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Conserved domains on  [gi|319803120|ref|NP_001188386|]
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inactive serine/threonine-protein kinase TEX14 isoform c [Homo sapiens]

Protein Classification

Graphical summary

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List of domain hits

Name Accession Description Interval E-value
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
175-513 1.15e-63

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: 218.73  E-value: 1.15e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  175 SPSWCGGLVQGNPNGSPNRllkagviSAQNIYSFGFGKampwfqFYLTGATQMaylgslpvigekeviqaddeptfsffs 254
Cdd:cd14011     1 VASAGPGLPWKIYNGSKKS-------TKQEVSVFVFEK------KQLEEYSKR--------------------------- 40
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  255 gpymvmtnlvwngsrvtvkelnlpthphcSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQDlEKTRLVYERITiGTL 334
Cdd:cd14011    41 -----------------------------DREQILELLKRGVKQLTRLRHPRILTVQHPLEESR-ESLAFATEPVF-ASL 89
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  335 FSVLHERRS--------QFPVLHMEVIVHLLLQISDALRYLHF-QGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRG 405
Cdd:cd14011    90 ANVLGERDNmpspppelQDYKLYDVEIKYGLLQISEALSFLHNdVKLVHGNICPESVVINSNGEWKLAGFDFCISSEQAT 169
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  406 VQR------DLTRVPLPTQLYNWAAPEVILQKAATVKSDIYSFSMIMQEILTddipwkglDGSVVKKAVvsGNYLEADVR 479
Cdd:cd14011   170 DQFpyfreyDPNLPPLAQPNLNYLAPEYILSKTCDPASDMFSLGVLIYAIYN--------KGKPLFDCV--NNLLSYKKN 239
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 319803120  480 L--------------PKPYYDIVKSGIHVKQKDRTMNLQDIRYILKND 513
Cdd:cd14011   240 SnqlrqlslsllekvPEELRDHVKTLLNVTPEVRPDAEQLSKIPFFDD 287
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
18-143 7.81e-21

Ankyrin repeat [Signal transduction mechanisms];


:

Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 94.64  E-value: 7.81e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   18 LRNDSLEAQLHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAA 97
Cdd:COG0666    82 AKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAA 161
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 319803120   98 FSGNQWILSKLLDAGGDLRLHDERGQNPKTWALTAGKersTQIVEF 143
Cdd:COG0666   162 ANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGH---LEIVKL 204
 
Name Accession Description Interval E-value
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
175-513 1.15e-63

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: 218.73  E-value: 1.15e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  175 SPSWCGGLVQGNPNGSPNRllkagviSAQNIYSFGFGKampwfqFYLTGATQMaylgslpvigekeviqaddeptfsffs 254
Cdd:cd14011     1 VASAGPGLPWKIYNGSKKS-------TKQEVSVFVFEK------KQLEEYSKR--------------------------- 40
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  255 gpymvmtnlvwngsrvtvkelnlpthphcSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQDlEKTRLVYERITiGTL 334
Cdd:cd14011    41 -----------------------------DREQILELLKRGVKQLTRLRHPRILTVQHPLEESR-ESLAFATEPVF-ASL 89
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  335 FSVLHERRS--------QFPVLHMEVIVHLLLQISDALRYLHF-QGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRG 405
Cdd:cd14011    90 ANVLGERDNmpspppelQDYKLYDVEIKYGLLQISEALSFLHNdVKLVHGNICPESVVINSNGEWKLAGFDFCISSEQAT 169
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  406 VQR------DLTRVPLPTQLYNWAAPEVILQKAATVKSDIYSFSMIMQEILTddipwkglDGSVVKKAVvsGNYLEADVR 479
Cdd:cd14011   170 DQFpyfreyDPNLPPLAQPNLNYLAPEYILSKTCDPASDMFSLGVLIYAIYN--------KGKPLFDCV--NNLLSYKKN 239
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 319803120  480 L--------------PKPYYDIVKSGIHVKQKDRTMNLQDIRYILKND 513
Cdd:cd14011   240 SnqlrqlslsllekvPEELRDHVKTLLNVTPEVRPDAEQLSKIPFFDD 287
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
270-483 3.33e-24

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: 103.73  E-value: 3.33e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   270 VTVKELNlpthPHCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFPVLH 349
Cdd:pfam07714   31 VAVKTLK----EGADEEEREDFL-EEASIMKKLDHPNIVKLLGVCTQG--EPLYIVTEYMPGGDLLDFLRKHKRKLTLKD 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   350 MeviVHLLLQISDALRYLHFQGFIHRSL--------SSYAVHIISPGEARLtnleymLESEDRGVQRDLTRVPLPtqlyn 421
Cdd:pfam07714  104 L---LSMALQIAKGMEYLESKNFVHRDLaarnclvsENLVVKISDFGLSRD------IYDDDYYRKRGGGKLPIK----- 169
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319803120   422 WAAPEVILQKAATVKSDIYSFSMIMQEILTD-DIPWKGLDGSVVKKAVVSGNyleadvRLPKP 483
Cdd:pfam07714  170 WMAPESLKDGKFTSKSDVWSFGVLLWEIFTLgEQPYPGMSNEEVLEFLEDGY------RLPQP 226
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
270-499 3.92e-22

