
80-315 5.80e-20

Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The AMPK-like subfamily is composed of AMPK, MARK, BRSK, NUAK, MELK, SNRK, TSSK, and SIK, among others. LKB1 serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. AMPK, also called SNF1 (sucrose non-fermenting1) in yeasts and SnRK1 (SNF1-related kinase1) in plants, is a heterotrimeric enzyme composed of a catalytic alpha subunit and two regulatory subunits, beta and gamma. It is a stress-activated kinase that serves as master regulator of glucose and lipid metabolism by monitoring carbon and energy supplies, via sensing the cell's AMP:ATP ratio. MARKs phosphorylate tau and related microtubule-associated proteins (MAPs), and regulates microtubule-based intracellular transport. They are involved in embryogenesis, epithelial cell polarization, cell signaling, and neuronal differentiation. BRSKs play important roles in establishing neuronal polarity. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. The AMPK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270905 [Multi-domain]  Cd Length: 252  Bit Score: 89.50  E-value: 5.80e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRI--ELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQD-ILENDSINLD---WMFRy 153
Cdd:cd14003    28 VAIKIIDKSKLkeEIEEKIKREIEIMKLLNHPNIIKLYEVIETENKIYLVMEYASGGELFDyIVNNGRLSEDearRFFQ- 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 154 slinDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFrstAEPDDSH------ALYAkklwtAPELLSG 226
Cdd:cd14003   107 ----QLISAVDYCHsNGIV--HRDLKLENILLDKNGNLKIIDFGLSNE---FRGGSLLktfcgtPAYA-----APEVLLG 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPlptTGMQKADVYSFGIILqeIALRSG--PFylEGLDLSpkEIVQKVRNGQrpYFRPSidrtQLNEELVLLMERCWAQD 304
Cdd:cd14003   173 RK---YDGPKADVWSLGVIL--YAMLTGylPF--DDDNDS--KLFRKILKGK--YPIPS----HLSPDARDLIRRMLVVD 237
                         250
                  ....*....|.
gi 1370514551 305 PAERPDFGQIK 315
Cdd:cd14003   238 PSKRITIEEIL 248
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
73-314 5.91e-20

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK2 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K10. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK2 is abundant in brain, skeletal muscle, and testis. It functions upstream of the MAPK, c-Jun N-terminal kinase. It binds hippocalcin, a calcium-sensor protein that protects neurons against calcium-induced cell death. Both MLK2 and hippocalcin may be associated with the pathogenesis of Parkinson's disease. MLK2 also binds to normal huntingtin (Htt), which is important in neuronal transcription, development, and survival. MLK2 does not bind to the polyglutamine-expanded Htt, which is implicated in the pathogeneis of Huntington's disease, leading to neuronal toxicity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271050 [Multi-domain]  Cd Length: 258  Bit Score: 89.66  E-value: 5.91e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVNK---KRIELT-RQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLD 148
Cdd:cd14148    13 GLWRGEEVAVKAARQdpdEDIAVTaENVRQEARLFWMLQHPNIIALRGVCLNPPHLCLVMEYARGGALNRALAGKKVPPH 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLinDLVKGMAFLHNSIISS--HGSLKSSNCVVDSRF--------VLKITDYGLASFRSTAEPDDSHALYAkklW 218
Cdd:cd14148    93 VLVNWAV--QIARGMNYLHNEAIVPiiHRDLKSSNILILEPIenddlsgkTLKITDFGLAREWHKTTKMSAAGTYA---W 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 219 TAPELLSGNPLPttgmQKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQRPYFRPSidrtQLNEELVLLME 298
Cdd:cd14148   168 MAPEVIRLSLFS----KSSDVWSFGVLLWELLTGEVPYR----EIDALAVAYGVAMNKLTLPIPS----TCPEPFARLLE 235
                         250
                  ....*....|....*.
gi 1370514551 299 RCWAQDPAERPDFGQI 314
Cdd:cd14148   236 ECWDPDPHGRPDFGSI 251
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
90-314 1.03e-19

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK1 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK) and is also called MAP3K9. MAP3Ks phosphorylate and activate MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Little is known about the specific function of MLK1. It is capable of activating the c-Jun N-terminal kinase pathway. Mice lacking both MLK1 and MLK2 are viable, fertile, and have normal life spans. There could be redundancy in the function of MLKs. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation. The MLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 89.33  E-value: 1.03e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  90 IELTRQvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLinDLVKGMAFLHNS 169
Cdd:cd14145    49 IENVRQ---EAKLFAMLKHPNIIALRGVCLKEPNLCLVMEFARGGPLNRVLSGKRIPPDILVNWAV--QIARGMNYLHCE 123
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 170 IISS--HGSLKSSNCVVDSRF--------VLKITDYGLASFRSTAEPDDSHALYAkklWTAPELLSGnplpTTGMQKADV 239
Cdd:cd14145   124 AIVPviHRDLKSSNILILEKVengdlsnkILKITDFGLAREWHRTTKMSAAGTYA---WMAPEVIRS----SMFSKGSDV 196
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370514551 240 YSFGIILQEIALRSGPFY-LEGLDLSPKEIVQKVrngQRPYfrPSidrtQLNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14145   197 WSYGVLLWELLTGEVPFRgIDGLAVAYGVAMNKL---SLPI--PS----TCPEPFARLMEDCWNPDPHSRPPFTNI 263
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
73-314 1.21e-19

Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TNNI3K, also called cardiac ankyrin repeat kinase (CARK), is a cardiac-specific troponin I-interacting kinase that promotes cardiac myogenesis, improves cardiac performance, and protects the myocardium from ischemic injury. It contains N-terminal ankyrin repeats, a catalytic kinase domain, and a C-terminal serine-rich domain. TNNI3K exerts a disease-accelerating effect on cardiac dysfunction and reduced survival in mouse models of cardiomyopathy. The TNNI3K subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270966 [Multi-domain]  Cd Length: 254  Bit Score: 88.74  E-value: 1.21e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVnkkrieltRQVLFELKHMRDV---------QFNH--LTRFIGACI-DPPNICIVTEYCPRGSLQDIL 140
Cdd:cd14064    12 GRCRNKIVAIKRY--------RANTYCSKSDVDMfcrevsilcRLNHpcVIQFVGACLdDPSQFAIVTQYVSGGSLFSLL 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 141 ENDSINLDWMFRYSLINDLVKGMAFLHNS---IIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKL 217
Cdd:cd14064    84 HEQKRVIDLQSKLIIAVDVAKGMEYLHNLtqpII--HRDLNSHNILLYEDGHAVVADFGESRFLQSLDEDNMTKQPGNLR 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 218 WTAPELLSGNplpTTGMQKADVYSFGIILQEIALRSGPF-YLE----GLDLSPKEIvqkvrngqrpyfRPSIDrTQLNEE 292
Cdd:cd14064   162 WMAPEVFTQC---TRYSIKADVFSYALCLWELLTGEIPFaHLKpaaaAADMAYHHI------------RPPIG-YSIPKP 225
                         250       260
                  ....*....|....*....|..
gi 1370514551 293 LVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14064   226 ISSLLMRGWNAEPESRPSFVEI 247
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
73-315 2.22e-19

Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal regulatory tyrosine and N-terminal myristylation sites (Srm) and Breast tumor kinase (Brk); PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Srm and Brk (also called protein tyrosine kinase 6) are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Brk has been found to be overexpressed in a majority of breast tumors. Src kinases in general contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr; they are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Srm and Brk however, lack the N-terminal myristylation sites. Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. The Srm/Brk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133248 [Multi-domain]  Cd Length: 261  Bit Score: 88.26  E-value: 2.22e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNV-VAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN-DSINLDwm 150
Cdd:cd05148    25 GLWKNRVrVAIKILKSDDLLKQQDFQKEVQALKRLRHKHLISLFAVCSVGEPVYIITELMEKGSLLAFLRSpEGQVLP-- 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 151 fRYSLIN---DLVKGMAFL--HNSIissHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEP---DDSHALYAKklWTAPE 222
Cdd:cd05148   103 -VASLIDmacQVAEGMAYLeeQNSI---HRDLAARNILVGEDLVCKVADFGLA--RLIKEDvylSSDKKIPYK--WTAPE 174
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 223 LLSGNplptTGMQKADVYSFGIILQEIALRSGPFYlEGLdlSPKEIVQKVRNGQR-PyfRPsidrTQLNEELVLLMERCW 301
Cdd:cd05148   175 AASHG----TFSTKSDVWSFGILLYEMFTYGQVPY-PGM--NNHEVYDQITAGYRmP--CP----AKCPQEIYKIMLECW 241
                         250
                  ....*....|....
gi 1370514551 302 AQDPAERPDFGQIK 315
Cdd:cd05148   242 AAEPEDRPSFKALR 255
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
97-321 2.24e-19

Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Lyn is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Lyn is expressed in B lymphocytes and myeloid cells. It exhibits both positive and negative regulatory roles in B cell receptor (BCR) signaling. Lyn, as well as Fyn and Blk, promotes B cell activation by phosphorylating ITAMs (immunoreceptor tyr activation motifs) in CD19 and in Ig components of BCR. It negatively regulates signaling by its unique ability to phosphorylate ITIMs (immunoreceptor tyr inhibition motifs) in cell surface receptors like CD22 and CD5. Lyn also plays an important role in G-CSF receptor signaling by phosphorylating a variety of adaptor molecules. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Lyn subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270657 [Multi-domain]  Cd Length: 272  Bit Score: 88.17  E-value: 2.24e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  97 LFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDS---INLDWMFRYSLinDLVKGMAFLH--NSIi 171
Cdd:cd05072    50 LEEANLMKTLQHDKLVRLYAVVTKEEPIYIITEYMAKGSLLDFLKSDEggkVLLPKLIDFSA--QIAEGMAYIErkNYI- 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 172 ssHGSLKSSNCVVDSRFVLKITDYGLAsfrSTAEPDDSHALYAKKL---WTAPELLSGNPLPTtgmqKADVYSFGIILQE 248
Cdd:cd05072   127 --HRDLRAANVLVSESLMCKIADFGLA---RVIEDNEYTAREGAKFpikWTAPEAINFGSFTI----KSDVWSFGILLYE 197
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 249 IaLRSGPFYLEGldLSPKEIVQKVrngQRPYFRPSIDRTQlnEELVLLMERCWAQDPAERPDFGQIKGFIRRF 321
Cdd:cd05072   198 I-VTYGKIPYPG--MSNSDVMSAL---QRGYRMPRMENCP--DELYDIMKTCWKEKAEERPTFDYLQSVLDDF 262
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
99-318 2.67e-19

Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow kinase on the X chromosome; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Btk and Bmx (also named Etk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. In addition, Btk contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Btk is expressed in B-cells, and a variety of myeloid cells including mast cells, platelets, neutrophils, and dendrictic cells. It interacts with a variety of partners, from cytosolic proteins to nuclear transcription factors, suggesting a diversity of functions. Stimulation of a diverse array of cell surface receptors, including antigen engagement of the B-cell receptor, leads to PH-mediated membrane translocation of Btk and subsequent phosphorylation by Src kinase and activation. Btk plays an important role in the life cycle of B-cells including their development, differentiation, proliferation, survival, and apoptosis. Mutations in Btk cause the primary immunodeficiency disease, X-linked agammaglobulinaemia (XLA) in humans. Bmx is primarily expressed in bone marrow and the arterial endothelium, and plays an important role in ischemia-induced angiogenesis. It facilitates arterial growth, capillary formation, vessel maturation, and bone marrow-derived endothelial progenitor cell mobilization. The Btk/Bmx subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173657 [Multi-domain]  Cd Length: 256  Bit Score: 87.63  E-value: 2.67e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHnSIISSHGSLK 178
Cdd:cd05113    49 EAKVMMNLSHEKLVQLYGVCTKQRPIFIITEYMANGCLLNYLREMRKRFQTQQLLEMCKDVCEAMEYLE-SKQFLHRDLA 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 179 SSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLsgnpLPTTGMQKADVYSFGIILQEI-ALRSGPFY 257
Cdd:cd05113   128 ARNCLVNDQGVVKVSDFGLSRYVLDDEYTSSVGSKFPVRWSPPEVL----MYSKFSSKSDVWAFGVLMWEVySLGKMPYE 203
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370514551 258 LegldLSPKEIVQKVRNGQRPYfRPSidrtQLNEELVLLMERCWAQDPAERPDFGQIKGFI 318
Cdd:cd05113   204 R----FTNSETVEHVSQGLRLY-RPH----LASEKVYTIMYSCWHEKADERPTFKILLSNI 255
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
95-318 3.04e-19

Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes a subset of Src-like PTKs including Src, Fyn, Yrk, and Yes, which are all widely expressed. Yrk has been detected only in chickens. It is primarily found in neuronal and epithelial cells and in macrophages. It may play a role in inflammation and in response to injury. Src (or c-Src) proteins are cytoplasmic (or non-receptor) PTKs which are anchored to the plasma membrane. They contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). Src proteins are involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. They were identified as the first proto-oncogene products, and they regulate cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. They are also implicated in acute inflammatory responses and osteoclast function. The Src/Fyn-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271105 [Multi-domain]  Cd Length: 248  Bit Score: 87.28  E-value: 3.04e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVQfnhltrfIGACIDPPNICIVTEYCPRGSLQDILEN-DSINLDWMFRYSLINDLVKGMAFLH--NSIi 171
Cdd:cd14203    42 QIMKKLRHDKLVQ-------LYAVVSEEPIYIVTEFMSKGSLLDFLKDgEGKYLKLPQLVDMAAQIASGMAYIErmNYI- 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 172 ssHGSLKSSNCVVDSRFVLKITDYGLASFrstAEPDDSHALYAKKL---WTAPELlsgnPLPTTGMQKADVYSFGIILQE 248
Cdd:cd14203   114 --HRDLRAANILVGDNLVCKIADFGLARL---IEDNEYTARQGAKFpikWTAPEA----ALYGRFTIKSDVWSFGILLTE 184
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 249 IALRSGPFYLeglDLSPKEIVQKVRNGQR---PYFRPsidrtqlnEELVLLMERCWAQDPAERPDFGQIKGFI 318
Cdd:cd14203   185 LVTKGRVPYP---GMNNREVLEQVERGYRmpcPPGCP--------ESLHELMCQCWRKDPEERPTFEYLQSFL 246
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
80-323 3.46e-19

Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER, ErbB) subfamily members include EGFR (HER1, ErbB1), HER2 (ErbB2), HER3 (ErbB3), HER4 (ErbB4), and similar proteins. They are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, resulting in the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Collectively, they can recognize a variety of ligands including EGF, TGFalpha, and neuregulins, among others. All four subfamily members can form homo- or heterodimers. HER3 contains an impaired kinase domain and depends on its heterodimerization partner for activation. EGFR subfamily members are involved in signaling pathways leading to a broad range of cellular responses including cell proliferation, differentiation, migration, growth inhibition, and apoptosis. Gain of function alterations, through their overexpression, deletions, or point mutations in their kinase domains, have been implicated in various cancers. These receptors are targets of many small molecule inhibitors and monoclonal antibodies used in cancer therapy. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270648 [Multi-domain]  Cd Length: 279  Bit Score: 87.86  E-value: 3.46e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKR-IELTRQVLFELKHMRDVQFNHLTRFIGACIDPpNICIVTEYCPRGSLQDILENDSINLDwmfRYSLIN- 157
Cdd:cd05057    39 VAIKVLREETgPKANEEILDEAYVMASVDHPHLVRLLGICLSS-QVQLITQLMPLGCLLDYVRNHRDNIG---SQLLLNw 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 --DLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFrstAEPDDSHALY-AKKL---WTAPELLSGNPLpt 231
Cdd:cd05057   115 cvQIAKGMSYLEEKRLV-HRDLAARNVLVKTPNHVKITDFGLAKL---LDVDEKEYHAeGGKVpikWMALESIQYRIY-- 188
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 232 tgMQKADVYSFGIILQEIaLRSGPFYLEGLDLspKEIVQKVRNGQRpYFRPSIdrtqLNEELVLLMERCWAQDPAERPDF 311
Cdd:cd05057   189 --THKSDVWSYGVTVWEL-MTFGAKPYEGIPA--VEIPDLLEKGER-LPQPPI----CTIDVYMVLVKCWMIDAESRPTF 258
                         250
                  ....*....|..
gi 1370514551 312 gqiKGFIRRFNK 323
Cdd:cd05057   259 ---KELANEFSK 267
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
73-315 5.02e-19

Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Chk is also referred to as megakaryocyte-associated tyrosine kinase (Matk). Chk inhibits Src kinases using a noncatalytic mechanism by simply binding to them. As a negative regulator of Src kinases, Chk may play important roles in cell proliferation, survival, and differentiation, and consequently, in cancer development and progression. Chk is expressed in brain and hematopoietic cells. Like Csk, it is a cytoplasmic (or nonreceptor) tyr kinase containing the Src homology domains, SH3 and SH2, N-terminal to the catalytic tyr kinase domain. To inhibit Src kinases that are anchored to the plasma membrane, Chk is translocated to the membrane via binding to specific transmembrane proteins, G-proteins, or adaptor proteins near the membrane. Studies in mice reveal that Chk is not functionally redundant with Csk and that it plays an important role as a regulator of immune responses. Chk also plays a role in neural differentiation in a manner independent of Src by enhancing Mapk activation via Ras-mediated signaling. The Chk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270666 [Multi-domain]  Cd Length: 254  Bit Score: 86.85  E-value: 5.02e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVnkkRIELTRQV-LFELKHMRDVQFNHLTRFIGAcIDPPNICIVTEYCPRGSLQDILENDS---INLD 148
Cdd:cd05083    25 GEYMGQKVAVKNI---KCDVTAQAfLEETAVMTKLQHKNLVRLLGV-ILHNGLYIVMELMSKGNLVNFLRSRGralVPVI 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLinDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAepDDSHALYAKklWTAPELLSGNP 228
Cdd:cd05083   101 QLLQFSL--DVAEGMEYLESKKLV-HRDLAARNILVSEDGVAKISDFGLAKVGSMG--VDNSRLPVK--WTAPEALKNKK 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 LPTtgmqKADVYSFGIILQEI-ALRSGPFylegLDLSPKEIVQKVRNGQR---PYFRPSidrtqlneELVLLMERCWAQD 304
Cdd:cd05083   174 FSS----KSDVWSYGVLLWEVfSYGRAPY----PKMSVKEVKEAVEKGYRmepPEGCPP--------DVYSIMTSCWEAE 237
                         250
                  ....*....|.
gi 1370514551 305 PAERPDFGQIK 315
Cdd:cd05083   238 PGKRPSFKKLR 248
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
73-314 6.55e-19

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK3 is a mitogen-activated protein kinase kinase kinases (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. MLK3 activates multiple MAPK pathways and plays a role in apoptosis, proliferation, migration, and differentiation, depending on the cellular context. It is highly expressed in breast cancer cells and its signaling through c-Jun N-terminal kinase has been implicated in the migration, invasion, and malignancy of cancer cells. MLK3 also functions as a negative regulator of Inhibitor of Nuclear Factor-KappaB Kinase (IKK) and consequently, it also impacts inflammation and immunity. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271049 [Multi-domain]  Cd Length: 267  Bit Score: 87.01  E-value: 6.55e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVNK---KRIELTRQ-VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLD 148
Cdd:cd14147    22 GSWRGELVAVKAARQdpdEDISVTAEsVRQEARLFAMLAHPNIIALKAVCLEEPNLCLVMEYAAGGPLSRALAGRRVPPH 101
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLinDLVKGMAFLHNSIISS--HGSLKSSNCVVDSRFV--------LKITDYGLASFRSTAEPDDSHALYAkklW 218
Cdd:cd14147   102 VLVNWAV--QIARGMHYLHCEALVPviHRDLKSNNILLLQPIEnddmehktLKITDFGLAREWHKTTQMSAAGTYA---W 176
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 219 TAPELLSGnplpTTGMQKADVYSFGIILQEIALRSGPFY-LEGLDLSPKEIVQKVrngQRPYfrPSidrtQLNEELVLLM 297
Cdd:cd14147   177 MAPEVIKA----STFSKGSDVWSFGVLLWELLTGEVPYRgIDCLAVAYGVAVNKL---TLPI--PS----TCPEPFAQLM 243
                         250
                  ....*....|....*..
gi 1370514551 298 ERCWAQDPAERPDFGQI 314
Cdd:cd14147   244 ADCWAQDPHRRPDFASI 260
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
80-318 9.93e-19

Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily includes Ack1, thirty-eight-negative kinase 1 (Tnk1), and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal catalytic domain, an SH3 domain, a Cdc42-binding CRIB domain, and a proline-rich region. They are mainly expressed in brain and skeletal tissues and are involved in the regulation of cell adhesion and growth, receptor degradation, and axonal guidance. Ack1 is also associated with androgen-independent prostate cancer progression. Tnk1 regulates TNFalpha signaling and may play an important role in cell death. The Ack-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270636 [Multi-domain]  Cd Length: 258  Bit Score: 86.24  E-value: 9.93e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVnkKRIELTRQVLF-----ELKHMRDVQFNHLTRFIGACIDPPnICIVTEYCPRGSLQDIL--ENDSINLDWMFR 152
Cdd:cd05040    26 VAVKCL--KSDVLSQPNAMddflkEVNAMHSLDHPNLIRLYGVVLSSP-LMMVTELAPLGSLLDRLrkDQGHFLISTLCD 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 YSLinDLVKGMAFL-HNSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYA-KKL---WTAPELLsgN 227
Cdd:cd05040   103 YAV--QIANGMAYLeSKRFI--HRDLAARNILLASKDKVKIGDFGLM--RALPQNEDHYVMQEhRKVpfaWCAPESL--K 174
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 228 PLPTTgmQKADVYSFGIILQEIalrsgpF-YLEG--LDLSPKEIVQKV-RNGQR---PYFRPsidrtqlnEELVLLMERC 300
Cdd:cd05040   175 TRKFS--HASDVWMFGVTLWEM------FtYGEEpwLGLNGSQILEKIdKEGERlerPDDCP--------QDIYNVMLQC 238
                         250
                  ....*....|....*...
gi 1370514551 301 WAQDPAERPDFGQIKGFI 318
Cdd:cd05040   239 WAHKPADRPTFVALRDFL 256
PK_KSR2 cd14153
Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to ...
63-323 1.00e-18

Pseudokinase domain of Kinase Suppressor of Ras 2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. KSR2 interacts with the protein phosphatase calcineurin and functions in calcium-mediated ERK signaling. It also functions in energy metabolism by regulating AMP kinase and AMPK-dependent processes such as glucose uptake and fatty acid oxidation. KSR proteins act as scaffold proteins that function downstream of Ras and upstream of Raf in the Extracellular signal-Regulated Kinase (ERK) pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. KSR proteins regulate the assembly and activation of the Raf/MEK/ERK module upon Ras activation at the membrane by direct association of its components. They are widely regarded as pseudokinases. The KSR2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271055 [Multi-domain]  Cd Length: 270  Bit Score: 86.22  E-value: 1.00e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  63 HGKYQifantGHFKGNVVAIKHVNKKRIELTRQvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN 142
Cdd:cd14153    18 HGRWH-----GEVAIRLIDIERDNEEQLKAFKR---EVMAYRQTRHENVVLFMGACMSPPHLAIITSLCKGRTLYSVVRD 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 143 DSINLDWMFRYSLINDLVKGMAFLHNSIIsSHGSLKSSNCVVDSRFVLkITDYGLASFRSTAEPDDSH-ALYAKKLW--- 218
Cdd:cd14153    90 AKVVLDVNKTRQIAQEIVKGMGYLHAKGI-LHKDLKSKNVFYDNGKVV-ITDFGLFTISGVLQAGRREdKLRIQSGWlch 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 219 TAPELL-------SGNPLPTTgmQKADVYSFGIILQEIALRSGPFYLEgldlsPKE-IVQKVRNGqrpyFRPSIDRTQLN 290
Cdd:cd14153   168 LAPEIIrqlspetEEDKLPFS--KHSDVFAFGTIWYELHAREWPFKTQ-----PAEaIIWQVGSG----MKPNLSQIGMG 236
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1370514551 291 EELVLLMERCWAQDPAERPDFGQIKGFIRRFNK 323
Cdd:cd14153   237 KEISDILLFCWAYEQEERPTFSKLMEMLEKLPK 269
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
77-309 1.42e-18

Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Byr1 from Schizosaccharomyces pombe, FUZ7 from Ustilago maydis, and related proteins. Byr1 phosphorylates its downstream target, the MAPK Spk1, and is regulated by the MAPKK kinase Byr2. The Spk1 cascade is pheromone-responsive and is essential for sporulation and sexual differentiation in fission yeast. FUZ7 phosphorylates and activates its target, the MAPK Crk1, which is required in mating and virulence in U. maydis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The Byr-1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270792 [Multi-domain]  Cd Length: 286  Bit Score: 86.34  E-value: 1.42e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIK--HVNKKRiELTRQVLFELKHMRDVQFNHLTRFIGACI-DPPNICIVTEYCPRGSLQDIL-ENDSINLDWMFR 152
Cdd:cd06620    30 GTIMAKKviHIDAKS-SVRKQILRELQILHECHSPYIVSFYGAFLnENNNIIICMEYMDCGSLDKILkKKGPFPEEVLGK 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 ysLINDLVKGMAFLHNS--IIssHGSLKSSNCVVDSRFVLKITDYGLasfrsTAEPDDSHA--LYAKKLWTAPELLSGNP 228
Cdd:cd06620   109 --IAVAVLEGLTYLYNVhrII--HRDIKPSNILVNSKGQIKLCDFGV-----SGELINSIAdtFVGTSTYMSPERIQGGK 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 LPTtgmqKADVYSFGIILQEIALRSGPFYLEGLD----LSPKEI---VQKVRNGQRPYFrPSIDRtqLNEELVLLMERCW 301
Cdd:cd06620   180 YSV----KSDVWSLGLSIIELALGEFPFAGSNDDddgyNGPMGIldlLQRIVNEPPPRL-PKDRI--FPKDLRDFVDRCL 252

                  ....*...
gi 1370514551 302 AQDPAERP 309
Cdd:cd06620   253 LKDPRERP 260
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
97-321 1.84e-18

Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Hck is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Hck is present in myeloid and lymphoid cells that play a role in the development of cancer. It may be important in the oncogenic signaling of the protein Tel-Abl, which induces a chronic myelogenous leukemia (CML)-like disease. Hck also acts as a negative regulator of G-CSF-induced proliferation of granulocytic precursors, suggesting a possible role in the development of acute myeloid leukemia (AML). In addition, Hck is essential in regulating the degranulation of polymorphonuclear leukocytes. Genetic polymorphisms affect the expression level of Hck, which affects PMN mediator release and influences the development of chronic obstructive pulmonary disease (COPD). Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Hck subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270658 [Multi-domain]  Cd Length: 265  Bit Score: 85.46  E-value: 1.84e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  97 LFELKHMRDVQFNHLTRFIGACIDPPnICIVTEYCPRGSLQDILENDSIN---LDWMFRYSLinDLVKGMAFLH--NSIi 171
Cdd:cd05073    54 LAEANVMKTLQHDKLVKLHAVVTKEP-IYIITEFMAKGSLLDFLKSDEGSkqpLPKLIDFSA--QIAEGMAFIEqrNYI- 129
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 172 ssHGSLKSSNCVVDSRFVLKITDYGLASFrstAEPDDSHALYAKKL---WTAPELLSGNPLPTtgmqKADVYSFGIILQE 248
Cdd:cd05073   130 --HRDLRAANILVSASLVCKIADFGLARV---IEDNEYTAREGAKFpikWTAPEAINFGSFTI----KSDVWSFGILLME 200
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 249 IaLRSGPFYLEGLdlSPKEIVQKVRNGQRpyfrpsIDRTQ-LNEELVLLMERCWAQDPAERPDFGQIKGFIRRF 321
Cdd:cd05073   201 I-VTYGRIPYPGM--SNPEVIRALERGYR------MPRPEnCPEELYNIMMRCWKNRPEERPTFEYIQSVLDDF 265
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
77-315 1.90e-18

Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent Protein Kinase Kinase, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Both LKB1 and CaMKKs can phosphorylate and activate AMP-activated protein kinase (AMPK). LKB1, also called STK11, serves as a master upstream kinase that activates AMPK and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMPK. Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The LKB1/CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270910 [Multi-domain]  Cd Length: 267  Bit Score: 85.30  E-value: 1.90e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDvQFNHLTRFIG--------------ACIDPPN---ICIVTEYCPRGSLQDI 139
Cdd:cd14008    18 GQLYAIKIFNKSRLRKRREGKNDRGKIKN-ALDDVRREIAimkkldhpnivrlyEVIDDPEsdkLYLVLEYCEGGPVMEL 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 140 LEND-SINLD-----WMFRyslinDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASF--RSTAEPDDSH 210
Cdd:cd14008    97 DSGDrVPPLPeetarKYFR-----DLVLGLEYLHeNGIV--HRDIKPENLLLTADGTVKISDFGVSEMfeDGNDTLQKTA 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 211 ALYAkklWTAPELLSGNPLPTTGmQKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQRPYFRPSidrtQLN 290
Cdd:cd14008   170 GTPA---FLAPELCDGDSKTYSG-KAADIWALGVTLYCLVFGRLPFN----GDNILELYEAIQNQNDEFPIPP----ELS 237
                         250       260
                  ....*....|....*....|....*
gi 1370514551 291 EELVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd14008   238 PELKDLLRRMLEKDPEKRITLKEIK 262
STKc_BMPR2_AMHR2 cd14054
Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and ...
73-308 2.08e-18

Catalytic domain of the Serine/Threonine Kinases, Bone Morphogenetic Protein and Anti-Muellerian Hormone Type II Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR2 and AMHR2 belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors (GDFs), and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. BMPR2 and AMHR2 act primarily as a receptor for BMPs and AMH, respectively. BMPs induce bone and cartilage formation, as well as regulate tooth, kidney, skin, hair, haematopoietic, and neuronal development. Mutations in BMPR2A is associated with familial pulmonary arterial hypertension. AMH is mainly responsible for the regression of Mullerian ducts during male sex differentiation. It is expressed exclusively by somatic cells of the gonads. Mutations in either AMH or AMHR2 cause persistent Mullerian duct syndrome (PMDS), a rare form of male pseudohermaphroditism characterized by the presence of Mullerian derivatives (ovary and tubes) in otherwise normally masculine males. The BMPR2/AMHR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270956 [Multi-domain]  Cd Length: 300  Bit Score: 85.88  E-value: 2.08e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIK---------HVNKKRIeltrqvlFELKHMRdvqFNHLTRFIGACIDPPNIC-----IVTEYCPRGSLQD 138
Cdd:cd14054    14 GSLDERPVAVKvfparhrqnFQNEKDI-------YELPLME---HSNILRFIGADERPTADGrmeylLVLEYAPKGSLCS 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 139 ILENDSinLDWMFRYSLINDLVKGMAFLHNSIIS--------SHGSLKSSNCVVDSRFVLKITDYGLA------SFRSTA 204
Cdd:cd14054    84 YLRENT--LDWMSSCRMALSLTRGLAYLHTDLRRgdqykpaiAHRDLNSRNVLVKADGSCVICDFGLAmvlrgsSLVRGR 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 205 EPDDSHALYAKK---LWTAPELLSG--NpL--PTTGMQKADVYSFGIILQEIALR-------------SGPFYLE-GLDL 263
Cdd:cd14054   162 PGAAENASISEVgtlRYMAPEVLEGavN-LrdCESALKQVDVYALGLVLWEIAMRcsdlypgesvppyQMPYEAElGNHP 240
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1370514551 264 SPKE-IVQKVRNGQRPYFRPSIDRTQLN-EELVLLMERCWAQDPAER 308
Cdd:cd14054   241 TFEDmQLLVSREKARPKFPDAWKENSLAvRSLKETIEDCWDQDAEAR 287
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
80-314 2.17e-18

Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Met and Ron are receptor PTKs (RTKs) composed of an alpha-beta heterodimer. The extracellular alpha chain is disulfide linked to the beta chain, which contains an extracellular ligand-binding region with a sema domain, a PSI domain and four IPT repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. Met binds to the ligand, hepatocyte growth factor/scatter factor (HGF/SF), and is also called the HGF receptor. HGF/Met signaling plays a role in growth, transformation, cell motility, invasion, metastasis, angiogenesis, wound healing, and tissue regeneration. Aberrant expression of Met through mutations or gene amplification is associated with many human cancers including hereditary papillary renal and gastric carcinomas. The ligand for Ron is macrophage stimulating protein (MSP). Ron signaling is important in regulating cell motility, adhesion, proliferation, and apoptosis. Aberrant Ron expression is implicated in tumorigenesis and metastasis. The Met/Ron subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270649 [Multi-domain]  Cd Length: 262  Bit Score: 85.22  E-value: 2.17e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNkkRIELTRQVLFELKH---MRDVQFNHLTRFIGACIDPPNI-CIVTEYCPRGSLQDILENDSINldwmfrySL 155
Cdd:cd05058    26 CAVKSLN--RITDIEEVEQFLKEgiiMKDFSHPNVLSLLGICLPSEGSpLVVLPYMKHGDLRNFIRSETHN-------PT 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 INDLV-------KGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKL---WTAPELLS 225
Cdd:cd05058    97 VKDLIgfglqvaKGMEYLASKKFV-HRDLAARNCMLDESFTVKVADFGLARDIYDKEYYSVHNHTGAKLpvkWMALESLQ 175
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 226 GNPLPTtgmqKADVYSFGIILQEIALRSGPFYlegLDLSPKEIVQKVRNGQR---PYFRPsidrtqlnEELVLLMERCWA 302
Cdd:cd05058   176 TQKFTT----KSDVWSFGVLLWELMTRGAPPY---PDVDSFDITVYLLQGRRllqPEYCP--------DPLYEVMLSCWH 240
                         250
                  ....*....|..
gi 1370514551 303 QDPAERPDFGQI 314
Cdd:cd05058   241 PKPEMRPTFSEL 252
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
79-314 2.24e-18

Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also called protein tyrosine kinase 7 (PTK7), is an orphan receptor PTK (RTK) containing an extracellular region with seven immunoglobulin domains, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Studies in mice reveal that CCK4 is essential for neural development. Mouse embryos containing a truncated CCK4 die perinatally and display craniorachischisis, a severe form of neural tube defect. The mechanism of action of the CCK4 pseudokinase is still unknown. Other pseudokinases such as HER3 rely on the activity of partner RTKs. The CCK4 subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133178 [Multi-domain]  Cd Length: 275  Bit Score: 85.59  E-value: 2.24e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  79 VVAIKHVNKKRIEltrQVLFELKHMRDV--QFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDIL--------ENDSIN 146
Cdd:cd05046    37 LVLVKALQKTKDE---NLQSEFRRELDMfrKLSHknVVRLLGLCREAEPHYMILEYTDLGDLKQFLratkskdeKLKPPP 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSG 226
Cdd:cd05046   114 LSTKQKVALCTQIALGMDHLSNARFV-HRDLAARNCLVSSQREVKVSLLSLSKDVYNSEYYKLRNALIPLRWLAPEAVQE 192
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPTtgmqKADVYSFGIILQEIaLRSG--PFYleglDLSPKEIVQKVRNGQRPYFRPSidrtQLNEELVLLMERCWAQD 304
Cdd:cd05046   193 DDFST----KSDVWSFGVLMWEV-FTQGelPFY----GLSDEEVLNRLQAGKLELPVPE----GCPSRLYKLMTRCWAVN 259
                         250
                  ....*....|
gi 1370514551 305 PAERPDFGQI 314
Cdd:cd05046   260 PKDRPSFSEL 269
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
95-311 2.76e-18

Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Frk and Srk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Frk, also known as Rak, is specifically expressed in liver, lung, kidney, intestine, mammary glands, and the islets of Langerhans. Rodent homologs were previously referred to as GTK (gastrointestinal tyr kinase), BSK (beta-cell Src-like kinase), or IYK (intestinal tyr kinase). Studies in mice reveal that Frk is not essential for viability. It plays a role in the signaling that leads to cytokine-induced beta-cell death in Type I diabetes. It also regulates beta-cell number during embryogenesis and early in life. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Frk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270653 [Multi-domain]  Cd Length: 267  Bit Score: 85.15  E-value: 2.76e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVQFnhltrfIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFL--HNSIis 172
Cdd:cd05068    55 QIMKKLRHPKLIQL------YAVCTLEEPIYIITELMKHGSLLEYLQGKGRSLQLPQLIDMAAQVASGMAYLesQNYI-- 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 173 sHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKKL---WTAPELLSGNPLPTtgmqKADVYSFGIILQEI 249
Cdd:cd05068   127 -HRDLAARNVLVGENNICKVADFGLA--RVIKVEDEYEAREGAKFpikWTAPEAANYNRFSI----KSDVWSFGILLTEI 199
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 250 aLRSGPFYLEGLdlSPKEIVQKVRNGQR---PYFRPsidrtqlnEELVLLMERCWAQDPAERPDF 311
Cdd:cd05068   200 -VTYGRIPYPGM--TNAEVLQQVERGYRmpcPPNCP--------PQLYDIMLECWKADPMERPTF 253
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
91-315 2.83e-18

Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; Fer kinase; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fer kinase is a member of the Fes subfamily of proteins which are cytoplasmic (or nonreceptor) tyr kinases containing an N-terminal region with FCH (Fes/Fer/CIP4 homology) and coiled-coil domains, followed by a SH2 domain, and a C-terminal catalytic domain. Fer kinase is expressed in a wide variety of tissues, and is found to reside in both the cytoplasm and the nucleus. It plays important roles in neuronal polarization and neurite development, cytoskeletal reorganization, cell migration, growth factor signaling, and the regulation of cell-cell interactions mediated by adherens junctions and focal adhesions. Fer kinase also regulates cell cycle progression in malignant cells.


Pssm-ID: 270668 [Multi-domain]  Cd Length: 251  Bit Score: 84.67  E-value: 2.83e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  91 ELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL--ENDSINLDWMFRYSLinDLVKGMAFLH- 167
Cdd:cd05085    35 ELKIKFLSEARILKQYDHPNIVKLIGVCTQRQPIYIVMELVPGGDFLSFLrkKKDELKTKQLVKFSL--DAAAGMAYLEs 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 168 -NSIissHGSLKSSNCVVDSRFVLKITDYGLasfrSTAEPDDSHALYAKKL----WTAPELLSGNPLPTtgmqKADVYSF 242
Cdd:cd05085   113 kNCI---HRDLAARNCLVGENNALKISDFGM----SRQEDDGVYSSSGLKQipikWTAPEALNYGRYSS----ESDVWSF 181
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 243 GIILQE-IALRSGPFylegldlsPKEIVQKVRNGQRPYFRPSIDRtQLNEELVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd05085   182 GILLWEtFSLGVCPY--------PGMTNQQAREQVEKGYRMSAPQ-RCPEDIYKIMQRCWDYNPENRPKFSELQ 246
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
77-322 2.97e-18

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MAPKKs are dual-specificity PKs that phosphorylate their downstream targets, MAPKs, at specific threonine and tyrosine residues. The MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The pathways involve a triple kinase core cascade comprising the MAPK, which is phosphorylated and activated by a MAPK kinase (MAPKK or MKK or MAP2K), which itself is phosphorylated and activated by a MAPKK kinase (MAPKKK or MKKK or MAP3K). There are three MAPK subfamilies: extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. In mammalian cells, there are seven MAPKKs (named MKK1-7) and 20 MAPKKKs. Each MAPK subfamily can be activated by at least two cognate MAPKKs and by multiple MAPKKKs. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 84.70  E-value: 2.97e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNK------KRIELT------RQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-END 143
Cdd:cd06605    15 GVVSKVRHRPSgqimavKVIRLEidealqKQILRELDVLHKCNSPYIVGFYGAFYSEGDISICMEYMDGGSLDKILkEVG 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 144 SINLDWMFRysLINDLVKGMAFLHN--SIIssHGSLKSSNCVVDSRFVLKITDYGLasfrSTAEPDDSHALYA-KKLWTA 220
Cdd:cd06605    95 RIPERILGK--IAVAVVKGLIYLHEkhKII--HRDVKPSNILVNSRGQVKLCDFGV----SGQLVDSLAKTFVgTRSYMA 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 221 PELLSGNPLPTtgmqKADVYSFGIILQEIALRSGPFYLEGLD--LSPKEIVQKVRNGQRPYFrPSidrTQLNEELVLLME 298
Cdd:cd06605   167 PERISGGKYTV----KSDIWSLGLSLVELATGRFPYPPPNAKpsMMIFELLSYIVDEPPPLL-PS---GKFSPDFQDFVS 238
                         250       260
                  ....*....|....*....|....*.
gi 1370514551 299 RCWAQDPAERPDFGQIKG--FIRRFN 322
Cdd:cd06605   239 QCLQKDPTERPSYKELMEhpFIKRYE 264
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
87-309 5.89e-18

Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: GCN2, protein kinase regulated by RNA (PKR), heme-regulated inhibitor kinase (HRI), and PKR-like endoplasmic reticulum kinase (PERK). GCN2 is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kappaB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. The degenerate pseudokinase domain of GCN2 may function as a regulatory domain. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270914 [Multi-domain]  Cd Length: 254  Bit Score: 83.56  E-value: 5.89e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  87 KKRIELTRQVLFELKHMRDvqfNHLTRFIGACIDPPN------ICIVTEYCPRGSLQDILEN-DSINLDWMFRYSLinDL 159
Cdd:cd14012    39 KKQIQLLEKELESLKKLRH---PNLVSYLAFSIERRGrsdgwkVYLLTEYAPGGSLSELLDSvGSVPLDTARRWTL--QL 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 160 VKGMAFLHNSIIsSHGSLKSSNCVVDSRF---VLKITDYGLasfrsTAEPDDSHALYAKK-----LWTAPELLSGNPLPT 231
Cdd:cd14012   114 LEALEYLHRNGV-VHKSLHAGNVLLDRDAgtgIVKLTDYSL-----GKTLLDMCSRGSLDefkqtYWLPPELAQGSKSPT 187
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 232 tgmQKADVYSFGIILqeIALRSGpfylegldlspKEIVQKVRNGQrpyfrPSIDRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd14012   188 ---RKTDVWDLGLLF--LQMLFG-----------LDVLEKYTSPN-----PVLVSLDLSASLQDFLSKCLSLDPKKRP 244
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
76-334 6.30e-18

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The EphA2 receptor is overexpressed in tumor cells and tumor blood vessels in a variety of cancers including breast, prostate, lung, and colon. As a result, it is an attractive target for drug design since its inhibition could affect several aspects of tumor progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 133194 [Multi-domain]  Cd Length: 268  Bit Score: 83.87  E-value: 6.30e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  76 KGNVVAIKHVNKKRIELTRQ-VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYS 154
Cdd:cd05063    32 KEVAVAIKTLKPGYTEKQRQdFLSEASIMGQFSHHNIIRLEGVVTKFKPAMIITEYMENGALDKYLRDHDGEFSSYQLVG 111
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNsIISSHGSLKSSNCVVDSRFVLKITDYGLasfrSTAEPDDSHALYAKK------LWTAPELLSGNP 228
Cdd:cd05063   112 MLRGIAAGMKYLSD-MNYVHRDLAARNILVNSNLECKVSDFGL----SRVLEDDPEGTYTTSggkipiRWTAPEAIAYRK 186
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 LPTTgmqkADVYSFGIILQEI-ALRSGPFYleglDLSPKEIVQKVRNGQR---PYFRPSidrtqlneELVLLMERCWAQD 304
Cdd:cd05063   187 FTSA----SDVWSFGIVMWEVmSFGERPYW----DMSNHEVMKAINDGFRlpaPMDCPS--------AVYQLMLQCWQQD 250
                         250       260       270
                  ....*....|....*....|....*....|
gi 1370514551 305 PAERPDFGQIkgfirrfnkeggTSILDNLL 334
Cdd:cd05063   251 RARRPRFVDI------------VNLLDKLL 268
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
107-314 1.13e-17

Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They can be classified into two classes (EphA and EphB), according to their extracellular sequences, which largely correspond to binding preferences for either GPI-anchored ephrin-A ligands or transmembrane ephrin-B ligands. Vertebrates have ten EphA and six EphB receptors, which display promiscuous ligand interactions within each class. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. This allows ephrin/EphR dimers to form, leading to the activation of the intracellular tyr kinase domain. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The main effect of ephrin/EphR interaction is cell-cell repulsion or adhesion. Ephrin/EphR signaling is important in neural development and plasticity, cell morphogenesis and proliferation, cell-fate determination, embryonic development, tissue patterning, and angiogenesis.The EphR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270629 [Multi-domain]  Cd Length: 266  Bit Score: 83.19  E-value: 1.13e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 107 QFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFL--HNSIissHGSLKSSNC 182
Cdd:cd05033    61 QFDHpnVIRLEGVVTKSRPVMIVTEYMENGSLDKFLRENDGKFTVTQLVGMLRGIASGMKYLseMNYV---HRDLAARNI 137
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 183 VVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKK---LWTAPELLSGNPLPTTgmqkADVYSFGIILQEI-ALRSGPFYl 258
Cdd:cd05033   138 LVNSDLVCKVSDFGLS--RRLEDSEATYTTKGGKipiRWTAPEAIAYRKFTSA----SDVWSFGIVMWEVmSYGERPYW- 210
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370514551 259 eglDLSPKEIVQKVRNGQR---PYFRPSIdrtqlneeLVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05033   211 ---DMSNQDVIKAVEDGYRlppPMDCPSA--------LYQLMLDCWQKDRNERPTFSQI 258
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
73-311 1.13e-17

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270665 [Multi-domain]  Cd Length: 283  Bit Score: 83.40  E-value: 1.13e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDP--PNICIVTEYCPRGSLQDILENDSINLDWM 150
Cdd:cd05081    29 GDNTGALVAVKQLQHSGPDQQRDFQREIQILKALHSDFIVKYRGVSYGPgrRSLRLVMEYLPSGCLRDFLQRHRARLDAS 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 151 FRYSLINDLVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAS-------FRSTAEPDDSHALyakklWTAPEL 223
Cdd:cd05081   109 RLLLYSSQICKGMEYL-GSRRCVHRDLAARNILVESEAHVKIADFGLAKllpldkdYYVVREPGQSPIF-----WYAPES 182
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 224 LSGNPLPttgmQKADVYSFGIILQEIalrsgpFYLEGLDLSPKE-----------------IVQKVRNGQRPYFRPSIDr 286
Cdd:cd05081   183 LSDNIFS----RQSDVWSFGVVLYEL------FTYCDKSCSPSAeflrmmgcerdvpalcrLLELLEEGQRLPAPPACP- 251
                         250       260
                  ....*....|....*....|....*
gi 1370514551 287 tqlnEELVLLMERCWAQDPAERPDF 311
Cdd:cd05081   252 ----AEVHELMKLCWAPSPQDRPSF 272
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
77-249 1.24e-17

Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LIMK2 activation is induced by transforming growth factor-beta l (TGFb-l) and shares the same subcellular location as the cofilin family member twinfilin, which may be its biological substrate. LIMK2 plays a role in spermatogenesis, and may contribute to tumor progression and metastasis formation in some cancer cells. LIMKs phosphorylate and inactivate cofilin, an actin depolymerizing factor, to induce the reorganization of the actin cytoskeleton. They act downstream of Rho GTPases and are expressed ubiquitously. As regulators of actin dynamics, they contribute to diverse cellular functions such as cell motility, morphogenesis, differentiation, apoptosis, meiosis, mitosis, and neurite extension. LIMKs contain the LIM (two repeats), PDZ, and catalytic kinase domains. The LIMK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271124 [Multi-domain]  Cd Length: 272  Bit Score: 83.07  E-value: 1.24e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSiNLDWMFRYSLI 156
Cdd:cd14222    18 GKVMVMKELIRCDEETQKTFLTEVKVMRSLDHPNVLKFIGVLYKDKRLNLLTEFIEGGTLKDFLRADD-PFPWQQKVSFA 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLASF----RSTAEPDDS---------------HALYAKK 216
Cdd:cd14222    97 KGIASGMAYLHSmSII--HRDLNSHNCLIKLDKTVVVADFGLSRLiveeKKKPPPDKPttkkrtlrkndrkkrYTVVGNP 174
                         170       180       190
                  ....*....|....*....|....*....|...
gi 1370514551 217 LWTAPELLSGNPLPttgmQKADVYSFGIILQEI 249
Cdd:cd14222   175 YWMAPEMLNGKSYD----EKVDIFSFGIVLCEI 203
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
77-314 1.28e-17

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Nek family is composed of 11 different mammalian members (Nek1-11) with similarity to the catalytic domain of Aspergillus nidulans NIMA kinase, the founding member of the Nek family, which was identified in a screen for cell cycle mutants that were prevented from entering mitosis. Neks contain a conserved N-terminal catalytic domain and a more divergent C-terminal regulatory region of various sizes and structures. They are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270855 [Multi-domain]  Cd Length: 258  Bit Score: 82.90  E-value: 1.28e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIEL--TRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSIN-------- 146
Cdd:cd08215    25 GKLYVLKEIDLSNMSEkeREEALNEVKLLSKLKHPNIVKYYESFEENGKLCIVMEYADGGDLAQKIKKQKKKgqpfpeeq 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 -LDWMFRYSLindlvkGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfrSTAEPDDSHA-------LYakkl 217
Cdd:cd08215   105 iLDWFVQICL------ALKYLHsRKIL--HRDLKTQNIFLTKDGVVKLGDFGIS---KVLESTTDLAktvvgtpYY---- 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 218 wTAPELLSGNPLPttgmQKADVYSFGIILQEIALRSGPFylEGLDLspKEIVQKVRNGQrpyfRPSIDrTQLNEELVLLM 297
Cdd:cd08215   170 -LSPELCENKPYN----YKSDIWALGCVLYELCTLKHPF--EANNL--PALVYKIVKGQ----YPPIP-SQYSSELRDLV 235
                         250
                  ....*....|....*..
gi 1370514551 298 ERCWAQDPAERPDFGQI 314
Cdd:cd08215   236 NSMLQKDPEKRPSANEI 252
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
80-315 1.40e-17

Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. FAK is a cytoplasmic (or nonreceptor) PTK that contains an autophosphorylation site and a FERM domain at the N-terminus, a central tyr kinase domain, proline-rich regions, and a C-terminal FAT (focal adhesion targeting) domain. FAK activity is dependent on integrin-mediated cell adhesion, which facilitates N-terminal autophosphorylation. Full activation is achieved by the phosphorylation of its two adjacent A-loop tyrosines. FAK is important in mediating signaling initiated at sites of cell adhesions and at growth factor receptors. Through diverse molecular interactions, FAK functions as a biosensor or integrator to control cell motility. It is a key regulator of cell survival, proliferation, migration and invasion, and thus plays an important role in the development and progression of cancer. Src binds to autophosphorylated FAK forming the FAK-Src dual kinase complex, which is activated in a wide variety of tumor cells and generates signals promoting growth and metastasis. FAK is being developed as a target for cancer therapy. The FAK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133187 [Multi-domain]  Cd Length: 270  Bit Score: 82.86  E-value: 1.40e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKhVNKKRIELTRQVLF--ELKHMRDVQFNHLTRFIGACIDPPnICIVTEYCPRGSLQDILE--NDSINLDWMFRYSL 155
Cdd:cd05056    37 VAVK-TCKNCTSPSVREKFlqEAYIMRQFDHPHIVKLIGVITENP-VWIVMELAPLGELRSYLQvnKYSLDLASLILYAY 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 inDLVKGMAFLHnSIISSHGSLKSSNCVVDSRFVLKITDYGLasfrSTAEPDDSHALYAK-KL---WTAPELLSGNPLPT 231
Cdd:cd05056   115 --QLSTALAYLE-SKRFVHRDIAARNVLVSSPDCVKLGDFGL----SRYMEDESYYKASKgKLpikWMAPESINFRRFTS 187
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 232 TgmqkADVYSFGIILQEIALRS-GPFylEGLDlsPKEIVQKVRNGQRPYFRPSIDRTqlneeLVLLMERCWAQDPAERPD 310
Cdd:cd05056   188 A----SDVWMFGVCMWEILMLGvKPF--QGVK--NNDVIGRIENGERLPMPPNCPPT-----LYSLMTKCWAYDPSKRPR 254

                  ....*
gi 1370514551 311 FGQIK 315
Cdd:cd05056   255 FTELK 259
STKc_TGFbR-like cd13998
Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; ...
126-308 1.63e-17

Catalytic domain of Transforming Growth Factor beta Receptor-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of receptors for the TGFbeta family of secreted signaling molecules including TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. There are two types of TGFbeta receptors included in this subfamily, I and II, that play different roles in signaling. For signaling to occur, the ligand first binds to the high-affinity type II receptor, which is followed by the recruitment of the low-affinity type I receptor to the complex and its activation through trans-phosphorylation by the type II receptor. The active type I receptor kinase starts intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. Different ligands interact with various combinations of types I and II receptors to elicit a specific signaling pathway. Activins primarily signal through combinations of ACVR1b/ALK7 and ACVR2a/b; myostatin and GDF11 through TGFbR1/ALK4 and ACVR2a/b; BMPs through ACVR1/ALK1 and BMPR2; and TGFbeta through TGFbR1 and TGFbR2. The TGFbR-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270900 [Multi-domain]  Cd Length: 289  Bit Score: 83.26  E-value: 1.63e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 126 IVTEYCPRGSLQDILENDSInlDWMFRYSLINDLVKGMAFLHNSIIS--------SHGSLKSSNCVVDSRFVLKITDYGL 197
Cdd:cd13998    70 LVTAFHPNGSL*DYLSLHTI--DWVSLCRLALSVARGLAHLHSEIPGctqgkpaiAHRDLKSKNILVKNDGTCCIADFGL 147
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 198 AsFR---STAEPD-DSHALYAKKLWTAPELLSG--NPLPTTGMQKADVYSFGIILQEIALRSG-----------PFYLE- 259
Cdd:cd13998   148 A-VRlspSTGEEDnANNGQVGTKRYMAPEVLEGaiNLRDFESFKRVDIYAMGLVLWEMASRCTdlfgiveeykpPFYSEv 226
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370514551 260 GLDLS---PKEIVqkVRNGQRPYFRPSIDRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd13998   227 PNHPSfedMQEVV--VRDKQRPNIPNRWLSHPGLQSLAETIEECWDHDAEAR 276
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
88-309 1.64e-17

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 85.45  E-value: 1.64e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  88 KRIELTRQVLfeLKHMRDVQFNH---LTRF-----IGACIDPPNI-------------CIVTEYCPRGSLQDILENDSiN 146
Cdd:COG0515    27 RDLRLGRPVA--LKVLRPELAADpeaRERFrrearALARLNHPNIvrvydvgeedgrpYLVMEYVEGESLADLLRRRG-P 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLS 225
Cdd:COG0515   104 LPPAEALRILAQLAEALAAAHaAGIV--HRDIKPANILLTPDGRVKLIDFGIARALGGATLTQTGTVVGTPGYMAPEQAR 181
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 226 GNPLpttgMQKADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNGQRPyfRPSIDRTQLNEELVLLMERCWAQDP 305
Cdd:COG0515   182 GEPV----DPRSDVYSLGVTLYELLTGRPPFDGD----SPAELLRAHLREPPP--PPSELRPDLPPALDAIVLRALAKDP 251

                  ....
gi 1370514551 306 AERP 309
Cdd:COG0515   252 EERY 255
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
77-310 1.77e-17

Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and similar proteins; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include MAPKKs from plants, kinetoplastids, alveolates, and mycetozoa. The MAPKK, LmxPK4, from Leishmania mexicana, is important in differentiation and virulence. Dictyostelium discoideum MEK1 is required for proper chemotaxis; MEK1 null mutants display severe defects in cell polarization and directional movement. Plants contain multiple MAPKKs like other eukaryotes. The Arabidopsis genome encodes for 10 MAPKKs while poplar and rice contain 13 MAPKKs each. The functions of these proteins have not been fully elucidated. There is evidence to suggest that MAPK cascades are involved in plant stress responses. In Arabidopsis, MKK3 plays a role in pathogen signaling; MKK2 is involved in cold and salt stress signaling; MKK4/MKK5 participates in innate immunity; and MKK7 regulates basal and systemic acquired resistance. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 82.64  E-value: 1.77e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTR-QVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEndsinldwmfRYSL 155
Cdd:cd06623    26 GKIYALKKIHVDGDEEFRkQLLRELKTLRSCESPYVVKCYGAFYKEGEISIVLEYMDGGSLADLLK----------KVGK 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 IND---------LVKGMAFLHNS--IIssHGSLKSSNCVVDSRFVLKITDYGLASF-RSTAEPDDSH---ALYakklwTA 220
Cdd:cd06623    96 IPEpvlayiarqILKGLDYLHTKrhII--HRDIKPSNLLINSKGEVKIADFGISKVlENTLDQCNTFvgtVTY-----MS 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 221 PELLSGNPLPTtgmqKADVYSFGIILQEIALRSGPFyLEGLDLSPKEIVQKVrNGQRPYFRPSidrTQLNEELVLLMERC 300
Cdd:cd06623   169 PERIQGESYSY----AADIWSLGLTLLECALGKFPF-LPPGQPSFFELMQAI-CDGPPPSLPA---EEFSPEFRDFISAC 239
                         250
                  ....*....|
gi 1370514551 301 WAQDPAERPD 310
Cdd:cd06623   240 LQKDPKKRPS 249
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
76-256 1.86e-17

Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of HAL4, Saccharomyces cerevisiae Ptk2/Stk2, and similar fungal proteins. Proteins in this subfamily are involved in regulating ion transporters. In budding and fission yeast, HAL4 promotes potassium ion uptake, which increases cellular resistance to other cations such as sodium, lithium, and calcium ions. HAL4 stabilizes the major high-affinity K+ transporter Trk1 at the plasma membrane under low K+ conditions, which prevents endocytosis and vacuolar degradation. Budding yeast Ptk2 phosphorylates and regulates the plasma membrane H+ ATPase, Pma1. The HAL4-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270896 [Multi-domain]  Cd Length: 265  Bit Score: 82.35  E-value: 1.86e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  76 KGNVVAIKHVNKKRIELTRQ-----VLFE---LKHMRDVqfnHLTRFIGACIDP-PNICIVTEYCPRGSLQDILEnDSIN 146
Cdd:cd13994    19 SGVLYAVKEYRRRDDESKRKdyvkrLTSEyiiSSKLHHP---NIVKVLDLCQDLhGKWCLVMEYCPGGDLFTLIE-KADS 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYSLINDLVKGMAFLHNSIIsSHGSLKSSNCVVDSRFVLKITDYGLAS-FRSTAEPD--DSHALYAKKLWTAPEL 223
Cdd:cd13994    95 LSLEEKDCFFKQILRGVAYLHSHGI-AHRDLKPENILLDEDGVLKLTDFGTAEvFGMPAEKEspMSAGLCGSEPYMAPEV 173
                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1370514551 224 LSG---NPLPttgmqkADVYSFGIILQEIALRSGPF 256
Cdd:cd13994   174 FTSgsyDGRA------VDVWSCGIVLFALFTGRFPW 203
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
76-310 2.34e-17

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. PAK deregulation is associated with tumor development. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). Group II PAKs contain a PBD and a catalytic domain, but lack other motifs found in group I PAKs. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. Group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX; no such binding has been demonstrated for group II PAKs. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270789 [Multi-domain]  Cd Length: 255  Bit Score: 81.87  E-value: 2.34e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  76 KGNVVAIK--HVNKKRIELtrqVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRY 153
Cdd:cd06614    24 TGKEVAIKkmRLRKQNKEL---IINEILIMKECKHPNIVDYYDSYLVGDELWVVMEYMDGGSLTDIITQNPVRMNESQIA 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 154 SLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASfRSTAEPDDSHALYAKKLWTAPELLSGNPLPTt 232
Cdd:cd06614   101 YVCREVLQGLEYLHsQNVI--HRDIKSDNILLSKDGSVKLADFGFAA-QLTKEKSKRNSVVGTPYWMAPEVIKRKDYGP- 176
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 233 gmqKADVYSFGIILQEIAlrsgpfylEG----LDLSPKEIVQKVRNGQRPYFRpsiDRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd06614   177 ---KVDIWSLGIMCIEMA--------EGeppyLEEPPLRALFLITTKGIPPLK---NPEKWSPEFKDFLNKCLVKDPEKR 242

                  ..
gi 1370514551 309 PD 310
Cdd:cd06614   243 PS 244
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
80-320 3.03e-17

Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Syk-like subfamily is composed of Syk, ZAP-70, Shark, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. They are involved in the signaling downstream of activated receptors (including B-cell, T-cell, and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. Syk is important in B-cell receptor signaling, while Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor signaling. Syk also plays a central role in Fc receptor-mediated phagocytosis in the adaptive immune system. Shark is exclusively expressed in ectodermally derived epithelia, and is localized preferentially to the apical surface of the epithelial cells, it may play a role in a signaling pathway for epithelial cell polarity. The Syk-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270650 [Multi-domain]  Cd Length: 257  Bit Score: 81.63  E-value: 3.03e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIE-LTRQVLFELKHMRDVQFNHLTRFIGACIDPPnICIVTEYCPRGSLQDILENDSIN-----LDWMFRY 153
Cdd:cd05060    26 VAVKTLKQEHEKaGKKEFLREASVMAQLDHPCIVRLIGVCKGEP-LMLVMELAPLGPLLKYLKKRREIpvsdlKELAHQV 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 154 SLindlvkGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSH-ALYAKKL---WTAPELLSGNPL 229
Cdd:cd05060   105 AM------GMAYLESKHFV-HRDLAARNVLLVNRHQAKISDFGMS--RALGAGSDYYrATTAGRWplkWYAPECINYGKF 175
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 230 PTtgmqKADVYSFGIILQEIALRSGPFYLEgldLSPKEIVQKVRNGQRpYFRPSidrtQLNEELVLLMERCWAQDPAERP 309
Cdd:cd05060   176 SS----KSDVWSYGVTLWEAFSYGAKPYGE---MKGPEVIAMLESGER-LPRPE----ECPQEIYSIMLSCWKYRPEDRP 243
                         250
                  ....*....|.
gi 1370514551 310 DFGQIKGFIRR 320
Cdd:cd05060   244 TFSELESTFRR 254
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
80-321 3.64e-17

Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Yes (or c-Yes) is a member of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. c-Yes kinase is the cellular homolog of the oncogenic protein (v-Yes) encoded by the Yamaguchi 73 and Esh sarcoma viruses. It displays functional overlap with other Src subfamily members, particularly Src. It also shows some unique functions such as binding to occludins, transmembrane proteins that regulate extracellular interactions in tight junctions. Yes also associates with a number of proteins in different cell types that Src does not interact with, like JAK2 and gp130 in pre-adipocytes, and Pyk2 in treated pulmonary vein endothelial cells. Although the biological function of Yes remains unclear, it appears to have a role in regulating cell-cell interactions and vesicle trafficking in polarized cells. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Yes subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270654 [Multi-domain]  Cd Length: 279  Bit Score: 82.04  E-value: 3.64e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVnKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPnICIVTEYCPRGSLQDIL-ENDSINLDWMFRYSLIND 158
Cdd:cd05069    39 VAIKTL-KPGTMMPEAFLQEAQIMKKLRHDKLVPLYAVVSEEP-IYIVTEFMGKGSLLDFLkEGDGKYLKLPQLVDMAAQ 116
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 159 LVKGMAFLH--NSIissHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELlsgnPLPTTGMQK 236
Cdd:cd05069   117 IADGMAYIErmNYI---HRDLRAANILVGDNLVCKIADFGLARLIEDNEYTARQGAKFPIKWTAPEA----ALYGRFTIK 189
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 237 ADVYSFGIILQEIALRSGPFYLEGLDlspKEIVQKVRNGQR---PYFRPsidrtqlnEELVLLMERCWAQDPAERPDFGQ 313
Cdd:cd05069   190 SDVWSFGILLTELVTKGRVPYPGMVN---REVLEQVERGYRmpcPQGCP--------ESLHELMKLCWKKDPDERPTFEY 258

                  ....*...
gi 1370514551 314 IKGFIRRF 321
Cdd:cd05069   259 IQSFLEDY 266
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
80-318 3.90e-17

Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The PDGFR subfamily consists of PDGFR alpha, PDGFR beta, KIT, CSF-1R, the mammalian FLT3, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. PDGFR kinase domains are autoinhibited by their juxtamembrane regions containing tyr residues. The binding to their ligands leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR subfamily receptors are important in the development of a variety of cells. PDGFRs are expressed in a many cells including fibroblasts, neurons, endometrial cells, mammary epithelial cells, and vascular smooth muscle cells. PDGFR signaling is critical in normal embryonic development, angiogenesis, and wound healing. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. Mammalian FLT3 plays an important role in the survival, proliferation, and differentiation of stem cells. The PDGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 133186 [Multi-domain]  Cd Length: 302  Bit Score: 82.15  E-value: 3.90e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIELTRQVLF-ELKHMRDV-QFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDS---INLDWMFRYS 154
Cdd:cd05055    68 VAVKMLKPTAHSSEREALMsELKIMSHLgNHENIVNLLGACTIGGPILVITEYCCYGDLLNFLRRKResfLTLEDLLSFS 147
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 liNDLVKGMAFL--HNSIissHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAepDDSHalYAKK-------LWTAPELLS 225
Cdd:cd05055   148 --YQVAKGMAFLasKNCI---HRDLAARNVLLTHGKIVKICDFGLA--RDIM--NDSN--YVVKgnarlpvKWMAPESIF 216
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 226 GNpLPTTgmqKADVYSFGIILQEI-ALRSGPFylEGLDLSPKeIVQKVRNGQR---PYFRPsidrtqlnEELVLLMERCW 301
Cdd:cd05055   217 NC-VYTF---ESDVWSYGILLWEIfSLGSNPY--PGMPVDSK-FYKLIKEGYRmaqPEHAP--------AEIYDIMKTCW 281
                         250
                  ....*....|....*..
gi 1370514551 302 AQDPAERPDFGQIKGFI 318
Cdd:cd05055   282 DADPLKRPTFKQIVQLI 298
STKc_IRAK1 cd14159
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; ...
107-249 5.64e-17

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK1 plays a role in the activation of IRF3/7, STAT, and NFkB. It mediates IL-6 and IFN-gamma responses following IL-1 and IL-18 stimulation, respectively. It also plays an essential role in IFN-alpha induction downstream of TLR7 and TLR9. The IRAK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271061 [Multi-domain]  Cd Length: 296  Bit Score: 81.80  E-value: 5.64e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 107 QFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDIL--ENDSINLDWMFRYSLINDLVKGMAFLHN---SIIssHGSLKS 179
Cdd:cd14159    48 RFRHpnIVDLAGYSAQQGNYCLIYVYLPNGSLEDRLhcQVSCPCLSWSQRLHVLLGTARAIQYLHSdspSLI--HGDVKS 125
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370514551 180 SNCVVDSRFVLKITDYGLASF-RSTAEPDDSHALYAKKL------WTAPELLSGNPLPTtgmqKADVYSFGIILQEI 249
Cdd:cd14159   126 SNILLDAALNPKLGDFGLARFsRRPKQPGMSSTLARTQTvrgtlaYLPEEYVKTGTLSV----EIDVYSFGVVLLEL 198
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
103-262 5.95e-17

Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TESK proteins phosphorylate cofilin and induce actin cytoskeletal reorganization. In the Drosphila eye, TESK is required for epithelial cell organization. Mammals contain two TESK proteins, TESK1 and TESK2, which are highly expressed in testis and play roles in spermatogenesis. TESK1 is found in testicular germ cells while TESK2 is expressed mainly in nongerminal Sertoli cells. TESK1 is stimulated by integrin-mediated signaling pathways. It regulates cell spreading and focal adhesion formation. The TESK subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271057 [Multi-domain]  Cd Length: 253  Bit Score: 80.98  E-value: 5.95e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 103 MRDVQF-NHLT-----RFIGACIDPPNICIVTEYCPRGSLQDILENDsINLDWMFRYSLINDLVKGMAFLHNSIISsHGS 176
Cdd:cd14155    36 LREVQLmNRLShpnilRFMGVCVHQGQLHALTEYINGGNLEQLLDSN-EPLSWTVRVKLALDIARGLSYLHSKGIF-HRD 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 177 LKSSNCVV---DSRFVLKITDYGLAsfrstaEPDDSHALYAKKL-------WTAPELLSGNPLPttgmQKADVYSFGIIL 246
Cdd:cd14155   114 LTSKNCLIkrdENGYTAVVGDFGLA------EKIPDYSDGKEKLavvgspyWMAPEVLRGEPYN----EKADVFSYGIIL 183
                         170       180
                  ....*....|....*....|...
gi 1370514551 247 QEIALR--SGPFYLE-----GLD 262
Cdd:cd14155   184 CEIIARiqADPDYLPrtedfGLD 206
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
113-314 6.16e-17

Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The FGFR subfamily consists of FGFR1, FGFR2, FGFR3, FGFR4, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, and to heparin/heparan sulfate (HS) results in the formation of a ternary complex, which leads to receptor dimerization and activation, and intracellular signaling. There are at least 23 FGFs and four types of FGFRs. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. FGF/FGFR signaling is important in the regulation of embryonic development, homeostasis, and regenerative processes. Depending on the cell type and stage, FGFR signaling produces diverse cellular responses including proliferation, growth arrest, differentiation, and apoptosis. Aberrant signaling leads to many human diseases such as skeletal, olfactory, and metabolic disorders, as well as cancer. The FGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase .