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 97.60  E-value: 3.92e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    270 VTVKELNlpthPHCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFPVLH 349
Cdd:smart00219   31 VAVKTLK----EDASEQQIEEFL-REARIMRKLDHPNVVKLLGVCTEE--EPLYIVMEYMEGGDLLSYLRKNRPKLSLSD 103
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    350 MeviVHLLLQISDALRYLHFQGFIHRSL--------SSYAVHIISPGEARLtnleymLESEDRGVQRDlTRVPlptqlYN 421
Cdd:smart00219  104 L---LSFALQIARGMEYLESKNFIHRDLaarnclvgENLVVKISDFGLSRD------LYDDDYYRKRG-GKLP-----IR 168
                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 319803120    422 WAAPEVILQKAATVKSDIYSFSMIMQEILTD-DIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:smart00219  169 WMAPESLKEGKFTSKSDVWSFGVLLWEIFTLgEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCWAEDPEDR 247
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
18-143 7.81e-21

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 94.64  E-value: 7.81e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   18 LRNDSLEAQLHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAA 97
Cdd:COG0666    82 AKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAA 161
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 319803120   98 FSGNQWILSKLLDAGGDLRLHDERGQNPKTWALTAGKersTQIVEF 143
Cdd:COG0666   162 ANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGH---LEIVKL 204
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
267-536 3.21e-14

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 76.98  E-value: 3.21e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNlptHPHCSRLRLADLLIAEQEHSSKLRHPYLLQLMAVclsqDLEKTR--LVYERITIGTLFSVLHERRsq 344
Cdd:COG0515    32 GRPVALKVLR---PELAADPEARERFRREARALARLNHPNIVRVYDV----GEEDGRpyLVMEYVEGESLADLLRRRG-- 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  345 fpVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPLP-------T 417
Cdd:COG0515   103 --PLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLI---------DFGIARALGGATLTqtgtvvgT 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  418 QLYnwAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNYL---EADVRLPKPYYDIVKSGIHV 494
Cdd:COG0515   172 PGY--MAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPppsELRPDLPPALDAIVLRALAK 249
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 319803120  495 KQKDRTMNLQDIRYILKNDLKDFTGAQRTQPTESPRVQRYGL 536
Cdd:COG0515   250 DPEERYQSAAELAAALRAVLRSLAAAAAAAAAAAAAAAAAAA 291
Ank_2 pfam12796
Ankyrin repeats (3 copies);
27-119 7.38e-13

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 65.52  E-value: 7.38e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    27 LHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGsDPNHRCfDGSTPVHAAAFSGNQWILS 106
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEHA-DVNLKD-NGRTALHYAARSGHLEIVK 78
                           90
                   ....*....|...
gi 319803120   107 KLLDAGGDLRLHD 119
Cdd:pfam12796   79 LLLEKGADINVKD 91
PHA02875 PHA02875
ankyrin repeat protein; Provisional
23-133 1.29e-07

ankyrin repeat protein; Provisional


Pssm-ID: 165206 [Multi-domain]  Cd Length: 413  Bit Score: 55.77  E-value: 1.29e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   23 LEAQLHEYVKQGNYVKVKKILKKGIYVDAV-NSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAAFSGN 101
Cdd:PHA02875   68 IESELHDAVEEGDVKAVEELLDLGKFADDVfYKDGMTPLHLATILKKLDIMKLLIARGADPDIPNTDKFSPLHLAVMMGD 147
                          90       100       110
                  ....*....|....*....|....*....|..
gi 319803120  102 QWILSKLLDAGGDLRLHDERGQNPKTWALTAG 133
Cdd:PHA02875  148 IKGIELLIDHKACLDIEDCCGCTPLIIAMAKG 179
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
320-473 1.33e-05

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 49.63  E-value: 1.33e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  320 EKTRLVYERITIGTLFSVLHER-RSQFPVLHMEVIVhLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYM 398
Cdd:PTZ00267  138 DKLLLIMEYGSGGDLNKQIKQRlKEHLPFQEYEVGL-LFYQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFS 216
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 319803120  399 LESEDrGVQRDLTRVPLPTQLYnwAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNY 473
Cdd:PTZ00267  217 KQYSD-SVSLDVASSFCGTPYY--LAPELWERKRYSKKADMWSLGVILYELLTLHRPFKGPSQREIMQQVLYGKY 288
TRPV5-6 cd22192
Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and ...
55-144 3.58e-03

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.


Pssm-ID: 411976 [Multi-domain]  Cd Length: 609  Bit Score: 41.92  E-value: 3.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   55 LGQTALFVAALLGLRKFVDVLVDYGSD--------------PNHRCFDGSTPVHAAAFSGNQWILSKLLDAGGDLRLHDE 120
Cdd:cd22192    88 QGETALHIAVVNQNLNLVRELIARGADvvspratgtffrpgPKNLIYYGEHPLSFAACVGNEEIVRLLIEHGADIRAQDS 167
                          90       100
                  ....*....|....*....|....*
gi 319803120  121 RGQNP-KTWALTAGKERSTQIVEFM 144
Cdd:cd22192   168 LGNTVlHILVLQPNKTFACQMYDLI 192
 
Name Accession Description Interval E-value
PK_SCY1_like cd14011
Pseudokinase domain of Scy1-like proteins; The pseudokinase domain shows similarity to protein ...
175-513 1.15e-63

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: 218.73  E-value: 1.15e-63
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  175 SPSWCGGLVQGNPNGSPNRllkagviSAQNIYSFGFGKampwfqFYLTGATQMaylgslpvigekeviqaddeptfsffs 254
Cdd:cd14011     1 VASAGPGLPWKIYNGSKKS-------TKQEVSVFVFEK------KQLEEYSKR--------------------------- 40
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  255 gpymvmtnlvwngsrvtvkelnlpthphcSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQDlEKTRLVYERITiGTL 334
Cdd:cd14011    41 -----------------------------DREQILELLKRGVKQLTRLRHPRILTVQHPLEESR-ESLAFATEPVF-ASL 89
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  335 FSVLHERRS--------QFPVLHMEVIVHLLLQISDALRYLHF-QGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRG 405
Cdd:cd14011    90 ANVLGERDNmpspppelQDYKLYDVEIKYGLLQISEALSFLHNdVKLVHGNICPESVVINSNGEWKLAGFDFCISSEQAT 169
                         250       260       270       280       290       300       310       320
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  406 VQR------DLTRVPLPTQLYNWAAPEVILQKAATVKSDIYSFSMIMQEILTddipwkglDGSVVKKAVvsGNYLEADVR 479
Cdd:cd14011   170 DQFpyfreyDPNLPPLAQPNLNYLAPEYILSKTCDPASDMFSLGVLIYAIYN--------KGKPLFDCV--NNLLSYKKN 239
                         330       340       350       360
                  ....*....|....*....|....*....|....*....|....*...
gi 319803120  480 L--------------PKPYYDIVKSGIHVKQKDRTMNLQDIRYILKND 513
Cdd:cd14011   240 SnqlrqlslsllekvPEELRDHVKTLLNVTPEVRPDAEQLSKIPFFDD 287
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
265-489 6.09e-30

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: 119.95  E-value: 6.09e-30
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGSRVTVKELnlptHPHCSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRsq 344
Cdd:cd13999    14 WRGTDVAIKKL----KVEDDNDELLKEFRREVSILSKLRHPNIVQFIGACLSPP--PLCIVTEYMPGGSLYDLLHKKK-- 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  345 fPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSS--------YAVHIISPGEARLTNLEYMLESEDRGvqrdlTrvplp 416
Cdd:cd13999    86 -IPLSWSLRLKIALDIARGMNYLHSPPIIHRDLKSlnilldenFTVKIADFGLSRIKNSTTEKMTGVVG-----T----- 154
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 319803120  417 tqlYNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNY-LEADVRLPKPYYDIVK 489
Cdd:cd13999   155 ---PRWMAPEVLRGEPYTEKADVYSFGIVLWELLTGEVPFKELSPIQIAAAVVQKGLrPPIPPDCPPELSKLIK 225
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
270-483 3.33e-24

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: 103.73  E-value: 3.33e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   270 VTVKELNlpthPHCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFPVLH 349
Cdd:pfam07714   31 VAVKTLK----EGADEEEREDFL-EEASIMKKLDHPNIVKLLGVCTQG--EPLYIVTEYMPGGDLLDFLRKHKRKLTLKD 103
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   350 MeviVHLLLQISDALRYLHFQGFIHRSL--------SSYAVHIISPGEARLtnleymLESEDRGVQRDLTRVPLPtqlyn 421
Cdd:pfam07714  104 L---LSMALQIAKGMEYLESKNFVHRDLaarnclvsENLVVKISDFGLSRD------IYDDDYYRKRGGGKLPIK----- 169
                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319803120   422 WAAPEVILQKAATVKSDIYSFSMIMQEILTD-DIPWKGLDGSVVKKAVVSGNyleadvRLPKP 483
Cdd:pfam07714  170 WMAPESLKDGKFTSKSDVWSFGVLLWEIFTLgEQPYPGMSNEEVLEFLEDGY------RLPQP 226
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
270-499 3.92e-22

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 97.60  E-value: 3.92e-22
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    270 VTVKELNlpthPHCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFPVLH 349
Cdd:smart00219   31 VAVKTLK----EDASEQQIEEFL-REARIMRKLDHPNVVKLLGVCTEE--EPLYIVMEYMEGGDLLSYLRKNRPKLSLSD 103
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    350 MeviVHLLLQISDALRYLHFQGFIHRSL--------SSYAVHIISPGEARLtnleymLESEDRGVQRDlTRVPlptqlYN 421
Cdd:smart00219  104 L---LSFALQIARGMEYLESKNFIHRDLaarnclvgENLVVKISDFGLSRD------LYDDDYYRKRG-GKLP-----IR 168
                           170       180       190       200       210       220       230
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 319803120    422 WAAPEVILQKAATVKSDIYSFSMIMQEILTD-DIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:smart00219  169 WMAPESLKEGKFTSKSDVWSFGVLLWEIFTLgEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCWAEDPEDR 247
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
264-499 6.55e-21

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: 94.40  E-value: 6.55e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNGS-RVTVKELNLPThphcsrLRLADLLiAEQEHSSKLRHPYLLQLMAVClSQDlEKTRLVYERITIGTLFSVLHERR 342
Cdd:cd05068    28 LWNNTtPVAVKTLKPGT------MDPEDFL-REAQIMKKLRHPKLIQLYAVC-TLE-EPIYIITELMKHGSLLEYLQGKG 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  343 SQfpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAV--------HIISPGEARLTNLEYMLESedrgvqRDLTRVP 414
Cdd:cd05068    99 RS---LQLPQLIDMAAQVASGMAYLESQNYIHRDLAARNVlvgennicKVADFGLARVIKVEDEYEA------REGAKFP 169
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  415 LptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIH 493
Cdd:cd05068   170 I-----KWTAPEAANYNRFSIKSDVWSFGILLTEIVTyGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQLYDIMLECWK 244

                  ....*.
gi 319803120  494 VKQKDR 499
Cdd:cd05068   245 ADPMER 250
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
18-143 7.81e-21

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 94.64  E-value: 7.81e-21
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   18 LRNDSLEAQLHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAA 97
Cdd:COG0666    82 AKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAA 161
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 319803120   98 FSGNQWILSKLLDAGGDLRLHDERGQNPKTWALTAGKersTQIVEF 143
Cdd:COG0666   162 ANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGH---LEIVKL 204
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
270-499 1.20e-20