Pssm-ID: 270646 [Multi-domain]  Cd Length: 294  Bit Score: 81.69  E-value: 6.16e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 113 RFIGACIDPPNICIVTEYCPRGSLQDIL-------ENDSINLDWMFRYSLIN-DLV-------KGMAFLHN-SIIssHGS 176
Cdd:cd05053    81 NLLGACTQDGPLYVVVEYASKGNLREFLrarrppgEEASPDDPRVPEEQLTQkDLVsfayqvaRGMEYLASkKCI--HRD 158
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 177 LKSSNCVVDSRFVLKITDYGLASfrstaepdDSHAL-YAKKL--------WTAPELLSGNPLPTtgmqKADVYSFGIILQ 247
Cdd:cd05053   159 LAARNVLVTEDNVMKIADFGLAR--------DIHHIdYYRKTtngrlpvkWMAPEALFDRVYTH----QSDVWSFGVLLW 226
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 248 EIALRSGPFYlEGLDLspKEIVQKVRNGQRpyfrpsIDRTQL-NEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05053   227 EIFTLGGSPY-PGIPV--EELFKLLKEGHR------MEKPQNcTQELYMLMRDCWHEVPSQRPTFKQL 285
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
95-321 6.51e-17

Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Fyn and Yrk are members of the Src subfamily of proteins, which are cytoplasmic (or non-receptor) PTKs. Fyn, together with Lck, plays a critical role in T-cell signal transduction by phosphorylating ITAM (immunoreceptor tyr activation motif) sequences on T-cell receptors, ultimately leading to the proliferation and differentiation of T-cells. In addition, Fyn is involved in the myelination of neurons, and is implicated in Alzheimer's and Parkinson's diseases. Src kinases contain an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region containing a conserved tyr. They are activated by autophosphorylation at the tyr kinase domain, but are negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). The Fyn/Yrk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase.


Pssm-ID: 270655 [Multi-domain]  Cd Length: 274  Bit Score: 81.27  E-value: 6.51e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVQfnhltrfIGACIDPPNICIVTEYCPRGSLQDIL---ENDSINLDWMFrySLINDLVKGMAFLH--NS 169
Cdd:cd05070    56 QIMKKLKHDKLVQ-------LYAVVSEEPIYIVTEYMSKGSLLDFLkdgEGRALKLPNLV--DMAAQVAAGMAYIErmNY 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 170 IissHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELlsgnPLPTTGMQKADVYSFGIILQEI 249
Cdd:cd05070   127 I---HRDLRSANILVGNGLICKIADFGLARLIEDNEYTARQGAKFPIKWTAPEA----ALYGRFTIKSDVWSFGILLTEL 199
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 250 ALRSGPFYLeglDLSPKEIVQKVRNGQR-PYfrPSIDRTQLNEelvlLMERCWAQDPAERPDFGQIKGFIRRF 321
Cdd:cd05070   200 VTKGRVPYP---GMNNREVLEQVERGYRmPC--PQDCPISLHE----LMIHCWKKDPEERPTFEYLQGFLEDY 263
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
73-314 7.81e-17

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK2 is one of two vertebrate LRRKs which show complementary expression in the brain. Mutations in LRRK2, found in the kinase, ROC-COR, and WD40 domains, are linked to both familial and sporadic forms of Parkinson's disease. The most prevalent mutation, G2019S located in the activation loop of the kinase domain, increases kinase activity. The R1441C/G mutations in the GTPase domain have also been reported to influence kinase activity. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270970 [Multi-domain]  Cd Length: 252  Bit Score: 80.38  E-value: 7.81e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVNK-KRIELTRQVLFELKHMRDVQfnhLTRFIGACIDPPniCIVTEYCPRGSLQDILENDSINLDWMF 151
Cdd:cd14068    13 AVYRGEDVAVKIFNKhTSFRLLRQELVVLSHLHHPS---LVALLAAGTAPR--MLVMELAPKGSLDALLQQDNASLTRTL 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLINDLVKGMAFLHNSIIsSHGSLKSSNCVV-----DSRFVLKITDYGLASFRSTAEPDDSHALYAkklWTAPELLSG 226
Cdd:cd14068    88 QHRIALHVADGLRYLHSAMI-IYRDLKPHNVLLftlypNCAIIAKIADYGIAQYCCRMGIKTSEGTPG---FRAPEVARG 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPTtgmQKADVYSFGIILQEIaLRSGPFYLEGLDLsPKEIVQKVRNGQRPyfrpsidrTQLNE-------ELVLLMER 299
Cdd:cd14068   164 NVIYN---QQADVYSFGLLLYDI-LTCGERIVEGLKF-PNEFDELAIQGKLP--------DPVKEygcapwpGVEALIKD 230
                         250
                  ....*....|....*
gi 1370514551 300 CWAQDPAERPDFGQI 314
Cdd:cd14068   231 CLKENPQCRPTSAQV 245
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
73-314 8.98e-17

Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLK4 is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The specific function of MLK4 is yet to be determined. Mutations in the kinase domain of MLK4 have been detected in colorectal cancers. Mammals have four MLKs, mostly conserved in vertebrates, which contain an SH3 domain, a catalytic kinase domain, a leucine zipper, a proline-rich region, and a CRIB domain that mediates binding to GTP-bound Cdc42 and Rac. MLKs play roles in immunity and inflammation, as well as in cell death, proliferation, and cell cycle regulation.The MLK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271048 [Multi-domain]  Cd Length: 268  Bit Score: 80.47  E-value: 8.98e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVNKKRIE----LTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL--ENDSIN 146
Cdd:cd14146    13 ATWKGQEVAVKAARQDPDEdikaTAESVRQEAKLFSMLRHPNIIKLEGVCLEEPNLCLVMEFARGGTLNRALaaANAAPG 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFR---YSLIN---DLVKGMAFLHNSIISS--HGSLKSSNCVVDSRF--------VLKITDYGLASFRSTAEPDDSH 210
Cdd:cd14146    93 PRRARRippHILVNwavQIARGMLYLHEEAVVPilHRDLKSSNILLLEKIehddicnkTLKITDFGLAREWHRTTKMSAA 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 211 ALYAkklWTAPELLSGNpLPTTGmqkADVYSFGIILQEIALRSGPFY-LEGLDLSPKEIVQKVrngQRPYfrPSidrtQL 289
Cdd:cd14146   173 GTYA---WMAPEVIKSS-LFSKG---SDIWSYGVLLWELLTGEVPYRgIDGLAVAYGVAVNKL---TLPI--PS----TC 236
                         250       260
                  ....*....|....*....|....*
gi 1370514551 290 NEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14146   237 PEPFAKLMKECWEQDPHIRPSFALI 261
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
81-309 1.00e-16

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. eIF-2 phosphorylation is induced in response to cellular stresses including virus infection, heat shock, nutrient deficiency, and the accummulation of unfolded proteins, among others. There are four distinct kinases that phosphorylate eIF-2 and control protein synthesis under different stress conditions: General Control Non-derepressible-2 (GCN2) which is activated during amino acid or serum starvation; protein kinase regulated by RNA (PKR) which is activated by double stranded RNA; heme-regulated inhibitor kinase (HRI) which is activated under heme-deficient conditions; and PKR-like endoplasmic reticulum kinase (PERK) which is activated when misfolded proteins accumulate in the ER. The EIF2AK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270898 [Multi-domain]  Cd Length: 273  Bit Score: 80.41  E-value: 1.00e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  81 AIK--HVNKKRIELTRqVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE--NDSINLDWMFRYSLI 156
Cdd:cd13996    35 AIKkiRLTEKSSASEK-VLREVKALAKLNHPNIVRYYTAWVEEPPLYIQMELCEGGTLRDWIDrrNSSSKNDRKLALELF 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLHNS-IIssHGSLKSSNCVVDSRF-VLKITDYGLASFRSTAEPDDSHA------LYAKK-------LWTAP 221
Cdd:cd13996   114 KQILKGVSYIHSKgIV--HRDLKPSNIFLDNDDlQVKIGDFGLATSIGNQKRELNNLnnnnngNTSNNsvgigtpLYASP 191
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 222 ELLSGNPLPttgmQKADVYSFGIILQEialrsgpfylegLDLSPK------EIVQKVRNGQRPyfrPSIDRtQLNEELVl 295
Cdd:cd13996   192 EQLDGENYN----EKADIYSLGIILFE------------MLHPFKtamersTILTDLRNGILP---ESFKA-KHPKEAD- 250
                         250
                  ....*....|....
gi 1370514551 296 LMERCWAQDPAERP 309
Cdd:cd13996   251 LIQSLLSKNPEERP 264
PKc_Wee1_like cd13997
Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the ...
63-314 1.21e-16

Catalytic domain of the Wee1-like Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine or tyrosine residues on protein substrates. This subfamily is composed of the dual-specificity kinase Myt1, the protein tyrosine kinase Wee1, and similar proteins. These proteins are cell cycle checkpoint kinases that are involved in the regulation of cyclin-dependent kinase CDK1, the master engine for mitosis. CDK1 is kept inactivated through phosphorylation of N-terminal thr (T14 by Myt1) and tyr (Y15 by Myt1 and Wee1) residues. Mitosis progression is ensured through activation of CDK1 by dephoshorylation and inactivation of Myt1/Wee1. The Wee1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270899 [Multi-domain]  Cd Length: 252  Bit Score: 79.73  E-value: 1.21e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  63 HGKY-QIFANTGHFKGNVVAIKHVNKK-RIELTRQvlfelKHMRDV-------QFNHLTRFIGACIDPPNICIVTEYCPR 133
Cdd:cd13997    10 SGSFsEVFKVRSKVDGCLYAVKKSKKPfRGPKERA-----RALREVeahaalgQHPNIVRYYSSWEEGGHLYIQMELCEN 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 134 GSLQDILENDSIN--LDWMFRYSLINDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPD--- 207
Cdd:cd13997    85 GSLQDALEELSPIskLSEAEVWDLLLQVALGLAFIHSkGIV--HLDIKPDNIFISNKGTCKIGDFGLATRLETSGDVeeg 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 208 DSHALyakklwtAPELLSGNPLPTTgmqKADVYSFGIILQEIAL-----RSGPFYlegldlspkeivQKVRNGQRPYFRP 282
Cdd:cd13997   163 DSRYL-------APELLNENYTHLP---KADIFSLGVTVYEAATgeplpRNGQQW------------QQLRQGKLPLPPG 220
                         250       260       270
                  ....*....|....*....|....*....|..
gi 1370514551 283 SIDRTQLNEELVLLMERcwaqDPAERPDFGQI 314
Cdd:cd13997   221 LVLSQELTRLLKVMLDP----DPTRRPTADQL 248
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
80-314 1.48e-16

Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular carcinoma and Resting lymphocyte kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tec and Rlk (also named Txk) are members of the Tec-like subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs with similarity to Src kinases in that they contain Src homology protein interaction domains (SH3, SH2) N-terminal to the catalytic tyr kinase domain. Unlike Src kinases, most Tec subfamily members except Rlk also contain an N-terminal pleckstrin homology (PH) domain, which binds the products of PI3K and allows membrane recruitment and activation. Instead of PH, Rlk contains an N-terminal cysteine-rich region. In addition to PH, Tec also contains the Tec homology (TH) domain with proline-rich and zinc-binding regions. Tec kinases are expressed mainly by haematopoietic cells. Tec is more widely-expressed than other Tec-like subfamily kinases. It is found in endothelial cells, both B- and T-cells, and a variety of myeloid cells including mast cells, erythroid cells, platelets, macrophages and neutrophils. Rlk is expressed in T-cells and mast cell lines. Tec and Rlk are both key components of T-cell receptor (TCR) signaling. They are important in TCR-stimulated proliferation, IL-2 production and phopholipase C-gamma1 activation. The Tec/Rlk subfamily is part of a larger superfamily, that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270685 [Multi-domain]  Cd Length: 260  Bit Score: 79.91  E-value: 1.48e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIElTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDL 159
Cdd:cd05114    31 VAIKAIREGAMS-EEDFIEEAKVMMKLTHPKLVQLYGVCTQQKPIYIVTEFMENGCLLNYLRQRRGKLSRDMLLSMCQDV 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 160 VKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGNPLPTtgmqKAD 238
Cdd:cd05114   110 CEGMEYLErNNFI--HRDLAARNCLVNDTGVVKVSDFGMTRYVLDDQYTSSSGAKFPVKWSPPEVFNYSKFSS----KSD 183
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370514551 239 VYSFGIILQEIaLRSGPFYLEglDLSPKEIVQKVRNGQRPYfRPSIDRTQLNEelvlLMERCWAQDPAERPDFGQI 314
Cdd:cd05114   184 VWSFGVLMWEV-FTEGKMPFE--SKSNYEVVEMVSRGHRLY-RPKLASKSVYE----VMYSCWHEKPEGRPTFADL 251
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
81-309 1.52e-16

Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. Vertebrates contain two members, LRRK1 and LRRK2, which show complementary expression in the brain. Mutations in LRRK2 are linked to both familial and sporadic forms of Parkinson's disease. The normal roles of LRRKs are not clearly defined. They may be involved in mitogen-activated protein kinase (MAPK) pathways, protein translation control, programmed cell death pathways, and cytoskeletal dynamics. The LRRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270902 [Multi-domain]  Cd Length: 275  Bit Score: 79.97  E-value: 1.52e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  81 AIKHVNKKRIELTrqVLFELKHmrdvqfNHLTRFIGACIDPpnICIVTEYCPRGSLQDILENDS---INLDWMFRYSLIN 157
Cdd:cd14000    50 AMKNFRLLRQELT--VLSHLHH------PSIVYLLGIGIHP--LMLVLELAPLGSLDHLLQQDSrsfASLGRTLQQRIAL 119
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLHNSIISsHGSLKSSNCVV-----DSRFVLKITDYGLA--SFRSTAEPDDSHALYakklwTAPELLSGNPLP 230
Cdd:cd14000   120 QVADGLRYLHSAMII-YRDLKSHNVLVwtlypNSAIIIKIADYGISrqCCRMGAKGSEGTPGF-----RAPEIARGNVIY 193
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370514551 231 TtgmQKADVYSFGIILQEIALRSGPFyLEGLDLspkEIVQKVRNGQRPYFRPSidRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd14000   194 N---EKVDVFSFGMLLYEILSGGAPM-VGHLKF---PNEFDIHGGLRPPLKQY--ECAPWPEVEVLMKKCWKENPQQRP 263
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
80-318 2.13e-16

Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of most class EphA receptors including EphA3, EphA4, EphA5, and EphA7, but excluding EphA1, EphA2 and EphA10. Class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. One exception is EphA4, which also binds ephrins-B2/B3. EphA receptors and ephrin-A ligands are expressed in multiple areas of the developing brain, especially in the retina and tectum. They are part of a system controlling retinotectal mapping. EphRs comprise the largest subfamily of receptor PTKs (RTKs). EphRs contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. The EphA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270651 [Multi-domain]  Cd Length: 267  Bit Score: 79.53  E-value: 2.13e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIK-----HVNKKRieltRQVLFELKHMRdvQFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFR 152
Cdd:cd05066    35 VAIKtlkagYTEKQR----RDFLSEASIMG--QFDHpnIIHLEGVVTRSKPVMIVTEYMENGSLDAFLRKHDGQFTVIQL 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 YSLINDLVKGMAFLHNsIISSHGSLKSSNCVVDSRFVLKITDYGLasfrSTAEPDDSHALYAKK------LWTAPELLSG 226
Cdd:cd05066   109 VGMLRGIASGMKYLSD-MGYVHRDLAARNILVNSNLVCKVSDFGL----SRVLEDDPEAAYTTRggkipiRWTAPEAIAY 183
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPTTgmqkADVYSFGIILQEI-ALRSGPFYleglDLSPKEIVQKVRNGQR---PYFRPSIdrtqlneeLVLLMERCWA 302
Cdd:cd05066   184 RKFTSA----SDVWSYGIVMWEVmSYGERPYW----EMSNQDVIKAIEEGYRlpaPMDCPAA--------LHQLMLDCWQ 247
                         250
                  ....*....|....*.
gi 1370514551 303 QDPAERPDFGQIKGFI 318
Cdd:cd05066   248 KDRNERPKFEQIVSIL 263
PHA02988 PHA02988
hypothetical protein; Provisional
67-321 2.23e-16

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 79.79  E-value: 2.23e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  67 QIFANTGHFKGNVVAIK-----HVN-KKRIELTRQvlfELKHMRDVQFNHLTR----FIGACIDPPNICIVTEYCPRGSL 136
Cdd:PHA02988   33 QNSIYKGIFNNKEVIIRtfkkfHKGhKVLIDITEN---EIKNLRRIDSNNILKiygfIIDIVDDLPRLSLILEYCTRGYL 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 137 QDILENDSiNLDWMFRYSLINDLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALyakk 216
Cdd:PHA02988  110 REVLDKEK-DLSFKTKLDMAIDCCKGLYNLYKYTNKPYKNLTSVSFLVTENYKLKIICHGLEKILSSPPFKNVNFM---- 184
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 217 LWTAPELLSGNPLPTTgmQKADVYSFGIILQEIALRSGPFylEGLDLspKEIVQKVRNGQRPYFRPsidrTQLNEELVLL 296
Cdd:PHA02988  185 VYFSYKMLNDIFSEYT--IKDDIYSLGVVLWEIFTGKIPF--ENLTT--KEIYDLIINKNNSLKLP----LDCPLEIKCI 254
                         250       260
                  ....*....|....*....|....*
gi 1370514551 297 MERCWAQDPAERPDFGQIKGFIRRF 321
Cdd:PHA02988  255 VEACTSHDSIKRPNIKEILYNLSLY 279
STKc_ULK4 cd14010
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the ...
63-308 3.63e-16

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ULK4 is a functionally uncharacterized kinase that shows similarity to ATG1/ULKs. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. The ULK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270912 [Multi-domain]  Cd Length: 269  Bit Score: 78.87  E-value: 3.63e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  63 HGKYQIFantghFKG------NVVAIKHVNK-KRIELTRQVLF--ELKHMRDVQF-------NHLtrfigacidppniCI 126
Cdd:cd14010    10 RGKHSVV-----YKGrrkgtiEFVAIKCVDKsKRPEVLNEVRLthELKHPNVLKFyewyetsNHL-------------WL 71
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 127 VTEYCPRGSLQDILENDsINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLA------- 198
Cdd:cd14010    72 VVEYCTGGDLETLLRQD-GNLPESSVRKFGRDLVRGLHYIHsKGII--YCDLKPSNILLDGNGTLKLSDFGLArregeil 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 199 --SFRSTAEPDDSHALYAKK------LWTAPELLSGnplPTTGMQkADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQ 270
Cdd:cd14010   149 keLFGQFSDEGNVNKVSKKQakrgtpYYMAPELFQG---GVHSFA-SDLWALGCVLYEMFTGKPPFVAE----SFTELVE 220
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1370514551 271 KVRNGQRPYFRPSIdRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd14010   221 KILNEDPPPPPPKV-SSKPSPDFKSLLKGLLEKDPAKR 257
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
71-315 3.82e-16

Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily contains c-ros, Sevenless, and similar proteins. The proto-oncogene c-ros encodes an orphan receptor PTK (RTK) with an unknown ligand. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. C-ros is expressed in embryonic cells of the kidney, intestine and lung, but disappears soon after birth. It persists only in the adult epididymis. Male mice bearing inactive mutations of c-ros lack the initial segment of the epididymis and are infertile. The Drosophila protein, Sevenless, is required for the specification of the R7 photoreceptor cell during eye development. The c-ros subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270640 [Multi-domain]  Cd Length: 268  Bit Score: 78.61  E-value: 3.82e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  71 NTGHFKgnvVAIKHVNKKRIELTRQ-VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEND------ 143
Cdd:cd05044    23 GSGETK---VAVKTLRKGATDQEKAeFLKEAHLMSNFKHPNILKLLGVCLDNDPQYIILELMEGGDLLSYLRAArptaft 99
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 144 SINLDWMFRYSLINDLVKG------MAFLHNSiisshgsLKSSNCVVDSR----FVLKITDYGLAsfRSTAEPDdshalY 213
Cdd:cd05044   100 PPLLTLKDLLSICVDVAKGcvyledMHFVHRD-------LAARNCLVSSKdyreRVVKIGDFGLA--RDIYKND-----Y 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 214 AKK--------LWTAPE-LLSGnpLPTTgmqKADVYSFGIILQEIALRSGPFYLEgldLSPKEIVQKVRNG---QRPYFR 281
Cdd:cd05044   166 YRKegegllpvRWMAPEsLVDG--VFTT---QSDVWAFGVLMWEILTLGQQPYPA---RNNLEVLHFVRAGgrlDQPDNC 237
                         250       260       270
                  ....*....|....*....|....*....|....
gi 1370514551 282 PsidrtqlnEELVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd05044   238 P--------DDLYELMLRCWSTDPEERPSFARIL 263
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
95-321 6.43e-16

Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Src (or c-Src) is a cytoplasmic (or non-receptor) PTK, containing an N-terminal SH4 domain with a myristoylation site, followed by SH3 and SH2 domains, a tyr kinase domain, and a regulatory C-terminal region with a conserved tyr. It is activated by autophosphorylation at the tyr kinase domain, and is negatively regulated by phosphorylation at the C-terminal tyr by Csk (C-terminal Src Kinase). c-Src is the vertebrate homolog of the oncogenic protein (v-Src) from Rous sarcoma virus. Together with other Src subfamily proteins, it is involved in signaling pathways that regulate cytokine and growth factor responses, cytoskeleton dynamics, cell proliferation, survival, and differentiation. Src also play a role in regulating cell adhesion, invasion, and motility in cancer cells and tumor vasculature, contributing to cancer progression and metastasis. Elevated levels of Src kinase activity have been reported in a variety of human cancers. Several inhibitors of Src have been developed as anti-cancer drugs. Src is also implicated in acute inflammatory responses and osteoclast function. The Src subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270656 [Multi-domain]  Cd Length: 277  Bit Score: 78.19  E-value: 6.43e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVQfnhltrfIGACIDPPNICIVTEYCPRGSLQDILENDSINldwMFRYSLIND----LVKGMAFLHNsI 170
Cdd:cd05071    56 QVMKKLRHEKLVQ-------LYAVVSEEPIYIVTEYMSKGSLLDFLKGEMGK---YLRLPQLVDmaaqIASGMAYVER-M 124
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 171 ISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELlsgnPLPTTGMQKADVYSFGIILQEIA 250
Cdd:cd05071   125 NYVHRDLRAANILVGENLVCKVADFGLARLIEDNEYTARQGAKFPIKWTAPEA----ALYGRFTIKSDVWSFGILLTELT 200
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370514551 251 LRSGPFYLEGLDlspKEIVQKVRNGQRPYFRPsidrtQLNEELVLLMERCWAQDPAERPDFGQIKGFIRRF 321
Cdd:cd05071   201 TKGRVPYPGMVN---REVLDQVERGYRMPCPP-----ECPESLHDLMCQCWRKEPEERPTFEYLQAFLEDY 263
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
77-311 7.76e-16

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase catalytic domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270664 [Multi-domain]  Cd Length: 283  Bit Score: 78.02  E-value: 7.76e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKK-RIELTRQVLFELKHMRDVQFNHLTRFIGACIDP--PNICIVTEYCPRGSLQDILENDSINLDWMFRY 153
Cdd:cd05080    33 GEMVAVKALKADcGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEQggKSLQLIMEYVPLGSLRDYLPKHSIGLAQLLLF 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 154 SliNDLVKGMAFLHnSIISSHGSLKSSNCVVDSRFVLKITDYGLAS-------FRSTAEPDDSHALyakklWTAPELLSG 226
Cdd:cd05080   113 A--QQICEGMAYLH-SQHYIHRDLAARNVLLDNDRLVKIGDFGLAKavpegheYYRVREDGDSPVF-----WYAPECLKE 184
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLpttgMQKADVYSFGIILQEIALRSGPF------YLEGLDLSPKEI-----VQKVRNGQRpyfRPSIDRTQLneELVL 295
Cdd:cd05080   185 YKF----YYASDVWSFGVTLYELLTHCDSSqspptkFLEMIGIAQGQMtvvrlIELLERGER---LPCPDKCPQ--EVYH 255
                         250
                  ....*....|....*.
gi 1370514551 296 LMERCWAQDPAERPDF 311
Cdd:cd05080   256 LMKNCWETEASFRPTF 271
STKc_EIF2AK4_GCN2_rpt2 cd14046
Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation ...
73-309 2.14e-15

Catalytic domain, repeat 2, of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or General Control Non-derepressible-2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GCN2 (or EIF2AK4) is activated by amino acid or serum starvation and UV irradiation. It induces GCN4, a transcriptional activator of amino acid biosynthetic genes, leading to increased production of amino acids under amino acid-deficient conditions. In serum-starved cells, GCN2 activation induces translation of the stress-responsive transcription factor ATF4, while under UV stress, GCN2 triggers transcriptional rescue via NF-kB signaling. GCN2 contains an N-terminal RWD, a degenerate kinase-like (repeat 1), the catalytic kinase (repeat 2), a histidyl-tRNA synthetase (HisRS)-like, and a C-terminal ribosome-binding and dimerization (RB/DD) domains. Its kinase domain is activated via conformational changes as a result of the binding of uncharged tRNA to the HisRS-like domain. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the overall downregulation of protein synthesis. The GCN2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270948 [Multi-domain]  Cd Length: 278  Bit Score: 76.64  E-value: 2.14e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFkGNVVAIKhvNK--------KRIELT------RQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQD 138
Cdd:cd14046    17 GAF-GQVVKVR--NKldgryyaiKKIKLRsesknnSRILREVMLLSRLNHQHVVRYYQAWIERANLYIQMEYCEKSTLRD 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 139 ILEnDSINLDWMFRYSLINDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTA------------- 204
Cdd:cd14046    94 LID-SGLFQDTDRLWRLFRQILEGLAYIHSqGII--HRDLKPVNIFLDSNGNVKIGDFGLATSNKLNvelatqdinksts 170
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 205 ----EPDDSHALYAKKLWTAPELLSGnplpTTGM--QKADVYSFGIILQEIalrSGPFyleGLDLSPKEIVQKVRNgQRP 278
Cdd:cd14046   171 aalgSSGDLTGNVGTALYVAPEVQSG----TKSTynEKVDMYSLGIIFFEM---CYPF---STGMERVQILTALRS-VSI 239
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1370514551 279 YFrPSIDRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd14046   240 EF-PPDFDDNKHSKQAKLIRWLLNHDPAKRP 269
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
74-314 2.23e-15

Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. RET is a receptor PTK (RTK) containing an extracellular region with four cadherin-like repeats, a calcium-binding site, and a cysteine-rich domain, a transmembrane segment, and an intracellular catalytic domain. It is part of a multisubunit complex that binds glial-derived neurotropic factor (GDNF) family ligands (GFLs) including GDNF, neurturin, artemin, and persephin. GFLs bind RET along with four GPI-anchored coreceptors, bringing two RET molecules together, leading to autophosphorylation, activation, and intracellular signaling. RET is essential for the development of the sympathetic, parasympathetic and enteric nervous systems, and the kidney. RET disruption by germline mutations causes diseases in humans including congenital aganglionosis of the gastrointestinal tract (Hirschsprung's disease) and three related inherited cancers: multiple endocrine neoplasia type 2A (MEN2A), MEN2B, and familial medullary thyroid carcinoma. The RET subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173631 [Multi-domain]  Cd Length: 290  Bit Score: 76.93  E-value: 2.23e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  74 HFKG----NVVAIKHV--NKKRIELtRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL------- 140
Cdd:cd05045    23 RLKGragyTTVAVKMLkeNASSSEL-RDLLSEFNLLKQVNHPHVIKLYGACSQDGPLLLIVEYAKYGSLRSFLresrkvg 101
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 141 -----ENDSINLDWMF----RYSLINDLV-------KGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAsfRSTA 204
Cdd:cd05045   102 psylgSDGNRNSSYLDnpdeRALTMGDLIsfawqisRGMQYL-AEMKLVHRDLAARNVLVAEGRKMKISDFGLS--RDVY 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 205 EpDDSHALYAKKL----WTAPELLSGNPLPTtgmqKADVYSFGIILQEIALRSGPFYLeglDLSPKEIVQKVRNGQRpyf 280
Cdd:cd05045   179 E-EDSYVKRSKGRipvkWMAIESLFDHIYTT----QSDVWSFGVLLWEIVTLGGNPYP---GIAPERLFNLLKTGYR--- 247
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 1370514551 281 rpsIDRTQ-LNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05045   248 ---MERPEnCSEEMYNLMLTCWKQEPDKRPTFADI 279
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
77-276 2.28e-15

The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKs are multifunctional calcium and calmodulin (CaM) stimulated STKs involved in cell cycle regulation. There are several types of CaMKs including CaMKI, CaMKII, and CaMKIV. CaMKI proteins are monomeric and they play pivotal roles in the nervous system, including long-term potentiation, dendritic arborization, neurite outgrowth, and the formation of spines, synapses, and axons. CaMKII is a signaling molecule that translates upstream calcium and reactive oxygen species (ROS) signals into downstream responses that play important roles in synaptic function and cardiovascular physiology. CAMKIV is implicated in regulating several transcription factors like CREB, MEF2, and retinoid orphan receptors, as well as in T-cell development and signaling. The CAMK family also consists of other related kinases including the Phosphorylase kinase Gamma subunit (PhKG), the C-terminal kinase domains of Ribosomal S6 kinase (RSK) and Mitogen and stress-activated kinase (MSK), Doublecortin-like kinase (DCKL), and the MAPK-activated protein kinases MK2, MK3, and MK5, among others. The CAMK family is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270687 [Multi-domain]  Cd Length: 258  Bit Score: 76.36  E-value: 2.28e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLF--ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQD-ILENDSINLD---WM 150
Cdd:cd05117    25 GEEYAVKIIDKKKLKSEDEEMLrrEIEILKRLDHPNIVKLYEVFEDDKNLYLVMELCTGGELFDrIVKKGSFSEReaaKI 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 151 FRyslinDLVKGMAFLH-NSIIssHGSLKSSNCVVDSR---FVLKITDYGLASFRstaEPDDSH------ALYAkklwtA 220
Cdd:cd05117   105 MK-----QILSAVAYLHsQGIV--HRDLKPENILLASKdpdSPIKIIDFGLAKIF---EEGEKLktvcgtPYYV-----A 169
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 221 PELLSGNPLpttgMQKADVYSFGIILqeIALRSG--PFYLEgldlSPKEIVQKVRNGQ 276
Cdd:cd05117   170 PEVLKGKGY----GKKCDIWSLGVIL--YILLCGypPFYGE----TEQELFEKILKGK 217
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
107-314 3.72e-15

Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EphA10, which contains an inactive tyr kinase domain, may function to attenuate signals of co-clustered active receptors. EphA10 is mainly expressed in the testis. Ephrin/EphR interaction results in cell-cell repulsion or adhesion, making it important in neural development and plasticity, cell morphogenesis, cell-fate determination, embryonic development, tissue patterning, and angiogenesis. EphRs comprise the largest subfamily of receptor tyr kinases (RTKs). In general, class EphA receptors bind GPI-anchored ephrin-A ligands. There are ten vertebrate EphA receptors (EphA1-10), which display promiscuous interactions with six ephrin-A ligands. EphRs contain an ephrin binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). The EphA10 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133195 [Multi-domain]  Cd Length: 266  Bit Score: 75.73  E-value: 3.72e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 107 QFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLhNSIISSHGSLKSSNCVV 184
Cdd:cd05064    62 QFDHsnIVRLEGVITRGNTMMIVTEYMSNGALDSFLRKHEGQLVAGQLMGMLPGLASGMKYL-SEMGYVHKGLAAHKVLV 140
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 185 DSRFVLKITdyglaSFRSTAEpDDSHALYAK------KLWTAPELLSGNPLPTTgmqkADVYSFGIILQEI-ALRSGPFY 257
Cdd:cd05064   141 NSDLVCKIS-----GFRRLQE-DKSEAIYTTmsgkspVLWAAPEAIQYHHFSSA----SDVWSFGIVMWEVmSYGERPYW 210
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370514551 258 leglDLSPKEIVQKVRNGQRpyFRPSIDRTQLneeLVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05064   211 ----DMSGQDVIKAVEDGFR--LPAPRNCPNL---LHQLMLDCWQKERGERPRFSQI 258
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
159-322 3.91e-15

Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase (RTK) containing an extracellular region with two leucine-rich motifs, a transmembrane segment, and an intracellular inactive pseudokinase domain, which shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. The extracellular region of Ryk shows homology to the N-terminal domain of Wnt inhibitory factor-1 (WIF) and serves as the ligand (Wnt) binding domain of Ryk. Ryk is expressed in many different tissues both during development and in adults, suggesting a widespread function. It acts as a chemorepulsive axon guidance receptor of Wnt glycoproteins and is responsible for the establishment of axon tracts during the development of the central nervous system. In addition, studies in mice reveal that Ryk is essential in skeletal, craniofacial, and cardiac development. Thus, it appears Ryk is involved in signal transduction despite its lack of kinase activity. Ryk may function as an accessory protein that modulates the signals coming from catalytically active partner RTKs such as the Eph receptors. The Ryk subfamily is part of a larger superfamily that includes other pseudokinases and the catalytic domains of active kinases including PTKs, protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270639 [Multi-domain]  Cd Length: 279  Bit Score: 75.95  E-value: 3.91e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 159 LVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLAS--FrstaePDDSHAL----YAKKLWTAPELLSGNPLPT 231
Cdd:cd05043   125 IACGMSYLHRrGVI--HKDIAARNCVIDDELQVKITDNALSRdlF-----PMDYHCLgdneNRPIKWMSLESLVNKEYSS 197
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 232 TGmqkaDVYSFGIILQEIA-LRSGPFylegLDLSPKEIVQKVRNGQR---PYFRPsidrtqlnEELVLLMERCWAQDPAE 307
Cdd:cd05043   198 AS----DVWSFGVLLWELMtLGQTPY----VEIDPFEMAAYLKDGYRlaqPINCP--------DELFAVMACCWALDPEE 261
                         170
                  ....*....|....*
gi 1370514551 308 RPDFGQIKGFIRRFN 322
Cdd:cd05043   262 RPSFQQLVQCLTDFH 276
STKc_TSSK-like cd14080
Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs ...
44-315 4.31e-15

Catalytic domain of testis-specific serine/threonine kinases and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK1 and TSSK2 are expressed specifically in meiotic and postmeiotic spermatogenic cells, respectively. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. TSSK6, also called SSTK, is expressed at the head of elongated sperm. TSSK1/TSSK2 double knock-out and TSSK6 null mice are sterile without manifesting other defects, making these kinases viable targets for male contraception. The TSSK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270982 [Multi-domain]  Cd Length: 262  Bit Score: 75.30  E-value: 4.31e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  44 GSRLTLSLRGSSYGSLMTAHgkyqifaNTGHFKGNVVAIKHVNKKR-----IE--LTRqvlfELKHMRDVQFNHLTRFIG 116
Cdd:cd14080     1 GYRLGKTIGEGSYSKVKLAE-------YTKSGLKEKVACKIIDKKKapkdfLEkfLPR----ELEILRKLRHPNIIQVYS 69
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 117 ACIDPPNICIVTEYCPRGS-LQDILENDSI--NLDW-MFRyslinDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKI 192
Cdd:cd14080    70 IFERGSKVFIFMEYAEHGDlLEYIQKRGALseSQARiWFR-----QLALAVQYLHSLDIA-HRDLKCENILLDSNNNVKL 143
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 193 TDYGLASFrstAEPDDSHAL---------YAkklwtAPELLSGNP-LPTtgmqKADVYSFGIILQEIALRSGPFYleglD 262
Cdd:cd14080   144 SDFGFARL---CPDDDGDVLsktfcgsaaYA-----APEILQGIPyDPK----KYDIWSLGVILYIMLCGSMPFD----D 207
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 263 LSPKEIVQKVRNgQRPYFRPSidRTQLNEELVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd14080   208 SNIKKMLKDQQN-RKVRFPSS--VKKLSPECKDLIDQLLEPDPTKRATIEEIL 257
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
78-320 4.81e-15

Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The DDR subfamily consists of homologs of mammalian DDR1, DDR2, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270644 [Multi-domain]  Cd Length: 297  Bit Score: 75.84  E-value: 4.81e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  78 NVVAIKHVNKKRIELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN-------DSINLDW 149
Cdd:cd05051    47 VLVAVKMLRPDASKNAREDFLkEVKIMSQLKDPNIVRLLGVCTRDEPLCMIVEYMENGDLNQFLQKheaetqgASATNSK 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 150 MFRYS-LIN---DLVKGMAFL--HNSIissHGSLKSSNCVVDSRFVLKITDYGLasfrstaepddSHALYAKKLWTapel 223
Cdd:cd05051   127 TLSYGtLLYmatQIASGMKYLesLNFV---HRDLATRNCLVGPNYTIKIADFGM-----------SRNLYSGDYYR---- 188
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 224 LSGN-PLPTTGM-----------QKADVYSFGIILQEIAL--RSGPFYleglDLSPKEIVQKVRNGQRPYFRPSI-DRTQ 288
Cdd:cd05051   189 IEGRaVLPIRWMawesillgkftTKSDVWAFGVTLWEILTlcKEQPYE----HLTDEQVIENAGEFFRDDGMEVYlSRPP 264
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1370514551 289 L-NEELVLLMERCWAQDPAERPDFGQIKGFIRR 320
Cdd:cd05051   265 NcPKEIYELMLECWRRDEEDRPTFREIHLFLQR 297
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
77-308 5.06e-15

Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group II PAKs, also called non-conventional PAKs, include PAK4, PAK5, and PAK6. Group II PAKs contain PBD (p21-binding domain) and catalytic domains, but lack other motifs found in group I PAKs, such as an AID (autoinhibitory domain) and SH3 binding sites. Since group II PAKs do not contain an obvious AID, they may be regulated differently from group I PAKs. While group I PAKs interact with the SH3 containing proteins Nck, Grb2 and PIX, no such binding has been demonstrated for group II PAKs. Some known substrates of group II PAKs are also substrates of group I PAKs such as Raf, BAD, LIMK and GEFH1. Unique group II substrates include MARK/Par-1 and PDZ-RhoGEF. Group II PAKs play important roles in filopodia formation, neuron extension, cytoskeletal organization, and cell survival. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270815 [Multi-domain]  Cd Length: 261  Bit Score: 75.17  E-value: 5.06e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRiELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSL 155
Cdd:cd06648    32 GRQVAVKKMDLRK-QQRRELLFnEVVIMRDYQHPNIVEMYSSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQIATVCR 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 inDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPdDSHALYAKKLWTAPELLSGNPLPTtgm 234
Cdd:cd06648   111 --AVLKALSFLHSqGVI--HRDIKSDSILLTSDGRVKLSDFGFCAQVSKEVP-RRKSLVGTPYWMAPEVISRLPYGT--- 182
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 235 qKADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNGQRPYFRPSIdrtQLNEELVLLMERCWAQDPAER 308
Cdd:cd06648   183 -EVDIWSLGIMVIEMVDGEPPYFNE----PPLQAMKRIRDNEPPKLKNLH---KVSPRLRSFLDRMLVRDPAQR 248
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
77-309 6.15e-15

Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK4 is a MAPK kinase kinase that phosphorylates and activates the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. JNK and p38 are collectively known as stress-activated MAPKs, as they are activated in response to a variety of environmental stresses and pro-inflammatory cytokines. MEKK4 also plays roles in the re-polarization of the actin cytoskeleton in response to osmotic stress, in the proper closure of the neural tube, in cardiovascular development, and in immune responses. The MEKK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 75.03  E-value: 6.15e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVN--KKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSInLDWMF--R 152
Cdd:cd06626    25 GELMAMKEIRfqDNDPKTIKEIADEMKVLEGLDHPNLVRYYGVEVHREEVYIFMEYCQEGTLEELLRHGRI-LDEAVirV 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 YSLinDLVKGMAFLHNSIIsSHGSLKSSNCVVDSRFVLKITDYG----LASFRSTAEPDDSHALYAKKLWTAPELLSGNp 228
Cdd:cd06626   104 YTL--QLLEGLAYLHENGI-VHRDIKPANIFLDSNGLIKLGDFGsavkLKNNTTTMAPGEVNSLVGTPAYMAPEVITGN- 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 lPTTGMQKA-DVYSFGIILQEIALRSGPFYleGLDlSPKEIVQKVRNGQRPyfrPSIDRTQLNEELVLLMERCWAQDPAE 307
Cdd:cd06626   180 -KGEGHGRAaDIWSLGCVVLEMATGKRPWS--ELD-NEWAIMYHVGMGHKP---PIPDSLQLSPEGKDFLSRCLESDPKK 252

                  ..
gi 1370514551 308 RP 309
Cdd:cd06626   253 RP 254
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
76-314 6.16e-15

Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Class EphB receptors bind to transmembrane ephrin-B ligands. There are six vertebrate EphB receptors (EphB1-6), which display promiscuous interactions with three ephrin-B ligands. One exception is EphB2, which also interacts with ephrin A5. EphB receptors play important roles in synapse formation and plasticity, spine morphogenesis, axon guidance, and angiogenesis. In the intestinal epithelium, EphBs are Wnt signaling target genes that control cell compartmentalization. They function as suppressors of colon cancer progression. EphRs comprise the largest subfamily of receptor PTKs (RTKs). They contain an ephrin-binding domain and two fibronectin repeats extracellularly, a transmembrane segment, and a cytoplasmic tyr kinase domain. Binding of the ephrin ligand to EphR requires cell-cell contact since both are anchored to the plasma membrane. The resulting downstream signals occur bidirectionally in both EphR-expressing cells (forward signaling) and ephrin-expressing cells (reverse signaling). Ephrin/EphR interaction mainly results in cell-cell repulsion or adhesion. The EphB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173638 [Multi-domain]  Cd Length: 269  Bit Score: 75.29  E-value: 6.16e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  76 KGNVVAIK-----HVNKKRieltRQVLFELKHMRdvQFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDIL-ENDS--- 144
Cdd:cd05065    31 REIFVAIKtlksgYTEKQR----RDFLSEASIMG--QFDHpnIIHLEGVVTKSRPVMIITEFMENGALDSFLrQNDGqft 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 145 -INLDWMFRyslinDLVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLASF--RSTAEPDDSHALYAK--KLWT 219
Cdd:cd05065   105 vIQLVGMLR-----GIAAGMKYL-SEMNYVHRDLAARNILVNSNLVCKVSDFGLSRFleDDTSDPTYTSSLGGKipIRWT 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 220 APELLSGNPLPTTgmqkADVYSFGIILQEI-ALRSGPFYleglDLSPKEIVQKVRNGQRpyFRPSIDrtqLNEELVLLME 298
Cdd:cd05065   179 APEAIAYRKFTSA----SDVWSYGIVMWEVmSYGERPYW----DMSNQDVINAIEQDYR--LPPPMD---CPTALHQLML 245
                         250
                  ....*....|....*.
gi 1370514551 299 RCWAQDPAERPDFGQI 314
Cdd:cd05065   246 DCWQKDRNLRPKFGQI 261
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
103-322 6.40e-15

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily is composed of Jak1, Jak2, Jak3, TYK2, and similar proteins. They are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal catalytic tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. In the case of Jak2, the presumed pseudokinase (repeat 1) domain exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Most Jaks are expressed in a wide variety of tissues, except for Jak3, which is expressed only in hematopoietic cells. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). Jaks are also involved in regulating the surface expression of some cytokine receptors. The Jak-STAT pathway is involved in many biological processes including hematopoiesis, immunoregulation, host defense, fertility, lactation, growth, and embryogenesis. The Jak subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270633 [Multi-domain]  Cd Length: 259  Bit Score: 74.82  E-value: 6.40e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 103 MRDVQFNHLTRFIGACIDPPNIcIVTEYCPRGSLQDIL--ENDSINLDWMFRysLINDLVKGMAFLHNSIISsHGSLKSS 180
Cdd:cd05037    56 MSQISHKHLVKLYGVCVADENI-MVQEYVRYGPLDKYLrrMGNNVPLSWKLQ--VAKQLASALHYLEDKKLI-HGNVRGR 131
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 181 NCVVdsrfvlkiTDYGLAS---FRSTAEPDDSHALYAKKL------WTAPELLSGNPLPTTgmQKADVYSFGIILQEIAL 251
Cdd:cd05037   132 NILL--------AREGLDGyppFIKLSDPGVPITVLSREErvdripWIAPECLRNLQANLT--IAADKWSFGTTLWEICS 201
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370514551 252 RsGPFYLEGLDLSPKEIVQKVRNgQRPyfRPSIDrtqlneELVLLMERCWAQDPAERPDFGQIkgfIRRFN 322
Cdd:cd05037   202 G-GEEPLSALSSQEKLQFYEDQH-QLP--APDCA------ELAELIMQCWTYEPTKRPSFRAI---LRDLN 259
STKc_CDK7 cd07841
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs ...
77-309 9.69e-15

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK7 plays essential roles in the cell cycle and in transcription. It associates with cyclin H and MAT1 and acts as a CDK-Activating Kinase (CAK) by phosphorylating and activating cell cycle CDKs (CDK1/2/4/6). In the brain, it activates CDK5. CDK7 is also a component of the general transcription factor TFIIH, which phosphorylates the C-terminal domain (CTD) of RNA polymerase II when it is bound with unphosphorylated DNA, as present in the pre-initiation complex. Following phosphorylation, the CTD dissociates from the DNA which allows transcription initiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270833 [Multi-domain]  Cd Length: 298  Bit Score: 74.92  E-value: 9.69e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIE-----LTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPrGSLQDILENDSINLDWMF 151
Cdd:cd07841    25 GRIVAIKKIKLGERKeakdgINFTALREIKLLQELKHPNIIGLLDVFGHKSNINLVFEFME-TDLEKVIKDKSIVLTPAD 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDD--SHALYAkkLW-TAPELLSGNP 228
Cdd:cd07841   104 IKSYMLMTLRGLEYLHSNWIL-HRDLKPNNLLIASDGVLKLADFGLA--RSFGSPNRkmTHQVVT--RWyRAPELLFGAR 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 LPTTGmqkADVYSFGIILQEIALRSgPFY-----LEGLDL------SPKEI----VQKVRNGQRPYFRPSIDRTQL---- 289
Cdd:cd07841   179 HYGVG---VDMWSVGCIFAELLLRV-PFLpgdsdIDQLGKifealgTPTEEnwpgVTSLPDYVEFKPFPPTPLKQIfpaa 254
                         250       260
                  ....*....|....*....|
gi 1370514551 290 NEELVLLMERCWAQDPAERP 309
Cdd:cd07841   255 SDDALDLLQRLLTLNPNKRI 274
STKc_ACVR1_ALK1 cd14142
Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin ...
73-308 1.03e-14

Catalytic domain of the Serine/Threonine Kinases, Activin Type I Receptor and Activin receptor-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR1, also called Activin receptor-Like Kinase 2 (ALK2), and ALK1 act as receptors for bone morphogenetic proteins (BMPs) and they activate SMAD1/5/8. ACVR1 is widely expressed while ALK1 is limited mainly to endothelial cells. The specificity of BMP binding to type I receptors is affected by type II receptors. ACVR1 binds BMP6/7/9/10 and can also bind anti-Mullerian hormone (AMH) in the presence of AMHR2. ALK1 binds BMP9/10 as well as TGFbeta in endothelial cells. A missense mutation in the GS domain of ACVR1 causes fibrodysplasia ossificans progressiva, a complex and disabling disease characterized by congenital skeletal malformations and extraskeletal bone formation. ACVR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and AMH, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like ACVR1 and ALK1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The ACVR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271044 [Multi-domain]  Cd Length: 298  Bit Score: 75.17  E-value: 1.03e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVN-------KKRIELTRQVLfeLKHmrdvqfNHLTRFIGACIDPPNIC----IVTEYCPRGSLQDILE 141
Cdd:cd14142    24 GQWQGESVAVKIFSsrdekswFRETEIYNTVL--LRH------ENILGFIASDMTSRNSCtqlwLITHYHENGSLYDYLQ 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 142 NDSINLDWMFRYSLinDLVKGMAFLHNSIISSHGS-------LKSSNCVVDSRFVLKITDYGLASFRSTAE----PDDSH 210
Cdd:cd14142    96 RTTLDHQEMLRLAL--SAASGLVHLHTEIFGTQGKpaiahrdLKSKNILVKSNGQCCIADLGLAVTHSQETnqldVGNNP 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 211 ALYAKKlWTAPELL--SGNPLPTTGMQKADVYSFGIILQEIALR--SG--------PFY-LEGLDLSPKEIVQKVRNGQr 277
Cdd:cd14142   174 RVGTKR-YMAPEVLdeTINTDCFESYKRVDIYAFGLVLWEVARRcvSGgiveeykpPFYdVVPSDPSFEDMRKVVCVDQ- 251
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 1370514551 278 pyFRPSIDRTQLNEELVL----LMERCWAQDPAER 308
Cdd:cd14142   252 --QRPNIPNRWSSDPTLTamakLMKECWYQNPSAR 284
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
73-317 1.60e-14

Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. Jaks are crucial for cytokine receptor signaling. They are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173644 [Multi-domain]  Cd Length: 284  Bit Score: 74.20  E-value: 1.60e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIK---------HVN--KKRIELTRQVLFElkhmrdvqfnHLTRFIGACIDPPN--ICIVTEYCPRGSLQDI 139
Cdd:cd05079    29 GDNTGEQVAVKslkpesggnHIAdlKKEIEILRNLYHE----------NIVKYKGICTEDGGngIKLIMEFLPSGSLKEY 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 140 LEND--SINLDWMFRYSLinDLVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE-----PDDshaL 212
Cdd:cd05079    99 LPRNknKINLKQQLKYAV--QICKGMDYL-GSRQYVHRDLAARNVLVESEHQVKIGDFGLTKAIETDKeyytvKDD---L 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 213 YAKKLWTAPELLsgnpLPTTGMQKADVYSFGIILQEIAL----RSGPFYLEGLDLSPKE-------IVQKVRNGQR-Pyf 280
Cdd:cd05079   173 DSPVFWYAPECL----IQSKFYIASDVWSFGVTLYELLTycdsESSPMTLFLKMIGPTHgqmtvtrLVRVLEEGKRlP-- 246
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1370514551 281 RPSidrtQLNEELVLLMERCWAQDPAERPDFGQ-IKGF 317
Cdd:cd05079   247 RPP----NCPEEVYQLMRKCWEFQPSKRTTFQNlIEGF 280
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
71-310 1.61e-14

Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily include Schizosaccharomyces pombe Cdc7, Saccharomyces cerevisiae Cdc15, Arabidopsis thaliana mitogen-activated protein kinase kinase kinase (MAPKKK) epsilon, and related proteins. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. Fission yeast Cdc7 is essential for cell division by playing a key role in the initiation of septum formation and cytokinesis. Budding yeast Cdc15 functions to coordinate mitotic exit with cytokinesis. Arabidopsis MAPKKK epsilon is required for pollen development in the plasma membrane. The Cdc7-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270797 [Multi-domain]  Cd Length: 254  Bit Score: 73.80  E-value: 1.61e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  71 NTGHFkgnvVAIK--HVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE-NDSINL 147
Cdd:cd06627    23 NTGEF----VAIKqiSLEKIPKSDLKSVMGEIDLLKKLNHPNIVKYIGSVKTKDSLYIILEYVENGSLASIIKkFGKFPE 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 148 DWMFRYslINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASfRSTAEPDDSHALYAKKLWTAPELLSG 226
Cdd:cd06627    99 SLVAVY--IYQVLEGLAYLHeQGVI--HRDIKGANILTTKDGLVKLADFGVAT-KLNEVEKDENSVVGTPYWMAPEVIEM 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPTtgmqKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQRPYFRPSIdrtqlNEELVLLMERCWAQDPA 306
Cdd:cd06627   174 SGVTT----ASDIWSVGCTVIELLTGNPPYY----DLQPMAALFRIVQDDHPPLPENI-----SPELRDFLLQCFQKDPT 240