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: 93.38  E-value: 1.20e-20
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    270 VTVKELNlpthPHCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFpvLH 349
Cdd:smart00221   31 VAVKTLK----EDASEQQIEEFL-REARIMRKLDHPNIVKLLGVCTEE--EPLMIVMEYMPGGDLLDYLRKNRPKE--LS 101
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    350 MEVIVHLLLQISDALRYLHFQGFIHRSL--------SSYAVHIISPGEAR-LTNLEYMLESedrgvqrdLTRVPlptqlY 420
Cdd:smart00221  102 LSDLLSFALQIARGMEYLESKNFIHRDLaarnclvgENLVVKISDFGLSRdLYDDDYYKVK--------GGKLP-----I 168
                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    421 NWAAPEVILQKAATVKSDIYSFSMIMQEILTD-DIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:smart00221  169 RWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLgEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQCWAEDPEDR 248
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
269-490 3.27e-20

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: 92.22  E-value: 3.27e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  269 RVTVKELnlptHPHCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFP-- 346
Cdd:cd00192    25 DVAVKTL----KEDASESERKDFL-KEARVMKKLGHPNVVRLLGVCTEE--EPLYLVMEYMEGGDLLDFLRKSRPVFPsp 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 ---VLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDLTRVPLPTQlynWA 423
Cdd:cd00192    98 epsTLSLKDLLSFAIQIAKGMEYLASKKFVHRDLAARNCLVGEDLVVKISDFGLSRDIYDDDYYRKKTGGKLPIR---WM 174
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 319803120  424 APEVILQKAATVKSDIYSFSMIMQEILTD-DIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKS 490
Cdd:cd00192   175 APESLKDGIFTSKSDVWSFGVLLWEIFTLgATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYELMLS 242
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
290-499 5.91e-20

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: 91.36  E-value: 5.91e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  290 DLLIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSqfpVLHMEVIVHLLLQISDALRYLHF 369
Cdd:cd05059    44 DDFIEEAKVMMKLSHPKLVQLYGVCTKQ--RPIFIVTEYMANGCLLNYLRERRG---KFQTEQLLEMCKDVCEAMEYLES 118
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  370 QGFIHRSL--------SSYAVHIISPGEARltnleYMLEseDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYS 441
Cdd:cd05059   119 NGFIHRDLaarnclvgEQNVVKVSDFGLAR-----YVLD--DEYTSSVGTKFPV-----KWSPPEVFMYSKFSSKSDVWS 186
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 319803120  442 FSMIMQEILTD-DIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05059   187 FGVLMWEVFSEgKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVYTIMYSCWHEKPEER 245
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
265-464 6.58e-20

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: 90.92  E-value: 6.58e-20
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGSRVTVKELNLptHPHCSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRsq 344
Cdd:cd14061    15 WRGEEVAVKAARQ--DPDEDISVTLENVRQEARLFWMLRHPNIIALRGVCLQP--PNLCLVMEYARGGALNRVLAGRK-- 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  345 fpvLHMEVIVHLLLQISDALRYLHFQG---FIHRSLSSYAVHIISP-GEARLTNleYMLESEDRGVQRDLTRVplpTQL- 419
Cdd:cd14061    89 ---IPPHVLVDWAIQIARGMNYLHNEApvpIIHRDLKSSNILILEAiENEDLEN--KTLKITDFGLAREWHKT---TRMs 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 319803120  420 ----YNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVV 464
Cdd:cd14061   161 aagtYAWMAPEVIKSSTFSKASDVWSYGVLLWELLTGEVPYKGIDGLAV 209
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
19-136 1.91e-19

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 90.40  E-value: 1.91e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   19 RNDSLEAQLHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAAF 98
Cdd:COG0666   116 RDKDGETPLHLAAYNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAE 195
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 319803120   99 SGNQWILSKLLDAGGDLRLHDERGQNPKTWALTAGKER 136
Cdd:COG0666   196 NGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLE 233
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
266-449 8.06e-19

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: 86.56  E-value: 8.06e-19
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLPthphcSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRSQF 345
Cdd:cd00180    17 TGKKVAVKVIPKE-----KLKKLLEELLREIEILKKLNHPNIVKLYDVFETEN--FLYLVMEYCEGGSLKDLLKENKGPL 89
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 PvlhMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDrgvQRDLTRVPLPTQLYNWAAP 425
Cdd:cd00180    90 S---EEEALSILRQLLSALEYLHSNGIIHRDLKPENILLDSDGTVKLADFGLAKDLDS---DDSLLKTTGGTTPPYYAPP 163
                         170       180
                  ....*....|....*....|....
gi 319803120  426 EVILQKAATVKSDIYSFSMIMQEI 449
Cdd:cd00180   164 ELLGGRYYGPKVDIWSLGVILYEL 187
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
264-487 2.42e-18

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: 86.18  E-value: 2.42e-18
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNGS-RVTVKELNLPThphcsrLRLADLLiAEQEHSSKLRHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLHERR 342
Cdd:cd05034    15 VWNGTtKVAVKTLKPGT------MSPEAFL-QEAQIMKKLRHDKLVQLYAVC--SDEEPIYIVTELMSKGSLLDYLRTGE 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  343 SQfpVLHMEVIVHLLLQISDALRYLHFQGFIHRSLS--------SYAVHIISPGEARLTNleymlesEDRGVQRDLTRVP 414
Cdd:cd05034    86 GR--ALRLPQLIDMAAQIASGMAYLESRNYIHRDLAarnilvgeNNVCKVADFGLARLIE-------DDEYTAREGAKFP 156
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  415 LptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGnYleadvRLPKP------YYDI 487
Cdd:cd05034   157 I-----KWTAPEAALYGRFTIKSDVWSFGILLYEIVTyGRVPYPGMTNREVLEQVERG-Y-----RMPKPpgcpdeLYDI 225
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
267-499 1.61e-17