                  ....
gi 1370514551 307 ERPD 310
Cdd:cd06627   241 LRPS 244
PKc_Pek1_like cd06621
Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
77-309 1.65e-14

Catalytic domain of fungal Pek1-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Pek1/Skh1 from Schizosaccharomyces pombe and MKK2 from Saccharomyces cerevisiae, and related proteins. Both fission yeast Pek1 and baker's yeast MKK2 are components of the cell integrity MAPK pathway. In fission yeast, Pek1 phosphorylates and activates Pmk1/Spm1 and is regulated by the MAPKK kinase Mkh1. In baker's yeast, the pathway involves the MAPK Slt2, the MAPKKs MKK1 and MKK2, and the MAPKK kinase Bck1. The cell integrity MAPK cascade is activated by multiple stress conditions, and is essential in cell wall construction, morphogenesis, cytokinesis, and ion homeostasis. MAPK signaling pathways are important mediators of cellular responses to extracellular signals. The MAPKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270793 [Multi-domain]  Cd Length: 287  Bit Score: 74.38  E-value: 1.65e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRI------------ELTRQVLFELKHMRDVQFNHLTRFIGACID--PPNICIVTEYCPRGSLQDILEN 142
Cdd:cd06621    15 GSVTKCRLRNTKTIfalktittdpnpDVQKQILRELEINKSCASPYIVKYYGAFLDeqDSSIGIAMEYCEGGSLDSIYKK 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 143 DSINLDWMFRYSL---INDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLA-----SFRSTaepddshaLY 213
Cdd:cd06621    95 VKKKGGRIGEKVLgkiAESVLKGLSYLHSrKII--HRDIKPSNILLTRKGQVKLCDFGVSgelvnSLAGT--------FT 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 214 AKKLWTAPELLSGNPLPTTgmqkADVYSFGIILQEIALRSGPFYLEGLD-LSPKEIVQKVRNGQRPYFR--PSIDRtQLN 290
Cdd:cd06621   165 GTSYYMAPERIQGGPYSIT----SDVWSLGLTLLEVAQNRFPFPPEGEPpLGPIELLSYIVNMPNPELKdePENGI-KWS 239
                         250
                  ....*....|....*....
gi 1370514551 291 EELVLLMERCWAQDPAERP 309
Cdd:cd06621   240 ESFKDFIEKCLEKDGTRRP 258
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
97-318 2.65e-14

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR1 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR1 results in a slow but sustained receptor activation. DDR1 binds to all collagens tested to date (types I-IV). It is widely expressed in many tissues. It is abundant in the brain and is also found in keratinocytes, colonic mucosa epithelium, lung epithelium, thyroid follicles, and the islets of Langerhans. During embryonic development, it is found in the developing neuroectoderm. DDR1 is a key regulator of cell morphogenesis, differentiation and proliferation. It is important in the development of the mammary gland, the vasculator and the kidney. DDR1 is also found in human leukocytes, where it facilitates cell adhesion, migration, maturation, and cytokine production. The DDR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133227 [Multi-domain]  Cd Length: 304  Bit Score: 73.82  E-value: 2.65e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  97 LFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE-----------NDSINLD-------WMFRYSLIND 158
Cdd:cd05096    67 LKEVKILSRLKDPNIIRLLGVCVDEDPLCMITEYMENGDLNQFLSshhlddkeengNDAVPPAhclpaisYSSLLHVALQ 146
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 159 LVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLasfrstaepddSHALYAKKL------------WTAPELLSG 226
Cdd:cd05096   147 IASGMKYL-SSLNFVHRDLATRNCLVGENLTIKIADFGM-----------SRNLYAGDYyriqgravlpirWMAWECILM 214
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPTTgmqkADVYSFGIILQEIAL--RSGPFYleglDLSPKEIVQKV-----RNGQRPY-FRPSIDRTQLNEelvlLME 298
Cdd:cd05096   215 GKFTTA----SDVWAFGVTLWEILMlcKEQPYG----ELTDEQVIENAgeffrDQGRQVYlFRPPPCPQGLYE----LML 282
                         250       260
                  ....*....|....*....|
gi 1370514551 299 RCWAQDPAERPDFGQIKGFI 318
Cdd:cd05096   283 QCWSRDCRERPSFSDIHAFL 302
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
80-316 4.52e-14

Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. EGFR (HER1, ErbB1) is a receptor PTK (RTK) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands for EGFR include EGF, heparin binding EGF-like growth factor (HBEGF), epiregulin, amphiregulin, TGFalpha, and betacellulin. Upon ligand binding, EGFR can form homo- or heterodimers with other EGFR subfamily members. The EGFR signaling pathway is one of the most important pathways regulating cell proliferation, differentiation, survival, and growth. Overexpression and mutation in the kinase domain of EGFR have been implicated in the development and progression of a variety of cancers. A number of monoclonal antibodies and small molecule inhibitors have been developed that target EGFR, including the antibodies Cetuximab and Panitumumab, which are used in combination with other therapies for the treatment of colorectal cancer and non-small cell lung carcinoma (NSCLC). The small molecule inhibitors Gefitinib (Iressa) and Erlotinib (Tarceva), already used for NSCLC, are undergoing clinical trials for other types of cancer including gastrointestinal, breast, head and neck, and bladder. The EGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270683 [Multi-domain]  Cd Length: 313  Bit Score: 73.52  E-value: 4.52e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRI-ELTRQVLFELKHMRDVQFNHLTRFIGACIDPpNICIVTEYCPRGSLQDILE--NDSINLDWMFRYSLi 156
Cdd:cd05108    39 VAIKELREATSpKANKEILDEAYVMASVDNPHVCRLLGICLTS-TVQLITQLMPFGCLLDYVRehKDNIGSQYLLNWCV- 116
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 nDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRsTAEPDDSHALYAKK--LWTAPELLsgnpLPTTGM 234
Cdd:cd05108   117 -QIAKGMNYLEDRRLV-HRDLAARNVLVKTPQHVKITDFGLAKLL-GAEEKEYHAEGGKVpiKWMALESI----LHRIYT 189
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 235 QKADVYSFGIILQEIAlrsgPFYLEGLDLSP-KEIVQKVRNGQR-PyfRPSIdrtqLNEELVLLMERCWAQDPAERPDFG 312
Cdd:cd05108   190 HQSDVWSYGVTVWELM----TFGSKPYDGIPaSEISSILEKGERlP--QPPI----CTIDVYMIMVKCWMIDADSRPKFR 259

                  ....
gi 1370514551 313 QIKG 316
Cdd:cd05108   260 ELII 263
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
77-315 5.64e-14

Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAST kinases, MAST-like (MASTL) kinases (also called greatwall kinase or Gwl), and fungal kinases with similarity to Saccharomyces cerevisiae Rim15 and Schizosaccharomyces pombe cek1. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. MASTL kinases carry only a catalytic domain which contains a long insert relative to other kinases. The fungal kinases in this subfamily harbor other domains in addition to a central catalytic domain, which like in MASTL, also contains an insert relative to MAST kinases. Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MASTL/Gwl is involved in the regulation of mitotic entry, mRNA stabilization, and DNA checkpoint recovery. The fungal proteins Rim15 and cek1 are involved in the regulation of meiosis and mitosis, respectively. The MAST-like kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270731 [Multi-domain]  Cd Length: 272  Bit Score: 72.25  E-value: 5.64e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKK---RIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN-DSINLDWMFR 152
Cdd:cd05579    18 GDLYAIKVIKKRdmiRKNQVDSVLAERNILSQAQNPFVVKLYYSFQGKKNLYLVMEYLPGGDLYSLLENvGALDEDVARI 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 YslINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASF---------------RSTAEPDDSHAL---- 212
Cdd:cd05579    98 Y--IAEIVLALEYLHsHGII--HRDLKPDNILIDANGHLKLTDFGLSKVglvrrqiklsiqkksNGAPEKEDRRIVgtpd 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 213 YAkklwtAPELLSGNPLPTTgmqkADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNGQRPYfrPSIDrtQLNEE 292
Cdd:cd05579   174 YL-----APEILLGQGHGKT----VDWWSLGVILYEFLVGIPPFHAE----TPEEIFQNILNGKIEW--PEDP--EVSDE 236
                         250       260
                  ....*....|....*....|...
gi 1370514551 293 LVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd05579   237 AKDLISKLLTPDPEKRLGAKGIE 259
STKc_ULK3 cd14121
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the ...
79-311 6.13e-14

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK3 mRNA is up-regulated in fibroblasts after Ras-induced senescence, and its overexpression induces both autophagy and senescence in a fibroblast cell line. ULK3, through its kinase activity, positively regulates Gli proteins, mediators of the Sonic hedgehog (Shh) signaling pathway that is implicated in tissue homeostasis maintenance and neurogenesis. It is inhibited by binding to Suppressor of Fused (Sufu). The ULK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271023 [Multi-domain]  Cd Length: 252  Bit Score: 71.94  E-value: 6.13e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  79 VVAIKHVNKKRIE--LTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLi 156
Cdd:cd14121    23 VVAVKCVSKSSLNkaSTENLLTEIELLKKLKHPHIVELKDFQWDEEHIYLIMEYCSGGDLSRFIRSRRTLPESTVRRFL- 101
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLHNSIISsHGSLKSSNCVVDSRF--VLKITDYGLASFRStaEPDDSHALYAKKLWTAPELLsgnpLPTTGM 234
Cdd:cd14121   102 QQLASALQFLREHNIS-HMDLKPQNLLLSSRYnpVLKLADFGFAQHLK--PNDEAHSLRGSPLYMAPEMI----LKKKYD 174
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370514551 235 QKADVYSFGIILQEIALRSGPFYLEGLdlspKEIVQKVRNgQRPYFRPSidRTQLNEELVLLMERCWAQDPAERPDF 311
Cdd:cd14121   175 ARVDLWSVGVILYECLFGRAPFASRSF----EELEEKIRS-SKPIEIPT--RPELSADCRDLLLRLLQRDPDRRISF 244
STKc_STK36 cd14002
Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the ...
75-257 7.48e-14

Catalytic domain of Serine/Threonine Kinase 36; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK36, also called Fused (or Fu) kinase, is involved in the Hedgehog signaling pathway. It is activated by the Smoothened (SMO) signal transducer, resulting in the stabilization of GLI transcription factors and the phosphorylation of SUFU to facilitate the nuclear accumulation of GLI. In Drosophila, Fused kinase is maternally required for proper segmentation during embryonic development and for the development of legs and wings during the larval stage. In mice, STK36 is not necessary for embryonic development, although mice deficient in STK36 display growth retardation postnatally. The STK36 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270904 [Multi-domain]  Cd Length: 253  Bit Score: 71.51  E-value: 7.48e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  75 FKGNVVAIKHVNK-----KRIELTRQvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCpRGSLQDILENDSiNLDW 149
Cdd:cd14002    24 YTGQVVALKFIPKrgkseKELRNLRQ---EIEILRKLNHPNIIEMLDSFETKKEFVVVTEYA-QGELFQILEDDG-TLPE 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 150 MFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTaepdDSHALYAKK---LWTAPELLS 225
Cdd:cd14002    99 EEVRSIAKQLVSALHYLHsNRII--HRDMKPQNILIGKGGVVKLCDFGFARAMSC----NTLVLTSIKgtpLYMAPELVQ 172
                         170       180       190
                  ....*....|....*....|....*....|..
gi 1370514551 226 GNPLPTTgmqkADVYSFGIILQEIALRSGPFY 257
Cdd:cd14002   173 EQPYDHT----ADLWSLGCILYELFVGQPPFY 200
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
78-319 7.49e-14

Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR-like proteins are members of the DDR subfamily, which are receptor PTKs (RTKs) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDRs results in a slow but sustained receptor activation. DDRs regulate cell adhesion, proliferation, and extracellular matrix remodeling. They have been linked to a variety of human cancers including breast, colon, ovarian, brain, and lung. There is no evidence showing that DDRs act as transforming oncogenes. They are more likely to play a role in the regulation of tumor growth and metastasis. The DDR-like subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133228 [Multi-domain]  Cd Length: 295  Bit Score: 72.32  E-value: 7.49e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  78 NVVAIKHVNKKRIELTRQ-VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSI--------NLD 148
Cdd:cd05097    45 VLVAVKMLRADVTKTARNdFLKEIKIMSRLKNPNIIRLLGVCVSDDPLCMITEYMENGDLNQFLSQREIestfthanNIP 124
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLIN---DLVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAepdDSHALYAKKL----WTAP 221
Cdd:cd05097   125 SVSIANLLYmavQIASGMKYL-ASLNFVHRDLATRNCLVGNHYTIKIADFGMSRNLYSG---DYYRIQGRAVlpirWMAW 200
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 222 ELLSGNPLPTTgmqkADVYSFGIILQEIAL--RSGPFYLegldLSPKEIVQKV----RNGQRPYFrpsIDRTQLNEELVL 295
Cdd:cd05097   201 ESILLGKFTTA----SDVWAFGVTLWEMFTlcKEQPYSL----LSDEQVIENTgeffRNQGRQIY---LSQTPLCPSPVF 269
                         250       260
                  ....*....|....*....|....*
gi 1370514551 296 -LMERCWAQDPAERPDFGQIKGFIR 319
Cdd:cd05097   270 kLMMRCWSRDIKDRPTFNKIHHFLR 294
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
107-314 8.08e-14

Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie proteins, consisting of Tie1 and Tie2, are receptor PTKs (RTKs) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2, while no specific ligand has been identified for Tie1. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. In vivo studies of Tie1 show that it is critical in vascular development. The Tie subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270641 [Multi-domain]  Cd Length: 270  Bit Score: 72.00  E-value: 8.08e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 107 QFNHLTRFIGACIDPPNICIVTEYCPRGSLQD------ILEND-----------SINLDWMFRYSLinDLVKGMAFLHNS 169
Cdd:cd05047    54 HHPNIINLLGACEHRGYLYLAIEYAPHGNLLDflrksrVLETDpafaianstasTLSSQQLLHFAA--DVARGMDYLSQK 131
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 170 IISsHGSLKSSNCVVDSRFVLKITDYGLASfrstaepddSHALYAKKL-------WTAPELLSGNPLPTtgmqKADVYSF 242
Cdd:cd05047   132 QFI-HRDLAARNILVGENYVAKIADFGLSR---------GQEVYVKKTmgrlpvrWMAIESLNYSVYTT----NSDVWSY 197
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370514551 243 GIILQEIALRSGPFYLeglDLSPKEIVQKVRNGQRpYFRPsidrTQLNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05047   198 GVLLWEIVSLGGTPYC---GMTCAELYEKLPQGYR-LEKP----LNCDDEVYDLMRQCWREKPYERPSFAQI 261
STKc_BMPR1 cd14144
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; ...
126-308 8.77e-14

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type I Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1 functions as a receptor for morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Vertebrates contain two type I BMP receptors, BMPR1a and BMPR1b. BMPR1 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that also includes TGFbeta, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271046 [Multi-domain]  Cd Length: 287  Bit Score: 72.12  E-value: 8.77e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 126 IVTEYCPRGSLQDILENDSINLDWMFRysLINDLVKGMAFLHNSIIS-------SHGSLKSSNCVVDSRFVLKITDYGLA 198
Cdd:cd14144    70 LITDYHENGSLYDFLRGNTLDTQSMLK--LAYSAACGLAHLHTEIFGtqgkpaiAHRDIKSKNILVKKNGTCCIADLGLA 147
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 199 SfRSTAEPDDSH----ALYAKKLWTAPELLSGNPLPTT--GMQKADVYSFGIILQEIALR--SG--------PFYleglD 262
Cdd:cd14144   148 V-KFISETNEVDlppnTRVGTKRYMAPEVLDESLNRNHfdAYKMADMYSFGLVLWEIARRciSGgiveeyqlPYY----D 222
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 263 LSPK----EIVQKVRNGQRpyFRPSI-DRTQLNEELVL---LMERCWAQDPAER 308
Cdd:cd14144   223 AVPSdpsyEDMRRVVCVER--RRPSIpNRWSSDEVLRTmskLMSECWAHNPAAR 274
STKc_ATG1_ULK_like cd14009
Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like ...
77-311 1.03e-13

Catalytic domain of the Serine/Threonine kinases, Autophagy-related protein 1 and Unc-51-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes yeast ATG1 and metazoan homologs including vertebrate ULK1-3. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. It is involved in nutrient sensing and signaling, the assembly of autophagy factors and the execution of autophagy. In metazoans, ATG1 homologs display additional functions. Unc-51 and ULKs have been implicated in neuronal and axonal development. The ATG1/ULK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270911 [Multi-domain]  Cd Length: 251  Bit Score: 71.10  E-value: 1.03e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRI--ELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQD------ILENDSINld 148
Cdd:cd14009    18 GEVVAIKEISRKKLnkKLQENLESEIAILKSIKHPNIVRLYDVQKTEDFIYLVLEYCAGGDLSQyirkrgRLPEAVAR-- 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 wmfrySLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRF---VLKITDYGLASFRSTAepDDSHALYAKKLWTAPELL 224
Cdd:cd14009    96 -----HFMQQLASGLKFLRsKNII--HRDLKPQNLLLSTSGddpVLKIADFGFARSLQPA--SMAETLCGSPLYMAPEIL 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 225 SGNPLPTtgmqKADVYSFGIILQEIALRSGPFylegldlSPKEIVQKVRNGQRPYFRPSIDRT-QLNEELVLLMERCWAQ 303
Cdd:cd14009   167 QFQKYDA----KADLWSVGAILFEMLVGKPPF-------RGSNHVQLLRNIERSDAVIPFPIAaQLSPDCKDLLRRLLRR 235

                  ....*...
gi 1370514551 304 DPAERPDF 311
Cdd:cd14009   236 DPAERISF 243
STKc_TGFbR1_ACVR1b_ACVR1c cd14143
Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I ...
126-308 1.38e-13

Catalytic domain of the Serine/Threonine Kinases, Transforming Growth Factor beta Type I Receptor and Activin Type IB/IC Receptors; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR1, also called Activin receptor-Like Kinase 5 (ALK5), functions as a receptor for TGFbeta and phoshorylates SMAD2/3. TGFbeta proteins are cytokines that regulate cell growth, differentiation, and survival, and are critical in the development and progression of many human cancers. Mutations in TGFbR1 (and TGFbR2) can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. ACVR1b (also called ALK4) and ACVR1c (also called ALK7) act as receptors for activin A and B, respectively. TGFbR1, ACVR1b, and ACVR1c belong to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like TGFbR1, ACVR1b, and ACVR1c, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The TGFbR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271045 [Multi-domain]  Cd Length: 288  Bit Score: 71.32  E-value: 1.38e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 126 IVTEYCPRGSLQDILENDSINLDWMFRYSLinDLVKGMAFLHNSIISS-------HGSLKSSNCVVDSRFVLKITDYGLA 198
Cdd:cd14143    70 LVSDYHEHGSLFDYLNRYTVTVEGMIKLAL--SIASGLAHLHMEIVGTqgkpaiaHRDLKSKNILVKKNGTCCIADLGLA 147
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 199 ----SFRSTAEPDDSHALYAKKlWTAPELL--SGNPLPTTGMQKADVYSFGIILQEIALRSG----------PFYleglD 262
Cdd:cd14143   148 vrhdSATDTIDIAPNHRVGTKR-YMAPEVLddTINMKHFESFKRADIYALGLVFWEIARRCSiggihedyqlPYY----D 222
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 263 LSPK----EIVQKVRNGQRpyFRPSIDRTQLNEELVL----LMERCWAQDPAER 308
Cdd:cd14143   223 LVPSdpsiEEMRKVVCEQK--LRPNIPNRWQSCEALRvmakIMRECWYANGAAR 274
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
99-314 1.45e-13

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Alternative splicing of FGFR1 transcripts produces a variety of isoforms, which are differentially expressed in cells. FGFR1 binds the ligands, FGF1 and FGF2, with high affinity and has also been reported to bind FGF4, FGF6, and FGF9. FGFR1 signaling is critical in the control of cell migration during embryo development. It promotes cell proliferation in fibroblasts. Nuclear FGFR1 plays a role in the regulation of transcription. Mutations, insertions or deletions of FGFR1 have been identified in patients with Kallman's syndrome (KS), an inherited disorder characterized by hypogonadotropic hypogonadism and loss of olfaction. Aberrant FGFR1 expression has been found in some human cancers including 8P11 myeloproliferative syndrome (EMS), breast cancer, and pancreatic adenocarcinoma. FGFR1 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270678 [Multi-domain]  Cd Length: 302  Bit Score: 71.58  E-value: 1.45e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDV-QFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE-----------NDSINLDWMFRyslINDLV------ 160
Cdd:cd05098    68 EMEMMKMIgKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLQarrppgmeycyNPSHNPEEQLS---SKDLVscayqv 144
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 161 -KGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLASfrstaepDDSHALYAKKL--------WTAPELLsgnpLPT 231
Cdd:cd05098   145 aRGMEYL-ASKKCIHRDLAARNVLVTEDNVMKIADFGLAR-------DIHHIDYYKKTtngrlpvkWMAPEAL----FDR 212
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 232 TGMQKADVYSFGIILQEIALRSGPFYlEGLDLspKEIVQKVRNGQRpyfrpsIDR-TQLNEELVLLMERCWAQDPAERPD 310
Cdd:cd05098   213 IYTHQSDVWSFGVLLWEIFTLGGSPY-PGVPV--EELFKLLKEGHR------MDKpSNCTNELYMMMRDCWHAVPSQRPT 283

                  ....
gi 1370514551 311 FGQI 314
Cdd:cd05098   284 FKQL 287
PKc_Dusty cd13975
Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze ...
99-314 2.39e-13

Catalytic domain of the Dual-specificity Protein Kinase, Dusty; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Dusty protein kinase is also called Receptor-interacting protein kinase 5 (RIPK5 or RIP5) or RIP-homologous kinase. It is widely distributed in the central nervous system, and may be involved in inducing both caspase-dependent and caspase-independent cell death. The Dusty subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270877 [Multi-domain]  Cd Length: 262  Bit Score: 70.21  E-value: 2.39e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDV-QFNHLTRFIGACID-------PPNICIVTEYCPRgslqDILENDSINLDWMFRYSLINDLVKGMAFLHNSI 170
Cdd:cd13975    47 EFHYTRSLpKHERIVSLHGSVIDysygggsSIAVLLIMERLHR----DLYTGIKAGLSLEERLQIALDVVEGIRFLHSQG 122
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 171 ISsHGSLKSSNCVVDSRFVLKITDYGLASfrstAEPDDSHALYAKKLWTAPELLSGNPlpttgMQKADVYSFGIILQEIA 250
Cdd:cd13975   123 LV-HRDIKLKNVLLDKKNRAKITDLGFCK----PEAMMSGSIVGTPIHMAPELFSGKY-----DNSVDVYAFGILFWYLC 192
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 251 lrSG----PFYLEGLDlSPKEIVQKVRNGQRPYFRPSIDrtqlnEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd13975   193 --AGhvklPEAFEQCA-SKDHLWNNVRKGVRPERLPVFD-----EECWNLMEACWSGDPSQRPLLGIV 252
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
73-314 2.63e-13

Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A-Raf cooperates with C-Raf in regulating ERK transient phosphorylation that is associated with cyclin D expression and cell cycle progression. Mice deficient in A-Raf are born alive but show neurological and intestinal defects. A-Raf demonstrates low kinase activity to MEK, compared with B- and C-Raf, and may also have alternative functions other than in the ERK signaling cascade. It regulates the M2 type pyruvate kinase, a key glycolytic enzyme. It also plays a role in endocytic membrane trafficking. A-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The A-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271052 [Multi-domain]  Cd Length: 265  Bit Score: 70.43  E-value: 2.63e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNV-VAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGAcIDPPNICIVTEYCPRGSLQDILENDSINLDWMF 151
Cdd:cd14150    19 GKWHGDVaVKILKVTEPTPEQLQAFKNEMQVLRKTRHVNILLFMGF-MTRPNFAIITQWCEGSSLYRHLHVTETRFDTMQ 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFR---STAEPDDSHAlyAKKLWTAPELLS-G 226
Cdd:cd14150    98 LIDVARQTAQGMDYLHaKNII--HRDLKSNNIFLHEGLTVKIGDFGLATVKtrwSGSQQVEQPS--GSILWMAPEVIRmQ 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPTTGmqKADVYSFGIILQEIALRSGPFYLEGldlSPKEIVQKVRNGqrpYFRPSIDRTQLN--EELVLLMERCWAQD 304
Cdd:cd14150   174 DTNPYSF--QSDVYAYGVVLYELMSGTLPYSNIN---NRDQIIFMVGRG---YLSPDLSKLSSNcpKAMKRLLIDCLKFK 245
                         250
                  ....*....|
gi 1370514551 305 PAERPDFGQI 314
Cdd:cd14150   246 REERPLFPQI 255
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
79-320 2.76e-13

Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Musk is a receptor PTK (RTK) containing an extracellular region with four immunoglobulin-like domains and a cysteine-rich cluster, a transmembrane segment, and an intracellular catalytic domain. Musk is expressed and concentrated in the postsynaptic membrane in skeletal muscle. It is essential for the establishment of the neuromuscular junction (NMJ), a peripheral synapse that conveys signals from motor neurons to muscle cells. Agrin, a large proteoglycan released from motor neurons, stimulates Musk autophosphorylation and activation, leading to the clustering of acetylcholine receptors (AChRs). To date, there is no evidence to suggest that agrin binds directly to Musk. Mutations in AChR, Musk and other partners are responsible for diseases of the NMJ, such as the autoimmune syndrome myasthenia gravis. The Musk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 70.63  E-value: 2.76e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  79 VVAIKHVnKKRIELTRQVLFELKHMRDVQFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDILENDS------------ 144
Cdd:cd05050    37 MVAVKML-KEEASADMQADFQREAALMAEFDHpnIVKLLGVCAVGKPMCLLFEYMAYGDLNEFLRHRSpraqcslshsts 115
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 145 ---------INLDWMFRYSLINDLVKGMAFL-HNSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE---PDDSHA 211
Cdd:cd05050   116 sarkcglnpLPLSCTEQLCIAKQVAAGMAYLsERKFV--HRDLATRNCLVGENMVVKIADFGLSRNIYSADyykASENDA 193
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 212 LYAKklWTAPELLSGNPLPTtgmqKADVYSFGIILQEI-ALRSGPFYleglDLSPKEIVQKVRNGQR---PYFRPSidrt 287
Cdd:cd05050   194 IPIR--WMPPESIFYNRYTT----ESDVWAYGVVLWEIfSYGMQPYY----GMAHEEVIYYVRDGNVlscPDNCPL---- 259
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1370514551 288 qlneELVLLMERCWAQDPAERPDFGQIKGFIRR 320
Cdd:cd05050   260 ----ELYNLMRLCWSKLPSDRPSFASINRILQR 288
STKc_CCRK cd07832
Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the ...
77-257 2.92e-13

Catalytic domain of the Serine/Threonine Kinase, Cell Cycle-Related Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CCRK was previously called p42. It is a Cyclin-Dependent Kinase (CDK)-Activating Kinase (CAK) which is essential for the activation of CDK2. It is indispensable for cell growth and has been implicated in the progression of glioblastoma multiforme. In the heart, a splice variant of CCRK with a different C-terminal half is expressed; this variant promotes cardiac cell growth and survival and is significantly down-regulated during the development of heart failure. The CCRK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270826 [Multi-domain]  Cd Length: 287  Bit Score: 70.44  E-value: 2.92e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIE--LTRQVLFELKHMRDVQFN-HLTRFIGACIDPPNICIVTEYCPRgSLQDILEN--DSINLDWMF 151
Cdd:cd07832    25 GETVALKKVALRKLEggIPNQALREIKALQACQGHpYVVKLRDVFPHGTGFVLVFEYMLS-SLSEVLRDeeRPLTEAQVK 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLIndLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDD---SHALyAKKLWTAPELLSGN 227
Cdd:cd07832   104 RYMRM--LLKGVAYMHaNRIM--HRDLKPANLLISSTGVLKIADFGLA--RLFSEEDPrlySHQV-ATRWYRAPELLYGS 176
                         170       180       190
                  ....*....|....*....|....*....|
gi 1370514551 228 PLPTTGmqkADVYSFGIILQEIaLRSGPFY 257
Cdd:cd07832   177 RKYDEG---VDLWAVGCIFAEL-LNGSPLF 202
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
99-324 3.45e-13

Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. B-Raf activates ERK with the strongest magnitude, compared with other Raf kinases. Mice embryos deficient in B-Raf die around midgestation due to vascular hemorrhage caused by apoptotic endothelial cells. Mutations in B-Raf have been implicated in initiating tumorigenesis and tumor progression, and are found in malignant cutaneous melanoma, papillary thyroid cancer, as well as in ovarian and colorectal carcinomas. Most oncogenic B-Raf mutations are located at the activation loop of the kinase and surrounding regions; the V600E mutation accounts for around 90% of oncogenic mutations. The V600E mutant constitutively activates MEK, resulting in sustained activation of ERK. B-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. They function in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The B-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 70.09  E-value: 3.45e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQFNHLTRFIGACIDPpNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSL 177
Cdd:cd14151    54 EVGVLRKTRHVNILLFMGYSTKP-QLAIVTQWCEGSSLYHHLHIIETKFEMIKLIDIARQTAQGMDYLHaKSII--HRDL 130
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 178 KSSNCVVDSRFVLKITDYGLASFRST-AEPDDSHALYAKKLWTAPELL---SGNPLPTtgmqKADVYSFGIILQEiaLRS 253
Cdd:cd14151   131 KSNNIFLHEDLTVKIGDFGLATVKSRwSGSHQFEQLSGSILWMAPEVIrmqDKNPYSF----QSDVYAFGIVLYE--LMT 204
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 254 GPFYLEGLDlSPKEIVQKVRNGqrpYFRPSIDRTQLN--EELVLLMERCWAQDPAERPDFGQIKGFIRRFNKE 324
Cdd:cd14151   205 GQLPYSNIN-NRDQIIFMVGRG---YLSPDLSKVRSNcpKAMKRLMAECLKKKRDERPLFPQILASIELLARS 273
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
80-314 3.50e-13

Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. InsR is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the insulin ligand to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, stimulating downstream kinase activities, which initiate signaling cascades and biological function. InsR signaling plays an important role in many cellular processes including glucose homeostasis, glycogen synthesis, lipid and protein metabolism, ion and amino acid transport, cell cycle and proliferation, cell differentiation, gene transcription, and nitric oxide synthesis. Insulin resistance, caused by abnormalities in InsR signaling, has been described in diabetes, hypertension, cardiovascular disease, metabolic syndrome, heart failure, and female infertility. The InsR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133192 [Multi-domain]  Cd Length: 288  Bit Score: 70.38  E-value: 3.50e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVN-----KKRIELtrqvLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN---DSIN----- 146
Cdd:cd05061    39 VAVKTVNesaslRERIEF----LNEASVMKGFTCHHVVRLLGVVSKGQPTLVVMELMAHGDLKSYLRSlrpEAENnpgrp 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 ---LDWMFRYSliNDLVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDdshalYAKK------- 216
Cdd:cd05061   115 pptLQEMIQMA--AEIADGMAYL-NAKKFVHRDLAARNCMVAHDFTVKIGDFGMT--RDIYETD-----YYRKggkgllp 184
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 217 -LWTAPELLSGNPLPTTgmqkADVYSFGIILQEIA-LRSGPFylEGLdlSPKEIVQKVRNGQrpyfrpSIDRTQ-LNEEL 293
Cdd:cd05061   185 vRWMAPESLKDGVFTTS----SDMWSFGVVLWEITsLAEQPY--QGL--SNEQVLKFVMDGG------YLDQPDnCPERV 250
                         250       260
                  ....*....|....*....|.
gi 1370514551 294 VLLMERCWAQDPAERPDFGQI 314
Cdd:cd05061   251 TDLMRMCWQFNPKMRPTFLEI 271
STKc_TAO3 cd06633
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze ...
62-368 3.60e-13

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TAO3 is also known as JIK (c-Jun N-terminal kinase inhibitory kinase) or KFC (kinase from chicken). It specifically activates JNK, presumably by phosphorylating and activating MKK4/MKK7. In Saccharomyces cerevisiae, TAO3 is a component of the RAM (regulation of Ace2p activity and cellular morphogenesis) signaling pathway. TAO3 is upregulated in retinal ganglion cells after axotomy, and may play a role in apoptosis. TAO proteins possess mitogen-activated protein kinase (MAPK) kinase kinase activity. MAPK signaling cascades are important in mediating cellular responses to extracellular signals. The TAO3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270803 [Multi-domain]  Cd Length: 313  Bit Score: 70.45  E-value: 3.60e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  62 AHGKY-QIFANTGHFKGNVVAIKHVN---KKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCpRGSLQ 137
Cdd:cd06633    30 GHGSFgAVYFATNSHTNEVVAIKKMSysgKQTNEKWQDIIKEVKFLQQLKHPNTIEYKGCYLKDHTAWLVMEYC-LGSAS 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 138 DILENDSINLDWMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAepddsHALYAKKL 217
Cdd:cd06633   109 DLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNMI-HRDIKAGNILLTEPGQVKLADFGSASIASPA-----NSFVGTPY 182
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 218 WTAPE-LLSGNPLPTTGmqKADVYSFGIILQEIALRSGPFYLEGLDLSPKEIVQKVrngqrpyfRPSIDRTQLNEELVLL 296
Cdd:cd06633   183 WMAPEvILAMDEGQYDG--KVDIWSLGITCIELAERKPPLFNMNAMSALYHIAQND--------SPTLQSNEWTDSFRGF 252
                         250       260       270       280       290       300       310
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 297 MERCWAQDPAERPDFGQI--KGFIRRfnkEGGTSILDNLLLRMEQYANNLEKLveertqayleEKRKAEALLYQ 368
Cdd:cd06633   253 VDYCLQKIPQERPSSAELlrHDFVRR---ERPPRVLIDLIQRTKDAVRELDNL----------QYRKMKKILFQ 313
STKc_Chk1 cd14069
Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the ...
79-315 3.69e-13

Catalytic domain of the Serine/Threonine kinase, Checkpoint kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chk1 is implicated in many major checkpoints of the cell cycle, providing a link between upstream sensors and the cell cycle engine. It plays an important role in DNA damage response and maintaining genomic stability. Chk1 acts as an effector of the sensor kinase, ATR (ATM and Rad3-related), a member of the PI3K family, which is activated upon DNA replication stress. Chk1 delays mitotic entry in response to replication blocks by inhibiting cyclin dependent kinase (Cdk) activity. In addition, Chk1 contributes to the function of centrosome and spindle-based checkpoints, inhibits firing of origins of DNA replication (Ori), and represses transcription of cell cycle proteins including cyclin B and Cdk1. The Chk1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270971 [Multi-domain]  Cd Length: 261  Bit Score: 69.67  E-value: 3.69e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  79 VVAIKHVNKKR--IELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEND-SINLDWMFRYsl 155
Cdd:cd14069    28 AVAVKFVDMKRapGDCPENIKKEVCIQKMLSHKNVVRFYGHRREGEFQYLFLEYASGGELFDKIEPDvGMPEDVAQFY-- 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 INDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAS-FRSTAEPDDSHALYAKKLWTAPELLSGNPLPTtgm 234
Cdd:cd14069   106 FQQLMAGLKYLHSCGIT-HRDIKPENLLLDENDNLKISDFGLATvFRYKGKERLLNKMCGTLPYVAPELLAKKKYRA--- 181
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 235 QKADVYSFGIILqeIALRSG--PFyleglDLsPKEIVQKV---RNGQRPYFRP--SIDRTQLNeelvlLMERCWAQDPAE 307
Cdd:cd14069   182 EPVDVWSCGIVL--FAMLAGelPW-----DQ-PSDSCQEYsdwKENKKTYLTPwkKIDTAALS-----LLRKILTENPNK 248

                  ....*...
gi 1370514551 308 RPDFGQIK 315
Cdd:cd14069   249 RITIEDIK 256
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
80-319 3.94e-13

Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Ror subfamily consists of Ror1, Ror2, and similar proteins. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. Ror kinases are expressed in many tissues during development. They play important roles in bone and heart formation. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Drosophila Ror is expressed only in the developing nervous system during neurite outgrowth and neuronal differentiation, suggesting a role for Drosophila Ror in neural development. More recently, mouse Ror1 and Ror2 have also been found to play an important role in regulating neurite growth in central neurons. Ror1 and Ror2 are believed to have some overlapping and redundant functions. The Ror subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270642 [Multi-domain]  Cd Length: 283  Bit Score: 70.10  E-value: 3.94e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSL--I 156
Cdd:cd05048    38 VAIKTLKENASPKTQQDFRrEAELMSDLQHPNIVCLLGVCTKEQPQCMLFEYMAHGDLHEFLVRHSPHSDVGVSSDDdgT 117
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLHNSI--------ISS----HGSLKSSNCVVDSRFVLKITDYGLASFRSTAepdDSHALYAKKL----WTA 220
Cdd:cd05048   118 ASSLDQSDFLHIAIqiaagmeyLSShhyvHRDLAARNCLVGDGLTVKISDFGLSRDIYSS---DYYRVQSKSLlpvrWMP 194
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 221 PE-LLSGNPLPTTgmqkaDVYSFGIILQEI-ALRSGPFYleglDLSPKEIVQKVRNGQR---PYFRPSidrtqlneELVL 295
Cdd:cd05048   195 PEaILYGKFTTES-----DVWSFGVVLWEIfSYGLQPYY----GYSNQEVIEMIRSRQLlpcPEDCPA--------RVYS 257
                         250       260
                  ....*....|....*....|....
gi 1370514551 296 LMERCWAQDPAERPDFGQIKGFIR 319
Cdd:cd05048   258 LMVECWHEIPSRRPRFKEIHTRLR 281
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
114-341 4.38e-13

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Unlike other FGFRs, there is only one splice form of FGFR4. It binds FGF1, FGF2, FGF6, FGF19, and FGF23. FGF19 is a selective ligand for FGFR4. Although disruption of FGFR4 in mice causes no obvious phenotype, in vivo inhibition of FGFR4 in cultured skeletal muscle cells resulted in an arrest of muscle progenitor differentiation. FGF6 and FGFR4 are uniquely expressed in myofibers and satellite cells. FGF6/FGFR4 signaling appears to play a key role in the regulation of muscle regeneration. A polymorphism in FGFR4 is found in head and neck squamous cell carcinoma. FGFR4 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133230 [Multi-domain]  Cd Length: 314  Bit Score: 70.38  E-value: 4.38e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 114 FIGACIDPPNICIVTEYCPRGSLQDILE-------NDSINLDWMFRYSL-INDLV-------KGMAFLHnSIISSHGSLK 178
Cdd:cd05099    83 LLGVCTQEGPLYVIVEYAAKGNLREFLRarrppgpDYTFDITKVPEEQLsFKDLVscayqvaRGMEYLE-SRRCIHRDLA 161
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 179 SSNCVVDSRFVLKITDYGLAsfRSTAEPDdshalYAKKL--------WTAPELLsgnpLPTTGMQKADVYSFGIILQEIA 250
Cdd:cd05099   162 ARNVLVTEDNVMKIADFGLA--RGVHDID-----YYKKTsngrlpvkWMAPEAL----FDRVYTHQSDVWSFGILMWEIF 230
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 251 LRSGPFYlEGLDLspKEIVQKVRNGQRpYFRPSidrtQLNEELVLLMERCWAQDPAERPDFGQIKGFIRRFNKEGGTSIL 330
Cdd:cd05099   231 TLGGSPY-PGIPV--EELFKLLREGHR-MDKPS----NCTHELYMLMRECWHAVPTQRPTFKQLVEALDKVLAAVSEEYL 302
                         250
                  ....*....|.
gi 1370514551 331 DnLLLRMEQYA 341
Cdd:cd05099   303 D-LSMPFEQYS 312
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
76-310 4.77e-13

Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and Ste20-related proline alanine-rich kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. SPAK is also referred to as STK39 or PASK (proline-alanine-rich STE20-related kinase). OSR1 and SPAK regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. They are also implicated in cytoskeletal rearrangement, cell differentiation, transformation and proliferation. OSR1 and SPAK contain a conserved C-terminal (CCT) domain, which recognizes a unique motif ([RK]FX[VI]) present in their activating kinases (WNK1/WNK4) and their substrates. The OSR1 and SPAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270787 [Multi-domain]  Cd Length: 267  Bit Score: 69.69  E-value: 4.77e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  76 KGNVVAIKHVN--KKRIELtRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE--NDSINLDWMF 151
Cdd:cd06610    25 KKEKVAIKRIDleKCQTSM-DELRKEIQAMSQCNHPNVVSYYTSFVVGDELWLVMPLLSGGSLLDIMKssYPRGGLDEAI 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFrsTAEPDDSHALYAKKL-----WTAPELLS 225
Cdd:cd06610   104 IATVLKEVLKGLEYLHsNGQI--HRDVKAGNILLGEDGSVKIADFGVSAS--LATGGDRTRKVRKTFvgtpcWMAPEVME 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 226 gnplPTTGM-QKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQRPYFRPSIDRTQLNEELVLLMERCWAQD 304
Cdd:cd06610   180 ----QVRGYdFKADIWSFGITAIELATGAAPYS----KYPPMKVLMLTLQNDPPSLETGADYKKYSKSFRKMISLCLQKD 251

                  ....*.
gi 1370514551 305 PAERPD 310
Cdd:cd06610   252 PSKRPT 257
STKc_PLK cd14099
Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the ...
77-314 5.59e-13

Catalytic domain of the Serine/Threonine Kinases, Polo-like kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. PLKs derive their names from homology to polo, a kinase first identified in Drosophila. There are five mammalian PLKs (PLK1-5) from distinct genes. There is good evidence that PLK1 may function as an oncogene while PLK2-5 have tumor suppressive properties. PLK1 functions as a positive regulator of mitosis, meiosis, and cytokinesis. PLK2 functions in G1 progression, S-phase arrest, and centriole duplication. PLK3 regulates angiogenesis and responses to DNA damage. PLK4 is required for late mitotic progression, cell survival, and embryonic development. PLK5 was first identified as a pseudogene containing a stop codon within the kinase domain, however, both murine and human genes encode expressed proteins. PLK5 functions in cell cycle arrest.


Pssm-ID: 271001 [Multi-domain]  Cd Length: 258  Bit Score: 69.12  E-value: 5.59e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQ---VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-------ENDSin 146
Cdd:cd14099    26 GKVYAGKVVPKSSLTKPKQrekLKSEIKIHRSLKHPNIVKFHDCFEDEENVYILLELCSNGSLMELLkrrkaltEPEV-- 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 ldwmfRYsLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfrSTAEPDDshalyaKKLWT------ 219
Cdd:cd14099   104 -----RY-FMRQILSGVKYLHsNRII--HRDLKLGNLFLDENMNVKIGDFGLA---ARLEYDG------ERKKTlcgtpn 166
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 220 --APELLSGNplptTGM-QKADVYSFGIILQEIALRSGPFylEGLDLspKEIVQKVRNGQrpYFRPSidRTQLNEELVLL 296
Cdd:cd14099   167 yiAPEVLEKK----KGHsFEVDIWSLGVILYTLLVGKPPF--ETSDV--KETYKRIKKNE--YSFPS--HLSISDEAKDL 234
                         250
                  ....*....|....*...
gi 1370514551 297 MERCWAQDPAERPDFGQI 314
Cdd:cd14099   235 IRSMLQPDPTKRPSLDEI 252
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
81-314 5.90e-13

Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer T-cell-originated protein kinase; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. TOPK, also called PDZ-binding kinase (PBK), is activated at the early stage of mitosis and plays a critical role in cytokinesis. It partly functions as a mitogen-activated protein kinase (MAPK) kinase and is capable of phosphorylating p38, JNK1, and ERK2. TOPK also plays a role in DNA damage sensing and repair through its phosphorylation of histone H2AX. It contributes to cancer development and progression by downregulating the function of tumor suppressor p53 and reducing cell-cycle regulatory proteins. TOPK is found highly expressed in breast and skin cancer cells. The TOPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270903 [Multi-domain]  Cd Length: 292  Bit Score: 69.74  E-value: 5.90e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  81 AIKHVNKK-----------RIELTRQVLFELKHMRDVQFNHLTRfigacIDPPNICIVTEYCPRgSLQDILEN------D 143
Cdd:cd14001    32 AVKKINSKcdkgqrslyqeRLKEEAKILKSLNHPNIVGFRAFTK-----SEDGSLCLAMEYGGK-SLNDLIEEryeaglG 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 144 SINLDWMFRYSLinDLVKGMAFLHNSIISSHGSLKSSNCVVDSRF-VLKITDYGLaSFRSTAE---PDDSHALY-AKKLW 218
Cdd:cd14001   106 PFPAATILKVAL--SIARALEYLHNEKKILHGDIKSGNVLIKGDFeSVKLCDFGV-SLPLTENlevDSDPKAQYvGTEPW 182
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 219 TAPELLSGNPLPTtgmQKADVYSFGIILQEIALRSGP--FYLEGLDLSPKEIVQKVRNGQRPYF-----RPSIDRTQLNE 291
Cdd:cd14001   183 KAKEALEEGGVIT---DKADIFAYGLVLWEMMTLSVPhlNLLDIEDDDEDESFDEDEEDEEAYYgtlgtRPALNLGELDD 259
                         250       260
                  ....*....|....*....|....*.
gi 1370514551 292 E---LVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14001   260 SyqkVIELFYACTQEDPKDRPSAAHI 285
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
71-309 8.53e-13

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk1 (or simply Aatyk) is also called lemur tyrosine kinase 1 (Lmtk1). It is a cytoplasmic (or nonreceptor) kinase containing a long C-terminal region. The expression of Aatyk1 is upregulated during growth arrest and apoptosis in myeloid cells. Aatyk1 has been implicated in neural differentiation, and is a regulator of the Na-K-2Cl cotransporter, a membrane protein involved in cell proliferation and survival, epithelial transport, and blood pressure control. The Aatyk1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 68.86  E-value: 8.53e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  71 NTGHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN----DSIN 146
Cdd:cd05087    19 NSGLSSTQVVVKELKASASVQDQMQFLEEAQPYRALQHTNLLQCLAQCAEVTPYLLVMEFCPLGDLKGYLRScraaESMA 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTaepDD----SHALYAKKLWTAP 221
Cdd:cd05087    99 PDPLTLQRMACEVACGLLHLHrNNFV--HSDLALRNCLLTADLTVKIGDYGLSHCKYK---EDyfvtADQLWVPLRWIAP 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 222 ELLS---GNPLPTTGMQKADVYSFGIILQEI-ALRSGPFylegLDLSPKEIVQ-KVRNGQRPYFRPSIdRTQLNEELVLL 296
Cdd:cd05087   174 ELVDevhGNLLVVDQTKQSNVWSLGVTIWELfELGNQPY----RHYSDRQVLTyTVREQQLKLPKPQL-KLSLAERWYEV 248
                         250
                  ....*....|...
gi 1370514551 297 MERCWAQdPAERP 309
Cdd:cd05087   249 MQFCWLQ-PEQRP 260
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
77-314 9.54e-13

Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Rad53 and Cds1 are the checkpoint kinase 2 (Chk2) homologs found in budding and fission yeast, respectively. They play a central role in the cell's response to DNA lesions to prevent genome rearrangements and maintain genome integrity. They are phosphorylated in response to DNA damage and incomplete replication, and are essential for checkpoint control. They help promote DNA repair by stalling the cell cycle prior to mitosis in the presence of DNA damage. The Rad53/Cds1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271000 [Multi-domain]  Cd Length: 265  Bit Score: 68.66  E-value: 9.54e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQ----VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQD-ILENDSINLDwmF 151
Cdd:cd14098    25 GKMRAIKQIVKRKVAGNDKnlqlFQREINILKSLEHPGIVRLIDWYEDDQHIYLVMEYVEGGDLMDfIMAWGAIPEQ--H 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLINDLVKGMAFLHNSIISsHGSLKSSNCVV--DSRFVLKITDYGLASFRSTAEPDDShaLYAKKLWTAPELLSGN-- 227
Cdd:cd14098   103 ARELTKQILEAMAYTHSMGIT-HRDLKPENILItqDDPVIVKISDFGLAKVIHTGTFLVT--FCGTMAYLAPEILMSKeq 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 228 PLPTTGMQKADVYSFGIILQEIALRSGPFyleglDLSPKE-IVQKVRNGQrpYFRPSIDRTQLNEELVLLMERCWAQDPA 306
Cdd:cd14098   180 NLQGGYSNLVDMWSVGCLVYVMLTGALPF-----DGSSQLpVEKRIRKGR--YTQPPLVDFNISEEAIDFILRLLDVDPE 252

                  ....*...
gi 1370514551 307 ERPDFGQI 314
Cdd:cd14098   253 KRMTAAQA 260
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
99-341 1.18e-12

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Many FGFR3 splice variants have been reported with the IIIb and IIIc isoforms being the predominant forms. FGFR3 IIIc is the isoform expressed in chondrocytes, the cells affected in dwarfism, while IIIb is expressed in epithelial cells. FGFR3 ligands include FGF1, FGF2, FGF4, FGF8, FGF9, and FGF23. It is a negative regulator of long bone growth. In the cochlear duct and in the lens, FGFR3 is involved in differentiation while it appears to have a role in cell proliferation in epithelial cells. Germline mutations in FGFR3 are associated with skeletal disorders including several forms of dwarfism. Some missense mutations are associated with multiple myeloma and carcinomas of the bladder and cervix. Overexpression of FGFR3 is found in thyroid carcinoma. FGFR3 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173652 [Multi-domain]  Cd Length: 334  Bit Score: 69.28  E-value: 1.18e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDV-QFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE-NDSINLDWMFRYSLI-------NDLV-------KG 162
Cdd:cd05100    67 EMEMMKMIgKHKNIINLLGACTQDGPLYVLVEYASKGNLREYLRaRRPPGMDYSFDTCKLpeeqltfKDLVscayqvaRG 146
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 163 MAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLASfrstaepdDSHAL-YAKKL--------WTAPELLsgnpLPTTG 233
Cdd:cd05100   147 MEYL-ASQKCIHRDLAARNVLVTEDNVMKIADFGLAR--------DVHNIdYYKKTtngrlpvkWMAPEAL----FDRVY 213
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 234 MQKADVYSFGIILQEIaLRSGPFYLEGLDLspKEIVQKVRNGQRpyfrpsIDR-TQLNEELVLLMERCWAQDPAERPDFG 312
Cdd:cd05100   214 THQSDVWSFGVLLWEI-FTLGGSPYPGIPV--EELFKLLKEGHR------MDKpANCTHELYMIMRECWHAVPSQRPTFK 284
                         250       260
                  ....*....|....*....|....*....
gi 1370514551 313 QIKGFIRRFNKEGGTSILDNLLLRMEQYA 341
Cdd:cd05100   285 QLVEDLDRVLTVTSTDEYLDLSVPFEQYS 313
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
77-314 1.48e-12

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii FA2 was discovered in a genetic screen for deflagellation-defective mutants. It is essential for basal-body/centriole-associated microtubule severing, and plays a role in cell cycle progression. No cellular function has yet been ascribed to CNK4. The Chlamydomonas reinhardtii FA2-like subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily contains FA2 and CNK4. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270868 [Multi-domain]  Cd Length: 256  Bit Score: 67.82  E-value: 1.48e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVN------KKRIELTRQ--VLFELKHmrdvqfNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEND----- 143
Cdd:cd08529    25 GRVYALKQIDisrmsrKMREEAIDEarVLSKLNS------PYVIKYYDSFVDKGKLNIVMEYAENGDLHSLIKSQrgrpl 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 144 SINLDWMFrysLINDLVkGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTaEPDDSHALYAKKLWTAPE 222
Cdd:cd08529    99 PEDQIWKF---FIQTLL-GLSHLHsKKIL--HRDIKSMNIFLDKGDNVKIGDLGVAKILSD-TTNFAQTIVGTPYYLSPE 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 223 LLSGNPLPttgmQKADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNGQrpyFRPSidRTQLNEELVLLMERCWA 302
Cdd:cd08529   172 LCEDKPYN----EKSDVWALGCVLYELCTGKHPFEAQ----NQGALILKIVRGK---YPPI--SASYSQDLSQLIDSCLT 238
                         250
                  ....*....|..
gi 1370514551 303 QDPAERPDFGQI 314
Cdd:cd08529   239 KDYRQRPDTTEL 250
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
95-314 1.49e-12

Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; Tie1; catalytic (c) domain. The PTKc family is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K). PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie1 is a receptor tyr kinase (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie receptors are specifically expressed in endothelial cells and hematopoietic stem cells. No specific ligand has been identified for Tie1, although the angiopoietin, Ang-1, binds to Tie1 through integrins at high concentrations. In vivo studies of Tie1 show that it is critical in vascular development.