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: 84.18  E-value: 1.61e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNlptHPHCSRLRLADLLIAEQEHSSKLRHPYLLQLMAVclsqDLEKTR--LVYERITIGTLFSVLHERRSq 344
Cdd:cd14014    25 GRPVAIKVLR---PELAEDEEFRERFLREARALARLSHPNIVRVYDV----GEDDGRpyIVMEYVEGGSLADLLRERGP- 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  345 fpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPL-PTQLY--- 420
Cdd:cd14014    97 ---LPPREALRILAQIADALAAAHRAGIVHRDIKPANILLTEDGRVKLT---------DFGIARALGDSGLtQTGSVlgt 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  421 -NWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNYL---EADVRLPKPYYDIVKSGIHVKQ 496
Cdd:cd14014   165 pAYMAPEQARGGPVDPRSDIYSLGVVLYELLTGRPPFDGDSPAAVLAKHLQEAPPppsPLNPDVPPALDAIILRALAKDP 244

                  ...
gi 319803120  497 KDR 499
Cdd:cd14014   245 EER 247
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
304-484 4.52e-17

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: 83.23  E-value: 4.52e-17
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  304 HPYLLQLMAVCLSQDLEktrLVYERITIGTLFSVLHERRSQFPVLHMeviVHLLLQISDALRYLHFQGFIHRSLSSYAVH 383
Cdd:cd05057    68 HPHLVRLLGICLSSQVQ---LITQLMPLGCLLDYVRNHRDNIGSQLL---LNWCVQIAKGMSYLEEKRLVHRDLAARNVL 141
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  384 IISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLD 460
Cdd:cd05057   142 VKTPNHVKITDfgLAKLLDVDEKEYHAEGGKVPI-----KWMALESIQYRIYTHKSDVWSYGVTVWELMTfGAKPYEGIP 216
                         170       180
                  ....*....|....*....|....
gi 319803120  461 GSVVKKAVVSGNyleadvRLPKPY 484
Cdd:cd05057   217 AVEIPDLLEKGE------RLPQPP 234
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
298-483 1.20e-16

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: 81.00  E-value: 1.20e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  298 HSSKLRHPYLLQLMAVCLSQDLekTRLVYERITIGTLFSVLHERRSQFPVLhmevIVHLLLQISDALRYLHFQGFIHRSL 377
Cdd:cd14059    34 HLRKLNHPNIIKFKGVCTQAPC--YCILMEYCPYGQLYEVLRAGREITPSL----LVDWSKQIASGMNYLHLHKIIHRDL 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  378 SSYAVhiispgearLTNLEYMLESEDRGVQRDLTRVPlpTQL-----YNWAAPEVILQKAATVKSDIYSFSMIMQEILTD 452
Cdd:cd14059   108 KSPNV---------LVTYNDVLKISDFGTSKELSEKS--TKMsfagtVAWMAPEVIRNEPCSEKVDIWSFGVVLWELLTG 176
                         170       180       190
                  ....*....|....*....|....*....|.
gi 319803120  453 DIPWKGLDGSVVKKAVVSGNyleadVRLPKP 483
Cdd:cd14059   177 EIPYKDVDSSAIIWGVGSNS-----LQLPVP 202
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
266-451 2.06e-16

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: 81.17  E-value: 2.06e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNlPTHPHCSRLRLAdlliAEQEHSSKLRHPYLLQLMAVCLSQDlEKTrLVYERITIGTLFSVLHERRSQf 345
Cdd:cd14066    16 NGTVVAVKRLN-EMNCAASKKEFL----TELEMLGRLRHPNLVRLLGYCLESD-EKL-LVYEYMPNGSLEDRLHCHKGS- 87
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 PVLHMEVIVHLLLQISDALRYLHFQGF---IHRSLSSYAVHIISPGEARLTnlEYMLeSEDRGVQRDLTRVPLPTQLYNW 422
Cdd:cd14066    88 PPLPWPQRLKIAKGIARGLEYLHEECPppiIHGDIKSSNILLDEDFEPKLT--DFGL-ARLIPPSESVSKTSAVKGTIGY 164
                         170       180
                  ....*....|....*....|....*....
gi 319803120  423 AAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd14066   165 LAPEYIRTGRVSTKSDVYSFGVVLLELLT 193
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
290-484 8.30e-16

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: 79.11  E-value: 8.30e-16
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  290 DLLIAEQEHSSKLRHPYLLQLMAVCLsQDLEKTRLVYERITIGTLFSVLHERRSqfpVLHMEVIVHLLLQISDALRYLH- 368
Cdd:cd14064    36 DMFCREVSILCRLNHPCVIQFVGACL-DDPSQFAIVTQYVSGGSLFSLLHEQKR---VIDLQSKLIIAVDVAKGMEYLHn 111
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  369 -FQGFIHRSLSSYAVHIISPGEARLTNLeymleSEDRGVQR----DLTRVPLPTQlynWAAPEVILQKAA-TVKSDIYSF 442
Cdd:cd14064   112 lTQPIIHRDLNSHNILLYEDGHAVVADF-----GESRFLQSldedNMTKQPGNLR---WMAPEVFTQCTRySIKADVFSY 183
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|..
gi 319803120  443 SMIMQEILTDDIPWKGLdgsvvKKAVVSGNYLEADVRLPKPY 484
Cdd:cd14064   184 ALCLWELLTGEIPFAHL-----KPAAAAADMAYHHIRPPIGY 220
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
289-499 1.50e-15