Pssm-ID: 270671 [Multi-domain]  Cd Length: 297  Bit Score: 68.49  E-value: 1.49e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVqfnhlTRFIGACIDPPNICIVTEYCPRGSLQD------ILEND-----------SINLDWMFRYSliN 157
Cdd:cd05089    54 EVLCKLGHHPNI-----INLLGACENRGYLYIAIEYAPYGNLLDflrksrVLETDpafakehgtasTLTSQQLLQFA--S 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASfrstaepddSHALYAKKL-------WTAPELLSGNPLP 230
Cdd:cd05089   127 DVAKGMQYLSEKQFI-HRDLAARNVLVGENLVSKIADFGLSR---------GEEVYVKKTmgrlpvrWMAIESLNYSVYT 196
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 231 TtgmqKADVYSFGIILQEIALRSGPFYLeglDLSPKEIVQKVRNGqrpyFRPSIDRtQLNEELVLLMERCWAQDPAERPD 310
Cdd:cd05089   197 T----KSDVWSFGVLLWEIVSLGGTPYC---GMTCAELYEKLPQG----YRMEKPR-NCDDEVYELMRQCWRDRPYERPP 264

                  ....
gi 1370514551 311 FGQI 314
Cdd:cd05089   265 FSQI 268
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
57-314 1.56e-12

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK3, also called Prk or Fnk (FGF-inducible kinase), regulates angiogenesis and responses to DNA damage. Activated PLK3 mediates Chk2 phosphorylation by ATM and the resulting checkpoint activation. PLK3 phosphorylates DNA polymerase delta and may be involved in DNA repair. It also inhibits Cdc25c, thereby regulating the onset of mitosis. The PLK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271091 [Multi-domain]  Cd Length: 255  Bit Score: 67.64  E-value: 1.56e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  57 GSLMTAHGKYQIFANTGHFKGNVVAIKHVNKKRIELTRQ---VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPR 133
Cdd:cd14189     6 GRLLGKGGFARCYEMTDLATNKTYAVKVIPHSRVAKPHQrekIVNEIELHRDLHHKHVVKFSHHFEDAENIYIFLELCSR 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 134 GSLQDILENDSINLDWMFRYSLiNDLVKGMAFLHNSIIsSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEpDDSHALY 213
Cdd:cd14189    86 KSLAHIWKARHTLLEPEVRYYL-KQIISGLKYLHLKGI-LHRDLKLGNFFINENMELKVGDFGLAARLEPPE-QRKKTIC 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 214 AKKLWTAPELLsgnpLPTTGMQKADVYSFGIILQEIALRSGPFylEGLDLspKEIVQKVRngQRPYFRPSIDRTQLNEEL 293
Cdd:cd14189   163 GTPNYLAPEVL----LRQGHGPESDVWSLGCVMYTLLCGNPPF--ETLDL--KETYRCIK--QVKYTLPASLSLPARHLL 232
                         250       260
                  ....*....|....*....|.
gi 1370514551 294 VLLMERcwaqDPAERPDFGQI 314
Cdd:cd14189   233 AGILKR----NPGDRLTLDQI 249
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
79-308 1.80e-12

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkA is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkA to its ligand, nerve growth factor (NGF), results in receptor oligomerization and activation of the catalytic domain. TrkA is expressed mainly in neural-crest-derived sensory and sympathetic neurons of the peripheral nervous system, and in basal forebrain cholinergic neurons of the central nervous system. It is critical for neuronal growth, differentiation and survival. Alternative TrkA splicing has been implicated as a pivotal regulator of neuroblastoma (NB) behavior. Normal TrkA expression is associated with better NB prognosis, while the hypoxia-regulated TrkAIII splice variant promotes NB pathogenesis and progression. Aberrant TrkA expression has also been demonstrated in non-neural tumors including prostate, breast, lung, and pancreatic cancers. The TrkA subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270674 [Multi-domain]  Cd Length: 280  Bit Score: 68.07  E-value: 1.80e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  79 VVAIKHVnKKRIELTRQVL-FELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQ----------DILENDS--- 144
Cdd:cd05092    37 LVAVKAL-KEATESARQDFqREAELLTVLQHQHIVRFYGVCTEGEPLIMVFEYMRHGDLNrflrshgpdaKILDGGEgqa 115
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 145 ---INLDWMFRysLINDLVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLA-SFRSTaepdDSHALYAKKL--- 217
Cdd:cd05092   116 pgqLTLGQMLQ--IASQIASGMVYL-ASLHFVHRDLATRNCLVGQGLVVKIGDFGMSrDIYST----DYYRVGGRTMlpi 188
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 218 -WTAPELLSGNPLPTtgmqKADVYSFGIILQEI-ALRSGPFYleglDLSPKEIVQKVRNG---QRPYFRPSidrtqlneE 292
Cdd:cd05092   189 rWMPPESILYRKFTT----ESDIWSFGVVLWEIfTYGKQPWY----QLSNTEAIECITQGrelERPRTCPP--------E 252
                         250
                  ....*....|....*.
gi 1370514551 293 LVLLMERCWAQDPAER 308
Cdd:cd05092   253 VYAIMQGCWQREPQQR 268
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
99-314 1.89e-12

Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Chlamydomonas reinhardtii CNK2 has both cilliary and cell cycle functions. It influences flagellar length through promoting flagellar disassembly, and it regulates cell size, through influencing the size threshold at which cells commit to mitosis. This subfamily belongs to the (NIMA)-related kinase (Nek) family, which includes seven different Chlamydomonas Neks (CNKs 1-6 and Fa2). This subfamily includes CNK1, and -2. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270869 [Multi-domain]  Cd Length: 256  Bit Score: 67.42  E-value: 1.89e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDS-----INLDWMFRYSLinDLVKGMAFLHNSIIsS 173
Cdd:cd08530    49 EIRLLASVNHPNIIRYKEAFLDGNRLCIVMEYAPFGDLSKLISKRKkkrrlFPEDDIWRIFI--QMLRGLKALHDQKI-L 125
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 174 HGSLKSSNCVVDSRFVLKITDYGLASF--RSTAEPDDSHALYAkklwtAPELLSGNPLPttgmQKADVYSFGIILQEIAL 251
Cdd:cd08530   126 HRDLKSANILLSAGDLVKIGDLGISKVlkKNLAKTQIGTPLYA-----APEVWKGRPYD----YKSDIWSLGCLLYEMAT 196
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 252 RSGPFylEGLDLSpkEIVQKVRNGQRPYFRPSidrtqLNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd08530   197 FRPPF--EARTMQ--ELRYKVCRGKFPPIPPV-----YSQDLQQIIRSLLQVNPKKRPSCDKL 250
STKc_Trio_C cd14113
C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide ...
79-309 2.01e-12

C-terminal kinase domain of the Large Serine/Threonine Kinase and Rho Guanine Nucleotide Exchange Factor, Triple functional domain protein; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Triple functional domain protein (Trio), also called PTPRF-interacting protein, is a large multidomain protein containing a series of spectrin-like repeats, two each of RhoGEF and SH3 domains, an immunoglobulin-like (Ig) domain and a C-terminal kinase. Trio plays important roles in neuronal cell migration and axon guidance. It was originally identified as an interacting partner of the of the receptor-like tyrosine phosphatase (RPTP) LAR (leukocyte-antigen-related protein), a family of receptors that function in the signaling to the actin cytoskeleton during development. Trio functions as a GEF for Rac1, RhoG, and RhoA, and is involved in the regulation of lamellipodia formation, mediating Rac1-dependent cell spreading and migration. The Trio subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271015 [Multi-domain]  Cd Length: 263  Bit Score: 67.69  E-value: 2.01e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  79 VVAIKHVNKKRIElTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLqdilendsinLDWMFRY----- 153
Cdd:cd14113    34 AVATKFVNKKLMK-RDQVTHELGVLQSLQHPQLVGLLDTFETPTSYILVLEMADQGRL----------LDYVVRWgnlte 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 154 ----SLINDLVKGMAFLHNSIISsHGSLKSSNCVVD---SRFVLKITDYGLASFRSTAEPddSHALYAKKLWTAPELLSG 226
Cdd:cd14113   103 ekirFYLREILEALQYLHNCRIA-HLDLKPENILVDqslSKPTIKLADFGDAVQLNTTYY--IHQLLGSPEFAAPEIILG 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 227 NPLPTTgmqkADVYSFGIILQEIALRSGPFYLEGLDLSPKEIVQKVRNGQRPYFRPSidrTQLNEELVLLMERcwaQDPA 306
Cdd:cd14113   180 NPVSLT----SDLWSIGVLTYVLLSGVSPFLDESVEETCLNICRLDFSFPDDYFKGV---SQKAKDFVCFLLQ---MDPA 249

                  ...
gi 1370514551 307 ERP 309
Cdd:cd14113   250 KRP 252
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
99-314 3.91e-12

Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. There are many splice variants of FGFR2 which show differential expression and binding to FGF ligands. Disruption of either FGFR2 or FGFR2b is lethal in mice, due to defects in the placenta or severe impairment of tissue development including lung, limb, and thyroid, respectively. Disruption of FGFR2c in mice results in defective bone and skull development. Genetic alterations of FGFR2 are associated with many human skeletal disorders including Apert syndrome, Crouzon syndrome, Jackson-Weiss syndrome, and Pfeiffer syndrome. FGFR2 is part of the FGFR subfamily, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with three immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of FGFRs to their ligands, the FGFs, results in receptor dimerization and activation, and intracellular signaling. The binding of FGFs to FGFRs is promiscuous, in that a receptor may be activated by several ligands and a ligand may bind to more that one type of receptor. The FGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270679 [Multi-domain]  Cd Length: 313  Bit Score: 67.35  E-value: 3.91e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDV-QFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE-NDSINLDWMFRYSLIND--------------LVKG 162
Cdd:cd05101    79 EMEMMKMIgKHKNIINLLGACTQDGPLYVIVEYASKGNLREYLRaRRPPGMEYSYDINRVPEeqmtfkdlvsctyqLARG 158
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 163 MAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLASfrstaepDDSHALYAKKL--------WTAPELLsgnpLPTTGM 234
Cdd:cd05101   159 MEYL-ASQKCIHRDLAARNVLVTENNVMKIADFGLAR-------DINNIDYYKKTtngrlpvkWMAPEAL----FDRVYT 226
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 235 QKADVYSFGIILQEIALRSGPFYlEGLDLspKEIVQKVRNGQRpyfrpsIDR-TQLNEELVLLMERCWAQDPAERPDFGQ 313
Cdd:cd05101   227 HQSDVWSFGVLMWEIFTLGGSPY-PGIPV--EELFKLLKEGHR------MDKpANCTNELYMMMRDCWHAVPSQRPTFKQ 297

                  .
gi 1370514551 314 I 314
Cdd:cd05101   298 L 298
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
74-314 4.42e-12

Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of fungal Wee1 proteins, also called Swe1 in budding yeast and Mik1 in fission yeast. Yeast Wee1 is required to control cell size. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The fungal Wee1 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270954 [Multi-domain]  Cd Length: 278  Bit Score: 66.68  E-value: 4.42e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  74 HFKGNVVAIKHVNKKRIELT---RQvLFELKHMRDVQFN---HLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSI-- 145
Cdd:cd14052    23 VPTGKVYAVKKLKPNYAGAKdrlRR-LEEVSILRELTLDghdNIVQLIDSWEYHGHLYIQTELCENGSLDVFLSELGLlg 101
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 146 NLDWMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfrsTAEPDDSH-ALYAKKLWTAPELL 224
Cdd:cd14052   102 RLDEFRVWKILVELSLGLRFIHDHHFV-HLDLKPANVLITFEGTLKIGDFGMA----TVWPLIRGiEREGDREYIAPEIL 176
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 225 SGNPLPttgmQKADVYSFGIILQEIA--------------LRSGpfyleglDLSPKEIVQKVRNGQRPYFRPSIDRTQLN 290
Cdd:cd14052   177 SEHMYD----KPADIFSLGLILLEAAanvvlpdngdawqkLRSG-------DLSDAPRLSSTDLHSASSPSSNPPPDPPN 245
                         250       260
                  ....*....|....*....|....*....
gi 1370514551 291 -----EELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14052   246 mpilsGSLDRVVRWMLSPEPDRRPTADDV 274
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
77-336 4.53e-12

Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Nak1, Saccharomyces cerevisiae Kic1p (kinase that interacts with Cdc31p) and related proteins. Nak1 (also called N-rich kinase 1), is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Kic1p is required by budding yeast for cell integrity and morphogenesis. Kic1p interacts with Cdc31p, the yeast homologue of centrin, and phosphorylates substrates in a Cdc31p-dependent manner. The Nak1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270822 [Multi-domain]  Cd Length: 277  Bit Score: 66.73  E-value: 4.53e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVN-----KKRIELTRQVLFeLKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSInlDWMF 151
Cdd:cd06917    26 GRVVALKVLNldtddDDVSDIQKEVAL-LSQLKLGQPKNIIKYYGSYLKGPSLWIIMDYCEGGSIRTLMRAGPI--AERY 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGL-ASFRSTAEPDDSHAlyAKKLWTAPELLsgnpl 229
Cdd:cd06917   103 IAVIMREVLVALKFIHkDGII--HRDIKAANILVTNTGNVKLCDFGVaASLNQNSSKRSTFV--GTPYWMAPEVI----- 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 230 pTTGM---QKADVYSFGIILQEIALRSGPFylegLDLSPKEIVQKVRNGQRPYFRPSIDRTQLNEELVLlmerCWAQDPA 306
Cdd:cd06917   174 -TEGKyydTKADIWSLGITTYEMATGNPPY----SDVDALRAVMLIPKSKPPRLEGNGYSPLLKEFVAA----CLDEEPK 244
                         250       260       270
                  ....*....|....*....|....*....|..
gi 1370514551 307 ERPDFGQI--KGFIRRFNKEgGTSILDNLLLR 336
Cdd:cd06917   245 DRLSADELlkSKWIKQHSKT-PTSVLKELISR 275
STKc_ACVR2b cd14140
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the ...
106-323 4.66e-12

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIB Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2b (or ActRIIB) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271042 [Multi-domain]  Cd Length: 291  Bit Score: 66.98  E-value: 4.66e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 106 VQFNHLTRFIGACIDPPNI----CIVTEYCPRGSLQDILENDSINldWMFRYSLINDLVKGMAFLHNSIISS-------- 173
Cdd:cd14140    46 MKHENLLQFIAAEKRGSNLemelWLITAFHDKGSLTDYLKGNIVS--WNELCHIAETMARGLSYLHEDVPRCkgeghkpa 123
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 174 --HGSLKSSNCVVDSRFVLKITDYGLA-SFRSTAEPDDSHALYAKKLWTAPELLSGN-PLPTTGMQKADVYSFGIILQEI 249
Cdd:cd14140   124 iaHRDFKSKNVLLKNDLTAVLADFGLAvRFEPGKPPGDTHGQVGTRRYMAPEVLEGAiNFQRDSFLRIDMYAMGLVLWEL 203
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 250 ALR----SGPF--YL----EGLDLSPK-EIVQK--VRNGQRPYFRPSIDRTQLNEELVLLMERCWAQDPAERPDFGQIKG 316
Cdd:cd14140   204 VSRckaaDGPVdeYMlpfeEEIGQHPSlEDLQEvvVHKKMRPVFKDHWLKHPGLAQLCVTIEECWDHDAEARLSAGCVEE 283

                  ....*..
gi 1370514551 317 FIRRFNK 323
Cdd:cd14140   284 RISQIRR 290
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
80-324 5.09e-12

Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER4 (ErbB4) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. Ligands that bind HER4 fall into two groups, the neuregulins (or heregulins) and some EGFR (HER1) ligands including betacellulin, HBEGF, and epiregulin. All four neuregulins (NRG1-4) interact with HER4. Upon ligand binding, HER4 forms homo- or heterodimers with other HER proteins. HER4 is essential in embryonic development. It is implicated in mammary gland, cardiac, and neural development. As a postsynaptic receptor of NRG1, HER4 plays an important role in synaptic plasticity and maturation. The impairment of NRG1/HER4 signaling may contribute to schizophrenia. The HER4 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173655 [Multi-domain]  Cd Length: 303  Bit Score: 67.01  E-value: 5.09e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVN-----KKRIELTRQVLFelkhMRDVQFNHLTRFIGACIDPpNICIVTEYCPRGSLQDILENDSINLDWMFRYS 154
Cdd:cd05110    39 VAIKILNettgpKANVEFMDEALI----MASMDHPHLVRLLGVCLSP-TIQLVTQLMPHGCLLDYVHEHKDNIGSQLLLN 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPD---DSHALYAKklWTAPELLSGNPLpt 231
Cdd:cd05110   114 WCVQIAKGMMYLEERRLV-HRDLAARNVLVKSPNHVKITDFGLARLLEGDEKEynaDGGKMPIK--WMALECIHYRKF-- 188
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 232 tgMQKADVYSFGIILQEIALRSGPFYlEGLdlSPKEIVQKVRNGQR-PyfRPSIdrtqLNEELVLLMERCWAQDPAERPD 310
Cdd:cd05110   189 --THQSDVWSYGVTIWELMTFGGKPY-DGI--PTREIPDLLEKGERlP--QPPI----CTIDVYMVMVKCWMIDADSRPK 257
                         250
                  ....*....|....
gi 1370514551 311 FGQIKGFIRRFNKE 324
Cdd:cd05110   258 FKELAAEFSRMARD 271
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
96-314 5.39e-12

Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of the subfamily include SLK, STK10 (also called LOK for Lymphocyte-Oriented Kinase), SmSLK (Schistosoma mansoni SLK), and related proteins. SLK promotes apoptosis through apoptosis signal-regulating kinase 1 (ASK1) and the mitogen-activated protein kinase (MAPK) p38. It also plays a role in mediating actin reorganization. STK10 is responsible in regulating the CD28 responsive element in T cells, as well as leukocyte function associated antigen (LFA-1)-mediated lymphocyte adhesion. SmSLK is capable of activating the MAPK Jun N-terminal kinase (JNK) pathway in human embryonic kidney cells as well as in Xenopus oocytes. It may participate in regulating MAPK cascades during host-parasite interactions. The SLK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132942 [Multi-domain]  Cd Length: 280  Bit Score: 66.69  E-value: 5.39e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  96 VLFELKHmrdvqfNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLH-NSIIssH 174
Cdd:cd06611    55 ILSECKH------PNIVGLYEAYFYENKLWILIEFCDGGALDSIMLELERGLTEPQIRYVCRQMLEALNFLHsHKVI--H 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 175 GSLKSSNCVVDSRFVLKITDYGLaSFRSTAEPDDSHALYAKKLWTAPELL-----SGNPLPTtgmqKADVYSFGIILQEI 249
Cdd:cd06611   127 RDLKAGNILLTLDGDVKLADFGV-SAKNKSTLQKRDTFIGTPYWMAPEVVacetfKDNPYDY----KADIWSLGITLIEL 201
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370514551 250 ALRSGPFYleglDLSPKEIVQKVRNGQRPYF-RPSIDRTQLNEelvlLMERCWAQDPAERPDFGQI 314
Cdd:cd06611   202 AQMEPPHH----ELNPMRVLLKILKSEPPTLdQPSKWSSSFND----FLKSCLVKDPDDRPTAAEL 259
STKc_Nek6 cd08228
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
73-324 6.10e-12

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 is required for the transition from metaphase to anaphase. It also plays important roles in mitotic spindle formation and cytokinesis. Activated by Nek9 during mitosis, Nek6 phosphorylates Eg5, a kinesin that is important for spindle bipolarity. Nek6 localizes to spindle microtubules during metaphase and anaphase, and to the midbody during cytokinesis. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270865 [Multi-domain]  Cd Length: 268  Bit Score: 66.20  E-value: 6.10e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKHVNKKRIELTRQVLFEL---KHMRDV--------QFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDI 139
Cdd:cd08228    13 GQFSEVYRATCLLDRKPVALKKVQIFEMmdaKARQDCvkeidllkQLNHpnVIKYLDSFIEDNELNIVLELADAGDLSQM 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 140 L-----ENDSINLDWMFRYSLinDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTaEPDDSHALYA 214
Cdd:cd08228    93 IkyfkkQKRLIPERTVWKYFV--QLCSAVEHMHSRRVM-HRDIKPANVFITATGVVKLGDLGLGRFFSS-KTTAAHSLVG 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 215 KKLWTAPELLSGNplpttGMQ-KADVYSFGIILQEIALRSGPFYLEGLDLSpkEIVQKVRngQRPYfrPSIDRTQLNEEL 293
Cdd:cd08228   169 TPYYMSPERIHEN-----GYNfKSDIWSLGCLLYEMAALQSPFYGDKMNLF--SLCQKIE--QCDY--PPLPTEHYSEKL 237
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1370514551 294 VLLMERCWAQDPAERPDFgqikGFIRRFNKE 324
Cdd:cd08228   238 RELVSMCIYPDPDQRPDI----GYVHQIAKQ 264
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
56-311 1.02e-11

Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The TAM subfamily consists of Tyro3 (or Sky), Axl, Mer (or Mertk), and similar proteins. TAM subfamily members are receptor tyr kinases (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. TAM proteins are implicated in a variety of cellular effects including survival, proliferation, migration, and phagocytosis. They are also associated with several types of cancer as well as inflammatory, autoimmune, vascular, and kidney diseases. The TAM subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270631 [Multi-domain]  Cd Length: 273  Bit Score: 65.63  E-value: 1.02e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  56 YGSLMTAhgkyQIFANTGHF-KGNVVAIKHVNKKRIELtRQVLFELKHMRDVQFNHLTRFIGACID------PPNICIVT 128
Cdd:cd05035    12 FGSVMEA----QLKQDDGSQlKVAVKTMKVDIHTYSEI-EEFLSEAACMKDFDHPNVMRLIGVCFTasdlnkPPSPMVIL 86
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 129 EYCPRGSLQDIL-----ENDSINLDWMFRYSLINDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRS 202
Cdd:cd05035    87 PFMKHGDLHSYLlysrlGGLPEKLPLQTLLKFMVDIAKGMEYLSNrNFI--HRDLAARNCMLDENMTVCVADFGLS--RK 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 203 TAEPDDSHALYAKKL---WTAPELLSGNPLPTtgmqKADVYSFGIILQEIALRSGPFYlEGLDLSpkEIVQKVRNGQRpY 279
Cdd:cd05035   163 IYSGDYYRQGRISKMpvkWIALESLADNVYTS----KSDVWSFGVTMWEIATRGQTPY-PGVENH--EIYDYLRNGNR-L 234
                         250       260       270
                  ....*....|....*....|....*....|..
gi 1370514551 280 FRPSidrtQLNEELVLLMERCWAQDPAERPDF 311
Cdd:cd05035   235 KQPE----DCLDEVYFLMYFCWTVDPKDRPTF 262
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
78-309 1.05e-11

Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNKs comprise a subfamily of STKs with an unusual placement of a catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. They are also involved in cell signaling, survival, proliferation, and organ development. WNKs are activated by hyperosmotic or low-chloride hypotonic stress and they function upstream of SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. There are four vertebrate WNKs which show varying expression patterns. WNK1 and WNK2 are widely expressed while WNK3 and WNK4 show a more restricted expression pattern. Because mutations in human WNK1 and WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension (due to increased sodium reabsorption) and hyperkalemia (due to impaired renal potassium secretion), there are more studies conducted on these two proteins, compared to WNK2 and WNK3. The WNK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 65.32  E-value: 1.05e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  78 NVVAIKHVNKKRIELTRQvlfELKHMRDVQFNHLTRFIGACIDPPNICIV--TEYCPRGSLQDILeNDSINLDWMFRYSL 155
Cdd:cd13983    32 NEIKLRKLPKAERQRFKQ---EIEILKSLKHPNIIKFYDSWESKSKKEVIfiTELMTSGTLKQYL-KRFKRLKLKVIKSW 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 INDLVKGMAFLHN---SIIssHGSLKSSNCVVD-SRFVLKITDYGLASFRSTAEPddsHALYAKKLWTAPELLSGNPLPt 231
Cdd:cd13983   108 CRQILEGLNYLHTrdpPII--HRDLKCDNIFINgNTGEVKIGDLGLATLLRQSFA---KSVIGTPEFMAPEMYEEHYDE- 181
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 232 tgmqKADVYSFGIILQEIALRSGPfYLEGldLSPKEIVQKVRNGQRPyfrPSIDRTQlNEELVLLMERCWAQdPAERP 309
Cdd:cd13983   182 ----KVDIYAFGMCLLEMATGEYP-YSEC--TNAAQIYKKVTSGIKP---ESLSKVK-DPELKDFIEKCLKP-PDERP 247
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
94-314 1.43e-11

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The VEGFR subfamily consists of VEGFR1 (Flt1), VEGFR2 (Flk1), VEGFR3 (Flt4), and similar proteins. VEGFR subfamily members are receptor PTKss (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. There are five VEGF ligands in mammals, which bind, in an overlapping pattern to the three VEGFRs, which can form homo or heterodimers. VEGFRs regulate the cardiovascular system. They are critical for vascular development during embryogenesis and blood vessel formation in adults. They induce cellular functions common to other growth factor receptors such as cell migration, survival, and proliferation. The VEGFR subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270647 [Multi-domain]  Cd Length: 298  Bit Score: 65.59  E-value: 1.43e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  94 RQVLFELKHMRDVQfNHLT--RFIGACIDP--PNICIVtEYCPRGSLQDIL------------------ENDSINLDWMF 151
Cdd:cd05054    55 KALMTELKILIHIG-HHLNvvNLLGACTKPggPLMVIV-EFCKFGNLSNYLrskreefvpyrdkgardvEEEEDDDELYK 132
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLINDLV-------KGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAsfRST-AEPDdshalYAKK------- 216
Cdd:cd05054   133 EPLTLEDLIcysfqvaRGMEFL-ASRKCIHRDLAARNILLSENNVVKICDFGLA--RDIyKDPD-----YVRKgdarlpl 204
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 217 LWTAPELLSGNPLPTtgmqKADVYSFGIILQEI-ALRSGPFylEGLDLSpKEIVQKVRNGQR----PYFRPSIDRTQLNe 291
Cdd:cd05054   205 KWMAPESIFDKVYTT----QSDVWSFGVLLWEIfSLGASPY--PGVQMD-EEFCRRLKEGTRmrapEYTTPEIYQIMLD- 276
                         250       260
                  ....*....|....*....|...
gi 1370514551 292 elvllmerCWAQDPAERPDFGQI 314
Cdd:cd05054   277 --------CWHGEPKERPTFSEL 291
STKc_ACVR2a cd14141
Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the ...
91-308 1.43e-11

Catalytic domain of the Serine/Threonine Kinase, Activin Type IIA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ACVR2a (or ActRIIA) belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins (BMPs), activins, growth and differentiation factors (GDFs), and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. ACVR2b is one of two ACVR2 receptors found in vertebrates. Type II receptors are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. ACVR2 acts primarily as the receptors for activins, nodal, myostatin, GDF11, and a subset of BMPs. ACVR2 signaling impacts many cellular and physiological processes including reproductive and gonadal functions, myogenesis, bone remodeling and tooth development, kidney organogenesis, apoptosis, fibrosis, inflammation, and neurogenesis. The ACVR2a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271043 [Multi-domain]  Cd Length: 290  Bit Score: 65.45  E-value: 1.43e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  91 ELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICI----VTEYCPRGSLQDILENDSINldWMFRYSLINDLVKGMAFL 166
Cdd:cd14141    31 KLSWQNEYEIYSLPGMKHENILQFIGAEKRGTNLDVdlwlITAFHEKGSLTDYLKANVVS--WNELCHIAQTMARGLAYL 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 167 HNSIIS---------SHGSLKSSNCVVDSRFVLKITDYGLA-SFRSTAEPDDSHALYAKKLWTAPELLSGN-PLPTTGMQ 235
Cdd:cd14141   109 HEDIPGlkdghkpaiAHRDIKSKNVLLKNNLTACIADFGLAlKFEAGKSAGDTHGQVGTRRYMAPEVLEGAiNFQRDAFL 188
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 236 KADVYSFGIILQEIALR----SGPF------YLEGLDLSP-----KEIVqkVRNGQRPYFRPSIDRTQLNEELVLLMERC 300
Cdd:cd14141   189 RIDMYAMGLVLWELASRctasDGPVdeymlpFEEEVGQHPsledmQEVV--VHKKKRPVLRECWQKHAGMAMLCETIEEC 266

                  ....*...
gi 1370514551 301 WAQDPAER 308
Cdd:cd14141   267 WDHDAEAR 274
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
80-319 1.47e-11

Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. IGF-1R is a receptor PTK (RTK) that is composed of two alphabeta heterodimers. Binding of the ligand (IGF-1 or IGF-2) to the extracellular alpha subunit activates the intracellular tyr kinase domain of the transmembrane beta subunit. Receptor activation leads to autophosphorylation, which stimulates downstream kinase activities and biological function. IGF-1R signaling is important in the differentiation, growth, and survival of normal cells. In cancer cells, where it is frequently overexpressed, IGF-1R is implicated in proliferation, the suppression of apoptosis, invasion, and metastasis. IGF-1R is being developed as a therapeutic target in cancer treatment. The IGF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133193 [Multi-domain]  Cd Length: 277  Bit Score: 65.44  E-value: 1.47e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVN-----KKRIELtrqvLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-------ENDSI-- 145
Cdd:cd05062    39 VAIKTVNeaasmRERIEF----LNEASVMKEFNCHHVVRLLGVVSQGQPTLVIMELMTRGDLKSYLrslrpemENNPVqa 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 146 --NLDWMFRysLINDLVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDdshalYAKK------- 216
Cdd:cd05062   115 ppSLKKMIQ--MAGEIADGMAYL-NANKFVHRDLAARNCMVAEDFTVKIGDFGMT--RDIYETD-----YYRKggkgllp 184
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 217 -LWTAPELLSGNPLPTtgmqKADVYSFGIILQEIA-LRSGPFYleglDLSPKEIVQKVRNG---QRPYFRPSIdrtqlne 291
Cdd:cd05062   185 vRWMSPESLKDGVFTT----YSDVWSFGVVLWEIAtLAEQPYQ----GMSNEQVLRFVMEGgllDKPDNCPDM------- 249
                         250       260
                  ....*....|....*....|....*...
gi 1370514551 292 eLVLLMERCWAQDPAERPDFGQIKGFIR 319
Cdd:cd05062   250 -LFELMRMCWQYNPKMRPSFLEIISSIK 276
STKc_PLK2 cd14188
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the ...
88-314 1.51e-11

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PLKs play important roles in cell cycle progression and in DNA damage responses. They regulate mitotic entry, mitotic exit, and cytokinesis. In general PLKs contain an N-terminal catalytic kinase domain and a C-terminal regulatory polo box domain (PBD), which is comprised by two bipartite polo-box motifs (or polo boxes) and is involved in protein interactions. There are five mammalian PLKs (PLK1-5) from distinct genes. PLK2, also called Snk (serum-inducible kinase), functions in G1 progression, S-phase arrest, and centriole duplication. Its gene is responsive to both growth factors and cellular stress, is a transcriptional target of p53, and activates a G2-M checkpoint. The PLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271090 [Multi-domain]  Cd Length: 255  Bit Score: 65.03  E-value: 1.51e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  88 KRIELTRQvlfeLKHMRDVQFNHLTRfigaciDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLiNDLVKGMAFLH 167
Cdd:cd14188    50 KEIELHRI----LHHKHVVQFYHYFE------DKENIYILLEYCSRRSMAHILKARKVLTEPEVRYYL-RQIVSGLKYLH 118
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 168 NSIIsSHGSLKSSNCVVDSRFVLKITDYGLAsfrSTAEPDDSHalyAKKLWTAPELLSGNPLPTTGMQ-KADVYSFGIIL 246
Cdd:cd14188   119 EQEI-LHRDLKLGNFFINENMELKVGDFGLA---ARLEPLEHR---RRTICGTPNYLSPEVLNKQGHGcESDIWALGCVM 191
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 247 QEIALRSGPFYLEGLdlspKEIVQKVRNGQrpYFRPSIDRTQLNEelvlLMERCWAQDPAERPDFGQI 314
Cdd:cd14188   192 YTMLLGRPPFETTNL----KETYRCIREAR--YSLPSSLLAPAKH----LIASMLSKNPEDRPSLDEI 249
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
79-323 1.60e-11

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkC is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkC to its ligand, neurotrophin 3 (NT3), results in receptor oligomerization and activation of the catalytic domain. TrkC is broadly expressed in the nervous system and in some non-neural tissues including the developing heart. NT3/TrkC signaling plays an important role in the innervation of the cardiac conducting system and the development of smooth muscle cells. Mice deficient with NT3 and TrkC have multiple heart defects. NT3/TrkC signaling is also critical for the development and maintenance of enteric neurons that are important for the control of gut peristalsis. The TrkC subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270676 [Multi-domain]  Cd Length: 287  Bit Score: 65.42  E-value: 1.60e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  79 VVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE----------------- 141
Cdd:cd05094    37 LVAVKTLKDPTLAARKDFQREAELLTNLQHDHIVKFYGVCGDGDPLIMVFEYMKHGDLNKFLRahgpdamilvdgqprqa 116
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 142 NDSINLDWMFRysLINDLVKGMAFLHNSIIsSHGSLKSSNCVVDSRFVLKITDYGLAS--FRSTAEPDDSHALYAKKlWT 219
Cdd:cd05094   117 KGELGLSQMLH--IATQIASGMVYLASQHF-VHRDLATRNCLVGANLLVKIGDFGMSRdvYSTDYYRVGGHTMLPIR-WM 192
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 220 APELLSGNPLPTtgmqKADVYSFGIILQEI-ALRSGPFYleglDLSPKEIVQKVRNGqRPYFRPSIdrtqLNEELVLLME 298
Cdd:cd05094   193 PPESIMYRKFTT----ESDVWSFGVILWEIfTYGKQPWF----QLSNTEVIECITQG-RVLERPRV----CPKEVYDIML 259
                         250       260
                  ....*....|....*....|....*
gi 1370514551 299 RCWAQDPAERPDFGQIKGFIRRFNK 323
Cdd:cd05094   260 GCWQREPQQRLNIKEIYKILHALGK 284
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
92-321 1.76e-11

Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Syk is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Syk was first cloned from the spleen, and its function in hematopoietic cells is well-established. It is involved in the signaling downstream of activated receptors (including B-cell and Fc receptors) that contain ITAMs (immunoreceptor tyr activation motifs), leading to processes such as cell proliferation, differentiation, survival, adhesion, migration, and phagocytosis. More recently, Syk expression has been detected in other cell types (including epithelial cells, vascular endothelial cells, neurons, hepatocytes, and melanocytes), suggesting a variety of biological functions in non-immune cells. Syk plays a critical role in maintaining vascular integrity and in wound healing during embryogenesis. It also regulates Vav3, which is important in osteoclast function including bone development. In breast epithelial cells, where Syk acts as a negative regulator for EGFR signaling, loss of Syk expression is associated with abnormal proliferation during cancer development suggesting a potential role as a tumor suppressor. In mice, Syk has been shown to inhibit malignant transformation of mammary epithelial cells induced with murine mammary tumor virus (MMTV). The Syk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133247 [Multi-domain]  Cd Length: 257  Bit Score: 64.60  E-value: 1.76e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  92 LTRQVLFELKHMRDVQFNHLTRFIGACiDPPNICIVTEYCPRGSLQDILENDSiNLDWMFRYSLINDLVKGMAFL--HNS 169
Cdd:cd05116    39 LKDELLREANVMQQLDNPYIVRMIGIC-EAESWMLVMEMAELGPLNKFLQKNR-HVTEKNITELVHQVSMGMKYLeeSNF 116
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 170 IissHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE---PDDSHALYAKKlWTAPELLSGNPLPTtgmqKADVYSFGIIL 246
Cdd:cd05116   117 V---HRDLAARNVLLVTQHYAKISDFGLSKALRADEnyyKAQTHGKWPVK-WYAPECMNYYKFSS----KSDVWSFGVLM 188
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370514551 247 QEiALRSG--PFylegLDLSPKEIVQKVRNGQRPYFRPSIDRtqlneELVLLMERCWAQDPAERPDFGQIKGFIRRF 321
Cdd:cd05116   189 WE-AFSYGqkPY----KGMKGNEVTQMIEKGERMECPAGCPP-----EMYDLMKLCWTYDVDERPGFAAVELRLRNY 255
PK_IRAK3 cd14160
Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain ...
94-249 1.88e-11

Pseudokinase domain of Interleukin-1 Receptor Associated Kinase 3; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain (a pseudokinase in the case of IRAK3), and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK3 (or IRAK-M) is the only IRAK that does not show kinase activity. It is found only in monocytes and macrophages in humans, and functions as a negative regulator of TLR signaling including TLR-2 induced p38 activation. It also negatively regulates the alternative NFkB pathway in a TLR-2 specific manner. IRAK3 is downregulated in the monocytes of obese people, and is associated with high SOD2, a marker of mitochondrial oxidative stress. It is an important inhibitor of inflammation in association with obesity and metabolic syndrome. The IRAK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271062 [Multi-domain]  Cd Length: 276  Bit Score: 64.91  E-value: 1.88e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  94 RQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE--NDSINLDWMFRYSLINDLVKGMAFLHNS-- 169
Cdd:cd14160    37 KRFLSELEVLLLFQHPNILELAAYFTETEKFCLVYPYMQNGTLFDRLQchGVTKPLSWHERINILIGIAKAIHYLHNSqp 116
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 170 --IISshGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDS----HALYAKKLWTAP-ELLSGNPLPTtgmqKADVYSF 242
Cdd:cd14160   117 ctVIC--GNISSANILLDDQMQPKLTDFALAHFRPHLEDQSCtinmTTALHKHLWYMPeEYIRQGKLSV----KTDVYSF 190

                  ....*..
gi 1370514551 243 GIILQEI 249
Cdd:cd14160   191 GIVIMEV 197
STKc_Nek11 cd08222
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
95-314 2.19e-11

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 11; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek11 is involved, through direct phosphorylation, in regulating the degradation of Cdc25A (Cell Division Cycle 25 homolog A), which plays a role in cell cycle progression and in activating cyclin dependent kinases. Nek11 is activated by CHK1 (CHeckpoint Kinase 1) and may be involved in the G2/M checkpoint. Nek11 may also play a role in the S-phase checkpoint as well as in DNA replication and genotoxic stress responses. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270861 [Multi-domain]  Cd Length: 260  Bit Score: 64.37  E-value: 2.19e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHmrdvqfNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE---------NDSINLDWMFRyslindLVKGMAF 165
Cdd:cd08222    54 KLLSKLDH------PAIVKFHDSFVEKESFCIVTEYCEGGDLDDKISeykksgttiDENQILDWFIQ------LLLAVQY 121
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 166 LHNSIIsSHGSLKSSNcVVDSRFVLKITDYGLASFRStAEPDDSHALYAKKLWTAPELLSGNPLPTtgmqKADVYSFGII 245
Cdd:cd08222   122 MHERRI-LHRDLKAKN-IFLKNNVIKVGDFGISRILM-GTSDLATTFTGTPYYMSPEVLKHEGYNS----KSDIWSLGCI 194
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370514551 246 LQEIALRSGPFYLEGLdLSpkeIVQKVRNGQRPYFrPSIDRTQLNeelvLLMERCWAQDPAERPDFGQI 314
Cdd:cd08222   195 LYEMCCLKHAFDGQNL-LS---VMYKIVEGETPSL-PDKYSKELN----AIYSRMLNKDPALRPSAAEI 254
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
123-308 2.55e-11

Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include Saccharomyces cerevisiae Rim15, Schizosaccharomyces pombe cek1, and similar fungal proteins. They contain a central catalytic domain, which contains an insert relative to MAST kinases. In addition, Rim15 contains a C-terminal signal receiver (REC) domain while cek1 contains an N-terminal PAS domain. Rim15 (or Rim15p) functions as a regulator of meiosis. It acts as a downstream effector of PKA and regulates entry into stationary phase (G0). Thus, it plays a crucial role in regulating yeast proliferation, differentiation, and aging. Cek1 may facilitate progression of mitotic anaphase. The Rim15-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270762 [Multi-domain]  Cd Length: 263  Bit Score: 64.42  E-value: 2.55e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 123 NICIVTEYCPRGSLQDILEN-DSINLDWMFRYslINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsf 200
Cdd:cd05611    71 YLYLVMEYLNGGDCASLIKTlGGLPEDWAKQY--IAEVVLGVEDLHqRGII--HRDIKPENLLIDQTGHLKLTDFGLS-- 144
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 201 RSTAEPDDSHALYAKKLWTAPELLSGNPlpttGMQKADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNGQRPYf 280
Cdd:cd05611   145 RNGLEKRHNKKFVGTPDYLAPETILGVG----DDKMSDWWSLGCVIFEFLFGYPPFHAE----TPDAVFDNILSRRINW- 215
                         170       180
                  ....*....|....*....|....*...
gi 1370514551 281 rPSIDRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd05611   216 -PEEVKEFCSPEAVDLINRLLCMDPAKR 242
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
94-309 4.04e-11

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Aatyk subfamily is also referred to as the lemur tyrosine kinase (Lmtk) subfamily. It consists of Aatyk1 (Lmtk1), Aatyk2 (Lmtk2, Brek), Aatyk3 (Lmtk3), and similar proteins. Aatyk proteins are mostly receptor PTKs (RTKs) containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk1 does not contain a transmembrane segment and is a cytoplasmic (or nonreceptor) kinase. Aatyk proteins are classified as PTKs based on overall sequence similarity and the phylogenetic tree. However, analysis of catalytic residues suggests that Aatyk proteins may be multispecific kinases, functioning also as serine/threonine kinases. They are involved in neural differentiation, nerve growth factor (NGF) signaling, apoptosis, and spermatogenesis. The Aatyk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270638 [Multi-domain]  Cd Length: 269  Bit Score: 63.76  E-value: 4.04e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  94 RQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL----ENDSINLDWMFRYSLINDLVKGMAFLHnS 169
Cdd:cd05042    40 DTFLKEGQPYRILQHPNILQCLGQCVEAIPYLLVMEFCDLGDLKAYLrserEHERGDSDTRTLQRMACEVAAGLAHLH-K 118
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 170 IISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTaepdDSHALYAKKL-----WTAPELLS---GNPLPTTGMQKADVYS 241
Cdd:cd05042   119 LNFVHSDLALRNCLLTSDLTVKIGDYGLAHSRYK----EDYIETDDKLwfplrWTAPELVTefhDRLLVVDQTKYSNIWS 194
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 242 FGIILQEI-ALRSGPFYleglDLSPKEIV-QKVRNGQRPYFRPSIDRTqLNEELVLLMERCWAQdPAERP 309
Cdd:cd05042   195 LGVTLWELfENGAQPYS----NLSDLDVLaQVVREQDTKLPKPQLELP-YSDRWYEVLQFCWLS-PEQRP 258
STKc_CDK_like cd07829
Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs ...
76-256 4.61e-11

Catalytic domain of Cyclin-Dependent protein Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. CDKs are partly regulated by their subcellular localization, which defines substrate phosphorylation and the resulting specific function. CDK1, CDK2, CDK4, and CDK6 have well-defined functions in the cell cycle, such as the regulation of the early G1 phase by CDK4 or CDK6, the G1/S phase transition by CDK2, or the entry of mitosis by CDK1. They also exhibit overlapping cyclin specificity and functions in certain conditions. Knockout mice with a single CDK deleted remain viable with specific phenotypes, showing that some CDKs can compensate for each other. For example, CDK4 can compensate for the loss of CDK6, however, double knockout mice with both CDK4 and CDK6 deleted die in utero. CDK8 and CDK9 are mainly involved in transcription while CDK5 is implicated in neuronal function. CDK7 plays essential roles in both the cell cycle as a CDK-Activating Kinase (CAK) and in transcription as a component of the general transcription factor TFIIH. The CDK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270823 [Multi-domain]  Cd Length: 282  Bit Score: 63.66  E-value: 4.61e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  76 KGNVVAIKhvnKKRIELT---------RQV--LFELKH-----MRDVqfnhltrfigaCIDPPNICIVTEYCPRgSLQDI 139
Cdd:cd07829    23 TGEIVALK---KIRLDNEeegipstalREIslLKELKHpnivkLLDV-----------IHTENKLYLVFEYCDQ-DLKKY 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 140 LENDSINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDShalYAKK-- 216
Cdd:cd07829    88 LDKRPGPLPPNLIKSIMYQLLRGLAYCHsHRIL--HRDLKPQNLLINRDGVLKLADFGLA--RAFGIPLRT---YTHEvv 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 1370514551 217 -LW-TAPELLSGNPLPTTGmqkADVYSFGIILQEIALRSGPF 256
Cdd:cd07829   161 tLWyRAPEILLGSKHYSTA---VDIWSVGCIFAELITGKPLF 199
STKc_SnRK3 cd14663
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
77-315 4.77e-11

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK3 is represented in this cd. The SnRK3 group contains members also known as CBL-interacting protein kinase, salt overly sensitive 2, SOS3-interacting proteins and protein kinase S. These kinases interact with calcium-binding proteins such as SOS3, SCaBPs, and CBL proteins, and are involved in responses to salt stress and in sugar and ABA signaling. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271133 [Multi-domain]  Cd Length: 256  Bit Score: 63.19  E-value: 4.77e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIE---LTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQD-ILENDSINLDWMFR 152
Cdd:cd14663    25 GESVAIKIIDKEQVAregMVEQIKREIAIMKLLRHPNIVELHEVMATKTKIFFVMELVTGGELFSkIAKNGRLKEDKARK 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 YslINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDS-HALYAKKLWTAPELLSGNplpt 231
Cdd:cd14663   105 Y--FQQLIDAVDYCHSRGVF-HRDLKPENLLLDEDGNLKISDFGLSALSEQFRQDGLlHTTCGTPNYVAPEVLARR---- 177
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 232 tGMQ--KADVYSFGIILQEIALRSGPFYLEGLdlspKEIVQKVRNGQRPYFRpsidrtQLNEELVLLMERCWAQDPAERP 309
Cdd:cd14663   178 -GYDgaKADIWSCGVILFVLLAGYLPFDDENL----MALYRKIMKGEFEYPR------WFSPGAKSLIKRILDPNPSTRI 246

                  ....*.
gi 1370514551 310 DFGQIK 315
Cdd:cd14663   247 TVEQIM 252
STKc_TSSK6-like cd14164
Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs ...
80-316 5.19e-11

Catalytic domain of testis-specific serine/threonine kinase 6 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK6, also called SSTK, is expressed at the head of elongated sperm. It can phosphorylate histones and associate with heat shock protens HSP90 and HSC70. Male mice deficient in TSSK6 are infertile, showing spermatogenic impairment including reduced sperm counts, impaired DNA condensation, abnormal morphology and decreased motility rates. The TSSK6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271066 [Multi-domain]  Cd Length: 256  Bit Score: 63.34  E-value: 5.19e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIE---LTRQVLFELKHMRDVQFNHLTRfIGACIDPPN--ICIVTEYCPRGSLQDILENDSINLDwmFRYS 154
Cdd:cd14164    28 VAIKIVDRRRASpdfVQKFLPRELSILRRVNHPNIVQ-MFECIEVANgrLYIVMEAAATDLLQKIQEVHHIPKD--LARD 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNSIISsHGSLKSSNCVV--DSRFVlKITDYGLASFRSTAePDDSHALYAKKLWTAPELLSGNPLPTt 232
Cdd:cd14164   105 MFAQMVGAVNYLHDMNIV-HRDLKCENILLsaDDRKI-KIADFGFARFVEDY-PELSTTFCGSRAYTPPEVILGTPYDP- 180
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 233 gmQKADVYSFGIILQEIALRSGPFYlegldlspKEIVQKVRNGQRPYFRPsidrtqlneELVLLMERCWA-------QDP 305
Cdd:cd14164   181 --KKYDVWSLGVVLYVMVTGTMPFD--------ETNVRRLRLQQRGVLYP---------SGVALEEPCRAlirtllqFNP 241
                         250
                  ....*....|.
gi 1370514551 306 AERPDFGQIKG 316
Cdd:cd14164   242 STRPSIQQVAG 252
STKc_TGFbR2_like cd14055
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II ...
125-308 5.63e-11

Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Type II Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TGFbR2 belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, bone morphogenetic proteins, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane region, and a cytoplasmic catalytic kinase domain. Type II receptors, such as TGFbR2, are high-affinity receptors which bind ligands, autophosphorylate, as well as trans-phosphorylate and activate low-affinity type I receptors. TGFbR2 acts as the receptor for TGFbeta, which is crucial in growth control and homeostasis in many different tissues. It plays roles in regulating apoptosis and in maintaining the balance between self renewal and cell loss. It also plays a key role in maintaining vascular integrity and in regulating responses to genotoxic stress. Mutations in TGFbR2 can cause aortic aneurysm disorders such as Loeys-Dietz and Marfan syndromes. The TGFbR2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270957 [Multi-domain]  Cd Length: 295  Bit Score: 63.55  E-value: 5.63e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 125 CIVTEYCPRGSLQDILENDSINldWMFRYSLINDLVKGMAFLHN--------SIISSHGSLKSSNCVVDSRFVLKITDYG 196
Cdd:cd14055    75 WLITAYHENGSLQDYLTRHILS--WEDLCKMAGSLARGLAHLHSdrtpcgrpKIPIAHRDLKSSNILVKNDGTCVLADFG 152
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 197 LA-SFRSTAEPDDshalYAKK------LWTAPELLSG--NPLPTTGMQKADVYSFGIILQEIALR---SG------PFYL 258
Cdd:cd14055   153 LAlRLDPSLSVDE----LANSgqvgtaRYMAPEALESrvNLEDLESFKQIDVYSMALVLWEMASRceaSGevkpyeLPFG 228
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 259 EGLDLSP-----KEIVqkVRNGQRPYFRPSIDRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd14055   229 SKVRERPcvesmKDLV--LRDRGRPEIPDSWLTHQGMCVLCDTITECWDHDPEAR 281
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
77-314 5.76e-11

Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The CMGC family consists of Cyclin-Dependent protein Kinases (CDKs), Mitogen-activated protein kinases (MAPKs) such as Extracellular signal-regulated kinase (ERKs), c-Jun N-terminal kinases (JNKs), and p38, and other kinases. CDKs belong to a large subfamily of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Other members of the CMGC family include casein kinase 2 (CK2), Dual-specificity tYrosine-phosphorylated and -Regulated Kinase (DYRK), Glycogen Synthase Kinase 3 (GSK3), among many others. The CMGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270688 [Multi-domain]  Cd Length: 249  Bit Score: 63.02  E-value: 5.76e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVnKKRIELTRQVLFE---LKHMRDVQ--FN--HLTRFIGAcIDPPNICIVTEYCPRgSLQDILENDS--INL 147
Cdd:cd05118    24 GEKVAIKKI-KNDFRHPKAALREiklLKHLNDVEghPNivKLLDVFEH-RGGNHLCLVFELMGM-NLYELIKDYPrgLPL 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 148 DWMFRYSLinDLVKGMAFLH-NSIIssHGSLKSSNCVVD-SRFVLKITDYGLASFRSTAEPDDshalYAKKLW-TAPELL 224
Cdd:cd05118   101 DLIKSYLY--QLLQALDFLHsNGII--HRDLKPENILINlELGQLKLADFGLARSFTSPPYTP----YVATRWyRAPEVL 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 225 SGNPLPTTGMqkaDVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRngqrpyfrpsidRTQLNEELVLLMERCWAQD 304
Cdd:cd05118   173 LGAKPYGSSI---DIWSLGCILAELLTGRPLFP----GDSEVDQLAKIV------------RLLGTPEALDLLSKMLKYD 233
                         250
                  ....*....|
gi 1370514551 305 PAERPDFGQI 314
Cdd:cd05118   234 PAKRITASQA 243
STKc_Nek6_7 cd08224
Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related ...
77-314 8.16e-11

Catalytic domain of the Serine/Threonine Kinases, Never In Mitosis gene A (NIMA)-related kinase 6 and 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek6 and Nek7 are the shortest Neks, consisting only of the catalytic domain and a very short N-terminal extension. They show distinct expression patterns and both appear to be downstream substrates of Nek9. They are required for mitotic spindle formation and cytokinesis. They may also be regulators of the p70 ribosomal S6 kinase. Nek6/7 is part of a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270863 [Multi-domain]  Cd Length: 262  Bit Score: 62.67  E-value: 8.16e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVN-------KKRieltRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENdsinldw 149
Cdd:cd08224    25 GRLVALKKVQifemmdaKAR----QDCLKEIDLLQQLNHPNIIKYLASFIENNELNIVLELADAGDLSRLIKH------- 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 150 mFR-----------YSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLA---SFRSTAepddSHALYAK 215
Cdd:cd08224    94 -FKkqkrlipertiWKYFVQLCSALEHMHSKRIM-HRDIKPANVFITANGVVKLGDLGLGrffSSKTTA----AHSLVGT 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 216 KLWTAPELLSGNPLPTtgmqKADVYSFGIILQEIA-LRSgPFYLEGLDLSpkEIVQKVRNGQrpYfrPSIDRTQLNEELV 294
Cdd:cd08224   168 PYYMSPERIREQGYDF----KSDIWSLGCLLYEMAaLQS-PFYGEKMNLY--SLCKKIEKCE--Y--PPLPADLYSQELR 236
                         250       260
                  ....*....|....*....|
gi 1370514551 295 LLMERCWAQDPAERPDFGQI 314
Cdd:cd08224   237 DLVAACIQPDPEKRPDISYV 256
STKc_AGC cd05123
Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
77-316 8.28e-11

Catalytic domain of AGC family Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. AGC kinases regulate many cellular processes including division, growth, survival, metabolism, motility, and differentiation. Many are implicated in the development of various human diseases. Members of this family include cAMP-dependent Protein Kinase (PKA), cGMP-dependent Protein Kinase (PKG), Protein Kinase C (PKC), Protein Kinase B (PKB), G protein-coupled Receptor Kinase (GRK), Serum- and Glucocorticoid-induced Kinase (SGK), and 70 kDa ribosomal Protein S6 Kinase (p70S6K or S6K), among others. AGC kinases share an activation mechanism based on the phosphorylation of up to three sites: the activation loop (A-loop), the hydrophobic motif (HM) and the turn motif. Phosphorylation at the A-loop is required of most AGC kinases, which results in a disorder-to-order transition of the A-loop. The ordered conformation results in the access of substrates and ATP to the active site. A subset of AGC kinases with C-terminal extensions containing the HM also requires phosphorylation at this site. Phosphorylation at the HM allows the C-terminal extension to form an ordered structure that packs into the hydrophobic pocket of the catalytic domain, which then reconfigures the kinase into an active bi-lobed state. In addition, growth factor-activated AGC kinases such as PKB, p70S6K, RSK, MSK, PKC, and SGK, require phosphorylation at the turn motif (also called tail or zipper site), located N-terminal to the HM at the C-terminal extension. The AGC family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and Phosphoinositide 3-Kinase.


Pssm-ID: 270693 [Multi-domain]  Cd Length: 250  Bit Score: 62.53  E-value: 8.28e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLfelkHM---RDV--QFNHltRFI----GACIDPPNICIVTEYCPRGSLQDILEND-SIN 146
Cdd:cd05123    18 GKLYAMKVLRKKEIIKRKEVE----HTlneRNIleRVNH--PFIvklhYAFQTEEKLYLVLDYVPGGELFSHLSKEgRFP 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 147 LDWMFRYslINDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLAsfrSTAEPDDSHAlyakklWT------ 219
Cdd:cd05123    92 EERARFY--AAEIVLALEYLHSlGII--YRDLKPENILLDSDGHIKLTDFGLA---KELSSDGDRT------YTfcgtpe 158
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 220 --APELLSGNPlptTGMQkADVYSFGIILQEiaLRSG--PFYLEgldlSPKEIVQKVRNGQrPYFRPSIDrtqlnEELVL 295
Cdd:cd05123   159 ylAPEVLLGKG---YGKA-VDWWSLGVLLYE--MLTGkpPFYAE----NRKEIYEKILKSP-LKFPEYVS-----PEAKS 222
                         250       260
                  ....*....|....*....|....
gi 1370514551 296 LMERCWAQDPAER---PDFGQIKG 316
Cdd:cd05123   223 LISGLLQKDPTKRlgsGGAEEIKA 246
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
135-314 9.75e-11

Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR1 (or Flt1) binds VEGFA, VEGFB, and placenta growth factor (PLGF). It regulates monocyte and macrophage migration, vascular permeability, haematopoiesis, and the recruitment of haematopietic progenitor cells from the bone marrow. VEGFR1 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271109 [Multi-domain]  Cd Length: 340  Bit Score: 63.48  E-value: 9.75e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 135 SLQDILENDSINLDWMFRYSLINDLV-------KGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPD 207
Cdd:cd14207   158 SLSDVEEEEEDSGDFYKRPLTMEDLIsysfqvaRGMEFL-SSRKCIHRDLAARNILLSENNVVKICDFGLA--RDIYKNP 234
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 208 DshalYAKK-------LWTAPELLSGNPLPTtgmqKADVYSFGIILQEI-ALRSGPFYLEGLDlspKEIVQKVRNGQRpy 279
Cdd:cd14207   235 D----YVRKgdarlplKWMAPESIFDKIYST----KSDVWSYGVLLWEIfSLGASPYPGVQID---EDFCSKLKEGIR-- 301
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1370514551 280 FRPSidrTQLNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14207   302 MRAP---EFATSEIYQIMLDCWQGDPNERPRFSEL 333
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
134-320 1.04e-10

Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. CSF-1R, also called c-Fms, is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of CSF-1R to its ligand, CSF-1, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. CSF-1R signaling is critical in the regulation of macrophages and osteoclasts. It leads to increases in gene transcription and protein translation, and induces cytoskeletal remodeling. CSF-1R signaling leads to a variety of cellular responses including survival, proliferation, and differentiation of target cells. It plays an important role in innate immunity, tissue development and function, and the pathogenesis of some diseases including atherosclerosis and cancer. CSF-1R signaling is also implicated in mammary gland development during pregnancy and lactation. Aberrant CSF-1/CSF-1R expression correlates with tumor cell invasiveness, poor clinical prognosis, and bone metastasis in breast cancer. Although the structure of the human CSF-1R catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. The CSF-1R subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133237 [Multi-domain]  Cd Length: 374  Bit Score: 63.71  E-value: 1.04e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 134 GSLQDILENDS--INLDWMFRYSLinDLVKGMAFL--HNSIissHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAepDDS 209
Cdd:cd05106   196 DSKDEEDTEDSwpLDLDDLLRFSS--QVAQGMDFLasKNCI---HRDVAARNVLLTDGRVAKICDFGLA--RDIM--NDS 266
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 210 HalYAKK-------LWTAPELLsgnpLPTTGMQKADVYSFGIILQEI-ALRSGPFYLEGLDLSPKEIVQKVRNGQRPYFR 281
Cdd:cd05106   267 N--YVVKgnarlpvKWMAPESI----FDCVYTVQSDVWSYGILLWEIfSLGKSPYPGILVNSKFYKMVKRGYQMSRPDFA 340
                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1370514551 282 PsidrtqlnEELVLLMERCWAQDPAERPDFGQIKGFIRR 320
Cdd:cd05106   341 P--------PEIYSIMKMCWNLEPTERPTFSQISQLIQR 371
STKc_CDKL cd07833
Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs ...
55-310 1.53e-10

Catalytic domain of Cyclin-Dependent protein Kinase Like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDKL1-5 and similar proteins. Some CDKLs, like CDKL1 and CDKL3, may be implicated in transformation and others, like CDKL3 and CDKL5, are associated with mental retardation when impaired. CDKL2 plays a role in learning and memory. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270827 [Multi-domain]  Cd Length: 288  Bit Score: 62.33  E-value: 1.53e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  55 SYGSLMTAHGKyqifaNTGHfkgnVVAIKHVnkKRIELTRQV----LFELKHMRDVQFNHLTRFIGACIDPPNICIVTEY 130
Cdd:cd07833    13 AYGVVLKCRNK-----ATGE----IVAIKKF--KESEDDEDVkktaLREVKVLRQLRHENIVNLKEAFRRKGRLYLVFEY 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 131 CPRgSLQDILENDSINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDS 209
Cdd:cd07833    82 VER-TLLELLEASPGGLPPDAVRSYIWQLLQAIAYCHsHNII--HRDIKPENILVSESGVLKLCDFGFA--RALTARPAS 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 210 HAL-YAKKLW-TAPELLSGNPLPTTGmqkADVYSFGIILQEIalrsgpfyLEGLDLSPKE-------IVQKV------RN 274
Cdd:cd07833   157 PLTdYVATRWyRAPELLVGDTNYGKP---VDVWAIGCIMAEL--------LDGEPLFPGDsdidqlyLIQKClgplppSH 225
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 275 GQR----PYFR----PSID---------RTQLNEELVLLMERCWAQDPAERPD 310
Cdd:cd07833   226 QELfssnPRFAgvafPEPSqpeslerryPGKVSSPALDFLKACLRMDPKERLT 278
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
76-341 1.68e-10

Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST3, MST4, STK25, Schizosaccharomyces pombe Nak1 and Sid1, Saccharomyces cerevisiae sporulation-specific protein 1 (SPS1), and related proteins. Nak1 is required by fission yeast for polarizing the tips of actin cytoskeleton and is involved in cell growth, cell separation, cell morphology and cell-cycle progression. Sid1 is a component in the septation initiation network (SIN) signaling pathway, and plays a role in cytokinesis. SPS1 plays a role in regulating proteins required for spore wall formation. MST4 plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. STK25 may play a role in the regulation of cell migration and polarization. The MST3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270786 [Multi-domain]  Cd Length: 274  Bit Score: 61.88  E-value: 1.68e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  76 KGNVVAIKHVN----KKRIELTRQVLFELKHMRDVqfnHLTRFIGACIDPPNICIVTEYCPRGSLQDILEndSINLDWMF 151
Cdd:cd06609    25 TNQVVAIKVIDleeaEDEIEDIQQEIQFLSQCDSP---YITKYYGSFLKGSKLWIIMEYCGGGSVLDLLK--PGPLDETY 99
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLINDLVKGMAFLHNS--IissHGSLKSSNCVVDSRFVLKITDYGLAS-FRSTAepDDSHALYAKKLWTAPELLSGNP 228
Cdd:cd06609   100 IAFILREVLLGLEYLHSEgkI---HRDIKAANILLSEEGDVKLADFGVSGqLTSTM--SKRNTFVGTPFWMAPEVIKQSG 174
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 LPTtgmqKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKV-RNgqrpyFRPSIDRTQLNEELVLLMERCWAQDPAE 307
Cdd:cd06609   175 YDE----KADIWSLGITAIELAKGEPPLS----DLHPMRVLFLIpKN-----NPPSLEGNKFSKPFKDFVELCLNKDPKE 241
                         250       260       270
                  ....*....|....*....|....*....|....*..
gi 1370514551 308 RP---DFGQIKgFIRRFNKeggTSILDNLLLRMEQYA 341
Cdd:cd06609   242 RPsakELLKHK-FIKKAKK---TSYLTLLIERIKKWK 274
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
129-314 1.88e-10

Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Kit is important in the development of melanocytes, germ cells, mast cells, hematopoietic stem cells, the interstitial cells of Cajal, and the pacemaker cells of the GI tract. Kit signaling is involved in major cellular functions including cell survival, proliferation, differentiation, adhesion, and chemotaxis. Mutations in Kit, which result in constitutive ligand-independent activation, are found in human cancers such as gastrointestinal stromal tumor (GIST) and testicular germ cell tumor (TGCT). The aberrant expression of Kit and/or SCF is associated with other tumor types such as systemic mastocytosis and cancers of the breast, neurons, lung, prostate, colon, and rectum. Although the structure of the human Kit catalytic domain is known, it is excluded from this specific alignment model because it contains a deletion in its sequence. Kit is a member of the Platelet Derived Growth Factor Receptor (PDGFR) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of Kit to its ligand, the stem-cell factor (SCF), leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. The Kit subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 63.00  E-value: 1.88e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 129 EYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFL--HNSIissHGSLKSSNCVVDSRFVLKITDYGLASFRSTaep 206
Cdd:cd05104   193 SYVDQDVTSEILEEDELALDTEDLLSFSYQVAKGMEFLasKNCI---HRDLAARNILLTHGRITKICDFGLARDIRN--- 266
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 207 dDSHalYAKK-------LWTAPELLsgnpLPTTGMQKADVYSFGIILQEI-ALRSGPFylEGLDLSPKeIVQKVRNGQR- 277
Cdd:cd05104   267 -DSN--YVVKgnarlpvKWMAPESI----FECVYTFESDVWSYGILLWEIfSLGSSPY--PGMPVDSK-FYKMIKEGYRm 336
                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 1370514551 278 --PYFRPSidrtqlneELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05104   337 dsPEFAPS--------EMYDIMRSCWDADPLKRPTFKQI 367
STKc_CDK10 cd07845
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs ...
77-249 2.47e-10

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK10, also called PISSLRE, is essential for cell growth and proliferation, and acts through the G2/M phase of the cell cycle. CDK10 has also been identified as an important factor in endocrine therapy resistance in breast cancer. CDK10 silencing increases the transcription of c-RAF and the activation of the p42/p44 MAPK pathway, which leads to antiestrogen resistance. Patients who express low levels of CDK10 relapse early on tamoxifen. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK10 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173742 [Multi-domain]  Cd Length: 309  Bit Score: 62.00  E-value: 2.47e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHV--NKKR----IELTRQV--LFELKHMRDVQFNHLTrfIGACIDppNICIVTEYCPRgSLQDILENDSINLD 148
Cdd:cd07845    32 GEIVALKKVrmDNERdgipISSLREItlLLNLRHPNIVELKEVV--VGKHLD--SIFLVMEYCEQ-DLASLLDNMPTPFS 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKKLW-TAPELLSGN 227
Cdd:cd07845   107 ESQVKCLMLQLLRGLQYLHENFII-HRDLKVSNLLLTDKGCLKIADFGLA--RTYGLPAKPMTPKVVTLWyRAPELLLGC 183
                         170       180
                  ....*....|....*....|..
gi 1370514551 228 PLPTTGMqkaDVYSFGIILQEI 249
Cdd:cd07845   184 TTYTTAI---DMWAVGCILAEL 202
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
80-324 3.51e-10

Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER3 contains an impaired tyr kinase domain, which lacks crucial residues for catalytic activity against exogenous substrates but is still able to bind ATP and autophosphorylate. HER3 binds the neuregulin ligands, NRG1 and NRG2, and it relies on its heterodimerization partners for activity following ligand binding. The HER2-HER3 heterodimer constitutes a high affinity co-receptor capable of potent mitogenic signaling. HER3 participates in a signaling pathway involved in the proliferation, survival, adhesion, and motility of tumor cells. The HER3 subfamily is part of a larger superfamily that includes other pseudokinases and the the catalytic domains of active kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173656 [Multi-domain]  Cd Length: 279  Bit Score: 61.12  E-value: 3.51e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRielTRQVLFELK-HMR---DVQFNHLTRFIGACiDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSL 155
Cdd:cd05111    39 VAIKVIQDRS---GRQSFQAVTdHMLaigSLDHAYIVRLLGIC-PGASLQLVTQLLPLGSLLDHVRQHRGSLGPQLLLNW 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 INDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFrstAEPDDSHALYAKK----LWTAPELLsgnpLPT 231
Cdd:cd05111   115 CVQIAKGMYYLEEHRMV-HRNLAARNVLLKSPSQVQVADFGVADL---LYPDDKKYFYSEAktpiKWMALESI----HFG 186
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 232 TGMQKADVYSFGIILQEIALRSGPFYlegLDLSPKEIVQKVRNGQRpYFRPSIdrtqLNEELVLLMERCWAQDPAERPDF 311
Cdd:cd05111   187 KYTHQSDVWSYGVTVWEMMTFGAEPY---AGMRLAEVPDLLEKGER-LAQPQI----CTIDVYMVMVKCWMIDENIRPTF 258
                         250
                  ....*....|...
gi 1370514551 312 GQIKGFIRRFNKE 324
Cdd:cd05111   259 KELANEFTRMARD 271
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
95-315 4.46e-10

Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tyro3 (or Sky) is predominantly expressed in the central nervous system and the brain, and functions as a neurotrophic factor. It is also expressed in osteoclasts and has a role in bone resorption. Tyro3 is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Tyro3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270659 [Multi-domain]  Cd Length: 284  Bit Score: 60.70  E-value: 4.46e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVQFNHLTRFIGACIDP------PNICIVTEYCPRGSLQDIL-----ENDSINLDWMFRYSLINDLVKGM 163
Cdd:cd05074    57 EFLREAACMKEFDHPNVIKLIGVSLRSrakgrlPIPMVILPFMKHGDLHTFLlmsriGEEPFTLPLQTLVRFMIDIASGM 136
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 164 AFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKKL---WTAPELLSGNpLPTTgmqKADV 239
Cdd:cd05074   137 EYLSSkNFI--HRDLAARNCMLNENMTVCVADFGLS--KKIYSGDYYRQGCASKLpvkWLALESLADN-VYTT---HSDV 208
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370514551 240 YSFGIILQEIALRSGPFYlEGLDLSpkEIVQKVRNGQRPYFRPsidrtQLNEELVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd05074   209 WAFGVTMWEIMTRGQTPY-AGVENS--EIYNYLIKGNRLKQPP-----DCLEDVYELMCQCWSPEPKCRPSFQHLR 276
STKc_LRRK1 cd14067
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze ...
99-309 4.80e-10

Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LRRK1 is one of two vertebrate LRRKs which show complementary expression in the brain. It can form heterodimers with LRRK2, and may influence the age of onset of LRRK2-associated Parkinson's disease. LRRKs are also classified as ROCO proteins because they contain a ROC (Ras of complex proteins)/GTPase domain followed by a COR (C-terminal of ROC) domain of unknown function. In addition, LRRKs contain a catalytic kinase domain and protein-protein interaction motifs including a WD40 domain, LRRs and ankyrin (ANK) repeats. LRRKs possess both GTPase and kinase activities, with the ROC domain acting as a molecular switch for the kinase domain, cycling between a GTP-bound state which drives kinase activity and a GDP-bound state which decreases the activity. The LRRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270969 [Multi-domain]  Cd Length: 276  Bit Score: 60.75  E-value: 4.80e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQFNHLTRFIGACIDPpnICIVTEYCPRGSLQDILENDS-----INLDWMFRYSLINDLVKGMAFLH-NSIIS 172
Cdd:cd14067    60 EASMLHSLQHPCIVYLIGISIHP--LCFALELAPLGSLNTVLEENHkgssfMPLGHMLTFKIAYQIAAGLAYLHkKNIIF 137
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 173 ShgSLKSSNCVVDSRFV-----LKITDYGLA--SFRSTAEPDDSHALYakklwTAPELLSGnplpTTGMQKADVYSFGII 245
Cdd:cd14067   138 C--DLKSDNILVWSLDVqehinIKLSDYGISrqSFHEGALGVEGTPGY-----QAPEIRPR----IVYDEKVDMFSYGMV 206
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 246 LQEIALRSGPfyleGLDLSPKEIVQKVRNGQRPYF-RPsiDRTQLNEELVLLMErCWAQDPAERP 309
Cdd:cd14067   207 LYELLSGQRP----SLGHHQLQIAKKLSKGIRPVLgQP--EEVQFFRLQALMME-CWDTKPEKRP 264
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
95-329 5.39e-10

Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Tie2 is a receptor PTK (RTK) containing an extracellular region, a transmembrane segment, and an intracellular catalytic domain. The extracellular region contains an immunoglobulin (Ig)-like domain, three epidermal growth factor (EGF)-like domains, a second Ig-like domain, and three fibronectin type III repeats. Tie2 is expressed mainly in endothelial cells and hematopoietic stem cells. It is also found in a subset of tumor-associated monocytes and eosinophils. The angiopoietins (Ang-1 to Ang-4) serve as ligands for Tie2. The binding of Ang-1 to Tie2 leads to receptor autophosphorylation and activation, promoting cell migration and survival. In contrast, Ang-2 binding to Tie2 does not result in the same response, suggesting that Ang-2 may function as an antagonist. Tie2 signaling plays key regulatory roles in vascular integrity and quiescence, and in inflammation. The Tie2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 60.78  E-value: 5.39e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVqfnhlTRFIGACIDPPNICIVTEYCPRGSLQD------ILEND-----------SINLDWMFRYSLin 157
Cdd:cd05088    59 EVLCKLGHHPNI-----INLLGACEHRGYLYLAIEYAPHGNLLDflrksrVLETDpafaianstasTLSSQQLLHFAA-- 131
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASfrstaepddSHALYAKKL-------WTAPELLSGNPLP 230
Cdd:cd05088   132 DVARGMDYLSQKQFI-HRDLAARNILVGENYVAKIADFGLSR---------GQEVYVKKTmgrlpvrWMAIESLNYSVYT 201
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 231 TTgmqkADVYSFGIILQEIALRSGPFYLeglDLSPKEIVQKVRNGQRpYFRPsidrTQLNEELVLLMERCWAQDPAERPD 310
Cdd:cd05088   202 TN----SDVWSYGVLLWEIVSLGGTPYC---GMTCAELYEKLPQGYR-LEKP----LNCDDEVYDLMRQCWREKPYERPS 269
                         250
                  ....*....|....*....
gi 1370514551 311 FGQIKGFIRRFNKEGGTSI 329
Cdd:cd05088   270 FAQILVSLNRMLEERKTYV 288
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
135-314 5.46e-10

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR2 (or Flk1) binds the ligands VEGFA, VEGFC, VEGFD and VEGFE. VEGFR2 signaling is implicated in all aspects of normal and pathological vascular endothelial cell biology. It induces a variety of cellular effects including migration, survival, and proliferation. It is critical in regulating embryonic vascular development and angiogenesis. VEGFR2 is the major signal transducer in pathological angiogenesis including cancer and diabetic retinopathy, and is a target for inhibition in cancer therapy. The carboxyl terminus of VEGFR2 plays an important role in its autophosphorylation and activation. VEGFR2 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270681 [Multi-domain]  Cd Length: 343  Bit Score: 61.15  E-value: 5.46e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 135 SLQDILENDSINLDWMFRYSLINDLV-------KGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAsfRST-AEP 206
Cdd:cd05103   157 SLSDVEEEEAGQEDLYKDFLTLEDLIcysfqvaKGMEFL-ASRKCIHRDLAARNILLSENNVVKICDFGLA--RDIyKDP 233
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 207 DdshalYAKK-------LWTAPELLSGNPLPTtgmqKADVYSFGIILQEI-ALRSGPFylEGLDLSpKEIVQKVRNGQR- 277
Cdd:cd05103   234 D-----YVRKgdarlplKWMAPETIFDRVYTI----QSDVWSFGVLLWEIfSLGASPY--PGVKID-EEFCRRLKEGTRm 301
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 1370514551 278 ---PYFRPSIDRTQLNeelvllmerCWAQDPAERPDFGQI 314
Cdd:cd05103   302 rapDYTTPEMYQTMLD---------CWHGEPSQRPTFSEL 332
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
94-314 7.30e-10

Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. HER2 (ErbB2, HER2/neu) is a member of the EGFR (HER, ErbB) subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular EGF-related ligand-binding region, a transmembrane helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. Unlike other PTKs, phosphorylation of the activation loop of EGFR proteins is not critical to their activation. Instead, they are activated by ligand-induced dimerization, leading to the phosphorylation of tyr residues in the C-terminal tail, which serve as binding sites for downstream signaling molecules. HER2 does not bind to any known EGFR subfamily ligands, but contributes to the kinase activity of all possible heterodimers. It acts as the preferred partner of other ligand-bound EGFR proteins and functions as a signal amplifier, with the HER2-HER3 heterodimer being the most potent pair in mitogenic signaling. HER2 plays an important role in cell development, proliferation, survival and motility. Overexpression of HER2 results in its activation and downstream signaling, even in the absence of ligand. HER2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. HER2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. HER2 is a target for monoclonal antibodies and small molecule inhibitors, which are being developed as treatments for cancer. The first humanized antibody approved for clinical use is Trastuzumab (Herceptin), which is being used in combination with other therapies to improve the survival rates of patients with HER2-overexpressing breast cancer. The HER2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270684 [Multi-domain]  Cd Length: 279  Bit Score: 60.04  E-value: 7.30e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  94 RQVLFELKHMRDVQFNHLTRFIGACIDPpNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNsIISS 173
Cdd:cd05109    54 KEILDEAYVMAGVGSPYVCRLLGICLTS-TVQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAKGMSYLEE-VRLV 131
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 174 HGSLKSSNCVVDSRFVLKITDYGLASFRSTAEpDDSHALYAKK--LWTAPELLsgnpLPTTGMQKADVYSFGIILQEIAL 251
Cdd:cd05109   132 HRDLAARNVLVKSPNHVKITDFGLARLLDIDE-TEYHADGGKVpiKWMALESI----LHRRFTHQSDVWSYGVTVWELMT 206
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 252 RSGPFYlEGLdlSPKEIVQKVRNGQRpYFRPSIdrtqLNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05109   207 FGAKPY-DGI--PAREIPDLLEKGER-LPQPPI----CTIDVYMIMVKCWMIDSECRPRFREL 261
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
132-314 7.54e-10

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR beta is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR beta forms homodimers or heterodimers with PDGFR alpha, depending on the nature of the PDGF ligand. PDGF-BB and PDGF-DD induce PDGFR beta homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR beta signaling leads to a variety of cellular effects including the stimulation of cell growth and chemotaxis, as well as the inhibition of apoptosis and GAP junctional communication. It is critical in normal angiogenesis as it is involved in the recruitment of pericytes and smooth muscle cells essential for vessel stability. Aberrant PDGFR beta expression is associated with some human cancers. The continuously-active fusion proteins of PDGFR beta with COL1A1 and TEL are associated with dermatofibrosarcoma protuberans (DFSP) and a subset of chronic myelomonocytic leukemia (CMML), respectively. The PDGFR beta subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 133238 [Multi-domain]  Cd Length: 401  Bit Score: 61.18  E-value: 7.54e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 132 PRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAS--FRSTAEPDDS 209
Cdd:cd05107   221 PERTRRDTLINESPALSYMDLVGFSYQVANGMEFL-ASKNCVHRDLAARNVLICEGKLVKICDFGLARdiMRDSNYISKG 299
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 210 HALYAKKlWTAPELLSGNpLPTTgmqKADVYSFGIILQEIALRSGPFYLEgLDLSpKEIVQKVRNGQRpYFRPsidrTQL 289
Cdd:cd05107   300 STFLPLK-WMAPESIFNN-LYTT---LSDVWSFGILLWEIFTLGGTPYPE-LPMN-EQFYNAIKRGYR-MAKP----AHA 367
                         170       180
                  ....*....|....*....|....*
gi 1370514551 290 NEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05107   368 SDEIYEIMQKCWEEKFEIRPDFSQL 392
STKc_CDK9_like cd07840
Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs ...
77-256 8.50e-10

Catalytic domain of Cyclin-Dependent protein Kinase 9-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK9 and CDK12 from higher eukaryotes, yeast BUR1, C-type plant CDKs (CdkC), and similar proteins. CDK9, BUR1, and CdkC are functionally equivalent. They act as a kinase for the C-terminal domain of RNA polymerase II and participate in regulating mutliple steps of gene expression including transcription elongation and RNA processing. CDK9 and CdkC associate with T-type cyclins while BUR1 associates with the cyclin BUR2. CDK12 is a unique CDK that contains an arginine/serine-rich (RS) domain, which is predominantly found in splicing factors. CDK12 interacts with cyclins L1 and L2, and participates in regulating transcription and alternative splicing. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270832 [Multi-domain]  Cd Length: 291  Bit Score: 59.89  E-value: 8.50e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKR------IELTR--QVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRgSLQDILENDSINLD 148
Cdd:cd07840    24 GELVALKKIRMENekegfpITAIReiKLLQKLDHPNVVRLKEIVTSKGSAKYKGSIYMVFEYMDH-DLTGLLDNPEVKFT 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDshalYAKK---LW-TAPEL 223
Cdd:cd07840   103 ESQIKCYMKQLLEGLQYLHsNGIL--HRDIKGSNILINNDGVLKLADFGLARPYTKENNAD----YTNRvitLWyRPPEL 176
                         170       180       190
                  ....*....|....*....|....*....|...
gi 1370514551 224 LSGNPLPTTGMqkaDVYSFGIILQEIALRSGPF 256
Cdd:cd07840   177 LLGATRYGPEV---DMWSVGCILAELFTGKPIF 206
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
103-311 8.55e-10

Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Axl is widely expressed in a variety of organs and cells including epithelial, mesenchymal, hematopoietic, as well as non-transformed cells. It is important in many cellular functions such as survival, anti-apoptosis, proliferation, migration, and adhesion. Axl was originally isolated from patients with chronic myelogenous leukemia and a chronic myeloproliferative disorder. It is overexpressed in many human cancers including colon, squamous cell, thyroid, breast, and lung carcinomas. Axl is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to its ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Axl subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270660 [Multi-domain]  Cd Length: 277  Bit Score: 60.02  E-value: 8.55e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 103 MRDVQFNHLTRFIGACIDP------PNICIVTEYCPRGSLQDIL-----ENDSINLDWMFRYSLINDLVKGMAFLHN-SI 170
Cdd:cd05075    55 MKEFDHPNVMRLIGVCLQNtesegyPSPVVILPFMKHGDLHSFLlysrlGDCPVYLPTQMLVKFMTDIASGMEYLSSkNF 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 171 IssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKKL---WTAPELLSGNPLPTtgmqKADVYSFGIILQ 247
Cdd:cd05075   135 I--HRDLAARNCMLNENMNVCVADFGLS--KKIYNGDYYRQGRISKMpvkWIAIESLADRVYTT----KSDVWSFGVTMW 206
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 248 EIALRSGPFYlEGLDLSpkEIVQKVRNGQRpyFRPSIDRTqlnEELVLLMERCWAQDPAERPDF 311
Cdd:cd05075   207 EIATRGQTPY-PGVENS--EIYDYLRQGNR--LKQPPDCL---DGLYELMSSCWLLNPKDRPSF 262
PKc_Myt1 cd14050
Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze ...
101-309 9.13e-10

Catalytic domain of the Dual-specificity protein kinase, Myt1; Dual-specificity PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine as well as tyrosine residues on protein substrates. Myt1 is a cytoplasmic cell cycle checkpoint kinase that can keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of N-terminal thr (T14) and tyr (Y15) residues, leading to the delay of meiosis I entry. Meiotic progression is ensured by a two-step inhibition and downregulation of Myt1 by CDK1/XRINGO and p90Rsk during oocyte maturation. In addition, Myt1 targets cyclin B1/B2 and is essential for Golgi and ER assembly during telophase. In Drosophila, Myt1 may be a downstream target of Notch during eye development. The Myt1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine PKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270952 [Multi-domain]  Cd Length: 249  Bit Score: 59.24  E-value: 9.13e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 101 KHMRDVQFNHLTRFIGACIDPPNICIVTEYCpRGSLQDILE-NDSINLDWMFRYSLinDLVKGMAFLHNSIISsHGSLKS 179
Cdd:cd14050    53 RHEKLGEHPNCVRFIKAWEEKGILYIQTELC-DTSLQQYCEeTHSLPESEVWNILL--DLLKGLKHLHDHGLI-HLDIKP 128
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 180 SNCVVDSRFVLKITDYGLASFRSTAepDDSHALYAKKLWTAPELLSGNPLPttgmqKADVYSFGIILQEIALrsgpfyle 259
Cdd:cd14050   129 ANIFLSKDGVCKLGDFGLVVELDKE--DIHDAQEGDPRYMAPELLQGSFTK-----AADIFSLGITILELAC-------- 193
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 1370514551 260 GLDLsPKEIV--QKVRNGQRPyfRPSIDrtQLNEELVLLMERCWAQDPAERP 309
Cdd:cd14050   194 NLEL-PSGGDgwHQLRQGYLP--EEFTA--GLSPELRSIIKLMMDPDPERRP 240
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
99-323 9.58e-10

Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. TrkB is a receptor PTK (RTK) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding of TrkB to its ligands, brain-derived neurotrophic factor (BDNF) or neurotrophin 4 (NT4), results in receptor oligomerization and activation of the catalytic domain. TrkB is broadly expressed in the nervous system and in some non-neural tissues. It plays important roles in cell proliferation, differentiation, and survival. BDNF/Trk signaling plays a key role in regulating activity-dependent synaptic plasticity. TrkB also contributes to protection against gp120-induced neuronal cell death. TrkB overexpression is associated with poor prognosis in neuroblastoma (NB) and other human cancers. It acts as a suppressor of anoikis (detachment-induced apoptosis) and contributes to tumor metastasis. The TrkB subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270675 [Multi-domain]  Cd Length: 288  Bit Score: 60.05  E-value: 9.58e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE------------NDSINLDWMFRYSLINDLVKGMAFL 166
Cdd:cd05093    57 EAELLTNLQHEHIVKFYGVCVEGDPLIMVFEYMKHGDLNKFLRahgpdavlmaegNRPAELTQSQMLHIAQQIAAGMVYL 136
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 167 HNSIIsSHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPD----DSHALYAKKlWTAPELLSGNPLPTtgmqKADVYSF 242
Cdd:cd05093   137 ASQHF-VHRDLATRNCLVGENLLVKIGDFGMS--RDVYSTDyyrvGGHTMLPIR-WMPPESIMYRKFTT----ESDVWSL 208
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 243 GIILQEI-ALRSGPFYleglDLSPKEIVQKVRNG---QRPYFRPsidrtqlnEELVLLMERCWAQDPAERPDFGQIKGFI 318
Cdd:cd05093   209 GVVLWEIfTYGKQPWY----QLSNNEVIECITQGrvlQRPRTCP--------KEVYDLMLGCWQREPHMRLNIKEIHSLL 276

                  ....*
gi 1370514551 319 RRFNK 323
Cdd:cd05093   277 QNLAK 281
STKc_IRAK2 cd14157
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; ...
68-264 9.61e-10

Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRAKs are involved in Toll-like receptor (TLR) and interleukin-1 (IL-1) signalling pathways, and are thus critical in regulating innate immune responses and inflammation. IRAKs contain an N-terminal Death domain (DD), a proST region (rich in serines, prolines, and threonines), a central kinase domain, and a C-terminal domain; IRAK-4 lacks the C-terminal domain. Vertebrates contain four IRAKs (IRAK-1, -2, -3 (or -M), and -4) that display distinct functions and patterns of expression and subcellular distribution, and can differentially mediate TLR signaling. IRAK2 plays a role in mediating NFkB activation by TLR3, TLR4, and TLR8. It is specifically targeted by the viral protein A52, which is important for virulence, to inhibit all IL-1/TLR pathways, indicating that IRAK2 has a predominant role in NFkB activation. It is redundant with IRAK1 in early signaling but is critical for late and sustained activation. The IRAK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271059 [Multi-domain]  Cd Length: 289  Bit Score: 59.85  E-value: 9.61e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  68 IFANT--GHFKGNVVAIKHVnkKRIELTRQVLFELKHMRDVQFN------HLTRFIGACIDPPNICIVTEYCPRGSLQDI 139
Cdd:cd14157     5 TFADIykGYRHGKQYVIKRL--KETECESPKSTERFFQTEVQICfrcchpNILPLLGFCVESDCHCLIYPYMPNGSLQDR 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 140 LE--NDSINLDWMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFrstaePDDSHALYA--- 214
Cdd:cd14157    83 LQqqGGSHPLPWEQRLSISLGLLKAVQHLHNFGIL-HGNIKSSNVLLDGNLLPKLGHSGLRLC-----PVDKKSVYTmmk 156
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370514551 215 -KKLWTA----PELLSGNPLPTtgmQKADVYSFGIILQEI-----ALRSG--PFYLEGLDLS 264
Cdd:cd14157   157 tKVLQISlaylPEDFVRHGQLT---EKVDIFSCGVVLAEIltgikAMDEFrsPVYLKDLLLE 215
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
71-321 1.07e-09

Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Zap-70 is a cytoplasmic (or nonreceptor) PTK containing two Src homology 2 (SH2) domains N-terminal to the catalytic tyr kinase domain. Zap-70 is primarily expressed in T-cells and NK cells, and is a crucial component in T-cell receptor (TCR) signaling. Zap-70 binds the phosphorylated ITAM (immunoreceptor tyr activation motif) sequences of the activated TCR zeta-chain through its SH2 domains, leading to its phosphorylation and activation. It then phosphorylates target proteins, which propagate the signals to downstream pathways. Zap-70 is hardly detected in normal peripheral B-cells, but is present in some B-cell malignancies. It is used as a diagnostic marker for chronic lymphocytic leukemia (CLL) as it is associated with the more aggressive subtype of the disease. The Zap-70 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270686 [Multi-domain]  Cd Length: 269  Bit Score: 59.57  E-value: 1.07e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  71 NTGHFKGNVVAIKhvnKKRIELTRQVL-------FELKHMRDVQFNH------LTRFIGACiDPPNICIVTEYCPRGSLQ 137
Cdd:cd05115    16 NFGCVKKGVYKMR---KKQIDVAIKVLkqgnekaVRDEMMREAQIMHqldnpyIVRMIGVC-EAEALMLVMEMASGGPLN 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 138 DIL--ENDSINLDWMFRysLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASfrsTAEPDDSH--ALY 213
Cdd:cd05115    92 KFLsgKKDEITVSNVVE--LMHQVSMGMKYLEEKNFV-HRDLAARNVLLVNQHYAKISDFGLSK---ALGADDSYykARS 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 214 AKKL---WTAPELLSGNPLPTtgmqKADVYSFGIILQEiALRSG--PFYleglDLSPKEIVQKVRNGQRPYFRPSIDrtq 288
Cdd:cd05115   166 AGKWplkWYAPECINFRKFSS----RSDVWSYGVTMWE-AFSYGqkPYK----KMKGPEVMSFIEQGKRMDCPAECP--- 233
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1370514551 289 lnEELVLLMERCWAQDPAERPDFGQIKGFIRRF 321
Cdd:cd05115   234 --PEMYALMSDCWIYKWEDRPNFLTVEQRMRTY 264
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
159-314 1.08e-09

Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. VEGFR3 (or Flt4) preferentially binds the ligands VEGFC and VEGFD. VEGFR3 is essential for lymphatic endothelial cell (EC) development and function. It has been shown to regulate adaptive immunity during corneal transplantation. VEGFR3 is upregulated on blood vascular ECs in pathological conditions such as vascular tumors and the periphery of solid tumors. It plays a role in cancer progression and lymph node metastasis. Missense mutations in the VEGFR3 gene are associated with primary human lymphedema. VEGFR3 is a member of the VEGFR subfamily of proteins, which are receptor PTKs (RTKs) containing an extracellular ligand-binding region with seven immunoglobulin (Ig)-like domains, a transmembrane segment, and an intracellular catalytic domain. In VEGFR3, the fifth Ig-like domain is replaced by a disulfide bridge. The binding of VEGFRs to their ligands, the VEGFs, leads to receptor dimerization, activation, and intracellular signaling. The VEGFR3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270680 [Multi-domain]  Cd Length: 336  Bit Score: 60.38  E-value: 1.08e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 159 LVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAsfRST-AEPDdshalYAKK-------LWTAPELLSGNPLP 230
Cdd:cd05102   181 VARGMEFL-ASRKCIHRDLAARNILLSENNVVKICDFGLA--RDIyKDPD-----YVRKgsarlplKWMAPESIFDKVYT 252
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 231 TtgmqKADVYSFGIILQEI-ALRSGPFylEGLDLSpKEIVQKVRNGQR----PYFRPSIDRTQLNeelvllmerCWAQDP 305
Cdd:cd05102   253 T----QSDVWSFGVLLWEIfSLGASPY--PGVQIN-EEFCQRLKDGTRmrapEYATPEIYRIMLS---------CWHGDP 316

                  ....*....
gi 1370514551 306 AERPDFGQI 314
Cdd:cd05102   317 KERPTFSDL 325
STKc_GAK_like cd13985
Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of ...
77-323 1.34e-09

Catalytic domain of cyclin G-Associated Kinase-like proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes cyclin G-Associated Kinase (GAK), Drosophila melanogaster Numb-Associated Kinase (NAK)-like proteins, and similar protein kinases. GAK plays regulatory roles in clathrin-mediated membrane trafficking, the maintenance of centrosome integrity and chromosome congression, neural patterning, survival of neurons, and immune responses. NAK plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. The GAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270887 [Multi-domain]  Cd Length: 272  Bit Score: 59.27  E-value: 1.34e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDV-QFNHLTRFIGACI--DPPN--ICIVTEYCPrGSLQDILEND---SINLD 148
Cdd:cd13985    25 GRRYALKRMYFNDEEQLRVAIKEIEIMKRLcGHPNIVQYYDSAIlsSEGRkeVLLLMEYCP-GSLVDILEKSppsPLSEE 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYslINDLVKGMAFLHNS---IIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWT------ 219
Cdd:cd13985   104 EVLRI--FYQICQAVGHLHSQsppII--HRDIKIENILFSNTGRFKLCDFGSATTEHYPLERAEEVNIIEEEIQknttpm 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 220 --APELL---SGNPLPTtgmqKADVYSFGIILQEIALRSGPFylegldlSPKEIVQKVrNGQrpYFRPSIDRTqlNEELV 294
Cdd:cd13985   180 yrAPEMIdlySKKPIGE----KADIWALGCLLYKLCFFKLPF-------DESSKLAIV-AGK--YSIPEQPRY--SPELH 243
                         250       260
                  ....*....|....*....|....*....
gi 1370514551 295 LLMERCWAQDPAERPDFGQIKGFIRRFNK 323
Cdd:cd13985   244 DLIRHMLTPDPAERPDIFQVINIITKDTK 272
STKc_TLK cd13990
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the ...
80-310 1.47e-09

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270892 [Multi-domain]  Cd Length: 279  Bit Score: 59.25  E-value: 1.47e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIK--HVNK-----KRIELTRQVLFELKHMRDVQFNHLTRFIGAC-IDPPNICIVTEYCPRGSLQDIL-------ENDS 144
Cdd:cd13990    28 VACKihQLNKdwseeKKQNYIKHALREYEIHKSLDHPRIVKLYDVFeIDTDSFCTVLEYCDGNDLDFYLkqhksipEREA 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 145 InldwmfrySLINDLVKGMAFLHN---SIIssHGSLKSSNCVVDSRFV---LKITDYGLasfrSTAEPDDSHALYAKKL- 217
Cdd:cd13990   108 R--------SIIMQVVSALKYLNEikpPII--HYDLKPGNILLHSGNVsgeIKITDFGL----SKIMDDESYNSDGMELt 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 218 -------W-TAPELLSGNPLPTTGMQKADVYSFGIILQEIALRSGPFyleGLDLSPKEIVQ-----KVRNGQRPyFRPSI 284
Cdd:cd13990   174 sqgagtyWyLPPECFVVGKTPPKISSKVDVWSVGVIFYQMLYGRKPF---GHNQSQEAILEentilKATEVEFP-SKPVV 249
                         250       260
                  ....*....|....*....|....*.
gi 1370514551 285 drtqlNEELVLLMERCWAQDPAERPD 310
Cdd:cd13990   250 -----SSEAKDFIRRCLTYRKEDRPD 270
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
97-314 1.61e-09

Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. DDR2 is a receptor PTK (RTK) containing an extracellular discoidin homology domain, a transmembrane segment, an extended juxtamembrane region, and an intracellular catalytic domain. The binding of the ligand, collagen, to DDR2 results in a slow but sustained receptor activation. DDR2 binds mostly to fibrillar collagens as well as collagen X. DDR2 is widely expressed in many tissues with the highest levels found in skeletal muscle, skin, kidney and lung. It is important in cell proliferation and development. Mice, with a deletion of DDR2, suffer from dwarfism and delayed healing of epidermal wounds. DDR2 also contributes to collagen (type I) regulation by inhibiting fibrillogenesis and altering the morphology of collagen fibers. It is also expressed in immature dendritic cells (DCs), where it plays a role in DC activation and function. The DDR2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270677 [Multi-domain]  Cd Length: 297  Bit Score: 59.24  E-value: 1.61e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  97 LFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE-----------NDSINLDWMFRYSLINDLVKGMAF 165
Cdd:cd05095    67 LKEIKIMSRLKDPNIIRLLAVCITDDPLCMITEYMENGDLNQFLSrqqpegqlalpSNALTVSYSDLRFMAAQIASGMKY 146
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 166 LhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPD----DSHALYAKKLWTAPELLSGNplPTTGmqkADVYS 241
Cdd:cd05095   147 L-SSLNFVHRDLATRNCLVGKNYTIKIADFGMS--RNLYSGDyyriQGRAVLPIRWMSWESILLGK--FTTA---SDVWA 218
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 242 FGIILQEIA--LRSGPFYleglDLSPKEIVQKvrNGQrpYFRPSIDRTQL------NEELVLLMERCWAQDPAERPDFGQ 313
Cdd:cd05095   219 FGVTLWETLtfCREQPYS----QLSDEQVIEN--TGE--FFRDQGRQTYLpqpalcPDSVYKLMLSCWRRDTKDRPSFQE 290

                  .
gi 1370514551 314 I 314
Cdd:cd05095   291 I 291
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
35-314 1.62e-09

Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. C-Raf, also known as Raf-1 or c-Raf-1, is ubiquitously expressed and was the first Raf identified. It was characterized as the acquired oncogene from an acutely transforming murine sarcoma virus (3611-MSV) and the transforming agent from the avian retrovirus MH2. C-Raf-deficient mice embryos die around midgestation with increased apoptosis of embryonic tissues, especially in the fetal liver. One of the main functions of C-Raf is restricting caspase activation to promote survival in response to specific stimuli such as Fas stimulation, macrophage apoptosis, and erythroid differentiation. C-Raf is a mitogen-activated protein kinase kinase kinase (MAP3K, MKKK, MAPKKK), which phosphorylates and activates MAPK kinases (MAPKKs or MKKs or MAP2Ks), which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. It functions in the linear Ras-Raf-MEK-ERK pathway that regulates many cellular processes including cycle regulation, proliferation, differentiation, survival, and apoptosis. The C-Raf subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271051 [Multi-domain]  Cd Length: 283  Bit Score: 59.27  E-value: 1.62e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  35 NSERYHKGAGSRLTLSLRGSSyGSLMTAHgkyqifanTGHFKGNV-VAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTR 113
Cdd:cd14149     2 DSSYYWEIEASEVMLSTRIGS-GSFGTVY--------KGKWHGDVaVKILKVVDPTPEQFQAFRNEVAVLRKTRHVNILL 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 114 FIGAcIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKIT 193
Cdd:cd14149    73 FMGY-MTKDNLAIVTQWCEGSSLYKHLHVQETKFQMFQLIDIARQTAQGMDYLHAKNII-HRDMKSNNIFLHEGLTVKIG 150
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 194 DYGLASFRST-AEPDDSHALYAKKLWTAPELL---SGNPLPTtgmqKADVYSFGIILQEIALRSGPFYLEGldlSPKEIV 269
Cdd:cd14149   151 DFGLATVKSRwSGSQQVEQPTGSILWMAPEVIrmqDNNPFSF----QSDVYSYGIVLYELMTGELPYSHIN---NRDQII 223
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*..
gi 1370514551 270 QKVRNGqrpYFRPSIDRTQLN--EELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14149   224 FMVGRG---YASPDLSKLYKNcpKAMKRLVADCIKKVKEERPLFPQI 267
STKc_TSSK4-like cd14162
Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs ...
55-246 1.78e-09

Catalytic domain of testis-specific serine/threonine kinase 4 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK4, also called TSSK5, is expressed in testis from haploid round spermatids to mature spermatozoa. It phosphorylates Cre-Responsive Element Binding protein (CREB), facilitating the binding of CREB to the specific cis cAMP responsive element (CRE), which is important in activating genes related to germ cell differentiation. Mutations in the human TSSK4 gene is associated with infertile Chinese men with impaired spermatogenesis. The TSSK4-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271064 [Multi-domain]  Cd Length: 259  Bit Score: 58.85  E-value: 1.78e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  55 SYGSLMTAHGKYQifantghfkGNVVAIKHVNKKRIE---LTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYC 131
Cdd:cd14162    12 SYAVVKKAYSTKH---------KCKVAIKIVSKKKAPedyLQKFLPREIEVIKGLKHPNLICFYEAIETTSRVYIIMELA 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 132 PRGSLqdilendsinLDWMFRYSLIND---------LVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfRS 202
Cdd:cd14162    83 ENGDL----------LDYIRKNGALPEpqarrwfrqLVAGVEYCHSKGVV-HRDLKCENLLLDKNNNLKITDFGFA--RG 149
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 1370514551 203 TAEPDD-----------SHAlYAkklwtAPELLSGNPL-PttgmQKADVYSFGIIL 246
Cdd:cd14162   150 VMKTKDgkpklsetycgSYA-YA-----SPEILRGIPYdP----FLSDIWSMGVVL 195
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
77-318 1.87e-09

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 10; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. No function has yet been ascribed to Nek10. The gene encoding Nek10 is a putative causative gene for breast cancer; it is located within a breast cancer susceptibility loci on chromosome 3p24. Nek10 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270867 [Multi-domain]  Cd Length: 270  Bit Score: 58.67  E-value: 1.87e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVN----------KKRIELTRQVLFELKHMRDvQFNH--LTRFIGACIDPPNICIVTEY---CPRGSLQDILE 141
Cdd:cd08528    26 QTLLALKEINmtnpafgrteQERDKSVGDIISEVNIIKE-QLRHpnIVRYYKTFLENDRLYIVMELiegAPLGEHFSSLK 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 142 NDSINLDWMFRYSLINDLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRStaePDDSH--ALYAKKLWT 219
Cdd:cd08528   105 EKNEHFTEDRIWNIFVQMVLALRYLHKEKQIVHRDLKPNNIMLGEDDKVTITDFGLAKQKG---PESSKmtSVVGTILYS 181
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 220 APELLSGNPLPttgmQKADVYSFGIILQEIALRSGPFYLEGLdLSpkeIVQKVRNGQrpyFRPsIDRTQLNEELVLLMER 299
Cdd:cd08528   182 CPEIVQNEPYG----EKADIWALGCILYQMCTLQPPFYSTNM-LT---LATKIVEAE---YEP-LPEGMYSDDITFVIRS 249
                         250
                  ....*....|....*....
gi 1370514551 300 CWAQDPAERPDFGQIKGFI 318
Cdd:cd08528   250 CLTPDPEARPDIVEVSSMI 268
STKc_MAP4K3_like cd06613
Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like ...
77-310 1.88e-09

Catalytic domain of Mitogen-activated protein kinase kinase kinase kinase (MAP4K) 3-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily includes MAP4K3, MAP4K1, MAP4K2, MAP4K5, and related proteins. Vertebrate members contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. MAP4K1, also called haematopoietic progenitor kinase 1 (HPK1), is a hematopoietic-specific STK involved in many cellular signaling cascades including MAPK, antigen receptor, apoptosis, growth factor, and cytokine signaling. It participates in the regulation of T cell receptor signaling and T cell-mediated immune responses. MAP4K2 was referred to as germinal center (GC) kinase because of its preferred location in GC B cells. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. It is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). The MAP4K3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270788 [Multi-domain]  Cd Length: 259  Bit Score: 58.47  E-value: 1.88e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVN---KKRIELTRQvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDI------LENDSINl 147
Cdd:cd06613    25 GELAAVKVIKlepGDDFEIIQQ---EISMLKECRHPNIVAYFGSYLRRDKLWIVMEYCGGGSLQDIyqvtgpLSELQIA- 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 148 dWMFRYSLindlvKGMAFLHnSIISSHGSLKSSNCVVDSRFVLKITDYGLA-----------SFRSTAepddshalyakk 216
Cdd:cd06613   101 -YVCRETL-----KGLAYLH-STGKIHRDIKGANILLTEDGDVKLADFGVSaqltatiakrkSFIGTP------------ 161
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 217 LWTAPELLSGNPLPTTGmQKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVrnGQRPYFRPSI-DRTQLNEELVL 295
Cdd:cd06613   162 YWMAPEVAAVERKGGYD-GKCDIWALGITAIELAELQPPMF----DLHPMRALFLI--PKSNFDPPKLkDKEKWSPDFHD 234
                         250
                  ....*....|....*
gi 1370514551 296 LMERCWAQDPAERPD 310
Cdd:cd06613   235 FIKKCLTKNPKKRPT 249
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
107-314 1.89e-09

Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyr residues in protein substrates. ALK and LTK are orphan receptor PTKs (RTKs) whose ligands are not yet well-defined. ALK appears to play an important role in mammalian neural development as well as visceral muscle differentiation in Drosophila. ALK is aberrantly expressed as fusion proteins, due to chromosomal translocations, in about 60% of anaplastic large cell lymphomas (ALCLs). ALK fusion proteins are also found in rare cases of diffuse large B cell lymphomas (DLBCLs). LTK is mainly expressed in B lymphocytes and neuronal tissues. It is important in cell proliferation and survival. Transgenic mice expressing TLK display retarded growth and high mortality rate. In addition, a polymorphism in mouse and human LTK is implicated in the pathogenesis of systemic lupus erythematosus. RTKs contain an extracellular ligand-binding domain, a transmembrane region, and an intracellular tyr kinase domain. They are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The ALK/LTK subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270632 [Multi-domain]  Cd Length: 277  Bit Score: 58.94  E-value: 1.89e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 107 QFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDILENdsiNLDWMFRYSLIN---------DLVKGMAFLH-NSIIssH 174
Cdd:cd05036    65 KFNHpnIVRCIGVCFQRLPRFILLELMAGGDLKSFLRE---NRPRPEQPSSLTmldllqlaqDVAKGCRYLEeNHFI--H 139
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 175 GSLKSSNCVV---DSRFVLKITDYGLAS--FRSTAEPDDSHALYAKKlWTAPE-LLSGnpLPTTgmqKADVYSFGIILQE 248
Cdd:cd05036   140 RDIAARNCLLtckGPGRVAKIGDFGMARdiYRADYYRKGGKAMLPVK-WMPPEaFLDG--IFTS---KTDVWSFGVLLWE 213
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370514551 249 I-ALRSGPFYLEgldlSPKEIVQKVRNGQR---------PYFRpsidrtqlneelvlLMERCWAQDPAERPDFGQI 314
Cdd:cd05036   214 IfSLGYMPYPGK----SNQEVMEFVTSGGRmdppkncpgPVYR--------------IMTQCWQHIPEDRPNFSTI 271
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
103-319 2.17e-09

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 1; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror kinases are expressed in many tissues during development. Avian Ror1 was found to be involved in late limb development. Studies in mice reveal that Ror1 is important in the regulation of neurite growth in central neurons, as well as in respiratory development. Loss of Ror1 also enhances the heart and skeletal abnormalities found in Ror2-deficient mice. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270672 [Multi-domain]  Cd Length: 283  Bit Score: 58.87  E-value: 2.17e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 103 MRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-----END---SINLDWMFRYSLIN--------DLVKGMAFL 166
Cdd:cd05090    61 MTELHHPNIVCLLGVVTQEQPVCMLFEFMNQGDLHEFLimrspHSDvgcSSDEDGTVKSSLDHgdflhiaiQIAAGMEYL 140
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 167 hNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAepdDSHALYAKKL----WTAPELLSGNPLPTtgmqKADVYSF 242
Cdd:cd05090   141 -SSHFFVHKDLAARNILVGEQLHVKISDLGLSREIYSS---DYYRVQNKSLlpirWMPPEAIMYGKFSS----DSDIWSF 212
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 243 GIILQEI-ALRSGPFYleglDLSPKEIVQKVRNGQrpyFRPSIDrtQLNEELVLLMERCWAQDPAERPDFGQIKGFIR 319
Cdd:cd05090   213 GVVLWEIfSFGLQPYY----GFSNQEVIEMVRKRQ---LLPCSE--DCPPRMYSLMTECWQEIPSRRPRFKDIHARLR 281
STKc_BMPR1b cd14219
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs ...
126-308 2.17e-09

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IB; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1b, also called Activin receptor-Like Kinase 6 (ALK6), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Mutations in BMPR1b that led to inhibition of chondrogenesis can cause Brachydactyly (BD) type A2, a dominant hand malformation characterized by shortening and lateral deviation of the index fingers. A point mutation in the BMPR1b kinase domain is also associated with the Booroola phenotype, characterized by precocious differentiation of ovarian follicles. BMPR1b belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1b, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1b subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271121 [Multi-domain]  Cd Length: 305  Bit Score: 58.91  E-value: 2.17e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 126 IVTEYCPRGSLQDILENDSINLDWMFRysLINDLVKGMAFLHNSIISSHGS-------LKSSNCVVDSRFVLKITDYGLA 198
Cdd:cd14219    80 LITDYHENGSLYDYLKSTTLDTKAMLK--LAYSSVSGLCHLHTEIFSTQGKpaiahrdLKSKNILVKKNGTCCIADLGLA 157
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 199 S--FRSTAEPD-DSHALYAKKLWTAPELLSgNPLPTTGMQK---ADVYSFGIILQEIALR--SG----PFYLEGLDLSP- 265
Cdd:cd14219   158 VkfISDTNEVDiPPNTRVGTKRYMPPEVLD-ESLNRNHFQSyimADMYSFGLILWEVARRcvSGgiveEYQLPYHDLVPs 236
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370514551 266 -------KEIVQKVRngQRPYFRPSIDRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd14219   237 dpsyedmREIVCIKR--LRPSFPNRWSSDECLRQMGKLMTECWAHNPASR 284
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
77-308 2.43e-09

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK4 regulates cell morphology and cytoskeletal organization. It is essential for embryonic viability and proper neural development. Mice lacking PAK4 die due to defects in the fetal heart. In addition, their spinal cord motor neurons showed failure to differentiate and migrate. PAK4 also plays a role in cell survival and tumorigenesis. It is overexpressed in many primary tumors including colon, esophageal, and mammary tumors. PAK4 has also been implicated in viral and bacterial infection pathways. PAK4 belongs to the group II PAKs, which contain a PBD (p21-binding domain) and a C-terminal catalytic domain, but do not harbor an AID (autoinhibitory domain) or SH3 binding sites. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132988 [Multi-domain]  Cd Length: 292  Bit Score: 58.88  E-value: 2.43e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRiELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSL 155
Cdd:cd06657    45 GKLVAVKKMDLRK-QQRRELLFnEVVIMRDYQHENVVEMYNSYLVGDELWVVMEFLEGGALTDIVTHTRMNEEQIAAVCL 123
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 inDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASfRSTAEPDDSHALYAKKLWTAPELLSGNPLPTtgmq 235
Cdd:cd06657   124 --AVLKALSVLHAQGVI-HRDIKSDSILLTHDGRVKLSDFGFCA-QVSKEVPRRKSLVGTPYWMAPELISRLPYGP---- 195
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 236 KADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNGQRPYFRpsiDRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd06657   196 EVDIWSLGIMVIEMVDGEPPYFNE----PPLKAMKMIRDNLPPKLK---NLHKVSPSLKGFLDRLLVRDPAQR 261
STKc_PKA_like cd05580
Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs ...
76-285 2.61e-09

Catalytic subunit of the Serine/Threonine Kinases, cAMP-dependent protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the cAMP-dependent protein kinases, PKA and PRKX, and similar proteins. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. PRKX is also reulated by the R subunit and is is present in many tissues including fetal and adult brain, kidney, and lung. It is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PKA-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270732 [Multi-domain]  Cd Length: 290  Bit Score: 58.74  E-value: 2.61e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  76 KGNVVAIKHVNKKRIELTRQV---LFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-ENDSINLDWMF 151
Cdd:cd05580    25 SGKYYALKILKKAKIIKLKQVehvLNEKRILSEVRHPFIVNLLGSFQDDRNLYMVMEYVPGGELFSLLrRSGRFPNDVAK 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSliNDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGlasfrstaepddshalYAKKL----WT------- 219
Cdd:cd05580   105 FYA--AEVVLALEYLHSlDIV--YRDLKPENLLLDSDGHIKITDFG----------------FAKRVkdrtYTlcgtpey 164
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 220 -APELLSGnplptTGMQKA-DVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGqRPYFRPSID 285
Cdd:cd05580   165 lAPEIILS-----KGHGKAvDWWALGILIYEMLAGYPPFF----DENPMKIYEKILEG-KIRFPSFFD 222
STKc_TAO2 cd06634
Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze ...
36-368 2.81e-09

Catalytic domain of the Serine/Threonine Kinase, Thousand-and-One Amino acids 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Human TAO2 is also known as prostate-derived Ste20-like kinase (PSK) and was identified in a screen for overexpressed RNAs in prostate cancer. TAO2 possesses mitogen-activated protein kinase (MAPK) kinase kinase activity and activates both p38 and c-Jun N-terminal kinase (JNK), by phosphorylating and activating their respective MAP/ERK kinases, MEK3/MEK6 and MKK4/MKK7. It contains a long C-terminal extension with autoinhibitory segments, and is activated by the release of this inhibition and the phosphorylation of its activation loop serine. TAO2 functions as a regulator of actin cytoskeletal and microtubule organization. In addition, it regulates the transforming growth factor-activated kinase 1 (TAK1), which is a MAPKKK that plays an essential role in the signaling pathways of tumor necrosis factor, interleukin 1, and Toll-like receptor. The TAO2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270804 [Multi-domain]  Cd Length: 308  Bit Score: 58.88  E-value: 2.81e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  36 SERYHKGAGSRLTLSLRGSSYGSLMTAHGKYQIFANtghfkgNVVAIKHVN---KKRIELTRQVLFELKHMRDVQFNHLT 112
Cdd:cd06634     5 AELFFKDDPEKLFSDLREIGHGSFGAVYFARDVRNN------EVVAIKKMSysgKQSNEKWQDIIKEVKFLQKLRHPNTI 78
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 113 RFIGACIDPPNICIVTEYCpRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIIsSHGSLKSSNCVVDSRFVLKI 192
Cdd:cd06634    79 EYRGCYLREHTAWLVMEYC-LGSASDLLEVHKKPLQEVEIAAITHGALQGLAYLHSHNM-IHRDVKAGNILLTEPGLVKL 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 193 TDYGLASFRSTAepddsHALYAKKLWTAPE-LLSGNPLPTTGmqKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQK 271
Cdd:cd06634   157 GDFGSASIMAPA-----NSFVGTPYWMAPEvILAMDEGQYDG--KVDVWSLGITCIELAERKPPLF----NMNAMSALYH 225
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 272 VRNGQRPYFRPSidrtQLNEELVLLMERCWAQDPAERPDFGQIKGFiRRFNKEGGTSILDNLLLRMEQYANNLEKLveer 351
Cdd:cd06634   226 IAQNESPALQSG----HWSEYFRNFVDSCLQKIPQDRPTSDVLLKH-RFLLRERPPTVIMDLIQRTKDAVRELDNL---- 296
                         330
                  ....*....|....*..
gi 1370514551 352 tqayleEKRKAEALLYQ 368
Cdd:cd06634   297 ------QYRKMKKILFQ 307
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
56-315 3.06e-09

Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Mer (or Mertk) is named after its original reported expression pattern (monocytes, epithelial, and reproductive tissues). It is required for the ingestion of apoptotic cells by phagocytes such as macrophages, retinal pigment epithelial cells, and dendritic cells. Mer is also important in maintaining immune homeostasis. Mer is a member of the TAM subfamily, composed of receptor PTKs (RTKs) containing an extracellular ligand-binding region with two immunoglobulin-like domains followed by two fibronectin type III repeats, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, Gas6 and protein S, leads to receptor dimerization, autophosphorylation, activation, and intracellular signaling. The Mer subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271106 [Multi-domain]  Cd Length: 284  Bit Score: 58.41  E-value: 3.06e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  56 YGSLMTAHGKYQifANTGHfKGNVVAIKHVNKKRIELtRQVLFELKHMRDVQFNHLTRFIGACIDP-----PNICIVTEY 130
Cdd:cd14204    20 FGSVMEGELQQP--DGTNH-KVAVKTMKLDNFSQREI-EEFLSEAACMKDFNHPNVIRLLGVCLEVgsqriPKPMVILPF 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 131 CPRGSLQDIL-----ENDSINLDWMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAE 205
Cdd:cd14204    96 MKYGDLHSFLlrsrlGSGPQHVPLQTLLKFMIDIALGMEYLSSRNFL-HRDLAARNCMLRDDMTVCVADFGLS--KKIYS 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 206 PDDSHALYAKKL---WTAPELLSGNPLPTtgmqKADVYSFGIILQEIALRSGPFYLeglDLSPKEIVQKVRNGQRpYFRP 282
Cdd:cd14204   173 GDYYRQGRIAKMpvkWIAVESLADRVYTV----KSDVWAFGVTMWEIATRGMTPYP---GVQNHEIYDYLLHGHR-LKQP 244
                         250       260       270
                  ....*....|....*....|....*....|...
gi 1370514551 283 SidrtQLNEELVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd14204   245 E----DCLDELYDIMYSCWRSDPTDRPTFTQLR 273
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
75-308 3.67e-09

Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Schizosaccharomyces pombe Pat1 (also called Ran1), Saccharomyces cerevisiae VHS1 and KSP1, and similar fungal STKs. Pat1 blocks Mei2, an RNA-binding protein which is indispensable in the initiation of meiosis. Pat1 is inactivated and Mei2 activated, which initiates meiosis, under nutrient-deprived conditions through a signaling cascade involving Ste11. Meiosis induced by Pat1 inactivation may show different characteristics than normal meiosis including aberrant positioning of centromeres. VHS1 was identified in a screen for suppressors of cell cycle arrest at the G1/S transition, while KSP1 may be involved in regulating PRP20, which is required for mRNA export and maintenance of nuclear structure. The Pat1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270895 [Multi-domain]  Cd Length: 267  Bit Score: 57.75  E-value: 3.67e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  75 FKGNVVAIKHVNKK----RIELTRQVLFELKHMRdvqfnhLTRFIGAcidPPNIC-------------IVTEYCPRGSLQ 137
Cdd:cd13993    23 RTGRKYAIKCLYKSgpnsKDGNDFQKLPQLREID------LHRRVSR---HPNIItlhdvfetevaiyIVLEYCPNGDLF 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 138 D-ILENDSINLDWMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRF-VLKITDYGLAsfrsTAEPDDSHALYAK 215
Cdd:cd13993    94 EaITENRIYVGKTELIKNVFLQLIDAVKHCHSLGIY-HRDIKPENILLSQDEgTVKLCDFGLA----TTEKISMDFGVGS 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 216 KLWTAPELLSGNPLPTTGM--QKADVYSFGIILQEIALRSGPFylegldlspkEIVQKVRNGQRPYF--RPSIDRTQLN- 290
Cdd:cd13993   169 EFYMAPECFDEVGRSLKGYpcAAGDIWSLGIILLNLTFGRNPW----------KIASESDPIFYDYYlnSPNLFDVILPm 238
                         250
                  ....*....|....*....
gi 1370514551 291 -EELVLLMERCWAQDPAER 308
Cdd:cd13993   239 sDDFYNLLRQIFTVNPNNR 257
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
94-314 3.95e-09

Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk3, also called lemur tyrosine kinase 3 (Lmtk3) is a receptor kinase containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. The function of Aatyk3 is still unknown. The Aatyk3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 271108 [Multi-domain]  Cd Length: 276  Bit Score: 58.04  E-value: 3.95e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  94 RQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQ---------DILENDSINLDWMFRYSLINDLVKGMA 164
Cdd:cd14206    42 RKFISEAQPYRSLQHPNILQCLGLCTETIPFLLIMEFCQLGDLKrylraqrkaDGMTPDLPTRDLRTLQRMAYEITLGLL 121
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 165 FLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE----PDdshALYAKKLWTAPELLS---GNPLPTTGMQK 236
Cdd:cd14206   122 HLHkNNYI--HSDLALRNCLLTSDLTVRIGDYGLSHNNYKEDyyltPD---RLWIPLRWVAPELLDelhGNLIVVDQSKE 196
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 237 ADVYSFGIILQEI-ALRSGPFYleglDLSPKEIVQKV-RNGQRPYFRPSIdRTQLNEELVLLMERCWaQDPAERPDFGQI 314
Cdd:cd14206   197 SNVWSLGVTIWELfEFGAQPYR----HLSDEEVLTFVvREQQMKLAKPRL-KLPYADYWYEIMQSCW-LPPSQRPSVEEL 270
STKc_ASK cd06624
Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs ...
80-309 4.87e-09

Catalytic domain of the Serine/Threonine Kinase, Apoptosis signal-regulating kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this subfamily are mitogen-activated protein kinase (MAPK) kinase kinases (MAPKKKs or MKKKs) and include ASK1, ASK2, and MAPKKK15. ASK1 (also called MAPKKK5) functions in the c-Jun N-terminal kinase (JNK) and p38 MAPK signaling pathways by directly activating their respective MAPKKs, MKK4/MKK7 and MKK3/MKK6. It plays important roles in cytokine and stress responses, as well as in reactive oxygen species-mediated cellular responses. ASK1 is implicated in various diseases mediated by oxidative stress including inschemic heart disease, hypertension, vessel injury, brain ischemia, Fanconi anemia, asthma, and pulmonary edema, among others. ASK2 (also called MAPKKK6) functions only in a heteromeric complex with ASK1, and can activate ASK1 by direct phosphorylation. The function of MAPKKK15 is still unknown. The ASK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270794 [Multi-domain]  Cd Length: 268  Bit Score: 57.42  E-value: 4.87e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEND----SINLDWMFRYSl 155
Cdd:cd06624    36 IAIKEIPERDSREVQPLHEEIALHSRLSHKNIVQYLGSVSEDGFFKIFMEQVPGGSLSALLRSKwgplKDNENTIGYYT- 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 iNDLVKGMAFLHNSIISsHGSLKSSNCVVDS-RFVLKITDYG----LA-------SFRSTAEpddshalyakklWTAPEL 223
Cdd:cd06624   115 -KQILEGLKYLHDNKIV-HRDIKGDNVLVNTySGVVKISDFGtskrLAginpcteTFTGTLQ------------YMAPEV 180
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 224 LS------GNPlpttgmqkADVYSFGIILQEIALRSGPFYLEGldlSPKEIVQKVrngqrPYFR--PSIDrTQLNEELVL 295
Cdd:cd06624   181 IDkgqrgyGPP--------ADIWSLGCTIIEMATGKPPFIELG---EPQAAMFKV-----GMFKihPEIP-ESLSEEAKS 243
                         250
                  ....*....|....
gi 1370514551 296 LMERCWAQDPAERP 309
Cdd:cd06624   244 FILRCFEPDPDKRA 257
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
65-319 4.99e-09

Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Ror2 plays important roles in skeletal and heart formation. Ror2-deficient mice show widespread bone abnormalities, ventricular defects in the heart, and respiratory dysfunction. Mutations in human Ror2 result in two different bone development genetic disorders, recessive Robinow syndrome and brachydactyly type B. Ror2 is also implicated in neural development. Ror proteins are orphan receptor PTKs (RTKs) containing an extracellular region with immunoglobulin-like, cysteine-rich, and kringle domains, a transmembrane segment, and an intracellular catalytic domain. Ror RTKs are unrelated to the nuclear receptor subfamily called retinoid-related orphan receptors (RORs). RTKs are usually activated through ligand binding, which causes dimerization and autophosphorylation of the intracellular tyr kinase catalytic domain. The Ror2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270673 [Multi-domain]  Cd Length: 284  Bit Score: 57.72  E-value: 4.99e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  65 KYQIFANTGHFKGNVVAIKHVnKKRIELTRQVLFELKHMRDVQFNH--LTRFIGACIDPPNICIVTEYCPRGSLQDIL-- 140
Cdd:cd05091    24 KGHLFGTAPGEQTQAVAIKTL-KDKAEGPLREEFRHEAMLRSRLQHpnIVCLLGVVTKEQPMSMIFSYCSHGDLHEFLvm 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 141 -----ENDSINLDWMFRYSL--------INDLVKGMAFL--HNSIissHGSLKSSNCVVDSRFVLKITDYGLasFRSTAE 205
Cdd:cd05091   103 rsphsDVGSTDDDKTVKSTLepadflhiVTQIAAGMEYLssHHVV---HKDLATRNVLVFDKLNVKISDLGL--FREVYA 177
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 206 PDDSHALYAKKL---WTAPELLSGNPLPTtgmqKADVYSFGIILQEIalrsgpfYLEGLD----LSPKEIVQKVRNGQrp 278
Cdd:cd05091   178 ADYYKLMGNSLLpirWMSPEAIMYGKFSI----DSDIWSYGVVLWEV-------FSYGLQpycgYSNQDVIEMIRNRQ-- 244
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1370514551 279 yFRPSIDrtQLNEELVLLMERCWAQDPAERPDFGQIKGFIR 319
Cdd:cd05091   245 -VLPCPD--DCPAWVYTLMLECWNEFPSRRPRFKDIHSRLR 282
STKc_CDC2L1 cd07843
Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze ...
77-252 5.04e-09

Catalytic domain of the Serine/Threonine Kinase, Cell Division Cycle 2-like 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDC2L1, also called PITSLRE, exists in different isoforms which are named using the alias CDK11(p). The CDC2L1 gene produces two protein products, CDK11(p110) and CDK11(p58). CDC2L1 is also represented by the caspase-processed CDK11(p46). CDK11(p110), the major isoform, associates with cyclin L and is expressed throughout the cell cycle. It is involved in RNA processing and the regulation of transcription. CDK11(p58) associates with cyclin D3 and is expressed during the G2/M phase of the cell cycle. It plays roles in spindle morphogenesis, centrosome maturation, sister chromatid cohesion, and the completion of mitosis. CDK11(p46) is formed from the larger isoforms by caspases during TNFalpha- and Fas-induced apoptosis. It functions as a downstream effector kinase in apoptotic signaling pathways and interacts with eukaryotic initiation factor 3f (eIF3f), p21-activated kinase (PAK1), and Ran-binding protein (RanBPM). CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDC2L1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173741 [Multi-domain]  Cd Length: 293  Bit Score: 57.62  E-value: 5.04e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHV--NKKR----IELTR--QVLFELKHMRDVQFNHLTrfIGACIDppNICIVTEYCPRgSLQDILENDSINLD 148
Cdd:cd07843    30 GEIVALKKLkmEKEKegfpITSLReiNILLKLQHPNIVTVKEVV--VGSNLD--KIYMVMEYVEH-DLKSLMETMKQPFL 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 149 WMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKKLW-TAPELLSG 226
Cdd:cd07843   105 QSEVKCLMLQLLSGVAHLHdNWIL--HRDLKTSNLLLNNRGILKICDFGLA--REYGSPLKPYTQLVVTLWyRAPELLLG 180
                         170       180
                  ....*....|....*....|....*.
gi 1370514551 227 NPLPTTgmqKADVYSFGIILQEIALR 252
Cdd:cd07843   181 AKEYST---AIDMWSVGCIFAELLTK 203
STKc_BMPR1a cd14220
Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; ...
126-315 5.12e-09

Catalytic domain of the Serine/Threonine Kinase, Bone Morphogenetic Protein Type IA Receptor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BMPR1a, also called Activin receptor-Like Kinase 3 (ALK3), functions as a receptor for bone morphogenetic proteins (BMPs), which are involved in the regulation of cell proliferation, survival, differentiation, and apoptosis. BMPs are able to induce bone, cartilage, ligament, and tendon formation, and may play roles in bone diseases and tumors. Germline mutations in BMPR1a are associated with an increased risk to Juvenile Polyposis Syndrome, a hamartomatous disorder that may lead to gastrointestinal cancer. BMPR1a may also play an indirect role in the development of hematopoietic stem cells (HSCs) as osteoblasts are a major component of the HSC niche within the bone marrow. BMPR1a belongs to a group of receptors for the TGFbeta family of secreted signaling molecules that includes TGFbeta, BMPs, activins, growth and differentiation factors, and anti-Mullerian hormone, among others. These receptors contain an extracellular domain that binds ligands, a single transmembrane (TM) region, and a cytoplasmic catalytic kinase domain. Type I receptors, like BMPR1a, are low-affinity receptors that bind ligands only after they are recruited by the ligand/type II high-affinity receptor complex. Following activation, they start intracellular signaling to the nucleus by phosphorylating SMAD proteins. Type I receptors contain an additional domain located between the TM and kinase domains called the GS domain, which contains the activating phosphorylation site and confers preference for specific SMAD proteins. The BMPR1a subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271122 [Multi-domain]  Cd Length: 287  Bit Score: 57.74  E-value: 5.12e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 126 IVTEYCPRGSLQDILENDSINLDWMFRysLINDLVKGMAFLHNSIISSHGS-------LKSSNCVVDSRFVLKITDYGLA 198
Cdd:cd14220    70 LITDYHENGSLYDFLKCTTLDTRALLK--LAYSAACGLCHLHTEIYGTQGKpaiahrdLKSKNILIKKNGTCCIADLGLA 147
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 199 -SFRSTAEPDDS--HALYAKKLWTAPELLSgNPLPTTGMQK---ADVYSFGIILQEIALR--SG--------PFY-LEGL 261
Cdd:cd14220   148 vKFNSDTNEVDVplNTRVGTKRYMAPEVLD-ESLNKNHFQAyimADIYSFGLIIWEMARRcvTGgiveeyqlPYYdMVPS 226
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 262 DLSPKEIVQKV-RNGQRPYFRPSIDRTQLNEELVLLMERCWAQDPAERPDFGQIK 315
Cdd:cd14220   227 DPSYEDMREVVcVKRLRPTVSNRWNSDECLRAVLKLMSECWAHNPASRLTALRIK 281
STKc_PASK cd14004
Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs ...
154-309 6.16e-09