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: 78.10  E-value: 1.50e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  289 ADLLIAEQEHSSKLRHPYLLQLMAVcLSQDLEKTRLVYERITIGTLFSVLHER-RSqfpVLHMEVIVHLLLQISDALRYL 367
Cdd:cd05082    43 AQAFLAEASVMTQLRHSNLVQLLGV-IVEEKGGLYIVTEYMAKGSLVDYLRSRgRS---VLGGDCLLKFSLDVCEAMEYL 118
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  368 HFQGFIHRSLSSYAVHIISPGEARLTnlEYMLESEDRGVQrDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQ 447
Cdd:cd05082   119 EGNNFVHRDLAARNVLVSEDNVAKVS--DFGLTKEASSTQ-DTGKLPV-----KWTAPEALREKKFSTKSDVWSFGILLW 190
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 319803120  448 EILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05082   191 EIYSfGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYDVMKNCWHLDAAMR 243
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
265-489 1.77e-15

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: 78.16  E-value: 1.77e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGSRVTVKELNlpTHPHCSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVL------ 338
Cdd:cd14146    15 WKGQEVAVKAAR--QDPDEDIKATAESVRQEAKLFSMLRHPNIIKLEGVCLEE--PNLCLVMEFARGGTLNRALaaanaa 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  339 -HERRSQFPVLHmeVIVHLLLQISDALRYLHFQGF---IHRSLSSYAVHIISPGE----ARLTnleymLESEDRGVQRDL 410
Cdd:cd14146    91 pGPRRARRIPPH--ILVNWAVQIARGMLYLHEEAVvpiLHRDLKSSNILLLEKIEhddiCNKT-----LKITDFGLAREW 163
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  411 TRVplpTQL-----YNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAV-VSGNYLEADVRLPKPY 484
Cdd:cd14146   164 HRT---TKMsaagtYAWMAPEVIKSSLFSKGSDIWSYGVLLWELLTGEVPYRGIDGLAVAYGVaVNKLTLPIPSTCPEPF 240

                  ....*
gi 319803120  485 YDIVK 489
Cdd:cd14146   241 AKLMK 245
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
290-499 2.59e-15

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: 77.68  E-value: 2.59e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  290 DLLIAEQEHSSKLRHPYLLQLMAVCLSQDLektRLVYERITIGTLFSVLHERRSQFPVlhmEVIVHLLLQISDALRYLHF 369
Cdd:cd05115    49 DEMMREAQIMHQLDNPYIVRMIGVCEAEAL---MLVMEMASGGPLNKFLSGKKDEITV---SNVVELMHQVSMGMKYLEE 122
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  370 QGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQ-RDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIM 446
Cdd:cd05115   123 KNFVHRDLAARNVLLVNQHYAKISDfgLSKALGADDSYYKaRSAGKWPL-----KWYAPECINFRKFSSRSDVWSYGVTM 197
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 319803120  447 QEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05115   198 WEAFSyGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALMSDCWIYKWEDR 251
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
264-468 2.73e-15

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: 77.78  E-value: 2.73e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNGSRVTVKELNLPTHPHCSRLrlADLLIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRs 343
Cdd:cd14145    26 IWIGDEVAVKAARHDPDEDISQT--IENVRQEAKLFAMLKHPNIIALRGVCLKE--PNLCLVMEFARGGPLNRVLSGKR- 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 qfpvLHMEVIVHLLLQISDALRYLHFQGF---IHRSLSSYAVHIISPGE-ARLTNleYMLESEDRGVQRDLTRVplpTQL 419
Cdd:cd14145   101 ----IPPDILVNWAVQIARGMNYLHCEAIvpvIHRDLKSSNILILEKVEnGDLSN--KILKITDFGLAREWHRT---TKM 171
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 319803120  420 -----YNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAV 468
Cdd:cd14145   172 saagtYAWMAPEVIRSSMFSKGSDVWSYGVLLWELLTGEVPFRGIDGLAVAYGV 225
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
300-499 3.08e-15

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 77.18  E-value: 3.08e-15
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    300 SKLRHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLHERRSqfpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSS 379
Cdd:smart00220   52 KKLKHPNIVRLYDVF--EDEDKLYLVMEYCEGGDLFDLLKKRGR----LSEDEARFYLRQILSALEYLHSKGIVHRDLKP 125
                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    380 YAVHIISPGEARLTnleymleseDRGVQRDLTrvplPTQLYN-------WAAPEVILQKAATVKSDIYSFSMIMQEILTD 452
Cdd:smart00220  126 ENILLDEDGHVKLA---------DFGLARQLD----PGEKLTtfvgtpeYMAPEVLLGKGYGKAVDIWSLGVILYELLTG 192
                           170       180       190       200       210
                    ....*....|....*....|....*....|....*....|....*....|
gi 319803120    453 DIPWKG-LDGSVVKKAVVSGNY--LEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:smart00220  193 KPPFPGdDQLLELFKKIGKPKPpfPPPEWDISPEAKDLIRKLLVKDPEKR 242
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
292-499 4.42e-15

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: 77.00  E-value: 4.42e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKLRHPYLLQLMAVCLSqdlEKTRLVYERITIGTLFSVLHERRsQFPVLHMEVIVHlllQISDALRYLHFQG 371
Cdd:cd05060    43 FLREASVMAQLDHPCIVRLIGVCKG---EPLMLVMELAPLGPLLKYLKKRR-EIPVSDLKELAH---QVAMGMAYLESKH 115
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 FIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLT------------RVPLptqlyNWAAPEVILQKAATVKSDI 439
Cdd:cd05060   116 FVHRDLAARNVLLVNRHQAKIS---------DFGMSRALGagsdyyrattagRWPL-----KWYAPECINYGKFSSKSDV 181
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 319803120  440 YSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05060   182 WSYGVTLWEAFSyGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYRPEDR 242
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
288-489 7.50e-15