Catalytic domain of the Serine/Threonine kinase, Per-ARNT-Sim (PAS) domain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PASK (or PASKIN) is a nutrient and energy sensor and thus, plays an important role in maintaining cellular energy homeostasis. It coordinates the utilization of glucose in response to metabolic demand. It contains an N-terminal PAS domain which directly interacts and inhibits a C-terminal catalytic kinase domain. The PAS domain serves as a sensory module for different environmental signals such as light, redox state, and various metabolites. Binding of ligands to the PAS domain causes structural changes which leads to kinase activation and the phosphorylation of substrates to trigger the appropriate cellular response. The PASK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270906 [Multi-domain]  Cd Length: 256  Bit Score: 57.01  E-value: 6.16e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 154 SLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAS---------FRSTAEpddshalYAkklwtAPEL 223
Cdd:cd14004   113 YIFRQVADAVKHLHdQGIV--HRDIKDENVILDGNGTIKLIDFGSAAyiksgpfdtFVGTID-------YA-----APEV 178
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 224 LSGNPLpttGMQKADVYSFGIILQEIALRSGPFYlegldlspkEIVQKVRNGQRPYFrpsidrtQLNEELVLLMERCWAQ 303
Cdd:cd14004   179 LRGNPY---GGKEQDIWALGVLLYTLVFKENPFY---------NIEEILEADLRIPY-------AVSEDLIDLISRMLNR 239

                  ....*.
gi 1370514551 304 DPAERP 309
Cdd:cd14004   240 DVGDRP 245
STKc_Kin1_2 cd14077
Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the ...
77-317 8.67e-09

Catalytic domain of Kin1, Kin2, and simlar Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of yeast Kin1, Kin2, and similar proteins. Fission yeast Kin1 is a membrane-associated kinase that is involved in regulating cell surface cohesiveness during interphase. It also plays a role during mitosis, linking actomyosin ring assembly with septum synthesis and membrane closure to ensure separation of daughter cells. Budding yeast Kin1 and Kin2 act downstream of the Rab-GTPase Sec4 and are associated with the exocytic apparatus; they play roles in the secretory pathway. The Kin1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270979 [Multi-domain]  Cd Length: 267  Bit Score: 56.69  E-value: 8.67e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNK--KRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNIC-------------IVTEYCPRGSLQD-IL 140
Cdd:cd14077    26 GEKCAIKIIPRasNAGLKKEREKRLEKEISRDIRTIREAALSSLLNHPHICrlrdflrtpnhyyMLFEYVDGGQLLDyII 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 141 ENDSINLDWMFRYSliNDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRStaePDDSHALYAKKLW- 218
Cdd:cd14077   106 SHGKLKEKQARKFA--RQIASALDYLHrNSIV--HRDLKIENILISKSGNIKIIDFGLSNLYD---PRRLLRTFCGSLYf 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 219 TAPELLSGNPLptTGmQKADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQRPYfrPSidrtQLNEELVLLME 298
Cdd:cd14077   179 AAPELLQAQPY--TG-PEVDVWSFGVVLYVLVCGKVPFD----DENMPALHAKIKKGKVEY--PS----YLSSECKSLIS 245
                         250
                  ....*....|....*....
gi 1370514551 299 RCWAQDPAERPDFGQIKGF 317
Cdd:cd14077   246 RMLVVDPKKRATLEQVLNH 264
PKc_MKK5 cd06619
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
77-322 1.62e-08

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 5; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK5 (also called MEK5) is a dual-specificity PK that phosphorylates its downstream target, extracellular signal-regulated kinase 5 (ERK5), on specific threonine and tyrosine residues. MKK5 is activated by MEKK2 and MEKK3 in response to mitogenic and stress stimuli. The ERK5 cascade promotes cell proliferation, differentiation, neuronal survival, and neuroprotection. This cascade plays an essential role in heart development. Mice deficient in either ERK5 or MKK5 die around embryonic day 10 due to cardiovascular defects including underdevelopment of the myocardium. In addition, MKK5 is associated with metastasis and unfavorable prognosis in prostate cancer. The MKK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132950 [Multi-domain]  Cd Length: 279  Bit Score: 56.04  E-value: 1.62e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRI------------ELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLqDILEndS 144
Cdd:cd06619    15 GTVYKAYHLLTRRIlavkviplditvELQKQIMSELEILYKCDSPYIIGFYGAFFVENRISICTEFMDGGSL-DVYR--K 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 145 INLDWMFRYSLIndLVKGMAFLHnSIISSHGSLKSSNCVVDSRFVLKITDYGLasfrSTAEPDDSHALY-AKKLWTAPEL 223
Cdd:cd06619    92 IPEHVLGRIAVA--VVKGLTYLW-SLKILHRDVKPSNMLVNTRGQVKLCDFGV----STQLVNSIAKTYvGTNAYMAPER 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 224 LSGNPLPTtgmqKADVYSFGIILQEIALRSGP---FYLEGLDLSPKEIVQKVRNgQRPyfrPSIDRTQLNEELVLLMERC 300
Cdd:cd06619   165 ISGEQYGI----HSDVWSLGISFMELALGRFPypqIQKNQGSLMPLQLLQCIVD-EDP---PVLPVGQFSEKFVHFITQC 236
                         250       260
                  ....*....|....*....|....
gi 1370514551 301 WAQDPAERPDFGQIKG--FIRRFN 322
Cdd:cd06619   237 MRKQPKERPAPENLMDhpFIVQYN 260
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
77-309 1.63e-08

Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. YSK4 is a putative MAPKKK, whose mammalian gene has been isolated. MAPKKKs phosphorylate and activate MAPK kinases, which in turn phosphorylate and activate MAPKs during signaling cascades that are important in mediating cellular responses to extracellular signals. The YSK4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270801 [Multi-domain]  Cd Length: 266  Bit Score: 55.91  E-value: 1.63e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHV-----NKKRIELTRQVLFE----LKHMRDVqfnHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINL 147
Cdd:cd06631    25 GQLIAVKQVeldtsDKEKAEKEYEKLQEevdlLKTLKHV---NIVGYLGTCLEDNVVSIFMEFVPGGSIASILARFGALE 101
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 148 DWMF-RYSliNDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKL-----WTA 220
Cdd:cd06631   102 EPVFcRYT--KQILEGVAYLHnNNVI--HRDIKGNNIMLMPNGVIKLIDFGCAKRLCINLSSGSQSQLLKSMrgtpyWMA 177
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 221 PELLSgnplpTTGM-QKADVYSFGIILQEIALRSGPfyleGLDLSPKEIVQKVRNGQRPyfRPSIDRTqLNEELVLLMER 299
Cdd:cd06631   178 PEVIN-----ETGHgRKSDIWSIGCTVFEMATGKPP----WADMNPMAAIFAIGSGRKP--VPRLPDK-FSPEARDFVHA 245
                         250
                  ....*....|
gi 1370514551 300 CWAQDPAERP 309
Cdd:cd06631   246 CLTRDQDERP 255
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
115-309 2.32e-08

Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. Aatyk2 is a member of the Aatyk subfamily of proteins, which are receptor kinases containing a transmembrane segment and a long C-terminal cytoplasmic tail with a catalytic domain. Aatyk2 is also called lemur tyrosine kinase 2 (Lmtk2) or brain-enriched kinase (Brek). It is expressed at high levels in early postnatal brain, and has been shown to play a role in nerve growth factor (NGF) signaling. Studies with knockout mice reveal that Aatyk2 is essential for late stage spermatogenesis. Although it is classified as a PTK based on sequence similarity and the phylogenetic tree, Aatyk2 has been functionally characterized as a serine/threonine kinase. The Aatyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 55.64  E-value: 2.32e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 115 IGACIDPPNICIVTEYCPRGSLQDILENDSINL----DWMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVL 190
Cdd:cd05086    63 VGQCVEAIPYLLVFEFCDLGDLKTYLANQQEKLrgdsQIMLLQRMACEIAAGLAHMHKHNFL-HSDLALRNCYLTSDLTV 141
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 191 KITDYGLASFR---STAEPDDShaLYAKKLWTAPELLS---GNPLPTTGMQKADVYSFGIILQEIALRSGPFYlegLDLS 264
Cdd:cd05086   142 KVGDYGIGFSRykeDYIETDDK--KYAPLRWTAPELVTsfqDGLLAAEQTKYSNIWSLGVTLWELFENAAQPY---SDLS 216
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 1370514551 265 PKEIV-QKVRNGQRPYFRPSIDRTqLNEELVLLMERCWAQdPAERP 309
Cdd:cd05086   217 DREVLnHVIKERQVKLFKPHLEQP-YSDRWYEVLQFCWLS-PEKRP 260
STKc_NLK cd07853
Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer ...
159-308 2.42e-08

Catalytic domain of the Serine/Threonine Kinase, Nemo-Like Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NLK is an atypical mitogen-activated protein kinase (MAPK) that is not regulated by a MAPK kinase. It functions downstream of the MAPK kinase kinase Tak1, which also plays a role in activating the JNK and p38 MAPKs. The Tak1/NLK pathways are regulated by Wnts, a family of secreted proteins that is critical in the control of asymmetric division and cell polarity. NLK can phosphorylate transcription factors from the TCF/LEF family, inhibiting their ability to activate the transcription of target genes. In prostate cancer cells, NLK is involved in regulating androgen receptor-mediated transcription and its expression is altered during cancer progression. MAPKs are important mediators of cellular responses to extracellular signals. The NLK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173748 [Multi-domain]  Cd Length: 372  Bit Score: 56.29  E-value: 2.42e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 159 LVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfrSTAEPDDSHALYAK---KLWTAPELLSGNPLPTTgmq 235
Cdd:cd07853   112 ILRGLKYLHSAGIL-HRDIKPGNLLVNSNCVLKICDFGLA---RVEEPDESKHMTQEvvtQYYRAPEILMGSRHYTS--- 184
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 236 KADVYSFGIILQEIALR------SGPfyLEGLDL-------SPKEIVQKVRNG------QRPYFRPSIDR-----TQLNE 291
Cdd:cd07853   185 AVDIWSVGCIFAELLGRrilfqaQSP--IQQLDLitdllgtPSLEAMRSACEGarahilRGPHKPPSLPVlytlsSQATH 262
                         170
                  ....*....|....*..
gi 1370514551 292 ELVLLMERCWAQDPAER 308
Cdd:cd07853   263 EAVHLLCRMLVFDPDKR 279
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
132-311 2.58e-08

Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. PDGFR alpha is a receptor PTK (RTK) containing an extracellular ligand-binding region with five immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. The binding to its ligands, the PDGFs, leads to receptor dimerization, trans phosphorylation and activation, and intracellular signaling. PDGFR alpha forms homodimers or heterodimers with PDGFR beta, depending on the nature of the PDGF ligand. PDGF-AA, PDGF-AB, and PDGF-CC induce PDGFR alpha homodimerization. PDGFR signaling plays many roles in normal embryonic development and adult physiology. PDGFR alpha signaling is important in the formation of lung alveoli, intestinal villi, mesenchymal dermis, and hair follicles, as well as in the development of oligodendrocytes, retinal astrocytes, neural crest cells, and testicular cells. Aberrant PDGFR alpha expression is associated with some human cancers. Mutations in PDGFR alpha have been found within a subset of gastrointestinal stromal tumors (GISTs). An active fusion protein FIP1L1-PDGFR alpha, derived from interstitial deletion, is associated with idiopathic hypereosinophilic syndrome and chronic eosinophilic leukemia. The PDGFR alpha subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 56.19  E-value: 2.58e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 132 PRGSLQDILEND-SINLDWMFRYSLINDLVKGMAFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAS---FRSTAEPD 207
Cdd:cd05105   218 NDSEVKNLLSDDgSEGLTTLDLLSFTYQVARGMEFL-ASKNCVHRDLAARNVLLAQGKIVKICDFGLARdimHDSNYVSK 296
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 208 DSHALYAKklWTAPELLSGNpLPTTgmqKADVYSFGIILQEIalrsgpFYLEGLdLSPKEIV-----QKVRNGQRpYFRP 282
Cdd:cd05105   297 GSTFLPVK--WMAPESIFDN-LYTT---LSDVWSYGILLWEI------FSLGGT-PYPGMIVdstfyNKIKSGYR-MAKP 362
                         170       180
                  ....*....|....*....|....*....
gi 1370514551 283 SidrtQLNEELVLLMERCWAQDPAERPDF 311
Cdd:cd05105   363 D----HATQEVYDIMVKCWNSEPEKRPSF 387
STKc_CDKL2_3 cd07846
Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; ...
55-314 3.21e-08

Catalytic domain of the Serine/Threonine Kinases, Cyclin-Dependent protein Kinase Like 2 and 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDKL2, also called p56 KKIAMRE, is expressed in testis, kidney, lung, and brain. It functions mainly in mature neurons and plays an important role in learning and memory. Inactivation of CDKL3, also called NKIAMRE (NKIATRE in rat), by translocation is associated with mild mental retardation. It has been reported that CDKL3 is lost in leukemic cells having a chromosome arm 5q deletion, and may contribute to the transformed phenotype. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL2/3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270836 [Multi-domain]  Cd Length: 286  Bit Score: 55.12  E-value: 3.21e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  55 SYGSLMTAHGKyqifaNTGHFkgnvVAIKhvnkKRIELTRQVLFELKHMRDV----QFNH--LTRFIGACIDPPNICIVT 128
Cdd:cd07846    13 SYGMVMKCRHK-----ETGQI----VAIK----KFLESEDDKMVKKIAMREIkmlkQLRHenLVNLIEVFRRKKRWYLVF 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 129 EYCPRGSLQDiLENDSINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPD 207
Cdd:cd07846    80 EFVDHTVLDD-LEKYPNGLDESRVRKYLFQILRGIDFCHsHNII--HRDIKPENILVSQSGVVKLCDFGFA--RTLAAPG 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 208 DSHALYAKKLW-TAPELLSGNplptTGMQKA-DVYSFGIILQEIAlrSGPFYLEG---LD-----------LSPK--EIV 269
Cdd:cd07846   155 EVYTDYVATRWyRAPELLVGD----TKYGKAvDVWAVGCLVTEML--TGEPLFPGdsdIDqlyhiikclgnLIPRhqELF 228
                         250       260       270       280       290
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370514551 270 QKvrngqRPYFR----PSIDRTQ--------LNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd07846   229 QK-----NPLFAgvrlPEVKEVEplerrypkLSGVVIDLAKKCLHIDPDKRPSCSEL 280
STKc_ULK1_2-like cd14120
Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar ...
63-312 3.55e-08

Catalytic domain of the Serine/Threonine kinases, Unc-51-like kinases 1 and 2, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. ULK2 is ubiquitously expressed and is essential in autophagy induction. ULK1 and ULK2 have unique and cell-type specific roles, but also display partially redundant roles in starvation-induced autophagy. They both display neuron-specific functions: ULK1 is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, and axon branching; ULK2 plays a role in axon development. The ULK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271022 [Multi-domain]  Cd Length: 256  Bit Score: 54.68  E-value: 3.55e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  63 HGKYQIFantghFKGN-------VVAIKHVNKKRIELTRQVLF-ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRG 134
Cdd:cd14120     3 HGAFAVV-----FKGRhrkkpdlPVAIKCITKKNLSKSQNLLGkEIKILKELSHENVVALLDCQETSSSVYLVMEYCNGG 77
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 135 SLQDILE------NDSINLdwmfrysLINDLVKGMAFLHNS-IIssHGSLKSSNCVVD---------SRFVLKITDYGLA 198
Cdd:cd14120    78 DLADYLQakgtlsEDTIRV-------FLQQIAAAMKALHSKgIV--HRDLKPQNILLShnsgrkpspNDIRLKIADFGFA 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 199 SFRstaePDDSHA--LYAKKLWTAPELLsgnplptTGMQ---KADVYSFGIILQEIALRSGPFYLEgldlSP---KEIVQ 270
Cdd:cd14120   149 RFL----QDGMMAatLCGSPMYMAPEVI-------MSLQydaKADLWSIGTIVYQCLTGKAPFQAQ----TPqelKAFYE 213
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1370514551 271 KVRNgqrpyFRPSIDRT---QLNEELVLLMERcwaqDPAERPDFG 312
Cdd:cd14120   214 KNAN-----LRPNIPSGtspALKDLLLGLLKR----NPKDRIDFE 249
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
103-314 5.45e-08

Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK16 is associated with many names including Myristylated and Palmitylated Serine/threonine Kinase 1 (MPSK1), Kinase related to cerevisiae and thaliana (Krct), and Protein Kinase expressed in day 12 fetal liver (PKL12). It is widely expressed in mammals with highest levels found in liver, testis, and kidney. It is localized in the Golgi but is translocated to the nucleus upon disorganization of the Golgi. STK16 is constitutively active and is capable of phosphorylating itself and other substrates. It may be involved in regulating stromal-epithelial interactions during mammary gland ductal morphogenesis. It may also function as a transcriptional co-activator of type-C natriuretic peptide and VEGF. The STK16 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270888 [Multi-domain]  Cd Length: 282  Bit Score: 54.61  E-value: 5.45e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 103 MRDVQ----FNH--LTRFIGACIDP-----PNICIVTEYCPRGSLQDILENDSIN---------LDWMFRyslindLVKG 162
Cdd:cd13986    45 MREIEnyrlFNHpnILRLLDSQIVKeaggkKEVYLLLPYYKRGSLQDEIERRLVKgtffpedriLHIFLG------ICRG 118
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 163 MAFLH--NSIISSHGSLKSSNCVVDSRFVLKITDYGLASfRSTAEPDDSHALYAKKLWT---------APELLSGnPLPT 231
Cdd:cd13986   119 LKAMHepELVPYAHRDIKPGNVLLSEDDEPILMDLGSMN-PARIEIEGRREALALQDWAaehctmpyrAPELFDV-KSHC 196
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 232 TGMQKADVYSFGIILQEIALRSGPFYLEGLDLSPkeIVQKVRNGQRPYFRPSIdrtqLNEELVLLMERCWAQDPAERPDF 311
Cdd:cd13986   197 TIDEKTDIWSLGCTLYALMYGESPFERIFQKGDS--LALAVLSGNYSFPDNSR----YSEELHQLVKSMLVVNPAERPSI 270

                  ...
gi 1370514551 312 GQI 314
Cdd:cd13986   271 DDL 273
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
77-259 6.08e-08

Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine/threonine kinases (STKs), p21-activated kinase (PAK) 3, catalytic (c) domain. STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs from higher eukaryotes are classified into two groups (I and II), according to their biochemical and structural features. PAK3 belongs to group I. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAK3 is highly expressed in the brain. It is implicated in neuronal plasticity, synapse formation, dendritic spine morphogenesis, cell cycle progression, neuronal migration, and apoptosis. Inactivating mutations in the PAK3 gene cause X-linked non-syndromic mental retardation, the severity of which depends on the site of the mutation.


Pssm-ID: 132987 [Multi-domain]  Cd Length: 297  Bit Score: 54.34  E-value: 6.08e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMfrYSLI 156
Cdd:cd06656    44 GQEVAIKQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETCMDEGQI--AAVC 121
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASfRSTAEPDDSHALYAKKLWTAPELLSGNPLPTtgmq 235
Cdd:cd06656   122 RECLQALDFLHsNQVI--HRDIKSDNILLGMDGSVKLTDFGFCA-QITPEQSKRSTMVGTPYWMAPEVVTRKAYGP---- 194
                         170       180
                  ....*....|....*....|....
gi 1370514551 236 KADVYSFGIILQEIALRSGPFYLE 259
Cdd:cd06656   195 KVDIWSLGIMAIEMVEGEPPYLNE 218
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
60-311 1.06e-07

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK2 is ubiquitously expressed and is essential in autophagy induction. It displays partially redundant functions with ULK1 and is able to compensate for the loss of ULK1 in non-selective autophagy. It also displays neuron-specific functions and is important in axon development. The ULK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271103 [Multi-domain]  Cd Length: 271  Bit Score: 53.47  E-value: 1.06e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  60 MTAHGKYQIFANTGHFKGN--VVAIKHVNKKRIELTrQVLF--ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGS 135
Cdd:cd14201    13 LVGHGAFAVVFKGRHRKKTdwEVAIKSINKKNLSKS-QILLgkEIKILKELQHENIVALYDVQEMPNSVFLVMEYCNGGD 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 136 LQDILENDSINLDWMFRYsLINDLVKGMAFLHNSIIsSHGSLKSSNCVVD---------SRFVLKITDYGLASFRSTAEP 206
Cdd:cd14201    92 LADYLQAKGTLSEDTIRV-FLQQIAAAMRILHSKGI-IHRDLKPQNILLSyasrkkssvSGIRIKIADFGFARYLQSNMM 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 207 ddSHALYAKKLWTAPELLSGNPLPTtgmqKADVYSFGIILQEIALRSGPFYLEgldlSPKEI---VQKVRNgqrpyFRPS 283
Cdd:cd14201   170 --AATLCGSPMYMAPEVIMSQHYDA----KADLWSIGTVIYQCLVGKPPFQAN----SPQDLrmfYEKNKN-----LQPS 234
                         250       260       270
                  ....*....|....*....|....*....|.
gi 1370514551 284 IDR---TQLNEELVLLMERcwaqDPAERPDF 311
Cdd:cd14201   235 IPRetsPYLADLLLGLLQR----NQKDRMDF 261
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
77-258 1.23e-07

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK1 is important in the regulation of many cellular processes including cytoskeletal dynamics, cell motility, growth, and proliferation. Although PAK1 has been regarded mainly as a cytosolic protein, recent reports indicate that PAK1 also exists in significant amounts in the nucleus, where it is involved in transcription modulation and in cell cycle regulatory events. PAK1 is also involved in transformation and tumorigenesis. Its overexpression, hyperactivation and increased nuclear accumulation is correlated to breast cancer invasiveness and progression. Nuclear accumulation is also linked to tamoxifen resistance in breast cancer cells. PAK1 belongs to the group I PAKs, which contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270820 [Multi-domain]  Cd Length: 296  Bit Score: 53.57  E-value: 1.23e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMfrYSLI 156
Cdd:cd06654    45 GQEVAIRQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETCMDEGQI--AAVC 122
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASfRSTAEPDDSHALYAKKLWTAPELLSGNPLPTtgmq 235
Cdd:cd06654   123 RECLQALEFLHsNQVI--HRDIKSDNILLGMDGSVKLTDFGFCA-QITPEQSKRSTMVGTPYWMAPEVVTRKAYGP---- 195
                         170       180
                  ....*....|....*....|...
gi 1370514551 236 KADVYSFGIILQEIaLRSGPFYL 258
Cdd:cd06654   196 KVDIWSLGIMAIEM-IEGEPPYL 217
STKc_Nek8 cd08220
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
124-314 1.41e-07

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek8 contains an N-terminal kinase catalytic domain and a C-terminal RCC1 (regulator of chromosome condensation) domain. A double point mutation in Nek8 causes cystic kidney disease in mice that genetically resembles human autosomal recessive polycystic kidney disease (ARPKD). Nek8 is also associated with a rare form of juvenile renal cystic disease, nephronophthisis type 9. It has been suggested that a defect in the ciliary localization of Nek8 contributes to the development of cysts manifested by these diseases. Nek8 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270859 [Multi-domain]  Cd Length: 256  Bit Score: 52.81  E-value: 1.41e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 124 ICIVTEYCPRGSLQDILE---NDSINLDWMFRYslINDLVKGMAFLHNSIISsHGSLKSSNCVVDS-RFVLKITDYGLAS 199
Cdd:cd08220    74 LMIVMEYAPGGTLFEYIQqrkGSLLSEEEILHF--FVQILLALHHVHSKQIL-HRDLKTQNILLNKkRTVVKIGDFGISK 150
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 200 FRSTAEpdDSHALYAKKLWTAPELLSGNPLpttgMQKADVYSFGIILQEIALRSGPFYLEGLdlspKEIVQKVRNGqrpY 279
Cdd:cd08220   151 ILSSKS--KAYTVVGTPCYISPELCEGKPY----NQKSDIWALGCVLYELASLKRAFEAANL----PALVLKIMRG---T 217
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 1370514551 280 FRPSIDRtqLNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd08220   218 FAPISDR--YSEELRHLILSMLHLDPNKRPTLSEI 250
STKc_Nek7 cd08229
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
174-322 1.50e-07

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 7; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek7 is required for mitotic spindle formation and cytokinesis. It is enriched in the centrosome and is critical for microtubule nucleation. Nek7 is activated by Nek9 during mitosis, and may regulate the p70 ribosomal S6 kinase. It is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270866 [Multi-domain]  Cd Length: 292  Bit Score: 53.11  E-value: 1.50e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 174 HGSLKSSNCVVDSRFVLKITDYGLASFRSTaEPDDSHALYAKKLWTAPELLSGNPLPTtgmqKADVYSFGIILQEIALRS 253
Cdd:cd08229   151 HRDIKPANVFITATGVVKLGDLGLGRFFSS-KTTAAHSLVGTPYYMSPERIHENGYNF----KSDIWSLGCLLYEMAALQ 225
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370514551 254 GPFYLEGLDLSpkEIVQKVRngQRPYfrPSIDRTQLNEELVLLMERCWAQDPAERPDFGQIKGFIRRFN 322
Cdd:cd08229   226 SPFYGDKMNLY--SLCKKIE--QCDY--PPLPSDHYSEELRQLVNMCINPDPEKRPDITYVYDVAKRMH 288
PKc_MEK1 cd06650
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
95-324 1.61e-07

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase 1; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 is a dual-specificity PK and a MAPK kinase (MAPKK or MKK) that phosphorylates and activates the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. MEK1 also plays a role in cell cycle control. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270816 [Multi-domain]  Cd Length: 319  Bit Score: 53.52  E-value: 1.61e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN-DSINLDWMFRYSLIndLVKGMAFLHNSIISS 173
Cdd:cd06650    49 QIIRELQVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKaGRIPEQILGKVSIA--VIKGLTYLREKHKIM 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 174 HGSLKSSNCVVDSRFVLKITDYGLasfrsTAEPDDSHA--LYAKKLWTAPELLSGnplpTTGMQKADVYSFGIILQEIAL 251
Cdd:cd06650   127 HRDVKPSNILVNSRGEIKLCDFGV-----SGQLIDSMAnsFVGTRSYMSPERLQG----THYSVQSDIWSMGLSLVEMAV 197
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 252 RSGPF-----------YLEGLDLSPKEIVQKVRNGQRPY------FRPSIDRTQL-----NE------------ELVLLM 297
Cdd:cd06650   198 GRYPIpppdakelelmFGCQVEGDAAETPPRPRTPGRPLssygmdSRPPMAIFELldyivNEpppklpsgvfslEFQDFV 277
                         250       260
                  ....*....|....*....|....*....
gi 1370514551 298 ERCWAQDPAERPDFGQ--IKGFIRRFNKE 324
Cdd:cd06650   278 NKCLIKNPAERADLKQlmVHAFIKRSDAE 306
STKc_STK33 cd14097
Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the ...
81-256 1.76e-07

Catalytic domain of Serine/Threonine Kinase 33; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK33 is highly expressed in the testis and is present in low levels in most tissues. It may be involved in spermatogenesis and organ ontogenesis. It interacts with and phosphorylates vimentin and may be involved in regulating intermediate filament cytoskeletal dynamics. Its role in promoting the cell viability of KRAS-dependent cancer cells is under debate; some studies have found STK33 to promote cancer cell viability, while other studies have found it to be non-essential. KRAS is the most commonly mutated human oncogene, thus, studies on the role of STK33 in KRAS mutant cancer cells are important. The STK33 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270999 [Multi-domain]  Cd Length: 266  Bit Score: 52.94  E-value: 1.76e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  81 AIKHVNKKRIELTRQVLFE-----LKHMRDVQFNHLTRFIGAcidPPNICIVTEYCPRGSLQDILENDSINLDWMFRYsL 155
Cdd:cd14097    30 AIKKINREKAGSSAVKLLErevdiLKHVNHAHIIHLEEVFET---PKRMYLVMELCEDGELKELLLRKGFFSENETRH-I 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 INDLVKGMAFLHNSIISsHGSLKSSNCVVDS-------RFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGNP 228
Cdd:cd14097   106 IQSLASAVAYLHKNDIV-HRDLKLENILVKSsiidnndKLNIKVTDFGLSVQKYGLGEDMLQETCGTPIYMAPEVISAHG 184
                         170       180
                  ....*....|....*....|....*...
gi 1370514551 229 LPttgmQKADVYSFGIILQEIALRSGPF 256
Cdd:cd14097   185 YS----QQCDIWSIGVIMYMLLCGEPPF 208
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
77-258 2.29e-07

Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Group I PAKs, also called conventional PAKs, include PAK1, PAK2, and PAK3. Group I PAKs contain a PBD (p21-binding domain) overlapping with an AID (autoinhibitory domain), a C-terminal catalytic domain, SH3 binding sites and a non-classical SH3 binding site for PIX (PAK-interacting exchange factor). They interact with the SH3 domain containing proteins Nck, Grb2 and PIX. Binding of group I PAKs to activated GTPases leads to conformational changes that destabilize the AID, allowing autophosphorylation and full activation of the kinase domain. Known group I PAK substrates include MLCK, Bad, Raf, MEK1, LIMK, Merlin, Vimentin, Myc, Stat5a, and Aurora A, among others. PAKs are Rho family GTPase-regulated kinases that serve as important mediators in the function of Cdc42 (cell division cycle 42) and Rac. PAKs are implicated in the regulation of many cellular processes including growth factor receptor-mediated proliferation, cell polarity, cell motility, cell death and survival, and actin cytoskeleton organization. The PAK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270814 [Multi-domain]  Cd Length: 261  Bit Score: 52.24  E-value: 2.29e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSinLDWMFRYSLI 156
Cdd:cd06647    32 GQEVAIKQMNLQQQPKKELIINEILVMRENKNPNIVNYLDSYLVGDELWVVMEYLAGGSLTDVVTETC--MDEGQIAAVC 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASfRSTAEPDDSHALYAKKLWTAPELLSGNPLPTtgmq 235
Cdd:cd06647   110 RECLQALEFLHsNQVI--HRDIKSDNILLGMDGSVKLTDFGFCA-QITPEQSKRSTMVGTPYWMAPEVVTRKAYGP---- 182
                         170       180
                  ....*....|....*....|...
gi 1370514551 236 KADVYSFGIILQEIaLRSGPFYL 258
Cdd:cd06647   183 KVDIWSLGIMAIEM-VEGEPPYL 204
STKc_MAPK cd07834
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs ...
77-309 2.31e-07

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPKs serve as important mediators of cellular responses to extracellular signals. They control critical cellular functions including differentiation, proliferation, migration, and apoptosis. They are also implicated in the pathogenesis of many diseases including multiple types of cancer, stroke, diabetes, and chronic inflammation. Typical MAPK pathways involve a triple kinase core cascade comprising of the MAPK, which is phosphorylated and activated by a MAPK kinase (MAP2K or MKK), which itself is phosphorylated and activated by a MAPK kinase kinase (MAP3K or MKKK). Each cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. There are three typical MAPK subfamilies: Extracellular signal-Regulated Kinase (ERK), c-Jun N-terminal Kinase (JNK), and p38. Some MAPKs are atypical in that they are not regulated by MAP2Ks. These include MAPK4, MAPK6, NLK, and ERK7. The MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270828 [Multi-domain]  Cd Length: 329  Bit Score: 52.91  E-value: 2.31e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNK--KRIELTRQVLFELKHMRdvQFNH-----LTRFIGAcIDPPN---ICIVTEY----------CPRgsl 136
Cdd:cd07834    25 GRKVAIKKISNvfDDLIDAKRILREIKILR--HLKHeniigLLDILRP-PSPEEfndVYIVTELmetdlhkvikSPQ--- 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 137 qdILENDSINLdwmFRYSLIndlvKGMAFLHNS-IIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHAL--Y 213
Cdd:cd07834    99 --PLTDDHIQY---FLYQIL----RGLKYLHSAgVI--HRDLKPSNILVNSNCDLKICDFGLA--RGVDPDEDKGFLteY 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 214 AKKLW-TAPELLSGNPLPTTGMqkaDVYSFGIILQEIALR----SGPFYLEGLDL------SPK-EIVQKVRNG------ 275
Cdd:cd07834   166 VVTRWyRAPELLLSSKKYTKAI---DIWSVGCIFAELLTRkplfPGRDYIDQLNLivevlgTPSeEDLKFISSEkarnyl 242
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1370514551 276 QRPYFRPSIDRTQL----NEELVLLMERCWAQDPAERP 309
Cdd:cd07834   243 KSLPKKPKKPLSEVfpgaSPEAIDLLEKMLVFNPKKRI 280
PKc_MEK cd06615
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP) ...
95-324 2.50e-07

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MEK1 and MEK2 are MAPK kinases (MAPKKs or MKKs), and are dual-specificity PKs that phosphorylate and activate the downstream targets, ERK1 and ERK2, on specific threonine and tyrosine residues. The ERK cascade starts with extracellular signals including growth factors, hormones, and neurotransmitters, which act through receptors and ion channels to initiate intracellular signaling that leads to the activation at the MAPKKK (Raf-1 or MOS) level, which leads to the transmission of signals to MEK1/2, and finally to ERK1/2. The ERK cascade plays an important role in cell proliferation, differentiation, oncogenic transformation, and cell cycle control, as well as in apoptosis and cell survival under certain conditions. This cascade has also been implicated in synaptic plasticity, migration, morphological determination, and stress response immunological reactions. Gain-of-function mutations in genes encoding ERK cascade proteins, including MEK1/2, cause cardiofaciocutaneous (CFC) syndrome, a condition leading to multiple congenital anomalies and mental retardation in patients. The MEK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132946 [Multi-domain]  Cd Length: 308  Bit Score: 52.82  E-value: 2.50e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  95 QVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN-DSINLDWMFRYSLIndLVKGMAFLHNSIISS 173
Cdd:cd06615    45 QIIRELKVLHECNSPYIVGFYGAFYSDGEISICMEHMDGGSLDQVLKKaGRIPENILGKISIA--VLRGLTYLREKHKIM 122
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 174 HGSLKSSNCVVDSRFVLKITDYGLasfrsTAEPDDSHA--LYAKKLWTAPELLSGNPLPTtgmqKADVYSFGIILQEIAL 251
Cdd:cd06615   123 HRDVKPSNILVNSRGEIKLCDFGV-----SGQLIDSMAnsFVGTRSYMSPERLQGTHYTV----QSDIWSLGLSLVEMAI 193
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 252 RSGPF-------YLEGLDLSPKEIVQKVRNGQRPYFRPSIDRTQ---------LNE------------ELVLLMERCWAQ 303
Cdd:cd06615   194 GRYPIpppdakeLEAMFGRPVSEGEAKESHRPVSGHPPDSPRPMaifelldyiVNEpppklpsgafsdEFQDFVDKCLKK 273
                         250       260
                  ....*....|....*....|...
gi 1370514551 304 DPAERPDFGQIKG--FIRRFNKE 324
Cdd:cd06615   274 NPKERADLKELTKhpFIKRAELE 296
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
71-309 2.51e-07

Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 and CDK6 partner with D-type cyclins to regulate the early G1 phase of the cell cycle. They are the first kinases activated by mitogenic signals to release cells from the G0 arrested state. CDK4 and CDK6 are both expressed ubiquitously, associate with all three D cyclins (D1, D2 and D3), and phosphorylate the retinoblastoma (pRb) protein. They are also regulated by the INK4 family of inhibitors which associate with either the CDK alone or the CDK/cyclin complex. CDK4 and CDK6 show differences in subcellular localization, sensitivity to some inhibitors, timing in activation, tumor selectivity, and possibly substrate profiles. Although CDK4 and CDK6 seem to show some redundancy, they also have discrete, nonoverlapping functions. CDK6 plays an important role in cell differentiation. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK4/6-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270831 [Multi-domain]  Cd Length: 287  Bit Score: 52.66  E-value: 2.51e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  71 NTGHFkgnvVAIKHVnkkRIELTRQ-----VLFELKHMRDVQ-FNH--LTRFIGACIDPPN-----ICIVTEYCPRgSLQ 137
Cdd:cd07838    22 QDGRF----VALKKV---RVPLSEEgiplsTIREIALLKQLEsFEHpnVVRLLDVCHGPRTdrelkLTLVFEHVDQ-DLA 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 138 DILEN--------DSINldwmfrySLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLA---SFRSTAE 205
Cdd:cd07838    94 TYLDKcpkpglppETIK-------DLMRQLLRGLDFLHsHRIV--HRDLKPQNILVTSDGQVKLADFGLAriySFEMALT 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 206 PddshalYAKKLW-TAPELLSGNPLPTTgmqkADVYSFGIILQEIALRSGPF--YLEGLDLS--------------PKEI 268
Cdd:cd07838   165 S------VVVTLWyRAPEVLLQSSYATP----VDMWSVGCIFAELFNRRPLFrgSSEADQLGkifdviglpseeewPRNS 234
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|...
gi 1370514551 269 VQKvRNGQRPYFRPSI--DRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd07838   235 ALP-RSSFPSYTPRPFksFVPEIDEEGLDLLKKMLTFNPHKRI 276
STKc_CDKL5 cd07848
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs ...
60-308 2.83e-07

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase Like 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Mutations in the gene encoding CDKL5, previously called STK9, are associated with early onset epilepsy and severe mental retardation [X-linked infantile spasm syndrome (ISSX) or West syndrome]. In addition, CDKL5 mutations also sometimes cause a phenotype similar to Rett syndrome (RTT), a progressive neurodevelopmental disorder. These pathogenic mutations are located in the N-terminal portion of the protein within the kinase domain. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDKL5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270838 [Multi-domain]  Cd Length: 287  Bit Score: 52.31  E-value: 2.83e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  60 MTAHGKYQIFANTGHFKGN-VVAIKHV--NKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSL 136
Cdd:cd07848     8 VVGEGAYGVVLKCRHKETKeIVAIKKFkdSEENEEVKETTLRELKMLRTLKQENIVELKEAFRRRGKLYLVFEYVEKNML 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 137 QDILENDSINLDWMFRySLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSH--ALY 213
Cdd:cd07848    88 ELLEEMPNGVPPEKVR-SYIYQLIKAIHWCHkNDIV--HRDIKPENLLISHNDVLKLCDFGFA--RNLSEGSNANytEYV 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 214 AKKLWTAPELLSGNPLPttgmQKADVYSFGIILQEIAlrsgpfylEGLDLSPKE-------IVQKVRNG----------Q 276
Cdd:cd07848   163 ATRWYRSPELLLGAPYG----KAVDMWSVGCILGELS--------DGQPLFPGEseidqlfTIQKVLGPlpaeqmklfyS 230
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....*
gi 1370514551 277 RPYFR----PSIDRTQ---------LNEELVLLMERCWAQDPAER 308
Cdd:cd07848   231 NPRFHglrfPAVNHPQslerrylgiLSGVLLDLMKNLLKLNPTDR 275
STKc_MSK2_N cd05614
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
62-308 3.04e-07

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK2 and MSK1 play nonredundant roles in activating histone H3 kinases, which play pivotal roles in compaction of the chromatin fiber. MSK2 is the required H3 kinase in response to stress stimuli and activation of the p38 MAPK pathway. MSK2 also plays a role in the pathogenesis of psoriasis. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family, similar to 90 kDa ribosomal protein S6 kinases (RSKs). MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270765 [Multi-domain]  Cd Length: 332  Bit Score: 52.61  E-value: 3.04e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  62 AHGK-YQIFANTGHFKGNVVAIKHVNK-------KRIELTRQVLFELKHMRDVQFnhLTRFIGACIDPPNICIVTEYCPR 133
Cdd:cd05614    12 AYGKvFLVRKVSGHDANKLYAMKVLRKaalvqkaKTVEHTRTERNVLEHVRQSPF--LVTLHYAFQTDAKLHLILDYVSG 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 134 GSL-QDILENDSINLDWMFRYSliNDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHA 211
Cdd:cd05614    90 GELfTHLYQRDHFSEDEVRFYS--GEIILALEHLHKlGIV--YRDIKLENILLDSEGHVVLTDFGLSKEFLTEEKERTYS 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 212 LYAKKLWTAPELLSGNplptTGMQKA-DVYSFGIILQEIALRSGPFYLEGLDLSPKEIVQKVRNGQRPYfrPSIdrtqLN 290
Cdd:cd05614   166 FCGTIEYMAPEIIRGK----SGHGKAvDWWSLGILMFELLTGASPFTLEGEKNTQSEVSRRILKCDPPF--PSF----IG 235
                         250
                  ....*....|....*...
gi 1370514551 291 EELVLLMERCWAQDPAER 308
Cdd:cd05614   236 PVARDLLQKLLCKDPKKR 253
STKc_BRSK1_2 cd14081
Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the ...
77-276 3.31e-07

Catalytic domain of Brain-specific serine/threonine-protein kinases 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BRSK1, also called SAD-B or SAD1 (Synapses of Amphids Defective homolog 1), and BRSK2, also called SAD-A, are highly expressed in mammalian forebrain. They play important roles in establishing neuronal polarity. BRSK1/2 double knock-out mice die soon after birth, showing thin cerebral cortices due to disordered subplate layers and neurons that lack distinct axons and dendrites. BRSK1 regulates presynaptic neurotransmitter release. Its activity fluctuates during cell cysle progression and it acts as a regulator of centrosome duplication. BRSK2 is also abundant in pancreatic islets, where it is involved in the regulation of glucose-stimulated insulin secretion. The BRSK1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270983 [Multi-domain]  Cd Length: 255  Bit Score: 51.87  E-value: 3.31e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLF---ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQD-ILENDSINLDWMFR 152
Cdd:cd14081    26 GQKVAIKIVNKEKLSKESVLMKverEIAIMKLIEHPNVLKLYDVYENKKYLYLVLEYVSGGELFDyLVKKGRLTEKEARK 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 YslINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFrstaEPDDS---------HalYAkklwtAPEL 223
Cdd:cd14081   106 F--FRQIISALDYCHSHSIC-HRDLKPENLLLDEKNNIKIADFGMASL----QPEGSlletscgspH--YA-----CPEV 171
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 224 LSGNPLptTGmQKADVYSFGIILqeIALRSG--PFYLEGLDlspkEIVQKVRNGQ 276
Cdd:cd14081   172 IKGEKY--DG-RKADIWSCGVIL--YALLVGalPFDDDNLR----QLLEKVKRGV 217
STKc_SnRK2-3 cd14665
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
77-315 3.33e-07

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2, group 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271135 [Multi-domain]  Cd Length: 257  Bit Score: 51.91  E-value: 3.33e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRiELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSinldwmfRYS-- 154
Cdd:cd14665    25 KELVAVKYIERGE-KIDENVQREIINHRSLRHPNIVRFKEVILTPTHLAIVMEYAAGGELFERICNAG-------RFSed 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 ----LINDLVKGMAFLHnSIISSHGSLKSSNCVVDSRFV--LKITDYGLAsfRSTAEPDDSHALYAKKLWTAPELLSGNP 228
Cdd:cd14665    97 earfFFQQLISGVSYCH-SMQICHRDLKLENTLLDGSPAprLKICDFGYS--KSSVLHSQPKSTVGTPAYIAPEVLLKKE 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 LPTtgmQKADVYSFGIILQEIALRSGPFYLEGLDLSPKEIVQKVRNGQrpYFRPsiDRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd14665   174 YDG---KIADVWSCGVTLYVMLVGAYPFEDPEEPRNFRKTIQRILSVQ--YSIP--DYVHISPECRHLISRIFVADPATR 246

                  ....*..
gi 1370514551 309 PDFGQIK 315
Cdd:cd14665   247 ITIPEIR 253
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
99-314 3.35e-07

Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. The Trk subfamily consists of TrkA, TrkB, TrkC, and similar proteins. They are receptor PTKs (RTKs) containing an extracellular region with arrays of leucine-rich motifs flanked by two cysteine-rich clusters followed by two immunoglobulin-like domains, a transmembrane segment, and an intracellular catalytic domain. Binding to their ligands, the nerve growth factor (NGF) family of neutrotrophins, leads to Trk receptor oligomerization and activation of the catalytic domain. Trk receptors are mainly expressed in the peripheral and central nervous systems. They play important roles in cell fate determination, neuronal survival and differentiation, as well as in the regulation of synaptic plasticity. Altered expression of Trk receptors is associated with many human diseases. The Trk subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as protein serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270643 [Multi-domain]  Cd Length: 280  Bit Score: 52.08  E-value: 3.35e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-----------ENDS----INLDWMFRYSLinDLVKGM 163
Cdd:cd05049    58 EAELLTNLQHENIVKFYGVCTEGDPLLMVFEYMEHGDLNKFLrshgpdaaflaSEDSapgeLTLSQLLHIAV--QIASGM 135
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 164 AFLhNSIISSHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPD----DSHALYAKKlWTAPELLSGNPLPTtgmqKADV 239
Cdd:cd05049   136 VYL-ASQHFVHRDLATRNCLVGTNLVVKIGDFGMS--RDIYSTDyyrvGGHTMLPIR-WMPPESILYRKFTT----ESDV 207
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370514551 240 YSFGIILQEI-ALRSGPFYleglDLSPKEIVQKVRNG---QRPYFRPSidrtqlneELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05049   208 WSFGVVLWEIfTYGKQPWF----QLSNTEVIECITQGrllQRPRTCPS--------EVYAVMLGCWKREPQQRLNIKDI 274
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
77-309 4.99e-07

Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. STRAD forms a complex with the scaffolding protein MO25, and the serine/threonine kinase (STK), LKB1, resulting in the activation of the kinase. In the complex, LKB1 phosphorylates and activates adenosine monophosphate-activated protein kinases (AMPKs), which regulate cell energy metabolism and cell polarity. LKB1 is a tumor suppressor linked to the rare inherited disease, Peutz-Jeghers syndrome, which is characterized by a predisposition to benign polyps and hyperpigmentation of the buccal mucosa. There are two forms of STRAD, alpha and beta, that complex with LKB1 and MO25. The structure of STRAD-alpha is available and shows that this protein binds ATP, has an ordered activation loop, and adopts a closed conformation typical of fully active protein kinases. It does not possess activity due to nonconservative substitutions of essential catalytic residues. ATP binding enhances the affinity of STRAD for MO25. The conformation of STRAD-alpha stabilized through ATP and MO25 may be needed to activate LKB1. The STRAD subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270856 [Multi-domain]  Cd Length: 315  Bit Score: 51.91  E-value: 4.99e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVN-----KKRIELTRQvlfELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENdsinldwMF 151
Cdd:cd08216    25 NTLVAVKKINlesdsKEDLKFLQQ---EILTSRQLQHPNILPYVTSFVVDNDLYVVTPLMAYGSCRDLLKT-------HF 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSL--------INDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITdyGLASFRSTAEPD------DSHALYAKK 216
Cdd:cd08216    95 PEGLpelaiafiLRDVLNALEYIHsKGYI--HRSVKASHILISGDGKVVLS--GLRYAYSMVKHGkrqrvvHDFPKSSEK 170
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 217 L--WTAPELLSGNPLPTTgmQKADVYSFGIILQEIALRSGPF--------YLEG--------LDLS--PKEIVQKVRNGQ 276
Cdd:cd08216   171 NlpWLSPEVLQQNLLGYN--EKSDIYSVGITACELANGVVPFsdmpatqmLLEKvrgttpqlLDCStyPLEEDSMSQSED 248
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1370514551 277 RPYFRPSIDRT-------QLNEELVLLMERCWAQDPAERP 309
Cdd:cd08216   249 SSTEHPNNRDTrdipyqrTFSEAFHQFVELCLQRDPELRP 288
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
80-276 8.26e-07

Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDK1 carries an N-terminal catalytic domain and a C-terminal pleckstrin homology (PH) domain that binds phosphoinositides. It phosphorylates the activation loop of AGC kinases that are regulated by PI3K such as PKB, SGK, and PKC, among others, and is crucial for their activation. Thus, it contributes in regulating many processes including metabolism, growth, proliferation, and survival. PDK1 also has the ability to autophosphorylate and is constitutively active in mammalian cells. It is essential for normal embryo development and is important in regulating cell volume. The PDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270733 [Multi-domain]  Cd Length: 278  Bit Score: 50.68  E-value: 8.26e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRI---------ELTRQVLFELKHmrdvqfNHLTRFIGACIDPPNICIVTEYCPRGSLQDILE-NDSINLDW 149
Cdd:cd05581    29 YAIKVLDKRHIikekkvkyvTIEKEVLSRLAH------PGIVKLYYTFQDESKLYFVLEYAPNGDLLEYIRkYGSLDEKC 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 150 MFRYSliNDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASF-----RSTAEPDDSHALYAKKL------ 217
Cdd:cd05581   103 TRFYT--AEIVLALEYLHsKGII--HRDLKPENILLDEDMHIKITDFGTAKVlgpdsSPESTKGDADSQIAYNQaraasf 178
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 218 -----WTAPELLSGNPlptTGMQkADVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQ 276
Cdd:cd05581   179 vgtaeYVSPELLNEKP---AGKS-SDLWALGCIIYQMLTGKPPFR----GSNEYLTFQKIVKLE 234
STKc_WNK4 cd14033
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze ...
99-308 9.27e-07

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK4 shows a restricted expression pattern and is usually found in epithelial cells. It is expressed in nephrons and in extrarenal tissues including intestine, eye, mammary glands, and prostate. WNK4 regulates a variety of ion transport proteins including apical or basolateral ion transporters, ion channels in the transcellular pathway, and claudins in the paracellular pathway. Mutations in WNK4 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK4 inhibits the activity of the thiazide-sensitive Na-Cl cotransporter (NCC), which is responsible for about 15% of NaCl reabsorption in the kidney. It also inhibits the renal outer medullary potassium channel (ROMK) and decreases its surface expression. Hypertension and hyperkalemia in PHAII patients with WNK4 mutations may be partly due to increased NaCl reabsorption through NCC and impaired renal potassium secretion by ROMK, respectively. The WNK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270935 [Multi-domain]  Cd Length: 261  Bit Score: 50.39  E-value: 9.27e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQFNHLTRFIGA--CIDPPNICI--VTEYCPRGSLQDILEN-DSINLDWMFRYSliNDLVKGMAFLHNS---I 170
Cdd:cd14033    50 EVEMLKGLQHPNIVRFYDSwkSTVRGHKCIilVTELMTSGTLKTYLKRfREMKLKLLQRWS--RQILKGLHFLHSRcppI 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 171 IssHGSLKSSNCVVDS-RFVLKITDYGLASFRStaepddshALYAKKLWTAPELLSGNPLPTTGMQKADVYSFGIILQEI 249
Cdd:cd14033   128 L--HRDLKCDNIFITGpTGSVKIGDLGLATLKR--------ASFAKSVIGTPEFMAPEMYEEKYDEAVDVYAFGMCILEM 197
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370514551 250 ALRSGPfYLEGLDLSpkEIVQKVRNGQRPYFRPSIDRTQLNEelvlLMERCWAQDPAER 308
Cdd:cd14033   198 ATSEYP-YSECQNAA--QIYRKVTSGIKPDSFYKVKVPELKE----IIEGCIRTDKDER 249
STKc_WNK3 cd14031
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze ...
124-308 1.10e-06

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK3 shows a restricted expression pattern; it is found at high levels in the pituary glands and is also expressed in the kidney and brain. It has been shown to regulate many ion transporters including members of the SLC12A family of cation-chloride cotransporters such as NCC and NKCC2, the renal potassium channel ROMK, and the epithelial calcium channels TRPV5 and TRPV6. WNK3 appears to sense low-chloride hypotonic stress and under these conditions, it activates SPAK, which directly interacts and phosphorylates cation-chloride cotransporters. WNK3 has also been shown to promote cell survival, possibly through interaction with procaspase-3 and HSP70. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270933 [Multi-domain]  Cd Length: 275  Bit Score: 50.49  E-value: 1.10e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 124 ICIVTEYCPRGSLQDILENDSINLDWMFRySLINDLVKGMAFLHNS---IIssHGSLKSSNC-VVDSRFVLKITDYGLAS 199
Cdd:cd14031    88 IVLVTELMTSGTLKTYLKRFKVMKPKVLR-SWCRQILKGLQFLHTRtppII--HRDLKCDNIfITGPTGSVKIGDLGLAT 164
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 200 FRSTAepddshalYAKKLWTAPELLSGNPLPTTGMQKADVYSFGIILQEIALRSGPfYLEGLDLSpkEIVQKVRNGQRPY 279
Cdd:cd14031   165 LMRTS--------FAKSVIGTPEFMAPEMYEEHYDESVDVYAFGMCMLEMATSEYP-YSECQNAA--QIYRKVTSGIKPA 233
                         170       180
                  ....*....|....*....|....*....
gi 1370514551 280 FRPSIDRTQLNEelvlLMERCWAQDPAER 308
Cdd:cd14031   234 SFNKVTDPEVKE----IIEGCIRQNKSER 258
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
87-315 1.20e-06

Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LKB1, also called STK11, was first identified as a tumor suppressor responsible for Peutz-Jeghers syndrome, a disorder that leads to an increased risk of spontaneous epithelial cancer. It serves as a master upstream kinase that activates AMP-activated protein kinase (AMPK) and most AMPK-like kinases. LKB1 and AMPK are part of an energy-sensing pathway that links cell energy to metabolism and cell growth. They play critical roles in the establishment and maintenance of cell polarity, cell proliferation, cytoskeletal organization, as well as T-cell metabolism, including T-cell development, homeostasis, and effector function. To be activated, LKB1 requires the adaptor proteins STe20-Related ADaptor (STRAD) and mouse protein 25 (MO25). The LKB1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271021 [Multi-domain]  Cd Length: 255  Bit Score: 49.95  E-value: 1.20e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  87 KKRIELTRQvlfeLKH-----MRDVQFNHltrfigaciDPPNICIVTEYCpRGSLQDILENDSINLDWMFR-YSLINDLV 160
Cdd:cd14119    42 KREIQILRR----LNHrnvikLVDVLYNE---------EKQKLYMVMEYC-VGGLQEMLDSAPDKRLPIWQaHGYFVQLI 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 161 KGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDD-------SHAlyakklWTAPELLSGNplPTTG 233
Cdd:cd14119   108 DGLEYLHSQGII-HKDIKPGNLLLTTDGTLKISDFGVAEALDLFAEDDtcttsqgSPA------FQPPEIANGQ--DSFS 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 234 MQKADVYSFGIILQEIAlrSGPFYLEGldlspkEIVQKV-RN-GQRPYFRPsidrTQLNEELVLLMERCWAQDPAERPDF 311
Cdd:cd14119   179 GFKVDIWSAGVTLYNMT--TGKYPFEG------DNIYKLfENiGKGEYTIP----DDVDPDLQDLLRGMLEKDPEKRFTI 246

                  ....
gi 1370514551 312 GQIK 315
Cdd:cd14119   247 EQIR 250
STKc_SPEG_rpt2 cd14111
Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle ...
62-276 1.51e-06

Catalytic kinase domain, second repeat, of Giant Serine/Threonine Kinase Striated muscle preferentially expressed protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The Striated muscle preferentially expressed gene (SPEG) generates 4 different isoforms through alternative promoter use and splicing in a tissue-specific manner: SPEGalpha and SPEGbeta are expressed in cardiac and skeletal striated muscle; Aortic Preferentially Expressed Protein-1 (APEG-1) is expressed in vascular smooth muscle; and Brain preferentially expressed gene (BPEG) is found in the brain and aorta. SPEG proteins have mutliple immunoglobulin (Ig), 2 fibronectin type III (FN3), and two kinase domains. They are necessary for cardiac development and survival. The SPEG subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271013 [Multi-domain]  Cd Length: 257  Bit Score: 49.82  E-value: 1.51e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  62 AHGKyqifantgHFKGNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHltrfigACIDPPNICIVTEYCprgSLQDILE 141
Cdd:cd14111    26 ATGK--------NFPAKIVPYQAEEKQGVLQEYEILKSLHHERIMALHE------AYITPRYLVLIAEFC---SGKELLH 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 142 NdsinLDWMFRYS------LINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGlasfrsTAEPDDSHALYAK 215
Cdd:cd14111    89 S----LIDRFRYSeddvvgYLVQILQGLEYLHGRRVL-HLDIKPDNIMVTNLNAIKIVDFG------SAQSFNPLSLRQL 157
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370514551 216 KLWT------APELLSGNPLPTTgmqkADVYSFGiILQEIALrSG--PFYleglDLSPKEIVQKVRNGQ 276
Cdd:cd14111   158 GRRTgtleymAPEMVKGEPVGPP----ADIWSIG-VLTYIML-SGrsPFE----DQDPQETEAKILVAK 216
STKc_MAP4K5 cd06646
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
92-309 1.58e-06

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K5, also called germinal center kinase-related enzyme (GCKR), has been shown to activate the MAPK c-Jun N-terminal kinase (JNK). MAP4K5 also facilitates Wnt signaling in B cells, and may therefore be implicated in the control of cell fate, proliferation, and polarity. MAP4Ks are involved in some MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270813 [Multi-domain]  Cd Length: 268  Bit Score: 50.03  E-value: 1.58e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  92 LTRQVLFELKhmrDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYsLINDLVKGMAFLHnSII 171
Cdd:cd06646    52 LIQQEIFMVK---ECKHCNIVAYFGSYLSREKLWICMEYCGGGSLQDIYHVTGPLSELQIAY-VCRETLQGLAYLH-SKG 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 172 SSHGSLKSSNCVVDSRFVLKITDYGLASfRSTAEPDDSHALYAKKLWTAPELLSgnpLPTTG--MQKADVYSFGIILQEI 249
Cdd:cd06646   127 KMHRDIKGANILLTDNGDVKLADFGVAA-KITATIAKRKSFIGTPYWMAPEVAA---VEKNGgyNQLCDIWAVGITAIEL 202
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370514551 250 ALRSGPFYleglDLSPKE--IVQKVRNGQRPYFRpsiDRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd06646   203 AELQPPMF----DLHPMRalFLMSKSNFQPPKLK---DKTKWSSTFHNFVKISLTKNPKKRP 257
STKc_CDK9 cd07865
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs ...
64-310 1.64e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK9, together with a cyclin partner (cyclin T1, T2a, T2b, or K), is the main component of distinct positive transcription elongation factors (P-TEFb), which function as Ser2 C-terminal domain kinases of RNA polymerase II. P-TEFb participates in multiple steps of gene expression including transcription elongation, mRNA synthesis, processing, export, and translation. It also plays a role in mediating cytokine induced transcription networks such as IL6-induced STAT3 signaling. In addition, the CDK9/cyclin T2a complex promotes muscle differentiation and enhances the function of some myogenic regulatory factors. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK9 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270848 [Multi-domain]  Cd Length: 310  Bit Score: 50.06  E-value: 1.64e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  64 GKYQIFANTGH--FkGNVVAIKHVNKKRIELTRQVLFE----------LKHMRDVQ-FNH--LTRFIGACIDPPN----- 123
Cdd:cd07865    12 SKYEKLAKIGQgtF-GEVFKARHRKTGQIVALKKVLMEnekegfpitaLREIKILQlLKHenVVNLIEICRTKATpynry 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 124 ---ICIVTEYCPRgSLQDILENDSINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAS 199
Cdd:cd07865    91 kgsIYLVFEFCEH-DLAGLLSNKNVKFTLSEIKKVMKMLLNGLYYIHrNKIL--HRDMKAANILITKDGVLKLADFGLAR 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 200 FRSTAEPDDSHaLYAKK---LW-TAPELLSGN----PlpttgmqKADVYSFGIILQEIALRS------------------ 253
Cdd:cd07865   168 AFSLAKNSQPN-RYTNRvvtLWyRPPELLLGErdygP-------PIDMWGAGCIMAEMWTRSpimqgnteqhqltlisql 239
                         250       260       270       280       290       300
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1370514551 254 -GPFY------LEGLDLS-----PKEIVQKVRNGQRPYFRpsiDRTQLNeelvlLMERCWAQDPAERPD 310
Cdd:cd07865   240 cGSITpevwpgVDKLELFkkmelPQGQKRKVKERLKPYVK---DPYALD-----LIDKLLVLDPAKRID 300
PTK_Tyk2_rpt1 cd05076
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is ...
103-314 1.68e-06

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; Tyk2 is widely expressed in many tissues. It is involved in signaling via the cytokine receptors IFN-alphabeta, IL-6, IL-10, IL-12, IL-13, and IL-23. It mediates cell surface urokinase receptor (uPAR) signaling and plays a role in modulating vascular smooth muscle cell (VSMC) functional behavior in response to injury. Tyk2 is also important in dendritic cell function and T helper (Th)1 cell differentiation. A homozygous mutation of Tyk2 was found in a patient with hyper-IgE syndrome (HIES), a primary immunodeficiency characterized by recurrent skin abscesses, pneumonia, and elevated serum IgE. This suggests that Tyk2 may play important roles in multiple cytokine signaling involved in innate and adaptive immunity. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) PTKs containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Tyk2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270661 [Multi-domain]  Cd Length: 273  Bit Score: 49.91  E-value: 1.68e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 103 MRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIIsSHGSLKSSNC 182
Cdd:cd05076    69 MSQVSHTHLVFVHGVCVRGSENIMVEEFVEHGPLDVWLRKEKGHVPMAWKFVVARQLASALSYLENKNL-VHGNVCAKNI 147
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 183 VVDSRFVlkitDYGLASFRSTAEPDDSHALYAKK------LWTAPELL-SGNPLPTTgmqkADVYSFGIILQEIALrSGP 255
Cdd:cd05076   148 LLARLGL----EEGTSPFIKLSDPGVGLGVLSREerveriPWIAPECVpGGNSLSTA----ADKWGFGATLLEICF-NGE 218
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 1370514551 256 FYLEGLDLSPKEIVQKvRNGQRPyfRPSidrtqlNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05076   219 APLQSRTPSEKERFYQ-RQHRLP--EPS------CPELATLISQCLTYEPTQRPSFRTI 268
HNOBA pfam07701
Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and ...
330-378 2.08e-06

Heme NO binding associated; The HNOBA domain is found associated with the HNOB domain and pfam00211 in soluble cyclases and signalling proteins. The HNOB domain is predicted to function as a heme-dependent sensor for gaseous ligands, and transduce diverse downstream signals, in both bacteria and animals.