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: 76.15  E-value: 7.50e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  288 LADLLIAEQEHSSKLRHPYLLQLMAVClsqDLEKTRLVYERITIGTLFSVLHERRsqfpvlHMEV--IVHLLLQISDALR 365
Cdd:cd05116    39 LKDELLREANVMQQLDNPYIVRMIGIC---EAESWMLVMEMAELGPLNKFLQKNR------HVTEknITELVHQVSMGMK 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  366 YLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLeSEDRGVQRDLTRVPLPTQlynWAAPEVILQKAATVKSDIYSFS 443
Cdd:cd05116   110 YLEESNFVHRDLAARNVLLVTQHYAKISDfgLSKAL-RADENYYKAQTHGKWPVK---WYAPECMNYYKFSSKSDVWSFG 185
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 319803120  444 MIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVK 489
Cdd:cd05116   186 VLMWEAFSyGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMK 232
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
300-484 8.30e-15

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: 76.22  E-value: 8.30e-15
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRsqfpvLHMEVIVHLLLQISDALRYLHFQGF---IHRS 376
Cdd:cd14147    57 AMLAHPNIIALKAVCLEE--PNLCLVMEYAAGGPLSRALAGRR-----VPPHVLVNWAVQIARGMHYLHCEALvpvIHRD 129
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  377 LSSYAVHIISPGEARltNLEYM-LESEDRGVQRDLTRVplpTQL-----YNWAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd14147   130 LKSNNILLLQPIEND--DMEHKtLKITDFGLAREWHKT---TQMsaagtYAWMAPEVIKASTFSKGSDVWSFGVLLWELL 204
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 319803120  451 TDDIPWKGLDGSVVKKAV-VSGNYLEADVRLPKPY 484
Cdd:cd14147   205 TGEVPYRGIDCLAVAYGVaVNKLTLPIPSTCPEPF 239
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
27-136 1.28e-14

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 76.15  E-value: 1.28e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   27 LHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAAFSGNQWILS 106
Cdd:COG0666   157 LHLAAANGNLEIVKLLLEAGADVNARDNDGETPLHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVK 236
                          90       100       110
                  ....*....|....*....|....*....|
gi 319803120  107 KLLDAGGDLRLHDERGQNPKTWALTAGKER 136
Cdd:COG0666   237 LLLEAGADLNAKDKDGLTALLLAAAAGAAL 266
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
255-518 1.44e-14

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: 75.17  E-value: 1.44e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  255 GPYMVMTNLVWNGSRVTVKELNLPTHphcsrlRLAdlLIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTL 334
Cdd:cd14058     4 GSFGVVCKARWRNQIVAVKIIESESE------KKA--FEVEVRQLSRVDHPNIIKLYGACSNQ--KPVCLVMEYAEGGSL 73
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  335 FSVLHERRSQfPVLHMEVIVHLLLQISDALRYLHF---QGFIHRSLSsyavhiisPGEARLTNLEYMLESEDRGVQRDLT 411
Cdd:cd14058    74 YNVLHGKEPK-PIYTAAHAMSWALQCAKGVAYLHSmkpKALIHRDLK--------PPNLLLTNGGTVLKICDFGTACDIS 144
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  412 rvplpTQLYN------WAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDG--SVVKKAVVSGNYLEADVRLPKP 483
Cdd:cd14058   145 -----THMTNnkgsaaWMAPEVFEGSKYSEKCDVFSWGIILWEVITRRKPFDHIGGpaFRIMWAVHNGERPPLIKNCPKP 219
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 319803120  484 YYDIVKSGIHVKQKDRTmNLQDIRYILKNDLKDFT 518
Cdd:cd14058   220 IESLMTRCWSKDPEKRP-SMKEIVKIMSHLMQFFP 253
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
264-468 2.10e-14

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: 75.02  E-value: 2.10e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNGSRVTVKELNLptHPHCSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLsqDLEKTRLVYERITIGTLFSVLHERRs 343
Cdd:cd14148    14 LWRGEEVAVKAARQ--DPDEDIAVTAENVRQEARLFWMLQHPNIIALRGVCL--NPPHLCLVMEYARGGALNRALAGKK- 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 qfpvLHMEVIVHLLLQISDALRYLHFQGF---IHRSLSSYAVHIISPGEAR-LTNLeyMLESEDRGVQRDLTRVplpTQL 419
Cdd:cd14148    89 ----VPPHVLVNWAVQIARGMNYLHNEAIvpiIHRDLKSSNILILEPIENDdLSGK--TLKITDFGLAREWHKT---TKM 159
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 319803120  420 -----YNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAV 468
Cdd:cd14148   160 saagtYAWMAPEVIRLSLFSKSSDVWSFGVLLWELLTGEVPYREIDALAVAYGV 213
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
270-483 2.35e-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: 75.83  E-value: 2.35e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  270 VTVKELNLPTHPHCSRLRLADLLIAeqehsSKLRHPYLLQLMAVCLSQDLEktrLVYERITIGTLFSVLHERRSQFPVLH 349
Cdd:cd05108    39 VAIKELREATSPKANKEILDEAYVM-----ASVDNPHVCRLLGICLTSTVQ---LITQLMPFGCLLDYVREHKDNIGSQY 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  350 MeviVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqlyNWAAPEV 427
Cdd:cd05108   111 L---LNWCVQIAKGMNYLEDRRLVHRDLAARNVLVKTPQHVKITDfgLAKLLGAEEKEYHAEGGKVPI-----KWMALES 182
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  428 ILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVkkavvsGNYLEADVRLPKP 483
Cdd:cd05108   183 ILHRIYTHQSDVWSYGVTVWELMTfGSKPYDGIPASEI------SSILEKGERLPQP 233
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
290-489 2.86e-14