Pssm-ID: 462234  Cd Length: 214  Bit Score: 48.73  E-value: 2.08e-06
                          10        20        30        40        50
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370514551 330 LDNLLLRMEQYANNLEKLVEErtqayLE-EKRKAEALLYQILPHSVAEQL 378
Cdd:pfam07701 170 LKLALDQLEQKSAELEESMRE-----LEeEKKKTDELLYSMLPKSVADRL 214
STKc_EIF2AK1_HRI cd14049
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
154-314 2.15e-06

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 2 or Heme-Regulated Inhibitor kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. HRI (or EIF2AK1) contains an N-terminal regulatory heme-binding domain and a C-terminal catalytic kinase domain. It is suppressed under normal conditions by binding of the heme iron, and is activated during heme deficiency. It functions as a critical regulator that ensures balanced synthesis of globins and heme, in order to form stable hemoglobin during erythroid differentiation and maturation. HRI also protects cells and enhances survival under iron-deficient conditions. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The HRI subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270951 [Multi-domain]  Cd Length: 284  Bit Score: 49.81  E-value: 2.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 154 SLINDLVKGMAFLHNSIISsHGSLKSSNCVVD-SRFVLKITDYGLASFRSTAEPDDSHALYAKK-----------LWTAP 221
Cdd:cd14049   124 KILQQLLEGVTYIHSMGIV-HRDLKPRNIFLHgSDIHVRIGDFGLACPDILQDGNDSTTMSRLNglthtsgvgtcLYAAP 202
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 222 ELLSGNPLPTtgmqKADVYSFGIILQEIALrsgPFyleGLDLSPKEIVQKVRNGQRPYfrpsiDRTQLNEELVLLMERCW 301
Cdd:cd14049   203 EQLEGSHYDF----KSDMYSIGVILLELFQ---PF---GTEMERAEVLTQLRNGQIPK-----SLCKRWPVQAKYIKLLT 267
                         170
                  ....*....|...
gi 1370514551 302 AQDPAERPDFGQI 314
Cdd:cd14049   268 STEPSERPSASQL 280
STKc_MSK1_N cd05613
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
62-308 2.30e-06

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSK1 plays a role in the regulation of translational control and transcriptional activation. It phosphorylates the transcription factors, CREB and NFkB. It also phosphorylates the nucleosomal proteins H3 and HMG-14. Increased phosphorylation of MSK1 is associated with the development of cerebral ischemic/hypoxic preconditioning. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, which trigger phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. The MSK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270764 [Multi-domain]  Cd Length: 290  Bit Score: 49.61  E-value: 2.30e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  62 AHGK-YQIFANTGHFKGNVVAIKHVNK-------KRIELTRQVLFELKHMRDVQFnhLTRFIGACIDPPNICIVTEYCPR 133
Cdd:cd05613    12 AYGKvFLVRKVSGHDAGKLYAMKVLKKativqkaKTAEHTRTERQVLEHIRQSPF--LVTLHYAFQTDTKLHLILDYING 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 134 GSL-QDILENDSINLDWMFRYslINDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHA 211
Cdd:cd05613    90 GELfTHLSQRERFTENEVQIY--IGEIVLALEHLHKlGII--YRDIKLENILLDSSGHVVLTDFGLSKEFLLDENERAYS 165
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 212 LYAKKLWTAPELLSGNplpTTGMQKA-DVYSFGIILQEIALRSGPFYLEGLDLSPKEIVQKVRNGQRPYFRpsiDRTQLN 290
Cdd:cd05613   166 FCGTIEYMAPEIVRGG---DSGHDKAvDWWSLGVLMYELLTGASPFTVDGEKNSQAEISRRILKSEPPYPQ---EMSALA 239
                         250
                  ....*....|....*...
gi 1370514551 291 EELVllmERCWAQDPAER 308
Cdd:cd05613   240 KDII---QRLLMKDPKKR 254
STKc_ULK1 cd14202
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the ...
60-311 2.52e-06

Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The ATG1/ULK complex is conserved from yeast to humans and it plays a critical role in the initiation of autophagy, the intracellular system that leads to the lysosomal degradation of cellular components and their recycling into basic metabolic units. ULK1 is required for efficient amino acid starvation-induced autophagy and mitochondrial clearance. It associates with three autophagy-related proteins (Atg13, FIP200 amd Atg101) to form the ULK1 complex. All fours proteins are essential for autophagosome formation. ULK1 is regulated by both mammalian target-of rapamycin complex 1 (mTORC1) and AMP-activated protein kinase (AMPK). mTORC1 negatively regulates the ULK1 complex in a nutrient-dependent manner while AMPK stimulates autophagy by inhibiting mTORC1. ULK1 also plays neuron-specific roles and is involved in non-clathrin-coated endocytosis in growth cones, filopodia extension, neurite extension, and axon branching. The ULK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271104 [Multi-domain]  Cd Length: 267  Bit Score: 49.24  E-value: 2.52e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  60 MTAHGKYQI-FANTGHFKGNV-VAIKHVNKKRIELTR-------QVLFELKHMRDVQFNHLTRFIGAcidppnICIVTEY 130
Cdd:cd14202     9 LIGHGAFAVvFKGRHKEKHDLeVAVKCINKKNLAKSQtllgkeiKILKELKHENIVALYDFQEIANS------VYLVMEY 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 131 CPRGSLQD------ILENDSINLdwmfrysLINDLVKGMAFLHNSIISsHGSLKSSNCVVD---------SRFVLKITDY 195
Cdd:cd14202    83 CNGGDLADylhtmrTLSEDTIRL-------FLQQIAGAMKMLHSKGII-HRDLKPQNILLSysggrksnpNNIRIKIADF 154
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 196 GLASFRSTAEPddSHALYAKKLWTAPELLSGNPLPTtgmqKADVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKVRNG 275
Cdd:cd14202   155 GFARYLQNNMM--AATLCGSPMYMAPEVIMSQHYDA----KADLWSIGTIIYQCLTGKAPFQAS----SPQDLRLFYEKN 224
                         250       260       270
                  ....*....|....*....|....*....|....*....
gi 1370514551 276 QRpyFRPSIDR---TQLNEELVLLMERcwaqDPAERPDF 311
Cdd:cd14202   225 KS--LSPNIPRetsSHLRQLLLGLLQR----NQKDRMDF 257
PKc_MKK7 cd06618
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase ...
160-323 2.55e-06

Catalytic domain of the dual-specificity Protein Kinase, Mitogen-activated protein Kinase Kinase 7; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK7 is a dual-specificity PK that phosphorylates and activates its downstream target, c-Jun N-terminal kinase (JNK), on specific threonine and tyrosine residues. Although MKK7 is capable of dual phosphorylation, it prefers to phosphorylate the threonine residue of JNK. Thus, optimal activation of JNK requires both MKK4 and MKK7. MKK7 is primarily activated by cytokines. MKK7 is essential for liver formation during embryogenesis. It plays roles in G2/M cell cycle arrest and cell growth. In addition, it is involved in the control of programmed cell death, which is crucial in oncogenesis, cancer chemoresistance, and antagonism to TNFalpha-induced killing, through its inhibition by Gadd45beta and the subsequent suppression of the JNK cascade. The MKK7 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270791 [Multi-domain]  Cd Length: 295  Bit Score: 49.29  E-value: 2.55e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 160 VKGMAFL---HNSIissHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAkkLWTAPELLSGNPLPTTGMqK 236
Cdd:cd06618   124 VKALHYLkekHGVI---HRDVKPSNILLDESGNVKLCDFGISGRLVDSKAKTRSAGCA--AYMAPERIDPPDNPKYDI-R 197
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 237 ADVYSFGIILQEIALRSGPFYLEGLDLspkEIVQKVRNGQRPYFRPSIDRTQLNEELVllmERCWAQDPAERPDFGQI-- 314
Cdd:cd06618   198 ADVWSLGISLVELATGQFPYRNCKTEF---EVLTKILNEEPPSLPPNEGFSPDFCSFV---DLCLTKDHRYRPKYRELlq 271

                  ....*....
gi 1370514551 315 KGFIRRFNK 323
Cdd:cd06618   272 HPFIRRYET 280
STKc_MAP4K3 cd06645
Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase ...
77-309 3.05e-06

Catalytic domain of the Serine/Threonine Kinase, Mitogen-activated protein kinase kinase kinase kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP4K3 plays a role in the nutrient-responsive pathway of mTOR (mammalian target of rapamycin) signaling. MAP4K3 is required in the activation of S6 kinase by amino acids and for the phosphorylation of the mTOR-regulated inhibitor of eukaryotic initiation factor 4E. mTOR regulates ribosome biogenesis and protein translation, and is frequently deregulated in cancer. MAP4Ks are involved in MAPK signaling pathways by activating a MAPK kinase kinase. Each MAPK cascade is activated either by a small GTP-binding protein or by an adaptor protein, which transmits the signal either directly to a MAP3K to start the triple kinase core cascade or indirectly through a mediator kinase, a MAP4K. Members of this subfamily contain an N-terminal catalytic domain and a C-terminal citron homology (CNH) regulatory domain. The MAP4K3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270812 [Multi-domain]  Cd Length: 272  Bit Score: 48.89  E-value: 3.05e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYsLI 156
Cdd:cd06645    36 GELAAIKVIKLEPGEDFAVVQQEIIMMKDCKHSNIVAYFGSYLRRDKLWICMEFCGGGSLQDIYHVTGPLSESQIAY-VS 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLHNSiISSHGSLKSSNCVVDSRFVLKITDYGLASfRSTAEPDDSHALYAKKLWTAPELLSgnpLPTTG--M 234
Cdd:cd06645   115 RETLQGLYYLHSK-GKMHRDIKGANILLTDNGHVKLADFGVSA-QITATIAKRKSFIGTPYWMAPEVAA---VERKGgyN 189
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1370514551 235 QKADVYSFGIILQEIALRSGPFYleglDLSPKE--IVQKVRNGQRPYFRpsiDRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd06645   190 QLCDIWAVGITAIELAELQPPMF----DLHPMRalFLMTKSNFQPPKLK---DKMKWSNSFHHFVKMALTKNPKKRP 259
STKc_CDK1_CdkB_like cd07835
Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of ...
154-256 4.14e-06

Catalytic domain of Cyclin-Dependent protein Kinase 1-like Serine/Threonine Kinases and of Plant B-type Cyclin-Dependent protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of CDK, CDK2, and CDK3. CDK1 is also called Cell division control protein 2 (Cdc2) or p34 protein kinase, and is regulated by cyclins A, B, and E. The CDK1/cyclin A complex controls G2 phase entry and progression while the CDK1/cyclin B complex is critical for G2 to M phase transition. CDK2 is regulated by cyclin E or cyclin A. Upon activation by cyclin E, it phosphorylates the retinoblastoma (pRb) protein which activates E2F mediated transcription and allows cells to move into S phase. The CDK2/cyclin A complex plays a role in regulating DNA replication. Studies in knockout mice revealed that CDK1 can compensate for the loss of the cdk2 gene as it can also bind cyclin E and drive G1 to S phase transition. CDK3 is regulated by cyclin C and it phosphorylates pRB specifically during the G0/G1 transition. This phosphorylation is required for cells to exit G0 efficiently and enter the G1 phase. The plant-specific B-type CDKs are expressed from the late S to the M phase of the cell cycle. They are characterized by the cyclin binding motif PPT[A/T]LRE. They play a role in controlling mitosis and integrating developmental pathways, such as stomata and leaf development. CdkB has been shown to associate with both cyclin B, which controls G2/M transition, and cyclin D, which acts as a mediator in linking extracellular signals to the cell cycle. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The CDK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270829 [Multi-domain]  Cd Length: 283  Bit Score: 48.83  E-value: 4.14e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 154 SLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKKLW-TAPELLSGNPLPT 231
Cdd:cd07835   103 SYLYQLLQGIAFCHsHRVL--HRDLKPQNLLIDTEGALKLADFGLA--RAFGVPVRTYTHEVVTLWyRAPEILLGSKHYS 178
                          90       100
                  ....*....|....*....|....*
gi 1370514551 232 TGMqkaDVYSFGIILQEIALRSGPF 256
Cdd:cd07835   179 TPV---DIWSVGCIFAEMVTRRPLF 200
STKc_ERK5 cd07855
Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; ...
77-310 4.16e-06

Catalytic domain of the Serine/Threonine Kinase, Extracellular signal-Regulated Kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ERK5 (also called Big MAPK1 (BMK1) or MAPK7) has a unique C-terminal extension, making it approximately twice as big as other MAPKs. This extension contains transcriptional activation capability which is inhibited by the N-terminal half. ERK5 is activated in response to growth factors and stress by a cascade that leads to its phosphorylation by the MAP2K MEK5, which in turn is regulated by the MAP3Ks MEKK2 and MEKK3. Activated ERK5 phosphorylates its targets including myocyte enhancer factor 2 (MEF2), Sap1a, c-Myc, and RSK. It plays a role in EGF-induced cell proliferation during the G1/S phase transition. Studies on knockout mice revealed that ERK5 is essential for cardiovascular development and plays an important role in angiogenesis. It is also critical for neural differentiation and survival. The ERK5 pathway has been implicated in the pathogenesis of many diseases including cancer, cardiac hypertrophy, and atherosclerosis. MAPKs are important mediators of cellular responses to extracellular signals. The ERK5 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270842 [Multi-domain]  Cd Length: 336  Bit Score: 48.90  E-value: 4.16e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELT--RQVLFELKHMRdvQFNHltrfigacidpPNI-CIVTEYCPRGSLQ---------DILEND- 143
Cdd:cd07855    30 GQKVAIKKIPNAFDVVTtaKRTLRELKILR--HFKH-----------DNIiAIRDILRPKVPYAdfkdvyvvlDLMESDl 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 144 --------SINLDWMfRYSLINdLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTaEPDDsHALY-- 213
Cdd:cd07855    97 hhiihsdqPLTLEHI-RYFLYQ-LLRGLKYIHSANVI-HRDLKPSNLLVNENCELKIGDFGMARGLCT-SPEE-HKYFmt 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 214 ---AKKLWTAPELLSGNPLPTTGMqkaDVYSFGIILQEIALRS----GPFYLEGLDL-------SPKEIVQKVRNGQ-RP 278
Cdd:cd07855   172 eyvATRWYRAPELMLSLPEYTQAI---DMWSVGCIFAEMLGRRqlfpGKNYVHQLQLiltvlgtPSQAVINAIGADRvRR 248
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|.
gi 1370514551 279 YF-----RPSIDRTQL----NEELVLLMERCWAQDPAERPD 310
Cdd:cd07855   249 YIqnlpnKQPVPWETLypkaDQQALDLLSQMLRFDPSERIT 289
STKc_MAPKAPK3 cd14172
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated ...
155-313 4.48e-06

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase-activated protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK-activated protein kinase 3 (MAPKAP3 or MK3) contains an N-terminal proline-rich region that can bind to SH3 domains, a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. MK3 is a bonafide substrate for the MAPK p38. It is closely related to MK2 and thus far, MK2/3 show indistinguishable substrate specificity. They are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK3 activity is only significant when MK2 is absent. The MK3 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271074 [Multi-domain]  Cd Length: 267  Bit Score: 48.45  E-value: 4.48e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNSIISsHGSLKSSNCVVDSR---FVLKITDYGLAsfRSTAEPDDSHALYAKKLWTAPELLSgnplPT 231
Cdd:cd14172   108 IMRDIGTAIQYLHSMNIA-HRDVKPENLLYTSKekdAVLKLTDFGFA--KETTVQNALQTPCYTPYYVAPEVLG----PE 180
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 232 TGMQKADVYSFGIILQEIALRSGPFYLE-GLDLSPKeIVQKVRNGQrpYFRPSIDRTQLNEELVLLMERCWAQDPAERPD 310
Cdd:cd14172   181 KYDKSCDMWSLGVIMYILLCGFPPFYSNtGQAISPG-MKRRIRMGQ--YGFPNPEWAEVSEEAKQLIRHLLKTDPTERMT 257

                  ...
gi 1370514551 311 FGQ 313
Cdd:cd14172   258 ITQ 260
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
158-314 6.27e-06

Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. This subfamily is composed of the catalytically inactive kinases with similarity to yeast Scy1. It includes four mammalian proteins called SCY1-like protein 1 (SCYL1), SCYL2, SCYL3, as well as Testis-EXpressed protein 14 (TEX14). SCYL1 binds to and co-localizes with the membrane trafficking coatomer I (COPI) complex, and regulates COPI-mediated vesicle trafficking. Null mutations in the SCYL1 gene are responsible for the pathology in mdf (muscle-deficient) mice which display progressive motor neuropathy. SCYL2, also called coated vesicle-associated kinase of 104 kDa (CVAK104), is involved in the trafficking of clathrin-coated vesicles. It also binds the HIV-1 accessory protein Vpu and acts as a regulatory factor that promotes the dephosphorylation of Vpu, facilitating the restriction of HIV-1 release. SCYL3, also called ezrin-binding protein PACE-1, may be involved in regulating cell adhesion and migration. TEX14 is required for spermatogenesis and male fertility. It localizes to kinetochores (KT) during mitosis and is a target of the mitotic kinase PLK1. It regulates the maturation of the outer KT and the KT-microtubule attachment. The SCY1-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein serine/threonine kinases, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270913 [Multi-domain]  Cd Length: 287  Bit Score: 48.09  E-value: 6.27e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKL----------WTAPELLSGN 227
Cdd:cd14011   122 QISEALSFLHNDVKLVHGNICPESVVINSNGEWKLAGFDFCISSEQATDQFPYFREYDPNlpplaqpnlnYLAPEYILSK 201
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 228 PLPTtgmqKADVYSFGIILQEIALRSGPFYLEGLDL-SPKEIVQKVRNGQRPYFRPsidrtqLNEELVLLMERCWAQDPA 306
Cdd:cd14011   202 TCDP----ASDMFSLGVLIYAIYNKGKPLFDCVNNLlSYKKNSNQLRQLSLSLLEK------VPEELRDHVKTLLNVTPE 271

                  ....*...
gi 1370514551 307 ERPDFGQI 314
Cdd:cd14011   272 VRPDAEQL 279
PKc_MKK3_6 cd06617
Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase ...
159-314 7.54e-06

Catalytic domain of the dual-specificity Protein Kinases, Mitogen-activated protein Kinase Kinases 3 and 6; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. MKK3 and MKK6 are dual-specificity PKs that phosphorylate and activate their downstream target, p38 MAPK, on specific threonine and tyrosine residues. MKK3/6 play roles in the regulation of cell cycle progression, cytokine- and stress-induced apoptosis, oncogenic transformation, and adult tissue regeneration. In addition, MKK6 plays a critical role in osteoclast survival in inflammatory disease while MKK3 is associated with tumor invasion, progression, and poor patient survival in glioma. The MKK3/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173729 [Multi-domain]  Cd Length: 283  Bit Score: 47.80  E-value: 7.54e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 159 LVKGMAFLHNSIISSHGSLKSSNCVVDSRFVLKITDYGLASF--RSTAEPDDSHAlyakKLWTAPELLSgnplPTTGMQ- 235
Cdd:cd06617   112 IVKALEYLHSKLSVIHRDVKPSNVLINRNGQVKLCDFGISGYlvDSVAKTIDAGC----KPYMAPERIN----PELNQKg 183
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 236 ---KADVYSFGIILQEIALRSGPFYLEGldlSPKEIVQKVRNGQrpyfRPSIDRTQLNEELVLLMERCWAQDPAERPDFG 312
Cdd:cd06617   184 ydvKSDVWSLGITMIELATGRFPYDSWK---TPFQQLKQVVEEP----SPQLPAEKFSPEFQDFVNKCLKKNYKERPNYP 256

                  ..
gi 1370514551 313 QI 314
Cdd:cd06617   257 EL 258
STKc_TBK1 cd13988
Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the ...
126-291 8.07e-06

Catalytic domain of the Serine/Threonine kinase, TANK Binding Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TBK1 is also called T2K and NF-kB-activating kinase. It is widely expressed in most cell types and acts as an IkappaB kinase (IKK)-activating kinase responsible for NF-kB activation in response to growth factors. It plays a role in modulating inflammatory responses through the NF-kB pathway. TKB1 is also a major player in innate immune responses since it functions as a virus-activated kinase necessary for establishing an antiviral state. It phosphorylates IRF-3 and IRF-7, which are important transcription factors for inducing type I interferon during viral infection. In addition, TBK1 may also play roles in cell transformation and oncogenesis. The TBK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270890 [Multi-domain]  Cd Length: 316  Bit Score: 47.87  E-value: 8.07e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 126 IVTEYCPRGSLQDILENDSiNLdwmfrYSL--------INDLVKGMAFLH-NSIIssHGSLKSSNCVV----DSRFVLKI 192
Cdd:cd13988    70 LVMELCPCGSLYTVLEEPS-NA-----YGLpeseflivLRDVVAGMNHLReNGIV--HRDIKPGNIMRvigeDGQSVYKL 141
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 193 TDYGLAsfRSTAEPDDSHALYAKKLWTAPELLSGNPLPTTGMQK----ADVYSFGIILQEIALRSGPFYLEGLDLSPKEI 268
Cdd:cd13988   142 TDFGAA--RELEDDEQFVSLYGTEEYLHPDMYERAVLRKDHQKKygatVDLWSIGVTFYHAATGSLPFRPFEGPRRNKEV 219
                         170       180
                  ....*....|....*....|....*
gi 1370514551 269 VQKVRNGqrpyfRPS--IDRTQLNE 291
Cdd:cd13988   220 MYKIITG-----KPSgaISGVQKSE 239
PTK_Jak1_rpt1 cd05077
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely ...
67-314 9.61e-06

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1; Jak1 is widely expressed in many tissues. Many cytokines are dependent on Jak1 for signaling, including those that use the shared receptor subunits, common gamma chain (IL-2, IL-4, IL-7, IL-9, IL-15, IL-21) and gp130 (IL-6, IL-11, oncostatin M, G-CSF, and IFNs, among others). The many varied interactions of Jak1 and its ubiquitous expression suggest many biological roles. Jak1 is important in neurological development, as well as in lymphoid development and function. It also plays a role in the pathophysiology of cardiac hypertrophy and heart failure. A mutation in the ATP-binding site of Jak1 was identified in a human uterine leiomyosarcoma cell line, resulting in defective cytokine induction and antigen presentation, thus allowing the tumor to evade the immune system. Jak1 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. The Jak1 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270662 [Multi-domain]  Cd Length: 266  Bit Score: 47.62  E-value: 9.61e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  67 QIFANTGHFKGNVVAIKHVNKKRIELTRQVL-----------FELKHM-RDVQFNHLTRFIGACI-DPPNIcIVTEYCPR 133
Cdd:cd05077    14 QIYAGILNYKDDDEDEGYSYEKEIKVILKVLdpshrdislafFETASMmRQVSHKHIVLLYGVCVrDVENI-MVEEFVEF 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 134 GSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIISsHGSLKSSNCVV-----DSRF--VLKITDYGLA-SFRSTAE 205
Cdd:cd05077    93 GPLDLFMHRKSDVLTTPWKFKVAKQLASALSYLEDKDLV-HGNVCTKNILLaregiDGECgpFIKLSDPGIPiTVLSRQE 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 206 PDDshalyaKKLWTAPELLSGNPLPTTGmqkADVYSFGIILQEIALrSGPFYLEGLDLSPKEivqKVRNGQRPYFRPSID 285
Cdd:cd05077   172 CVE------RIPWIAPECVEDSKNLSIA---ADKWSFGTTLWEICY-NGEIPLKDKTLAEKE---RFYEGQCMLVTPSCK 238
                         250       260
                  ....*....|....*....|....*....
gi 1370514551 286 rtqlneELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd05077   239 ------ELADLMTHCMNYDPNQRPFFRAI 261
STKc_PDIK1L cd13977
Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs ...
118-320 1.20e-05

Catalytic domain of the Serine/Threonine kinase, PDLIM1 interacting kinase 1 like; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PDIK1L is also called STK35 or CLIK-1. It is predominantly a nuclear protein which is capable of autophosphorylation. Through its interaction with the PDZ-LIM protein CLP-36, it is localized to actin stress fibers. The PDIK1L subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270879 [Multi-domain]  Cd Length: 322  Bit Score: 47.55  E-value: 1.20e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 118 CIDPPNIC---IVTEYCPRGSLQDILEndSINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRF---VL 190
Cdd:cd13977   101 CFDPRSACylwFVMEFCDGGDMNEYLL--SRRPDRQTNTSFMLQLSSALAFLHrNQIV--HRDLKPDNILISHKRgepIL 176
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 191 KITDYGLASFRSTAEPDDSHALYAKKLW----------TAPELLSGNPlpttgMQKADVYSFGIIL----QEIALRS--- 253
Cdd:cd13977   177 KVADFGLSKVCSGSGLNPEEPANVNKHFlssacgsdfyMAPEVWEGHY-----TAKADIFALGIIIwamvERITFRDget 251
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 254 -----GPFYLEGLDLSP-KEIVqkVRNGQRPYFRPSIDRTQLNEELVLLMERCWAQDPAERPDFGQIKGFIRR 320
Cdd:cd13977   252 kkellGTYIQQGKEIVPlGEAL--LENPKLELQIPLKKKKSMNDDMKQLLRDMLAANPQERPDAFQLELRLRQ 322
STKc_TEY_MAPK cd07858
Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; ...
80-252 1.27e-05

Catalytic domain of the Serine/Threonine Kinases, Plant TEY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TEY subtype of plant MAPKs and is further subdivided into three groups (A, B, and C). Group A is represented by AtMPK3, AtMPK6, Nicotiana tabacum BTF4 (NtNTF4), among others. They are mostly involved in environmental and hormonal responses. AtMPK3 and AtMPK6 are also key regulators for stomatal development and patterning. Group B is represented by AtMPK4, AtMPK13, and NtNTF6, among others. They may be involved in both cell division and environmental stress response. AtMPK4 also participates in regulating innate immunity. Group C is represented by AtMPK1, AtMPK2, NtNTF3, Oryza sativa MAPK4 (OsMAPK4), among others. They may also be involved in stress responses. AtMPK1 and AtMPK2 are activated following mechanical injury and in the presence of stress chemicals such as jasmonic acid, hydrogen peroxide and abscisic acid. OsMAPK4 is also called OsMSRMK3 for Multiple Stress-Responsive MAPK3. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20. The TEY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143363 [Multi-domain]  Cd Length: 337  Bit Score: 47.37  E-value: 1.27e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNK---KRIElTRQVLFELKHMRDVQFNHLTRfIGACIDPPN------ICIVTEYCPRGSLQDILENDSINLDWM 150
Cdd:cd07858    33 VAIKKIANafdNRID-AKRTLREIKLLRHLDHENVIA-IKDIMPPPHreafndVYIVYELMDTDLHQIIRSSQTLSDDHC 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 151 fRYsLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAEPDDSHALYAKKLW-TAPELLsgnpL 229
Cdd:cd07858   111 -QY-FLYQLLRGLKYIHSANVL-HRDLKPSNLLLNANCDLKICDFGLA--RTTSEKGDFMTEYVVTRWyRAPELL----L 181
                         170       180
                  ....*....|....*....|....
gi 1370514551 230 PTTGMQKA-DVYSFGIILQEIALR 252
Cdd:cd07858   182 NCSEYTTAiDVWSVGCIFAELLGR 205
STKc_WNK1 cd14030
Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze ...
99-308 1.41e-05

Catalytic domain of the Serine/Threonine protein kinase, With No Lysine (WNK) 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK1 is widely expressed and is most abundant in the testis. In hyperosmotic or hypotonic low-chloride stress conditions, WNK1 is activated and it phosphorylates its substrates including SPAK and OSR1 kinases, which regulate the activity of cation-chloride cotransporters through direct interaction and phosphorylation. Mutations in WNK1 cause PseudoHypoAldosteronism type II (PHAII), characterized by hypertension and hyperkalemia. WNK1 negates WNK4-mediated inhibition of the sodium-chloride cotransporter NCC and activates the epithelial sodium channel ENaC by activating SGK1. WNK1 also decreases the surface expression of renal outer medullary potassium channel (ROMK) by stimulating their endocytosis. Hypertension and hyperkalemia in PHAII patients with WNK1 mutations may be due partly to increased activity of NCC and ENaC, and impaired renal potassium secretion by ROMK, respectively. In addition, WNK1 interacts with MEKK2/3 and acts as an activator of extracellular signal-regulated kinase (ERK) 5. It also negatively regulates TGFbeta signaling. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. The WNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270932 [Multi-domain]  Cd Length: 289  Bit Score: 46.97  E-value: 1.41e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQFNHLTRFIGACIDPPN----ICIVTEYCPRGSLQDILENDSINLDWMFRySLINDLVKGMAFLHNS---II 171
Cdd:cd14030    74 EAGMLKGLQHPNIVRFYDSWESTVKgkkcIVLVTELMTSGTLKTYLKRFKVMKIKVLR-SWCRQILKGLQFLHTRtppII 152
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 172 ssHGSLKSSNCVVDS-RFVLKITDYGLASFRSTAepddshalYAKKLWTAPELLSGNPLPTTGMQKADVYSFGIILQEIA 250
Cdd:cd14030   153 --HRDLKCDNIFITGpTGSVKIGDLGLATLKRAS--------FAKSVIGTPEFMAPEMYEEKYDESVDVYAFGMCMLEMA 222
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 251 LRSGPfYLEGLDlsPKEIVQKVRNGQRPyfrPSIDRTQLnEELVLLMERCWAQDPAER 308
Cdd:cd14030   223 TSEYP-YSECQN--AAQIYRRVTSGVKP---ASFDKVAI-PEVKEIIEGCIRQNKDER 273
STKc_MAPK4_6 cd07854
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also ...
80-249 1.46e-05

Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinases 4 (also called ERK4) and 6 (also called ERK3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK4 (also called ERK4 or p63MAPK) and MAPK6 (also called ERK3 or p97MAPK) are atypical MAPKs that are not regulated by MAPK kinases. MAPK6 is expressed ubiquitously with highest amounts in brain and skeletal muscle. It may be involved in the control of cell differentiation by negatively regulating cell cycle progression in certain conditions. It may also play a role in glucose-induced insulin secretion. MAPK6 and MAPK4 cooperate to regulate the activity of MAPK-activated protein kinase 5 (MK5), leading to its relocation to the cytoplasm and exclusion from the nucleus. The MAPK6/MK5 and MAPK4/MK5 pathways may play critical roles in embryonic and post-natal development. MAPKs are important mediators of cellular responses to extracellular signals. The MAPK4/6 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143359 [Multi-domain]  Cd Length: 342  Bit Score: 47.47  E-value: 1.46e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  80 VAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRF--------------IGACIDPPNICIVTEYCpRGSLQDILENDSI 145
Cdd:cd07854    33 VAVKKIVLTDPQSVKHALREIKIIRRLDHDNIVKVyevlgpsgsdltedVGSLTELNSVYIVQEYM-ETDLANVLEQGPL 111
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 146 NLDW--MFRYSLIndlvKGMAFLHNSIISsHGSLKSSNCVVDSR-FVLKITDYGLASFrstAEPDDSHALY-----AKKL 217
Cdd:cd07854   112 SEEHarLFMYQLL----RGLKYIHSANVL-HRDLKPANVFINTEdLVLKIGDFGLARI---VDPHYSHKGYlseglVTKW 183
                         170       180       190
                  ....*....|....*....|....*....|..
gi 1370514551 218 WTAPELLSGnplPTTGMQKADVYSFGIILQEI 249
Cdd:cd07854   184 YRSPRLLLS---PNNYTKAIDMWAAGCIFAEM 212
PKc_PBS2_like cd06622
Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; ...
63-314 1.46e-05

Catalytic domain of fungal PBS2-like dual-specificity Mitogen-Activated Protein Kinase Kinases; PKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine (ST) or tyrosine residues on protein substrates. Members of this group include the MAPKKs Polymyxin B resistance protein 2 (PBS2) from Saccharomyces cerevisiae, Wis1 from Schizosaccharomyces pombe, and related proteins. PBS2 and Wis1 are components of stress-activated MAPK cascades in budding and fission yeast, respectively. PBS2 is the specific activator of the MAPK Hog1, which plays a central role in the response of budding yeast to stress including exposure to arsenite and hyperosmotic environments. Wis1 phosphorylates and activates the MAPK Sty1 (also called Spc1 or Phh1), which stimulates a transcriptional response to a wide range of cellular insults through the bZip transcription factors Atf1, Pcr1, and Pap1. The PBS2 subfamily is part of a larger superfamily that includes the catalytic domains of STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132953 [Multi-domain]  Cd Length: 286  Bit Score: 47.15  E-value: 1.46e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  63 HGKYQIFANTGHFKGNVV-AIKHVnkkRIELT----RQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQ 137
Cdd:cd06622    11 KGNYGSVYKVLHRPTGVTmAMKEI---RLELDeskfNQIIMELDILHKAVSPYIVDFYGAFFIEGAVYMCMEYMDAGSLD 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 138 DI----LENDSINLDWMFRysLINDLVKGMAFL---HNSIissHGSLKSSNCVVDSRFVLKITDYGLAS--FRSTAEPDD 208
Cdd:cd06622    88 KLyaggVATEGIPEDVLRR--ITYAVVKGLKFLkeeHNII---HRDVKPTNVLVNGNGQVKLCDFGVSGnlVASLAKTNI 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 209 SHALYakklwTAPELLSG---NPLPTTGMQkADVYSFGIILQEIALRSGPFYLEGLDLSPKEIvQKVRNGQRPYFRPSID 285
Cdd:cd06622   163 GCQSY-----MAPERIKSggpNQNPTYTVQ-SDVWSLGLSILEMALGRYPYPPETYANIFAQL-SAIVDGDPPTLPSGYS 235
                         250       260
                  ....*....|....*....|....*....
gi 1370514551 286 RTQLNeelvlLMERCWAQDPAERPDFGQI 314
Cdd:cd06622   236 DDAQD-----FVAKCLNKIPNRRPTYAQL 259
STKc_TSSK3-like cd14163
Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs ...
124-256 1.70e-05

Catalytic domain of testis-specific serine/threonine kinase 3 and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TSSK proteins are almost exclusively expressed postmeiotically in the testis and play important roles in spermatogenesis and/or spermiogenesis. There are five mammalian TSSK proteins which show differences in their localization and timing of expression. TSSK3 has been reported to be expressed in the interstitial Leydig cells of adult testis. Its mRNA levels is low at birth, increases at puberty, and remains high throughout adulthood. The TSSK3-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271065 [Multi-domain]  Cd Length: 257  Bit Score: 46.52  E-value: 1.70e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 124 ICIVTEYCPRGSLQDILENDSINLDWMFRySLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSrFVLKITDYGLASFRST 203
Cdd:cd14163    76 IYLVMELAEDGDVFDCVLHGGPLPEHRAK-ALFRQLVEAIRYCHGCGVA-HRDLKCENALLQG-FTLKLTDFGFAKQLPK 152
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|...
gi 1370514551 204 AEPDDSHALYAKKLWTAPELLSGNPLPTtgmQKADVYSFGIILQEIALRSGPF 256
Cdd:cd14163   153 GGRELSQTFCGSTAYAAPEVLQGVPHDS---RKGDIWSMGVVLYVMLCAQLPF 202
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
174-314 1.70e-05

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 47.70  E-value: 1.70e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 174 HGSLKSSNCVVDSRFVLKITDYGLA-SFRSTAEPDDSHALYAKKLWTAPELLSGNPLPttgmQKADVYSFGIILQEIALR 252
Cdd:PTZ00267  192 HRDLKSANIFLMPTGIIKLGDFGFSkQYSDSVSLDVASSFCGTPYYLAPELWERKRYS----KKADMWSLGVILYELLTL 267
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370514551 253 SGPFylEGldLSPKEIVQKVRNGQRPYFRPSIDRTqlneeLVLLMERCWAQDPAERPDFGQI 314
Cdd:PTZ00267  268 HRPF--KG--PSQREIMQQVLYGKYDPFPCPVSSG-----MKALLDPLLSKNPALRPTTQQL 320
STKc_PKA cd14209
Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze ...
77-257 1.96e-05

Catalytic subunit of the Serine/Threonine Kinase, cAMP-dependent protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The inactive PKA holoenzyme is a heterotetramer composed of two phosphorylated and active catalytic subunits with a dimer of regulatory (R) subunits. Activation is achieved through the binding of the important second messenger cAMP to the R subunits, which leads to the dissociation of PKA into the R dimer and two active subunits. PKA is present ubiquitously in cells and interacts with many different downstream targets. It plays a role in the regulation of diverse processes such as growth, development, memory, metabolism, gene expression, immunity, and lipolysis. The PKA subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271111 [Multi-domain]  Cd Length: 290  Bit Score: 46.63  E-value: 1.96e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQV---LFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILEN-DSINLDWMFR 152
Cdd:cd14209    26 GNYYAMKILDKQKVVKLKQVehtLNEKRILQAINFPFLVKLEYSFKDNSNLYMVMEYVPGGEMFSHLRRiGRFSEPHARF 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 YSLinDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGlasfrstaepddshalYAKKL----WT---APELL 224
Cdd:cd14209   106 YAA--QIVLAFEYLHSlDLI--YRDLKPENLLIDQQGYIKVTDFG----------------FAKRVkgrtWTlcgTPEYL 165
                         170       180       190
                  ....*....|....*....|....*....|....
gi 1370514551 225 SGNPLPTTGMQKA-DVYSFGIILQEIALRSGPFY 257
Cdd:cd14209   166 APEIILSKGYNKAvDWWALGVLIYEMAAGYPPFF 199
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
124-308 2.21e-05

Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine/threonine kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAST kinases contain an N-terminal domain of unknown function, a central catalytic domain, and a C-terminal PDZ domain that mediates protein-protein interactions. There are four mammalian MAST kinases, named MAST1-MAST4. MAST1 is also called syntrophin-associated STK (SAST) while MAST2 is also called MAST205. MAST kinases are cytoskeletal associated kinases of unknown function that are also expressed at neuromuscular junctions and postsynaptic densities. MAST1, MAST2, and MAST3 bind and phosphorylate the tumor suppressor PTEN, and may contribute to the regulation and stabilization of PTEN. MAST2 is involved in the regulation of the Fc-gamma receptor of the innate immune response in macrophages, and may also be involved in the regulation of the Na+/H+ exchanger NHE3. The MAST kinase subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270760 [Multi-domain]  Cd Length: 280  Bit Score: 46.63  E-value: 2.21e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 124 ICIVTEYCPRGSLQDILEN-DSINLDWMFRYslINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASF-- 200
Cdd:cd05609    75 LCMVMEYVEGGDCATLLKNiGPLPVDMARMY--FAETVLALEYLHSYGIV-HRDLKPDNLLITSMGHIKLTDFGLSKIgl 151
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 201 --RST-----AEPDDSHALYAKKLWTAPELLSGNPLPTTGMQKA-DVYSFGIILQEIALRSGPFYLEgldlSPKEIVQKV 272
Cdd:cd05609   152 msLTTnlyegHIEKDTREFLDKQVCGTPEYIAPEVILRQGYGKPvDWWAMGIILYEFLVGCVPFFGD----TPEELFGQV 227
                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 1370514551 273 RNGQRPYfrPSIDRTqLNEELVLLMERCWAQDPAER 308
Cdd:cd05609   228 ISDEIEW--PEGDDA-LPDDAQDLITRLLQQNPLER 260
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
155-249 3.85e-05

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. They are also essential regulators of physiological and pathological processes and are involved in the pathogenesis of several diseases such as diabetes, atherosclerosis, stroke, Parkinson's and Alzheimer's. Vetebrates harbor three different JNK genes (Jnk1, Jnk2, and Jnk3) that are alternatively spliced to produce at least 10 isoforms. JNKs are specifically activated by the MAPK kinases MKK4 and MKK7, which are in turn activated by upstream MAPK kinase kinases as a result of different stimuli including stresses such as ultraviolet (UV) irradiation, hyperosmolarity, heat shock, or cytokines. JNKs activate a large number of different substrates based on specific stimulus, cell type, and cellular condition, and may be implicated in seemingly contradictory functions. The JNK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270840 [Multi-domain]  Cd Length: 337  Bit Score: 45.87  E-value: 3.85e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNS-IIssHGSLKSSNCVVDSRFVLKITDYGLA-----SFRSTAEpddshalYAKKLWTAPELLSGNP 228
Cdd:cd07850   107 LLYQMLCGIKHLHSAgII--HRDLKPSNIVVKSDCTLKILDFGLArtagtSFMMTPY-------VVTRYYRAPEVILGMG 177
                          90       100
                  ....*....|....*....|.
gi 1370514551 229 LPttgmQKADVYSFGIILQEI 249
Cdd:cd07850   178 YK----ENVDIWSVGCIMGEM 194
PTKc_Wee1a cd14138
Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the ...
107-309 4.20e-05

Catalytic domain of the Protein Tyrosine Kinase, Wee1a; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. This subfamily is composed of human Wee1a, Xenopus laevis Wee1b (XeWee1b) and similar vertebrate proteins. Members of this subfamily show a wide expression pattern. XeWee1b functions after the first zygotic cell divisions. It is expressed in all tissues and is also present after the gastrulation stage of embryos. Wee1 is a cell cycle checkpoint kinase that helps keep the cyclin-dependent kinase CDK1 in an inactive state through phosphorylation of an N-terminal tyr (Y15) residue. During the late G2 phase, CDK1 is activated and mitotic entry is promoted by the removal of this inhibitory phosphorylation by the phosphatase Cdc25. Although Wee1 is functionally a tyr kinase, it is more closely related to serine/threonine kinases (STKs). It contains a catalytic kinase domain sandwiched in between N- and C-terminal regulatory domains. It is regulated by phosphorylation and degradation, and its expression levels are also controlled by circadian clock proteins. The Wee1a subfamily is part of a larger superfamily that includes the catalytic domains of STKs, other PTKs, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271040 [Multi-domain]  Cd Length: 276  Bit Score: 45.78  E-value: 4.20e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 107 QFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWmFRYSLINDLV----KGMAFLHnSIISSHGSLKSSNC 182
Cdd:cd14138    63 QHSHVVRYYSAWAEDDHMLIQNEYCNGGSLADAISENYRIMSY-FTEPELKDLLlqvaRGLKYIH-SMSLVHMDIKPSNI 140
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 183 VVD-------------------SRFVLKITDYGLASFRST--AEPDDSHALyakklwtAPELLSGNplpTTGMQKADVYS 241
Cdd:cd14138   141 FISrtsipnaaseegdedewasNKVIFKIGDLGHVTRVSSpqVEEGDSRFL-------ANEVLQEN---YTHLPKADIFA 210
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1370514551 242 FGIILQEiALRSGPFYLEGldlspkEIVQKVRNGQRPYFrPSIdrtqLNEELVLLMERCWAQDPAERP 309
Cdd:cd14138   211 LALTVVC-AAGAEPLPTNG------DQWHEIRQGKLPRI-PQV----LSQEFLDLLKVMIHPDPERRP 266
STKc_p38alpha cd07877
Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase ...
155-249 5.45e-05

Catalytic domain of the Serine/Threonine Kinase, p38alpha Mitogen-Activated Protein Kinase (also called MAPK14); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38alpha/MAPK14 is expressed in most tissues and is the major isoform involved in the immune and inflammatory response. It is the central p38 MAPK involved in myogenesis. It plays a role in regulating cell cycle check-point transition and promoting cell differentiation. p38alpha also regulates cell proliferation and death through crosstalk with the JNK pathway. Its substrates include MAPK activated protein kinase 2 (MK2), MK5, and the transcription factors ATF2 and Mitf. p38 kinases MAPKs, serving as important mediators of cellular responses to extracellular signals. They are activated by the MAPK kinases MKK3 and MKK6, which in turn are activated by upstream MAPK kinase kinases including TAK1, ASK1, and MLK3, in response to cellular stresses or inflammatory cytokines. The p38alpha subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143382 [Multi-domain]  Cd Length: 345  Bit Score: 45.42  E-value: 5.45e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfRSTAepDDSHALYAKKLWTAPELLSgNPLPTTgm 234
Cdd:cd07877   125 LIYQILRGLKYIHSADII-HRDLKPSNLAVNEDCELKILDFGLA--RHTD--DEMTGYVATRWYRAPEIML-NWMHYN-- 196
                          90
                  ....*....|....*
gi 1370514551 235 QKADVYSFGIILQEI 249
Cdd:cd07877   197 QTVDIWSVGCIMAEL 211
STKc_PIM1 cd14100
Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) ...
57-314 5.80e-05

Catalytic domain of the Serine/Threonine kinase, Proviral Integration Moloney virus (PIM) kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The PIM gene locus was discovered as a result of the cloning of retroviral intergration sites in murine Moloney leukemia virus, leading to the identification of PIM kinases. They are constitutively active STKs with a broad range of cellular targets and are overexpressed in many haematopoietic malignancies and solid cancers. Vertebrates contain three distinct PIM kinase genes (PIM1-3); each gene may result in mutliple protein isoforms. There are two PIM1 isoforms resulting from alternative translation initiation sites. PIM1 is the founding member of the PIM subfamily. It is involved in regulating cell growth, differentiation, and apoptosis. It promotes cancer development when overexpressed by inhibiting apoptosis, promoting cell proliferation, and promoting genomic instability. The PIM1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271002 [Multi-domain]  Cd Length: 254  Bit Score: 44.96  E-value: 5.80e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  57 GSLMTAHGKYQIFANTGHFKGNVVAIKHVNKKRI----ELTR--QVLFELKHMRDVQ--FNHLTRFIGACIDPPNICIVT 128
Cdd:cd14100     5 GPLLGSGGFGSVYSGIRVADGAPVAIKHVEKDRVsewgELPNgtRVPMEIVLLKKVGsgFRGVIRLLDWFERPDSFVLVL 84
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 129 E-----------YCPRGSLQDILENdsinldwmfrySLINDLVKGMAFLHNSIIsSHGSLKSSNCVVD-SRFVLKITDYG 196
Cdd:cd14100    85 ErpepvqdlfdfITERGALPEELAR-----------SFFRQVLEAVRHCHNCGV-LHRDIKDENILIDlNTGELKLIDFG 152
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 197 L-ASFRSTAEPD-DSHALYAKKLWTAPELLSGnplpttgmQKADVYSFGIILQEIALRSGPFYLEgldlspKEIVqkvrn 274
Cdd:cd14100   153 SgALLKDTVYTDfDGTRVYSPPEWIRFHRYHG--------RSAAVWSLGILLYDMVCGDIPFEHD------EEII----- 213
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|
gi 1370514551 275 GQRPYFrpsidRTQLNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14100   214 RGQVFF-----RQRVSSECQHLIKWCLALRPSDRPSFEDI 248
STKc_WNK2_like cd14032
Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the ...
86-308 6.22e-05

Catalytic domain of With No Lysine (WNK) 2-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. WNK2 is widely expressed and has been shown to be epigenetically silenced in gliomas. It inhibits cell growth by acting as a negative regulator of MEK1-ERK1/2 signaling. WNK2 modulates growth factor-induced cancer cell proliferation, suggesting that it may be a tumor suppressor gene. WNKs comprise a subfamily of STKs with an unusual placement of the catalytic lysine relative to all other protein kinases. They are critical in regulating ion balance and are thus, important components in the control of blood pressure. The WNK2-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270934 [Multi-domain]  Cd Length: 266  Bit Score: 45.07  E-value: 6.22e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  86 NKKRIELTRQVLFELKHM-RDVQFNHLTRFI----GACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRySLINDLV 160
Cdd:cd14032    36 DRKLTKVERQRFKEEAEMlKGLQHPNIVRFYdfweSCAKGKRCIVLVTELMTSGTLKTYLKRFKVMKPKVLR-SWCRQIL 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 161 KGMAFLHNS---IIssHGSLKSSNCVVDSRF-VLKITDYGLASFRstaepddsHALYAKKLWTAPELLSGNPLPTTGMQK 236
Cdd:cd14032   115 KGLLFLHTRtppII--HRDLKCDNIFITGPTgSVKIGDLGLATLK--------RASFAKSVIGTPEFMAPEMYEEHYDES 184
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370514551 237 ADVYSFGIILQEIALRSGPfYLEGLDLSpkEIVQKVRNGQRPYFRPSIDRTQLNEelvlLMERCWAQDPAER 308
Cdd:cd14032   185 VDVYAFGMCMLEMATSEYP-YSECQNAA--QIYRKVTCGIKPASFEKVTDPEIKE----IIGECICKNKEER 249
STKc_TDY_MAPK cd07859
Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; ...
77-309 6.23e-05

Catalytic domain of the Serine/Threonine Kinases, Plant TDY Mitogen-Activated Protein Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Plant MAPKs are typed based on the conserved phosphorylation motif present in the activation loop, TEY and TDY. This subfamily represents the TDY subtype and is composed of Group D plant MAPKs including Arabidopsis thaliana MPK18 (AtMPK18), Oryza sativa Blast- and Wound-induced MAPK1 (OsBWMK1), OsWJUMK1 (Wound- and JA-Uninducible MAPK1), Zea mays MPK6, and the Medicago sativa TDY1 gene product. OsBWMK1 enhances resistance to pathogenic infections. It mediates stress-activated defense responses by activating a transcription factor that affects the expression of stress-related genes. AtMPK18 is involved in microtubule-related functions. In plants, MAPKs are associated with physiological, developmental, hormonal, and stress responses. Some plants show numerous gene duplications of MAPKs; Arabidopsis thaliana harbors at least 20 MAPKs, named AtMPK1-20 while Oryza sativa contains at least 17 MAPKs. Arabidopsis thaliana contains more TEY-type MAPKs than TDY-type, whereas the reverse is true for Oryza sativa. The TDY MAPK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143364 [Multi-domain]  Cd Length: 338  Bit Score: 45.54  E-value: 6.23e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNK--------KRIELTRQVLFELKHMRDVQFNHLtrfigacIDPPN------ICIVTEYCPRGSLQDILEN 142
Cdd:cd07859    25 GEKVAIKKINDvfehvsdaTRILREIKLLRLLRHPDIVEIKHI-------MLPPSrrefkdIYVVFELMESDLHQVIKAN 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 143 DSINLD--WMFRYSLIndlvKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLA--SFRSTAEPDDSHALYAKKLW 218
Cdd:cd07859    98 DDLTPEhhQFFLYQLL----RALKYIHTANVF-HRDLKPKNILANADCKLKICDFGLArvAFNDTPTAIFWTDYVATRWY 172
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 219 TAPELLSGnpLPTTGMQKADVYSFGIILQEIaLRSGPFY-----LEGLDL-------SPKEIVQKVRNGQ-RPYFR---- 281
Cdd:cd07859   173 RAPELCGS--FFSKYTPAIDIWSIGCIFAEV-LTGKPLFpgknvVHQLDLitdllgtPSPETISRVRNEKaRRYLSsmrk 249
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1370514551 282 ----------PSIDRTQLNeelvlLMERCWAQDPAERP 309
Cdd:cd07859   250 kqpvpfsqkfPNADPLALR-----LLERLLAFDPKDRP 282
STKc_IRE1 cd13982
Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze ...
126-310 6.76e-05

Catalytic domain of the Serine/Threonine kinase, Inositol-requiring protein 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IRE1, also called Endoplasmic reticulum (ER)-to-nucleus signaling protein (or ERN), is an ER-localized type I transmembrane protein with kinase and endoribonuclease domains in the cytoplasmic side. It acts as an ER stress sensor and is the oldest and most conserved component of the unfolded protein response (UPR) in eukaryotes. The UPR is activated when protein misfolding is detected in the ER in order to decrease the synthesis of new proteins and increase the capacity of the ER to cope with the stress. During ER stress, IRE1 dimerizes and forms oligomers, allowing the kinase domain to undergo trans-autophosphorylation. This leads to a conformational change that stimulates its endoribonuclease activity and results in the cleavage of its mRNA substrate, HAC1 in yeast and XBP1 in metazoans, promoting a splicing event that enables translation into a transcription factor which activates the UPR. Mammals contain two IRE1 proteins, IRE1alpha (or ERN1) and IRE1beta (or ERN2). The Ire1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270884 [Multi-domain]  Cd Length: 269  Bit Score: 44.96  E-value: 6.76e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 126 IVTEYCPrGSLQDILENDSINLDWMFR----YSLINDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFV-----LKITDY 195
Cdd:cd13982    72 IALELCA-ASLQDLVESPRESKLFLRPglepVRLLRQIASGLAHLHSlNIV--HRDLKPQNILISTPNAhgnvrAMISDF 148
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 196 GLA--------SFRSTAEPDDSHAlyakklWTAPELLSGNplPTTGMQKA-DVYSFGIILQEIaLRSG--PFyleGLDLS 264
Cdd:cd13982   149 GLCkkldvgrsSFSRRSGVAGTSG------WIAPEMLSGS--TKRRQTRAvDIFSLGCVFYYV-LSGGshPF---GDKLE 216
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 1370514551 265 -PKEIVQKVRNGQRPyfrpsIDRTQLNEELVLLMERCWAQDPAERPD 310
Cdd:cd13982   217 rEANILKGKYSLDKL-----LSLGEHGPEAQDLIERMIDFDPEKRPS 258
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
78-314 1.33e-04

Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Checkpoint Kinase 2 (Chk2) plays an important role in cellular responses to DNA double-strand breaks and related lesions. It is phosphorylated and activated by ATM kinase, resulting in its dissociation from sites of damage to phosphorylate downstream targets such as BRCA1, p53, cell cycle transcription factor E2F1, the promyelocytic leukemia protein (PML) involved in apoptosis, and CDC25 phosphatases, among others. Mutations in Chk2 is linked to a variety of cancers including familial breast cancer, myelodysplastic syndromes, prostate cancer, lung cancer, and osteosarcomas. Chk2 contains an N-terminal SQ/TQ cluster domain (SCD), a central forkhead-associated (FHA) domain, and a C-terminal catalytic kinase domain. The Chk2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270986 [Multi-domain]  Cd Length: 275  Bit Score: 43.92  E-value: 1.33e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  78 NVVAIKHVNKKR--------IELTRQVLFELKHMRdvQFNHltrfigACI--------DPPNICIVTEYCPRGSLQD--- 138
Cdd:cd14084    32 KKVAIKIINKRKftigsrreINKPRNIETEIEILK--KLSH------PCIikiedffdAEDDYYIVLELMEGGELFDrvv 103
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 139 ---ILENDSINLdwmFRYSLIndlvKGMAFLH-NSIIssHGSLKSSNCVVDS---RFVLKITDYGLASFRStaepDDS-- 209
Cdd:cd14084   104 snkRLKEAICKL---YFYQML----LAVKYLHsNGII--HRDLKPENVLLSSqeeECLIKITDFGLSKILG----ETSlm 170
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 210 HALYAKKLWTAPELLSGNplPTTGMQKA-DVYSFGIILQEIALRSGPFYLEGLDLSPKEivqKVRNGQRPYFRPSIDRtq 288
Cdd:cd14084   171 KTLCGTPTYLAPEVLRSF--GTEGYTRAvDCWSLGVILFICLSGYPPFSEEYTQMSLKE---QILSGKYTFIPKAWKN-- 243
                         250       260
                  ....*....|....*....|....*.
gi 1370514551 289 LNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14084   244 VSEEAKDLVKKMLVVDPSRRPSIEEA 269
STKc_CAMKK cd14118
Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; ...
158-315 1.37e-04

Catalytic domain of the Serine/Threonine kinase, Calmodulin Dependent Protein Kinase Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CaMKKs are upstream kinases of the CaM kinase cascade that phosphorylate and activate CaMKI and CamKIV. They may also phosphorylate other substrates including PKB and AMP-activated protein kinase (AMPK). Vertebrates contain two CaMKKs, CaMKK1 (or alpha) and CaMKK2 (or beta). CaMKK1 is involved in the regulation of glucose uptake in skeletal muscles. CaMKK2 is involved in regulating energy balance, glucose metabolism, adiposity, hematopoiesis, inflammation, and cancer. The CaMKK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271020 [Multi-domain]  Cd Length: 275  Bit Score: 43.89  E-value: 1.37e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGL--------ASFRSTAepdDSHAlyakklWTAPELLSGNP 228
Cdd:cd14118   123 DIVLGIEYLHyQKII--HRDIKPSNLLLGDDGHVKIADFGVsnefegddALLSSTA---GTPA------FMAPEALSESR 191
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 229 LPTTGmQKADVYSFGIILQEIALRSGPFylegLDLSPKEIVQKVRNgqRPYFRPsiDRTQLNEELVLLMERCWAQDPAER 308
Cdd:cd14118   192 KKFSG-KALDIWAMGVTLYCFVFGRCPF----EDDHILGLHEKIKT--DPVVFP--DDPVVSEQLKDLILRMLDKNPSER 262

                  ....*..
gi 1370514551 309 PDFGQIK 315
Cdd:cd14118   263 ITLPEIK 269
STKc_ERK1_2_like cd07849
Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine ...
77-310 1.38e-04

Catalytic domain of Extracellular signal-Regulated Kinase 1 and 2-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the mitogen-activated protein kinases (MAPKs) ERK1, ERK2, baker's yeast Fus3, and similar proteins. MAPK pathways are important mediators of cellular responses to extracellular signals. ERK1/2 activation is preferentially by mitogenic factors, differentiation stimuli, and cytokines, through a kinase cascade involving the MAPK kinases MEK1/2 and a MAPK kinase kinase from the Raf family. ERK1/2 have numerous substrates, many of which are nuclear and participate in transcriptional regulation of many cellular processes. They regulate cell growth, cell proliferation, and cell cycle progression from G1 to S phase. Although the distinct roles of ERK1 and ERK2 have not been fully determined, it is known that ERK2 can maintain most functions in the absence of ERK1, and that the deletion of ERK2 is embryonically lethal. The MAPK, Fus3, regulates yeast mating processes including mating-specific gene expression, G1 arrest, mating projection, and cell fusion. This ERK1/2-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270839 [Multi-domain]  Cd Length: 336  Bit Score: 44.22  E-value: 1.38e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKhvnkkRIELTRQVLFELKHMRDVQFnhLTRF-------IGACIDPPNIC------IVTEYCP----RGSLQDI 139
Cdd:cd07849    30 GQKVAIK-----KISPFEHQTYCLRTLREIKI--LLRFkheniigILDIQRPPTFEsfkdvyIVQELMEtdlyKLIKTQH 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 140 LENDSINldwMFRYSLIndlvKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLAsfRStAEPDDSHALY-----A 214
Cdd:cd07849   103 LSNDHIQ---YFLYQIL----RGLKYIHSANVL-HRDLKPSNLLLNTNCDLKICDFGLA--RI-ADPEHDHTGFlteyvA 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 215 KKLWTAPELLsgnpLPTTGMQKA-DVYSFGIILQEIALRS----GPFYLEGLDL------SP-KEIVQKVRNGQ-RPY-- 279
Cdd:cd07849   172 TRWYRAPEIM----LNSKGYTKAiDIWSVGCILAEMLSNRplfpGKDYLHQLNLilgilgTPsQEDLNCIISLKaRNYik 247
                         250       260       270
                  ....*....|....*....|....*....|....*...
gi 1370514551 280 ---FRPSIDRTQL----NEELVLLMERCWAQDPAERPD 310
Cdd:cd07849   248 slpFKPKVPWNKLfpnaDPKALDLLDKMLTFNPHKRIT 285
STKc_obscurin_rpt2 cd14110
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs ...
96-276 1.39e-04

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Obscurin; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Obscurin, approximately 800 kDa in size, is one of three giant proteins expressed in vetebrate striated muscle, together with titin and nebulin. It is a multidomain protein composed of tandem adhesion and signaling domains, including 49 immunoglobulin (Ig) and 2 fibronectin type III (FN3) domains at the N-terminus followed by a more complex region containing more Ig domains, a conserved SH3 domain near a RhoGEF and PH domains, non-modular regions, as well as IQ and phosphorylation motifs. The obscurin gene also encode two kinase domains, which are not expressed as part of the 800 kDa protein, but as a smaller, alternatively spliced product present mainly in the heart muscle, also called obscurin-MLCK. Obscurin is localized at the peripheries of Z-disks and M-lines, where it is able to communicate with the surrounding myoplasm. It interacts with diverse proteins including sAnk1, myosin, titin, and MyBP-C. It may act as a scaffold for the assembly of elements of the contractile apparatus. The obscurin subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271012 [Multi-domain]  Cd Length: 257  Bit Score: 43.75  E-value: 1.39e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  96 VLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCP-RGSLQDILENDSinldwmfrYS------LINDLVKGMAFLHN 168
Cdd:cd14110    46 VLREYQVLRRLSHPRIAQLHSAYLSPRHLVLIEELCSgPELLYNLAERNS--------YSeaevtdYLWQILSAVDYLHS 117
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 169 SIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE--PDDSHALYAKKLwtAPELLSGN-PLPTTgmqkaDVYSFGII 245
Cdd:cd14110   118 RRIL-HLDLRSENMIITEKNLLKIVDLGNAQPFNQGKvlMTDKKGDYVETM--APELLEGQgAGPQT-----DIWAIGVT 189
                         170       180       190
                  ....*....|....*....|....*....|.
gi 1370514551 246 LQEIALRSGPFYLEGldlsPKEIVQKVRNGQ 276
Cdd:cd14110   190 AFIMLSADYPVSSDL----NWERDRNIRKGK 216
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
103-322 1.51e-04

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely expressed in many tissues. It is essential for the signaling of hormone-like cytokines such as growth hormone, erythropoietin, thrombopoietin, and prolactin, as well as some IFNs and cytokines that signal through the IL-3 and gp130 receptors. Disruption of Jak2 in mice results in an embryonic lethal phenotype with multiple defects including erythropoietic and cardiac abnormalities. It is the only Jak gene that results in a lethal phenotype when disrupted in mice. A mutation in the pseudokinase domain of Jak2, V617F, is present in many myeloproliferative diseases, including almost all patients with polycythemia vera, and 50% of patients with essential thrombocytosis and myelofibrosis. Jak2 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. Despite this, the presumed pseudokinase (repeat 1) domain of Jak2 exhibits dual-specificity kinase activity, phosphorylating two negative regulatory sites in Jak2: Ser523 and Tyr570. Inactivation of the repeat 1 domain increased Jak2 basal activity, suggesting that it modulates the kinase activity of the C-terminal catalytic (repeat 2) domain. The Jak2 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 43.78  E-value: 1.51e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 103 MRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIIsSHGSLKSSNC 182
Cdd:cd05078    57 MSQLSHKHLVLNYGVCVCGDENILVQEYVKFGSLDTYLKKNKNCINILWKLEVAKQLAWAMHFLEEKTL-VHGNVCAKNI 135
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 183 VV----DSRF----VLKITDYGLAsfrSTAEPDDshALYAKKLWTAPELLSgNPLPTTgmQKADVYSFGIILQEIAlRSG 254
Cdd:cd05078   136 LLireeDRKTgnppFIKLSDPGIS---ITVLPKD--ILLERIPWVPPECIE-NPKNLS--LATDKWSFGTTLWEIC-SGG 206
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1370514551 255 PFYLEGLDLSPKEIVQKvrngqrpyfrpsiDRTQLNE----ELVLLMERCWAQDPAERPDFgqiKGFIRRFN 322
Cdd:cd05078   207 DKPLSALDSQRKLQFYE-------------DRHQLPApkwtELANLINNCMDYEPDHRPSF---RAIIRDLN 262
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
77-245 1.87e-04

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. The MLCK1 gene expresses three transcripts in a cell-specific manner: a short MLCK1 which contains three immunoglobulin (Ig)-like and one fibronectin type III (FN3) domains, PEVK and actin-binding regions, and a kinase domain near the C-terminus; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module. MLCK2, MLCK3, and MLCK4 share a simpler domain architecture of a single kinase domain near the C-terminus and the absence of Ig-like or FN3 domains. The MLCK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271005 [Multi-domain]  Cd Length: 250  Bit Score: 43.37  E-value: 1.87e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLI 156
Cdd:cd14103    18 GKELAAKFIKCRKAKDREDVRNEIEIMNQLRHPRLLQLYDAFETPREMVLVMEYVAGGELFERVVDDDFELTERDCILFM 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLH-NSIIssHGSLKSSN--CVVDSRFVLKITDYGLASFRstaEPDDShalyAKKLW-----TAPELLSGNP 228
Cdd:cd14103    98 RQICEGVQYMHkQGIL--HLDLKPENilCVSRTGNQIKIIDFGLARKY---DPDKK----LKVLFgtpefVAPEVVNYEP 168
                         170
                  ....*....|....*...
gi 1370514551 229 L-PTTgmqkaDVYSFGII 245
Cdd:cd14103   169 IsYAT-----DMWSVGVI 181
STKc_MPK1 cd07857
Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; ...
63-272 2.00e-04

Catalytic domain of the Serine/Threonine Kinase, Fungal Mitogen-Activated Protein Kinase MPK1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPKs MPK1 from Saccharomyces cerevisiae, Pmk1 from Schizosaccharomyces pombe, and similar proteins. MPK1 (also called Slt2) and Pmk1 (also called Spm1) are stress-activated MAPKs that regulate the cell wall integrity pathway, and are therefore important in the maintainance of cell shape, cell wall construction, morphogenesis, and ion homeostasis. MPK1 is activated in response to cell wall stress including heat stimulation, osmotic shock, UV irradiation, and any agents that interfere with cell wall biogenesis such as chitin antagonists, caffeine, or zymolase. MPK1 is regulated by the MAP2Ks Mkk1/2, which are regulated by the MAP3K Bck1. Pmk1 is also activated by multiple stresses including elevated temperatures, hyper- or hypotonic stress, glucose deprivation, exposure to cell-wall damaging compounds, and oxidative stress. It is regulated by the MAP2K Pek1, which is regulated by the MAP3K Mkh1. MAPKs are important mediators of cellular responses to extracellular signals. The MPK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173750 [Multi-domain]  Cd Length: 332  Bit Score: 43.93  E-value: 2.00e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  63 HGKYQIFA---NTGHFKGNVVAIKHVNK---KRIeLTRQVLFELKHMRDVQfNHltRFIGACIDppnICIVTEYCPRG-- 134
Cdd:cd07857    10 QGAYGIVCsarNAETSEEETVAIKKITNvfsKKI-LAKRALRELKLLRHFR-GH--KNITCLYD---MDIVFPGNFNEly 82
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 135 --------SLQDILENDSINLDWMFRySLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLA-SFRSTAE 205
Cdd:cd07857    83 lyeelmeaDLHQIIRSGQPLTDAHFQ-SFIYQILCGLKYIHSANVL-HRDLKPGNLLVNADCELKICDFGLArGFSENPG 160
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 206 PDDSHAL-YAKKLW-TAPELLSGNPLPTTGMqkaDVYSFGIILQEIaLRSGPFY------------LEGLDLSPKEIVQK 271
Cdd:cd07857   161 ENAGFMTeYVATRWyRAPEIMLSFQSYTKAI---DVWSVGCILAEL-LGRKPVFkgkdyvdqlnqiLQVLGTPDEETLSR 236

                  .
gi 1370514551 272 V 272
Cdd:cd07857   237 I 237
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
79-256 2.18e-04

Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Aurora kinases are key regulators of mitosis and are essential for the accurate and equal division of genomic material from parent to daughter cells. Vertebrates contain at least 2 Aurora kinases (A and B); mammals contains a third Aurora kinase gene (C). Aurora-A regulates cell cycle events from the late S-phase through the M-phase including centrosome maturation, mitotic entry, centrosome separation, spindle assembly, chromosome alignment, cytokinesis, and mitotic exit. Aurora-A activation depends on its autophosphorylation and binding to the microtubule-associated protein TPX2, which also localizes the kinase to spindle microtubules. Aurora-A is overexpressed in many cancer types such as prostate, ovarian, breast, bladder, gastric, and pancreatic. The Aurora subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271018 [Multi-domain]  Cd Length: 258  Bit Score: 43.41  E-value: 2.18e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  79 VVAIKHVNKKRIE-------LTRQVLFElKHMRDvqfNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSiNLDWMF 151
Cdd:cd14116    32 ILALKVLFKAQLEkagvehqLRREVEIQ-SHLRH---PNILRLYGYFHDATRVYLILEYAPLGTVYRELQKLS-KFDEQR 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 152 RYSLINDLVKGMAFLHN-SIIssHGSLKSSNCVVDSRFVLKITDYGLasfrSTAEPDDSHALYAKKL-WTAPELLSGNpl 229
Cdd:cd14116   107 TATYITELANALSYCHSkRVI--HRDIKPENLLLGSAGELKIADFGW----SVHAPSSRRTTLCGTLdYLPPEMIEGR-- 178
                         170       180
                  ....*....|....*....|....*..
gi 1370514551 230 ptTGMQKADVYSFGIILQEIALRSGPF 256
Cdd:cd14116   179 --MHDEKVDLWSLGVLCYEFLVGKPPF 203
STKc_NAK_like cd14037
Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze ...
67-323 2.36e-04

Catalytic domain of Numb-Associated Kinase (NAK)-like Serine/Threonine kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of Drosophila melanogaster NAK, human BMP-2-inducible protein kinase (BMP2K or BIKe) and similar vertebrate proteins, as well as the Saccharomyces cerevisiae proteins Prk1, Actin-regulating kinase 1 (Ark1), and Akl1. NAK was the first characterized member of this subfamily. It plays a role in asymmetric cell division through its association with Numb. It also regulates the localization of Dlg, a protein essential for septate junction formation. BMP2K contains a nuclear localization signal and a kinase domain that is capable of phosphorylating itself and myelin basic protein. The expression of the BMP2K gene is increase during BMP-2-induced osteoblast differentiation. It may function to control the rate of differentiation. Prk1, Ark1, and Akl1 comprise a subfamily of yeast proteins that are important regulators of the actin cytoskeleton and endocytosis. They share an N-terminal kinase domain but no significant homology in other regions of their sequences. The NAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270939 [Multi-domain]  Cd Length: 277  Bit Score: 43.43  E-value: 2.36e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  67 QIFANTGHFKGNVVAIKHV---NKKRIELTRQvlfELKHMRDVQFN-HLTRFIGACI--DPPNIC---IVTEYCPRGSLQ 137
Cdd:cd14037    18 HVYLVKTSNGGNRAALKRVyvnDEHDLNVCKR---EIEIMKRLSGHkNIVGYIDSSAnrSGNGVYevlLLMEYCKGGGVI 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 138 DILeNDsiNLDWMFRYSLI----NDLVKGMAFLHN---SIIssHGSLKSSNCVVDSRFVLKITDYGLAS--FRSTAEPDD 208
Cdd:cd14037    95 DLM-NQ--RLQTGLTESEIlkifCDVCEAVAAMHYlkpPLI--HRDLKVENVLISDSGNYKLCDFGSATtkILPPQTKQG 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 209 SHAL------YAKKLWTAPE---LLSGNPLPTtgmqKADVYSFGIILQEIALRSGPFYlEGLDLSpkeiVQKVrNGQRPY 279
Cdd:cd14037   170 VTYVeedikkYTTLQYRAPEmidLYRGKPITE----KSDIWALGCLLYKLCFYTTPFE-ESGQLA----ILNG-NFTFPD 239
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|....
gi 1370514551 280 FRPSIDRtqlneeLVLLMERCWAQDPAERPDFGQIKGFIRRFNK 323
Cdd:cd14037   240 NSRYSKR------LHKLIRYMLEEDPEKRPNIYQVSYEAFELAG 277
STKc_SnRK2 cd14662
Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein ...
77-315 2.51e-04

Catalytic domain of the Serine/Threonine Kinases, Sucrose nonfermenting 1-related protein kinase subfamily 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The SnRKs form three different subfamilies designated SnRK1-3. SnRK2 is represented in this cd. SnRK2s are involved in plant response to abiotic stresses and abscisic acid (ABA)-dependent plant development. The SnRK2s subfamily is in turn classed into three subgroups, all 3 of which are represented in this CD. Group 1 comprises kinases not activated by ABA, group 2 - kinases not activated or activated very weakly by ABA (depending on plant species), and group 3 - kinases strongly activated by ABA. The SnRKs belong to a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271132 [Multi-domain]  Cd Length: 257  Bit Score: 43.22  E-value: 2.51e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNK-KRIEltRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYsL 155
Cdd:cd14662    25 KELVAVKYIERgLKID--ENVQREIINHRSLRHPNIIRFKEVVLTPTHLAIVMEYAAGGELFERICNAGRFSEDEARY-F 101
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 156 INDLVKGMAFLHNSIIsSHGSLKSSNCVVDSRFV--LKITDYGLAsfRSTAEPDDSHALYAKKLWTAPELLSGNPLPTtg 233
Cdd:cd14662   102 FQQLISGVSYCHSMQI-CHRDLKLENTLLDGSPAprLKICDFGYS--KSSVLHSQPKSTVGTPAYIAPEVLSRKEYDG-- 176
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 234 mQKADVYSFGIILQEIALRSGPFylEGLDlSPKEI---VQKVRNGQrpYFRPsiDRTQLNEELVLLMERCWAQDPAERPD 310
Cdd:cd14662   177 -KVADVWSCGVTLYVMLVGAYPF--EDPD-DPKNFrktIQRIMSVQ--YKIP--DYVRVSQDCRHLLSRIFVANPAKRIT 248

                  ....*
gi 1370514551 311 FGQIK 315
Cdd:cd14662   249 IPEIK 253
STKc_Kin4 cd14076
Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the ...
70-246 2.60e-04

Catalytic domain of the yeast Serine/Threonine Kinase, Kin4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Kin4 is a central component of the spindle position checkpoint (SPOC), which monitors spindle position and regulates the mitotic exit network (MEN). Kin4 associates with spindle pole bodies in mother cells to inhibit MEN signaling and delay mitosis until the anaphase nucleus is properly positioned along the mother-bud axis. Kin4 activity is regulated by both the bud neck-associated kinase Elm1 and protein phosphatase 2A. The Kin4 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270978 [Multi-domain]  Cd Length: 270  Bit Score: 43.24  E-value: 2.60e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  70 ANTGHFKGNVVAIKHV-------NKKRIELTRQV--LFELKH-----MRDVQFNHltRFIGacidppnicIVTEYCPRGS 135
Cdd:cd14076    24 PKANHRSGVQVAIKLIrrdtqqeNCQTSKIMREIniLKGLTHpnivrLLDVLKTK--KYIG---------IVLEFVSGGE 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 136 LQD-ILENDSINLDWMFRysLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYA 214
Cdd:cd14076    93 LFDyILARRRLKDSVACR--LFAQLISGVAYLHKKGVV-HRDLKLENLLLDKNRNLVITDFGFANTFDHFNGDLMSTSCG 169
                         170       180       190
                  ....*....|....*....|....*....|..
gi 1370514551 215 KKLWTAPELLSGNPlPTTGmQKADVYSFGIIL 246
Cdd:cd14076   170 SPCYAAPELVVSDS-MYAG-RKADIWSCGVIL 199
STKc_nPKC_delta cd05620
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze ...
158-322 2.73e-04

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C delta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. It slows down cell proliferation, inducing cell cycle arrest and enhancing cell differentiation. PKC-delta is also involved in the regulation of transcription as well as immune and inflammatory responses. It plays a central role in the genotoxic stress response that leads to DNA damaged-induced apoptosis. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC-delta subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 173710 [Multi-domain]  Cd Length: 316  Bit Score: 43.39  E-value: 2.73e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEpDDSHALYAKKLWTAPELLSGNPLPTTgmqkA 237
Cdd:cd05620   104 EIVCGLQFLHSKGII-YRDLKLDNVMLDRDGHIKIADFGMCKENVFGD-NRASTFCGTPDYIAPEILQGLKYTFS----V 177
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 238 DVYSFGIILQEIALRSGPFYLEGLDlspkEIVQKVRNGQRPYFRpsidrtQLNEELVLLMERCWAQDPAERPDF-GQIKG 316
Cdd:cd05620   178 DWWSFGVLLYEMLIGQSPFHGDDED----ELFESIRVDTPHYPR------WITKESKDILEKLFERDPTRRLGVvGNIRG 247

                  ....*...
gi 1370514551 317 --FIRRFN 322
Cdd:cd05620   248 hpFFKTIN 255
PTZ00263 PTZ00263
protein kinase A catalytic subunit; Provisional
158-276 3.60e-04

protein kinase A catalytic subunit; Provisional


Pssm-ID: 140289 [Multi-domain]  Cd Length: 329  Bit Score: 42.88  E-value: 3.60e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASfrstAEPDDSHALYAKKLWTAPELLSgnplpTTGMQKA 237
Cdd:PTZ00263  126 ELVLAFEYLHSKDII-YRDLKPENLLLDNKGHVKVTDFGFAK----KVPDRTFTLCGTPEYLAPEVIQ-----SKGHGKA 195
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 1370514551 238 -DVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQ 276
Cdd:PTZ00263  196 vDWWTMGVLLYEFIAGYPPFF----DDTPFRIYEKILAGR 231
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
81-245 5.00e-04

Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PSKH1 is an autophosphorylating STK that is expressed ubiquitously and exhibits multiple intracellular localizations including the centrosome, Golgi apparatus, and splice factor compartments. It contains a catalytic kinase domain and an N-terminal SH4-like motif that is acylated to facilitate membrane attachment. PSKH1 plays a rile in the maintenance of the Golgi apparatus, an important organelle within the secretory pathway. It may also function as a novel splice factor and a regulator of prostate cancer cell growth. The PSKH1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270989 [Multi-domain]  Cd Length: 259  Bit Score: 42.14  E-value: 5.00e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  81 AIKHVNKKRieLTRQVL-FELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDIL-------ENDSINLDWMfr 152
Cdd:cd14087    30 AIKMIETKC--RGREVCeSELNVLRRVRHTNIIQLIEVFETKERVYMVMELATGGELFDRIiakgsftERDATRVLQM-- 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 153 yslindLVKGMAFLHnSIISSHGSLKSSNCV-----VDSRfvLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGN 227
Cdd:cd14087   106 ------VLDGVKYLH-GLGITHRDLKPENLLyyhpgPDSK--IMITDFGLASTRKKGPNCLMKTTCGTPEYIAPEILLRK 176
                         170
                  ....*....|....*...
gi 1370514551 228 PLpttgMQKADVYSFGII 245
Cdd:cd14087   177 PY----TQSVDMWAVGVI 190
STKc_PRKX_like cd05612
Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of ...
82-276 5.62e-04

Catalytic domain of PRKX-like Protein Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include human PRKX (X chromosome-encoded protein kinase), Drosophila DC2, and similar proteins. PRKX is present in many tissues including fetal and adult brain, kidney, and lung. The PRKX gene is located in the Xp22.3 subregion and has a homolog called PRKY on the Y chromosome. An abnormal interchange between PRKX aand PRKY leads to the sex reversal disorder of XX males and XY females. PRKX is implicated in granulocyte/macrophage lineage differentiation, renal cell epithelial migration, and tubular morphogenesis in the developing kidney. The PRKX-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270763 [Multi-domain]  Cd Length: 292  Bit Score: 42.04  E-value: 5.62e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  82 IKHV-NKKRieltrqVLFELKHmrdvqfNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYsLINDLV 160
Cdd:cd05612    45 EQHVhNEKR------VLKEVSH------PFIIRLFWTEHDQRFLYMLMEYVPGGELFSYLRNSGRFSNSTGLF-YASEIV 111
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 161 KGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGlasfrstaepddshalYAKKL----WT---APELLSGNPLPTTG 233
Cdd:cd05612   112 CALEYLHSKEIV-YRDLKPENILLDKEGHIKLTDFG----------------FAKKLrdrtWTlcgTPEYLAPEVIQSKG 174
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 1370514551 234 MQKA-DVYSFGIILQEIALRSGPFYleglDLSPKEIVQKVRNGQ 276
Cdd:cd05612   175 HNKAvDWWALGILIYEMLVGYPPFF----DDNPFGIYEKILAGK 214
STKc_MAPKAPK cd14089
Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated ...
154-319 5.84e-04

Catalytic domain of the Serine/Threonine kinases, Mitogen-activated protein kinase-activated protein kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of the MAPK-activated protein kinases MK2, MK3, MK5 (also called PRAK for p38-regulated/activated protein kinase), and related proteins. These proteins contain a catalytic kinase domain followed by a C-terminal autoinhibitory region that contains nuclear localization (NLS) and nuclear export (NES) signals with a p38 MAPK docking motif that overlaps the NLS. In addition, MK2 and MK3 contain an N-terminal proline-rich region that can bind to SH3 domains. MK2 and MK3 are bonafide substrates for the MAPK p38, while MK5 plays a functional role in the p38 MAPK pathway although their direct interaction has been difficult to detect. MK2 and MK3 are closely related and show, thus far, indistinguishable substrate specificity, while MK5 shows a distinct spectrum of substrates. MK2 and MK3 are mainly involved in the regulation of gene expression and they participate in diverse cellular processes such as endocytosis, cytokine production, cytoskeletal reorganization, cell migration, cell cycle control and chromatin remodeling. They are implicated in inflammation and cance and their substrates include mRNA-AU-rich-element (ARE)-binding proteins (TTP and hnRNP A0), Hsp proteins (Hsp27 and Hsp25) and RSK, among others. MK2/3 are both expressed ubiquitously but MK2 is expressed at significantly higher levels. MK5 is a ubiquitous protein that is implicated in neuronal morphogenesis, cell migration, and tumor angiogenesis. It interacts with PKA, which induces cytoplasmic translocation of MK5. Its substrates includes p53, ERK3/4, Hsp27, and cytosolic phospholipase A2 (cPLA2). The MAPKAPK subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270991 [Multi-domain]  Cd Length: 263  Bit Score: 41.89  E-value: 5.84e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 154 SLINDLVKGMAFLHNSIISsHGSLKSSNCVVDSR---FVLKITDYGLASfrstaEPDDSHAL--------YAkklwtAPE 222
Cdd:cd14089   104 EIMRQIGSAVAHLHSMNIA-HRDLKPENLLYSSKgpnAILKLTDFGFAK-----ETTTKKSLqtpcytpyYV-----APE 172
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 223 LLSgnplPTTGMQKADVYSFGIILqeIALRSG--PFY-LEGLDLSPKeIVQKVRNGQrpYFRPSIDRTQLNEELVLLMER 299
Cdd:cd14089   173 VLG----PEKYDKSCDMWSLGVIM--YILLCGypPFYsNHGLAISPG-MKKRIRNGQ--YEFPNPEWSNVSEEAKDLIRG 243
                         170       180
                  ....*....|....*....|
gi 1370514551 300 CWAQDPAERPDfgqIKGFIR 319
Cdd:cd14089   244 LLKTDPSERLT---IEEVMN 260
STKc_nPKC_theta_like cd05592
Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and ...
158-308 6.16e-04

Catalytic domain of the Serine/Threonine Kinases, Novel Protein Kinase C theta, delta, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. PKC-delta plays a role in cell cycle regulation and programmed cell death in many cell types. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. There are four nPKC isoforms, delta, epsilon, eta, and theta. The nPKC-theta-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270744 [Multi-domain]  Cd Length: 320  Bit Score: 41.99  E-value: 6.16e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAE---------PDdshalyakklWTAPELLSGN 227
Cdd:cd05592   104 EIICGLQFLHsRGII--YRDLKLDNVLLDREGHIKIADFGMCKENIYGEnkastfcgtPD----------YIAPEILKGQ 171
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 228 PLPttgmQKADVYSFGIILQEIALRSGPFYLEGLDlspkEIVQKVRNgQRPYFRPSIDRtQLNEELVLLMERcwaqDPAE 307
Cdd:cd05592   172 KYN----QSVDWWSFGVLLYEMLIGQSPFHGEDED----ELFWSICN-DTPHYPRWLTK-EAASCLSLLLER----NPEK 237

                  .
gi 1370514551 308 R 308
Cdd:cd05592   238 R 238
STKc_BUR1 cd07866
Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), ...
136-252 6.41e-04

Catalytic domain of the Serine/Threonine Kinase, Fungal Cyclin-Dependent protein Kinase (CDK), Bypass UAS Requirement 1, and similar proteins; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. BUR1, also called SGV1, is a yeast CDK that is functionally equivalent to mammalian CDK9. It associates with the cyclin BUR2. BUR genes were orginally identified in a genetic screen as factors involved in general transcription. The BUR1/BUR2 complex phosphorylates the C-terminal domain of RNA polymerase II. In addition, this complex regulates histone modification by phosporylating Rad6 and mediating the association of the Paf1 complex with chromatin. CDKs belong to a large family of STKs that are regulated by their cognate cyclins. Together, they are involved in the control of cell-cycle progression, transcription, and neuronal function. The BUR1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270849 [Multi-domain]  Cd Length: 311  Bit Score: 41.92  E-value: 6.41e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 136 LQDILENDSINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHA--- 211
Cdd:cd07866   101 LSGLLENPSVKLTESQIKCYMLQLLEGINYLHeNHIL--HRDIKAANILIDNQGILKIADFGLARPYDGPPPNPKGGggg 178
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*...
gi 1370514551 212 -------LYAKKLWTAPELLSGNPLPTTGMqkaDVYSFGIILQEIALR 252
Cdd:cd07866   179 gtrkytnLVVTRWYRPPELLLGERRYTTAV---DIWGIGCVFAEMFTR 223
STKc_ROCK2 cd05621
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
120-261 6.44e-04

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK2 was the first identified target of activated RhoA, and was found to play a role in stress fiber and focal adhesion formation. It is prominently expressed in the brain, heart, and skeletal muscles. It is implicated in vascular and neurological disorders, such as hypertension and vasospasm of the coronary and cerebral arteries. ROCK2 is also activated by caspase-2 cleavage, resulting in thrombin-induced microparticle generation in response to cell activation. Mice deficient in ROCK2 show intrauterine growth retardation and embryonic lethality because of placental dysfunction. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270771 [Multi-domain]  Cd Length: 379  Bit Score: 42.29  E-value: 6.44e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 120 DPPNICIVTEYCPRGSLQDILENDSINLDWMFRYS----LINDLVKGMAFLHNSIisshgslKSSNCVVDSRFVLKITDY 195
Cdd:cd05621   123 DDKYLYMVMEYMPGGDLVNLMSNYDVPEKWAKFYTaevvLALDAIHSMGLIHRDV-------KPDNMLLDKYGHLKLADF 195
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|.
gi 1370514551 196 GlasfrSTAEPDDSHALYAKKLWTAPELLSGNPLPTTGM-----QKADVYSFGIILQEIALRSGPFYLEGL 261
Cdd:cd05621   196 G-----TCMKMDETGMVHCDTAVGTPDYISPEVLKSQGGdgyygRECDWWSVGVFLFEMLVGDTPFYADSL 261
PHA03209 PHA03209
serine/threonine kinase US3; Provisional
97-274 6.90e-04

serine/threonine kinase US3; Provisional


Pssm-ID: 177557 [Multi-domain]  Cd Length: 357  Bit Score: 42.17  E-value: 6.90e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  97 LFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCpRGSLQDILENDSINLDWMFRYSLINDLVKGMAFLHNSIISsHGS 176
Cdd:PHA03209  105 LIEAMLLQNVNHPSVIRMKDTLVSGAITCMVLPHY-SSDLYTYLTKRSRPLPIDQALIIEKQILEGLRYLHAQRII-HRD 182
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 177 LKSSNCVVDSRFVLKITDYGLASFrSTAEPDDsHALYAKKLWTAPELLSGNPLPTtgmqKADVYSFGIILQE-IALRSGP 255
Cdd:PHA03209  183 VKTENIFINDVDQVCIGDLGAAQF-PVVAPAF-LGLAGTVETNAPEVLARDKYNS----KADIWSAGIVLFEmLAYPSTI 256
                         170
                  ....*....|....*....
gi 1370514551 256 FylEGLDLSPKEIVQKVRN 274
Cdd:PHA03209  257 F--EDPPSTPEEYVKSCHS 273
STKc_MSK_C cd14092
C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
159-276 7.73e-04

C-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270994 [Multi-domain]  Cd Length: 311  Bit Score: 41.90  E-value: 7.73e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 159 LVKGMAFLHNSIISsHGSLKSSNCVV---DSRFVLKITDYGLASFRSTAEPDDSHAL---YAkklwtAPELLSGNPLPTT 232
Cdd:cd14092   108 LVSAVSFMHSKGVV-HRDLKPENLLFtdeDDDAEIKIVDFGFARLKPENQPLKTPCFtlpYA-----APEVLKQALSTQG 181
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 1370514551 233 GMQKADVYSFGIILqeIALRSG--PFYLEGLDLSPKEIVQKVRNGQ 276
Cdd:cd14092   182 YDESCDLWSLGVIL--YTMLSGqvPFQSPSRNESAAEIMKRIKSGD 225
STKc_MAK_like cd07830
Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs ...
55-251 9.79e-04

Catalytic domain of Male germ cell-Associated Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of human MAK and MAK-related kinase (MRK), Saccharomyces cerevisiae Ime2p, Schizosaccharomyces pombe Mei4-dependent protein 3 (Mde3) and Pit1, Caenorhabditis elegans dyf-5, Arabidopsis thaliana MHK, and similar proteins. These proteins play important roles during meiosis. MAK is highly expressed in testicular cells specifically in the meiotic phase, but is not essential for spermatogenesis and fertility. It functions as a coactivator of the androgen receptor in prostate cells. MRK, also called Intestinal Cell Kinase (ICK), is expressed ubiquitously, with highest expression in the ovary and uterus. A missense mutation in MRK causes endocrine-cerebro-osteodysplasia, suggesting that this protein plays an important role in the development of many organs. MAK and MRK may be involved in regulating cell cycle and cell fate. Ime2p is a meiosis-specific kinase that is important during meiotic initiation and during the later stages of meiosis. Mde3 functions downstream of the transcription factor Mei-4 which is essential for meiotic prophase I. The MAK-like subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270824 [Multi-domain]  Cd Length: 283  Bit Score: 41.37  E-value: 9.79e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  55 SYGSLMTAhgkyqifanTGHFKGNVVAIKHVNKKRI---ELTRqvLFELKHMRDVQFN-HLTRFIGACIDPPNICIVTEY 130
Cdd:cd07830    11 TFGSVYLA---------RNKETGELVAIKKMKKKFYsweECMN--LREVKSLRKLNEHpNIVKLKEVFRENDELYFVFEY 79
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 131 CPRGSLQDILENDSInldwMFRYSLINDLV----KGMAFLHnsiisSHG----SLKSSNCVVDSRFVLKITDYGLAsfRS 202
Cdd:cd07830    80 MEGNLYQLMKDRKGK----PFSESVIRSIIyqilQGLAHIH-----KHGffhrDLKPENLLVSGPEVVKIADFGLA--RE 148
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 203 TaEPDDSHALYAKKLW-TAPELL--SGN---PLpttgmqkaDVYSFGIILQEIAL 251
Cdd:cd07830   149 I-RSRPPYTDYVSTRWyRAPEILlrSTSyssPV--------DIWALGCIMAELYT 194
STKc_GRK1 cd05608
Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs ...
159-311 9.97e-04

Catalytic domain of the Serine/Threonine Kinase, G protein-coupled Receptor Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GRK1 (also called rhodopsin kinase) belongs to the visual group of GRKs and is expressed in retinal cells. It phosphorylates rhodopsin in rod cells, which leads to termination of the phototransduction cascade. Mutations in GRK1 are associated to a recessively inherited form of stationary nightblindness called Oguchi disease. GRKs phosphorylate and regulate G protein-coupled receptors (GPCRs), the largest superfamily of cell surface receptors, which regulate some part of nearly all physiological functions. Phosphorylated GPCRs bind to arrestins, which prevents further G protein signaling despite the presence of activating ligand. The GRK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270759 [Multi-domain]  Cd Length: 288  Bit Score: 41.41  E-value: 9.97e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 159 LVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLASfrSTAEPDDSHALYAKKL-WTAPELLSGNPLPTTgmqk 236
Cdd:cd05608   114 IISGLEHLHqRRII--YRDLKPENVLLDDDGNVRISDLGLAV--ELKDGQTKTKGYAGTPgFMAPELLLGEEYDYS---- 185
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1370514551 237 ADVYSFGIILQEIALRSGPFYLEGLDLSPKEIVQKVRNGQRPY-FRPSIDRTQLNEELVllmercwAQDPAERPDF 311
Cdd:cd05608   186 VDYFTLGVTLYEMIAARGPFRARGEKVENKELKQRILNDSVTYsEKFSPASKSICEALL-------AKDPEKRLGF 254
STKc_nPKC_theta cd05619
Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze ...
158-320 1.30e-03

Catalytic domain of the Serine/Threonine Kinase, Novel Protein Kinase C theta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKC-theta is selectively expressed in T-cells and plays an important and non-redundant role in several aspects of T-cell biology. Although T-cells also express other PKC isoforms, PKC-theta is unique in that upon antigen stimulation, it is translocated to the plasma membrane at the immunological synapse, where it mediates signals essential for T-cell activation. It is essential for TCR-induced proliferation, cytokine production, T-cell survival, and the differentiation and effector function of T-helper (Th) cells, particularly Th2 and Th17. PKC-theta is being developed as a therapeutic target for Th2-mediated allergic inflammation and Th17-mediated autoimmune diseases. PKCs are classified into three groups (classical, atypical, and novel) depending on their mode of activation and the structural characteristics of their regulatory domain. nPKCs are calcium-independent, but require DAG (1,2-diacylglycerol) and phosphatidylserine (PS) for activity. The nPKC subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270770 [Multi-domain]  Cd Length: 331  Bit Score: 41.06  E-value: 1.30e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 158 DLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDShALYAKKLWTAPELLSGNPLPTTgmqkA 237
Cdd:cd05619   114 EIICGLQFLHSKGIV-YRDLKLDNILLDKDGHIKIADFGMCKENMLGDAKTS-TFCGTPDYIAPEILLGQKYNTS----V 187
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 238 DVYSFGIILQEIALRSGPFYleGLDlsPKEIVQKVRNGQRPYFRpsidrtQLNEELVLLMERCWAQDPAERpdFGqIKGF 317
Cdd:cd05619   188 DWWSFGVLLYEMLIGQSPFH--GQD--EEELFQSIRMDNPFYPR------WLEKEAKDILVKLFVREPERR--LG-VRGD 254

                  ...
gi 1370514551 318 IRR 320
Cdd:cd05619   255 IRQ 257
PKc_like cd13968
Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large ...
73-196 1.60e-03

Catalytic domain of the Protein Kinase superfamily; The PK superfamily contains the large family of typical PKs that includes serine/threonine kinases (STKs), protein tyrosine kinases (PTKs), and dual-specificity PKs that phosphorylate both serine/threonine and tyrosine residues of target proteins, as well as pseudokinases that lack crucial residues for catalytic activity and/or ATP binding. It also includes phosphoinositide 3-kinases (PI3Ks), aminoglycoside 3'-phosphotransferases (APHs), choline kinase (ChoK), Actin-Fragmin Kinase (AFK), and the atypical RIO and Abc1p-like protein kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to their target substrates; these include serine/threonine/tyrosine residues in proteins for typical or atypical PKs, the 3-hydroxyl of the inositol ring of D-myo-phosphatidylinositol (PtdIns) or its derivatives for PI3Ks, the 4-hydroxyl of PtdIns for PI4Ks, and other small molecule substrates for APH/ChoK and similar proteins such as aminoglycosides, macrolides, choline, ethanolamine, and homoserine.


Pssm-ID: 270870 [Multi-domain]  Cd Length: 136  Bit Score: 38.96  E-value: 1.60e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  73 GHFKGNVVAIKH---VNKKRIELTRQVLFELKHMRDVQFNHLtRFIGACI-DPPNIcIVTEYCPRGSLQDIL---ENDSI 145
Cdd:cd13968    14 GECTTIGVAVKIgddVNNEEGEDLESEMDILRRLKGLELNIP-KVLVTEDvDGPNI-LLMELVKGGTLIAYTqeeELDEK 91
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|.
gi 1370514551 146 NLDwmfrySLINDLVKGMAFLHnSIISSHGSLKSSNCVVDSRFVLKITDYG 196
Cdd:cd13968    92 DVE-----SIMYQLAECMRLLH-SFHLIHRDLNNDNILLSEDGNVKLIDFG 136
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
103-322 1.80e-03

Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is expressed only in hematopoietic cells. It binds the shared receptor subunit, common gamma chain and thus, is essential in the signaling of cytokines that use it such as IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21. Jak3 is important in lymphoid development and myeloid cell differentiation. Inactivating mutations in Jak3 have been reported in humans with severe combined immunodeficiency (SCID). Jak3 is a cytoplasmic (or nonreceptor) PTK containing an N-terminal FERM domain, followed by a Src homology 2 (SH2) domain, a pseudokinase domain, and a C-terminal tyr kinase domain. The pseudokinase domain shows similarity to tyr kinases but lacks crucial residues for catalytic activity and ATP binding. It modulates the kinase activity of the C-terminal catalytic domain. Jaks are activated by autophosphorylation upon cytokine-induced receptor aggregation, and subsequently trigger downstream signaling events such as the phosphorylation of signal transducers and activators of transcription (STATs). The Jak3 subfamily is part of a larger superfamily that includes the catalytic domains of other kinases such as serine/threonine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 40.27  E-value: 1.80e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 103 MRDVQFNHLTRFIGACIDPPNIcIVTEYCPRGSLQDILENDS----INLDWmfRYSLINDLVKGMAFLHNSIISsHGSLk 178
Cdd:cd14208    56 MSQISHKHLVLLHGVCVGKDSI-MVQEFVCHGALDLYLKKQQqkgpVAISW--KLQVVKQLAYALNYLEDKQLV-HGNV- 130
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 179 SSNCVVDSRFvlkiTDYGLASFRSTAEPDDSHALYAKKL------WTAPELLSGnplPTTGMQKADVYSFGIILQEIaLR 252
Cdd:cd14208   131 SAKKVLLSRE----GDKGSPPFIKLSDPGVSIKVLDEELlaeripWVAPECLSD---PQNLALEADKWGFGATLWEI-FS 202
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1370514551 253 SGPFYLEGLDlsPKEIVQkvrngqrpYFRpsiDRTQLNE----ELVLLMERCWAQDPAERPDFGQIkgfIRRFN 322
Cdd:cd14208   203 GGHMPLSALD--PSKKLQ--------FYN---DRKQLPAphwiELASLIQQCMSYNPLLRPSFRAI---IRDLN 260
STKc_ROCK1 cd05622
Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein ...
126-261 1.90e-03

Catalytic domain of the Serine/Threonine Kinase, Rho-associated coiled-coil containing protein kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. ROCK1 is preferentially expressed in the liver, lung, spleen, testes, and kidney. It mediates signaling from Rho to the actin cytoskeleton. It is implicated in the development of cardiac fibrosis, cardiomyocyte apoptosis, and hyperglycemia. Mice deficient with ROCK1 display eyelids open at birth (EOB) and omphalocele phenotypes due to the disorganization of actin filaments in the eyelids and the umbilical ring. ROCK contains an N-terminal extension, a catalytic kinase domain, and a C-terminal extension, which contains a coiled-coil region encompassing a Rho-binding domain (RBD) and a pleckstrin homology (PH) domain. ROCK is auto-inhibited by the RBD and PH domain interacting with the catalytic domain, and is activated via interaction with Rho GTPases. The ROCK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270772 [Multi-domain]  Cd Length: 405  Bit Score: 40.76  E-value: 1.90e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 126 IVTEYCPRGSLQDILENDSINLDWMFRYS----LINDLVKGMAFLHNSIisshgslKSSNCVVDSRFVLKITDYGLASFR 201
Cdd:cd05622   150 MVMEYMPGGDLVNLMSNYDVPEKWARFYTaevvLALDAIHSMGFIHRDV-------KPDNMLLDKSGHLKLADFGTCMKM 222
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 202 STAEPDDSHALYAKKLWTAPELLSGNPLPTTGMQKADVYSFGIILQEIALRSGPFYLEGL 261
Cdd:cd05622   223 NKEGMVRCDTAVGTPDYISPEVLKSQGGDGYYGRECDWWSVGVFLYEMLVGDTPFYADSL 282
STKc_MLCK4 cd14193
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze ...
77-245 1.94e-03

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. In vertebrates, different MLCKs function in smooth (MLCK1), skeletal (MLCK2), and cardiac (MLCK3) muscles. A fourth protein, MLCK4, has also been identified through comprehensive genome analysis although it has not been biochemically characterized. MLCK4 (or MYLK4 or SgK085) contains a single kinase domain near the C-terminus. The MLCK4 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 271095 [Multi-domain]  Cd Length: 261  Bit Score: 40.28  E-value: 1.94e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  77 GNVVAIKHVNKKRIELTRQVLFELKHMRDVQFNHLTRFIGACIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRYSLI 156
Cdd:cd14193    29 GLKLAAKIIKARSQKEKEEVKNEIEVMNQLNHANLIQLYDAFESRNDIVLVMEYVDGGELFDRIIDENYNLTELDTILFI 108
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 157 NDLVKGMAFLHNSIISsHGSLKSSN--CVVDSRFVLKITDYGLASFRSTAEPDDSHalYAKKLWTAPELLSGN--PLPTt 232
Cdd:cd14193   109 KQICEGIQYMHQMYIL-HLDLKPENilCVSREANQVKIIDFGLARRYKPREKLRVN--FGTPEFLAPEVVNYEfvSFPT- 184
                         170
                  ....*....|...
gi 1370514551 233 gmqkaDVYSFGII 245
Cdd:cd14193   185 -----DMWSLGVI 192
STKc_MSK_N cd05583
N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated ...
177-279 2.03e-03

N-terminal catalytic domain of the Serine/Threonine Kinase, Mitogen and stress-activated kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. MSKs are activated by two major signaling cascades, the Ras-MAPK and p38 stress kinase pathways, in response to various stimuli such as growth factors, hormones, neurotransmitters, cellular stress, and pro-inflammatory cytokines. This triggers phosphorylation in the activation loop (A-loop) of the CTD of MSK. The active CTD phosphorylates the hydrophobic motif (HM) in the C-terminal extension of NTD, which facilitates the phosphorylation of the A-loop and activates the NTD, which in turn phosphorylates downstream targets. MSKs are predominantly nuclear proteins. They are widely expressed in many tissues including heart, brain, lung, liver, kidney, and pancreas. There are two isoforms of MSK, called MSK1 and MSK2. The MSK subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270735 [Multi-domain]  Cd Length: 268  Bit Score: 40.45  E-value: 2.03e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 177 LKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALYAKKLWTAPELLSGnplPTTGMQKA-DVYSFGIILQEIALRSGP 255
Cdd:cd05583   125 IKLENILLDSEGHVVLTDFGLSKEFLPGENDRAYSFCGTIEYMAPEVVRG---GSDGHDKAvDWWSLGVLTYELLTGASP 201
                          90       100
                  ....*....|....*....|....
gi 1370514551 256 FYLEGLDLSPKEIVQKVRNGQRPY 279
Cdd:cd05583   202 FTVDGERNSQSEISKRILKSHPPI 225
KIND smart00750
kinase non-catalytic C-lobe domain; It is an interaction domain identified as being similar to ...
134-319 2.52e-03

kinase non-catalytic C-lobe domain; It is an interaction domain identified as being similar to the C-terminal protein kinase catalytic fold (C lobe). Its presence at the N terminus of signalling proteins and the absence of the active-site residues in the catalytic and activation loops suggest that it folds independently and is likely to be non-catalytic. The occurrence of KIND only in metazoa implies that it has evolved from the catalytic protein kinase domain into an interaction domain possibly by keeping the substrate-binding features


Pssm-ID: 214801  Cd Length: 176  Bit Score: 39.31  E-value: 2.52e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  134 GSLQDILE--NDSINLD--WmfrySLINDLVKGMAFLHNSIISshGSLKSSNcvvDSRFVLKitdyGLASFRS--TAEPD 207
Cdd:smart00750   1 VSLADILEvrGRPLNEEeiW----AVCLQCLGALRELHRQAKS--GNILLTW---DGLLKLD----GSVAFKTpeQSRPD 67
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  208 dshalyakKLWTAPELLSGNPLPttgmQKADVYSFGIILQEiALRSGPFYLEGLDLSP-KEIVQKVRNGQRPYFRPS--- 283
Cdd:smart00750  68 --------PYFMAPEVIQGQSYT----EKADIYSLGITLYE-ALDYELPYNEERELSAiLEILLNGMPADDPRDRSNleg 134
                          170       180       190
                   ....*....|....*....|....*....|....*..
gi 1370514551  284 -IDRTQLNEElvllMERCWAQDPAERPDFGQIKGFIR 319
Cdd:smart00750 135 vSAARSFEDF----MRLCASRLPQRREAANHYLAHCR 167
STKc_TLK1 cd14040
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the ...
99-325 2.95e-03

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. A splice variant of TLK1, called TLK1B, is expressed in the presence of double strand breaks (DSBs). It lacks the N-terminal part of TLK1, but is expected to phosphorylate the same substrates. TLK1/1B interacts with Rad9, which is critical in DNA damage-activated checkpoint response, and plays a role in the repair of linearized DNA with incompatible ends. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. The TLK1 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270942 [Multi-domain]  Cd Length: 299  Bit Score: 40.04  E-value: 2.95e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQ-FNHLTrfigacIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRySLINDLVKGMAFLHN---SIIssH 174
Cdd:cd14040    66 ELDHPRIVKlYDYFS------LDTDTFCTVLEYCEGNDLDFYLKQHKLMSEKEAR-SIVMQIVNALRYLNEikpPII--H 136
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 175 GSLKSSNCV-VDSRFV--LKITDYGLASFRStaepDDSHALYAKKL---------WTAPELLSGNPLPTTGMQKADVYSF 242
Cdd:cd14040   137 YDLKPGNILlVDGTACgeIKITDFGLSKIMD----DDSYGVDGMDLtsqgagtywYLPPECFVVGKEPPKISNKVDVWSV 212
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 243 GIILQEIALRSGPFyleGLDLSPKEIVQ-----KVRNGQRPyFRPSIdrtqlNEELVLLMERCWAQDPAERPDFGQIKG- 316
Cdd:cd14040   213 GVIFFQCLYGRKPF---GHNQSQQDILQentilKATEVQFP-VKPVV-----SNEAKAFIRRCLAYRKEDRFDVHQLASd 283
                         250
                  ....*....|....
gi 1370514551 317 -----FIRRFNKEG 325
Cdd:cd14040   284 pyllpHMRRSNSSG 297
STKc_Nek4 cd08223
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
87-314 3.21e-03

Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek4 is highly abundant in the testis. Its specific function is unknown. Neks are involved in the regulation of downstream processes following the activation of Cdc2, and many of their functions are cell cycle-related. They play critical roles in microtubule dynamics during ciliogenesis and mitosis. Nek4 is one in a family of 11 different Neks (Nek1-11). The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270862 [Multi-domain]  Cd Length: 257  Bit Score: 39.73  E-value: 3.21e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  87 KKRIELTRQVLFELKHMRDVQFNhlTRFIGaciDPPNICIVTEYCPRGSLQDILEN-------DSINLDWMFRYSLindl 159
Cdd:cd08223    43 RKAAEQEAKLLSKLKHPNIVSYK--ESFEG---EDGFLYIVMGFCEGGDLYTRLKEqkgvlleERQVVEWFVQIAM---- 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 160 vkGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEpDDSHALYAKKLWTAPELLSGNPLPttgmQKADV 239
Cdd:cd08223   114 --ALQYMHERNIL-HRDLKTQNIFLTKSNIIKVGDLGIARVLESSS-DMATTLIGTPYYMSPELFSNKPYN----HKSDV 185
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 240 YSFGIILQEIALRSGPFYLEGLDlspkEIVQKVRNGQRPYFrPsidrTQLNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd08223   186 WALGCCVYEMATLKHAFNAKDMN----SLVYKILEGKLPPM-P----KQYSPELGELIKAMLHQDPEKRPSVKRI 251
STKc_LATS cd05598
Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the ...
120-274 3.43e-03

Catalytic domain of the Serine/Threonine Kinase, Large Tumor Suppressor; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. LATS was originally identified in Drosophila using a screen for genes whose inactivation led to overproliferation of cells. In tetrapods, there are two LATS isoforms, LATS1 and LATS2. Inactivation of LATS1 in mice results in the development of various tumors, including sarcomas and ovarian cancer. LATS functions as a tumor suppressor and is implicated in cell cycle regulation. The LATS subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270749 [Multi-domain]  Cd Length: 333  Bit Score: 39.99  E-value: 3.43e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 120 DPPNICIVTEYCPRGSLQDILENDSInldwmFRYSL----INDL------VKGMAFLHNSIisshgslKSSNCVVDSRFV 189
Cdd:cd05598    72 DKENLYFVMDYIPGGDLMSLLIKKGI-----FEEDLarfyIAELvcaiesVHKMGFIHRDI-------KPDNILIDRDGH 139
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 190 LKITDYGLAS-FRSTaepDDS-----HALYAKKLWTAPELLsgnpLPTTGMQKADVYSFGIILQEIALRSGPFylegLDL 263
Cdd:cd05598   140 IKLTDFGLCTgFRWT---HDSkyylaHSLVGTPNYIAPEVL----LRTGYTQLCDWWSVGVILYEMLVGQPPF----LAQ 208
                         170
                  ....*....|.
gi 1370514551 264 SPKEIVQKVRN 274
Cdd:cd05598   209 TPAETQLKVIN 219
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
155-262 3.81e-03

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK2 is expressed in every cell and tissue type. It is specifically translocated to the mitochondria during dopaminergic cell death. Specific substrates include the microtubule-associated proteins DCX and Tau, as well as TIF-IA which is involved in ribosomal RNA synthesis regulation. Mice deficient in Jnk2 show protection against arthritis, type 1 diabetes, atherosclerosis, abdominal aortic aneurysm, cardiac cell death, TNF-induced liver damage, and tumor growth, indicating that JNK2 may play roles in the pathogenesis of these diseases. Initially it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143381 [Multi-domain]  Cd Length: 359  Bit Score: 39.63  E-value: 3.81e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALyaKKLWTAPELLSGNPLPttgm 234
Cdd:cd07876   128 LLYQMLCGIKHLHSAGII-HRDLKPSNIVVKSDCTLKILDFGLARTACTNFMMTPYVV--TRYYRAPEVILGMGYK---- 200
                          90       100
                  ....*....|....*....|....*...
gi 1370514551 235 QKADVYSFGIILQEIAlrSGPFYLEGLD 262
Cdd:cd07876   201 ENVDIWSVGCIMGELV--KGSVIFQGTD 226
STKc_Nek9 cd08221
Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA) ...
108-309 3.91e-03

Catalytic domain of the Protein Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase 9; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Nek9, also called Nercc1, is primarily a cytoplasmic protein but can also localize in the nucleus. It is involved in modulating chromosome alignment and splitting during mitosis. It interacts with the gamma-tubulin ring complex and the Ran GTPase, and is implicated in microtubule organization. Nek9 associates with FACT (FAcilitates Chromatin Transcription) and modulates interphase progression. It also interacts with Nek6, and Nek7, during mitosis, resulting in their activation. Nek9 is one in a family of 11 different Neks (Nek1-11) that are involved in cell cycle control. The Nek family is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270860 [Multi-domain]  Cd Length: 256  Bit Score: 39.33  E-value: 3.91e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 108 FNHLtrfigacIDPPNICIVTEYCPRGSLQD-ILENDSINLD-----WMFRyslinDLVKGMAFLH-NSIIssHGSLKSS 180
Cdd:cd08221    65 YNHF-------LDGESLFIEMEYCNGGNLHDkIAQQKNQLFPeevvlWYLY-----QIVSAVSHIHkAGIL--HRDIKTL 130
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 181 NCVVDSRFVLKITDYGLASFRSTaEPDDSHALYAKKLWTAPELLSGNPLPttgmQKADVYSFGIILQEIALRSGPFyleg 260
Cdd:cd08221   131 NIFLTKADLVKLGDFGISKVLDS-ESSMAESIVGTPYYMSPELVQGVKYN----FKSDIWAVGCVLYELLTLKRTF---- 201
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 1370514551 261 lDLS-PKEIVQKVRNGQRpyfrpSIDRTQLNEELVLLMERCWAQDPAERP 309
Cdd:cd08221   202 -DATnPLRLAVKIVQGEY-----EDIDEQYSEEIIQLVHDCLHQDPEDRP 245
STKc_PhKG cd14093
Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs ...
124-257 6.58e-03

Catalytic domain of the Serine/Threonine Kinase, Phosphorylase kinase Gamma subunit; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Phosphorylase kinase (PhK) catalyzes the phosphorylation of inactive phosphorylase b to form the active phosphorylase a. It coordinates hormonal, metabolic, and neuronal signals to initiate the breakdown of glycogen stores, which enables the maintenance of blood-glucose homeostasis during fasting, and is also used as a source of energy for muscle contraction. PhK is one of the largest and most complex protein kinases, composed of a heterotetramer containing four molecules each of four subunit types: one catalytic (gamma) and three regulatory (alpha, beta, and delta). Each subunit has tissue-specific isoforms or splice variants. Vertebrates contain two isoforms of the gamma subunit (gamma 1 and gamma 2). The gamma subunit, when isolated, is constitutively active and does not require phosphorylation of the A-loop for activity. The regulatory subunits restrain this kinase activity until signals are received to relieve this inhibition. For example, the kinase is activated in response to hormonal stimulation, after autophosphorylation or phosphorylation by cAMP-dependent kinase of the alpha and beta subunits. The high-affinity binding of ADP to the beta subunit also stimulates kinase activity, whereas calcium relieves inhibition by binding to the delta (calmodulin) subunit. The PhKG subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270995 [Multi-domain]  Cd Length: 272  Bit Score: 38.87  E-value: 6.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 124 ICIVTEYCPRGSLQDILeNDSINLDWMFRYSLINDLVKGMAFLH-NSIIssHGSLKSSNCVVDSRFVLKITDYGLAsfRS 202
Cdd:cd14093    84 IFLVFELCRKGELFDYL-TEVVTLSEKKTRRIMRQLFEAVEFLHsLNIV--HRDLKPENILLDDNLNVKISDFGFA--TR 158
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 1370514551 203 TAEPDDSHALYAKKLWTAPELLSGNPLPTTG--MQKADVYSFGIILQEIALRSGPFY 257
Cdd:cd14093   159 LDEGEKLRELCGTPGYLAPEVLKCSMYDNAPgyGKEVDMWACGVIMYTLLAGCPPFW 215
STKc_JNK1 cd07875
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the ...
155-249 8.06e-03

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK1 is expressed in every cell and tissue type. It specifically binds with JAMP (JNK1-associated membrane protein), which regulates the duration of JNK1 activity in response to stimuli. Specific JNK1 substrates include Itch and SG10, which are implicated in Th2 responses and airway inflammation, and microtubule dynamics and axodendritic length, respectively. Mice deficient in JNK1 are protected against arthritis, obesity, type 2 diabetes, cardiac cell death, and non-alcoholic liver disease, suggesting that JNK1 may play roles in the pathogenesis of these diseases. Initially, it was thought that JNK1 and JNK2 were functionally redundant as mice deficient in either genes could survive but disruption of both genes resulted in lethality. However, recent studies have shown that JNK1 and JNK2 perform distinct functions through specific binding partners and substrates. JNKs are mitogen-activated protein kinases that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK1 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143380 [Multi-domain]  Cd Length: 364  Bit Score: 38.87  E-value: 8.06e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTA---EPDdshalYAKKLWTAPELLSGNPLPt 231
Cdd:cd07875   131 LLYQMLCGIKHLHSAGII-HRDLKPSNIVVKSDCTLKILDFGLARTAGTSfmmTPY-----VVTRYYRAPEVILGMGYK- 203
                          90
                  ....*....|....*...
gi 1370514551 232 tgmQKADVYSFGIILQEI 249
Cdd:cd07875   204 ---ENVDIWSVGCIMGEM 218
STKc_TLK2 cd14041
Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the ...
99-314 9.02e-03

Catalytic domain of the Serine/Threonine kinase, Tousled-Like Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TLKs play important functions during the cell cycle and are implicated in chromatin remodeling, DNA replication and repair, and mitosis. They phosphorylate and regulate Anti-silencing function 1 protein (Asf1), a histone H3/H4 chaperone that helps facilitate the assembly of chromatin following DNA replication during S phase. TLKs also phosphorylate the H3 histone tail and are essential in transcription. Vertebrates contain two subfamily members, TLK1 and TLK2. The TLK2 subfamily is part of a larger superfamily that includes the catalytic domains of other protein STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase (PI3K).


Pssm-ID: 270943 [Multi-domain]  Cd Length: 309  Bit Score: 38.50  E-value: 9.02e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551  99 ELKHMRDVQ-FNHLTrfigacIDPPNICIVTEYCPRGSLQDILENDSINLDWMFRySLINDLVKGMAFLHN---SIIssH 174
Cdd:cd14041    66 ELDHPRIVKlYDYFS------LDTDSFCTVLEYCEGNDLDFYLKQHKLMSEKEAR-SIIMQIVNALKYLNEikpPII--H 136
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 175 GSLKSSNCVVDSRFV---LKITDYGLASFRStaepDDSHALY---------AKKLW-TAPELLSGNPLPTTGMQKADVYS 241
Cdd:cd14041   137 YDLKPGNILLVNGTAcgeIKITDFGLSKIMD----DDSYNSVdgmeltsqgAGTYWyLPPECFVVGKEPPKISNKVDVWS 212
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 1370514551 242 FGIILQEIALRSGPFyleGLDLSPKEIVQK--VRNGQRPYFRPsidRTQLNEELVLLMERCWAQDPAERPDFGQI 314
Cdd:cd14041   213 VGVIFYQCLYGRKPF---GHNQSQQDILQEntILKATEVQFPP---KPVVTPEAKAFIRRCLAYRKEDRIDVQQL 281
STKc_JNK3 cd07874
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the ...
155-249 9.24e-03

Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. JNK3 is expressed primarily in the brain, and to a lesser extent in the heart and testis. Mice deficient in JNK3 are protected against kainic acid-induced seizures, stroke, sciatic axotomy neural death, and neuronal death due to NGF deprivation, oxidative stress, or exposure to beta-amyloid peptide. This suggests that JNK3 may play roles in the pathogenesis of these diseases. JNKs are mitogen-activated protein kinases (MAPKs) that are involved in many stress-activated responses including those during inflammation, neurodegeneration, apoptosis, and persistent pain sensitization, among others. The JNK3 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 143379 [Multi-domain]  Cd Length: 355  Bit Score: 38.53  E-value: 9.24e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1370514551 155 LINDLVKGMAFLHNSIISsHGSLKSSNCVVDSRFVLKITDYGLASFRSTAEPDDSHALyaKKLWTAPELLSGNPLPttgm 234
Cdd:cd07874   124 LLYQMLCGIKHLHSAGII-HRDLKPSNIVVKSDCTLKILDFGLARTAGTSFMMTPYVV--TRYYRAPEVILGMGYK---- 196
                          90
                  ....*....|....*
gi 1370514551 235 QKADVYSFGIILQEI 249
Cdd:cd07874   197 ENVDIWSVGCIMGEM 211
 
Blast search parameters
Data Source: Precalculated data, version = cdd.v.3.21
Preset Options:Database: CDSEARCH/cdd   Low complexity filter: no  Composition Based Adjustment: yes   E-value threshold: 0.01

References:

  • Wang J et al. (2023), "The conserved domain database in 2023", Nucleic Acids Res.51(D)384-8.
  • Lu S et al. (2020), "The conserved domain database in 2020", Nucleic Acids Res.48(D)265-8.
  • Marchler-Bauer A et al. (2017), "CDD/SPARCLE: functional classification of proteins via subfamily domain architectures.", Nucleic Acids Res.45(D)200-3.
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