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: 74.69  E-value: 2.86e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  290 DLLIAEQEHSSKLRHPYLLQLMAVCLSQDLektRLVYERITIGTLFSVLHERRSQFPVlhmEVIVHLLLQISDALRYLHF 369
Cdd:cd05040    43 DDFLKEVNAMHSLDHPNLIRLYGVVLSSPL---MMVTELAPLGSLLDRLRKDQGHFLI---STLCDYAVQIANGMAYLES 116
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  370 QGFIHRSLSSYAVHIISPGEARLTNLEYML---ESEDRGVQRDLTRVPLPtqlynWAAPEVILQKAATVKSDIYSFSMIM 446
Cdd:cd05040   117 KRFIHRDLAARNILLASKDKVKIGDFGLMRalpQNEDHYVMQEHRKVPFA-----WCAPESLKTRKFSHASDVWMFGVTL 191
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 319803120  447 QEILT-DDIPWKGLDGSVVKKAVVsgnylEADVRLPKP------YYDIVK 489
Cdd:cd05040   192 WEMFTyGEEPWLGLNGSQILEKID-----KEGERLERPddcpqdIYNVML 236
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
267-536 3.21e-14

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 76.98  E-value: 3.21e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNlptHPHCSRLRLADLLIAEQEHSSKLRHPYLLQLMAVclsqDLEKTR--LVYERITIGTLFSVLHERRsq 344
Cdd:COG0515    32 GRPVALKVLR---PELAADPEARERFRREARALARLNHPNIVRVYDV----GEEDGRpyLVMEYVEGESLADLLRRRG-- 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  345 fpVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPLP-------T 417
Cdd:COG0515   103 --PLPPAEALRILAQLAEALAAAHAAGIVHRDIKPANILLTPDGRVKLI---------DFGIARALGGATLTqtgtvvgT 171
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  418 QLYnwAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNYL---EADVRLPKPYYDIVKSGIHV 494
Cdd:COG0515   172 PGY--MAPEQARGEPVDPRSDVYSLGVTLYELLTGRPPFDGDSPAELLRAHLREPPPppsELRPDLPPALDAIVLRALAK 249
                         250       260       270       280
                  ....*....|....*....|....*....|....*....|..
gi 319803120  495 KQKDRTMNLQDIRYILKNDLKDFTGAQRTQPTESPRVQRYGL 536
Cdd:COG0515   250 DPEERYQSAAELAAALRAVLRSLAAAAAAAAAAAAAAAAAAA 291
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
264-487 4.42e-14

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: 74.01  E-value: 4.42e-14
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNG-----SRVTVKELNLPTHPHcsrlrlADLLIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVL 338
Cdd:cd05148    22 VWEGlwknrVRVAIKILKSDDLLK------QQDFQKEVQALKRLRHKHLISLFAVCSVG--EPVYIITELMEKGSLLAFL 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  339 heRRSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSS--------YAVHIISPGEARLTNLEYMLESEdrgvqrdl 410
Cdd:cd05148    94 --RSPEGQVLPVASLIDMACQVAEGMAYLEEQNSIHRDLAArnilvgedLVCKVADFGLARLIKEDVYLSSD-------- 163
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 319803120  411 TRVPlptqlYNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDI 487
Cdd:cd05148   164 KKIP-----YKWTAPEAASHGTFSTKSDVWSFGILLYEMFTyGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYKI 236
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
305-510 1.10e-13

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: 73.15  E-value: 1.10e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  305 PYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQ------FPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLS 378
Cdd:cd05032    69 HHVVRLLGVVSTG--QPTLVVMELMAKGDLKSYLRSRRPEaennpgLGPPTLQKFIQMAAEIADGMAYLAAKKFVHRDLA 146
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  379 syavhiispgeAR--LTNLEYMLESEDRGVQRDL---------TRVPLPTQlynWAAPEVILQKAATVKSDIYSFSMIMQ 447
Cdd:cd05032   147 -----------ARncMVAEDLTVKIGDFGMTRDIyetdyyrkgGKGLLPVR---WMAPESLKDGVFTTKSDVWSFGVVLW 212
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 319803120  448 EILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDRTMNLQDIRYIL 510
Cdd:cd05032   213 EMATlAEQPYQGLSNEEVLKFVIDGGHLDLPENCPDKLLELMRMCWQYNPKMRPTFLEIVSSLK 276
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
264-524 1.11e-13

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: 73.15  E-value: 1.11e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VW-----NGSRVTVKELNLPTHPHCSRLRLADLLiaeqehsSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVL 338
Cdd:cd05072    23 VWmgyynNSTKVAVKTLKPGTMSVQAFLEEANLM-------KTLQHDKLVRLYAVVTKE--EPIYIITEYMAKGSLLDFL 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  339 HER---RSQFPVLhmeviVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLEsEDRGVQRDLTRV 413
Cdd:cd05072    94 KSDeggKVLLPKL-----IDFSAQIAEGMAYIERKNYIHRDLRAANVLVSESLMCKIADfgLARVIE-DNEYTAREGAKF 167
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  414 PLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGI 492
Cdd:cd05072   168 PI-----KWTAPEAINFGSFTIKSDVWSFGILLYEIVTyGKIPYPGMSNSDVMSALQRGYRMPRMENCPDELYDIMKTCW 242
                         250       260       270
                  ....*....|....*....|....*....|...
gi 319803120  493 HVKQKDR-TMNLqdiryiLKNDLKDFTGAQRTQ 524
Cdd:cd05072   243 KEKAEERpTFDY------LQSVLDDFYTATEGQ 269
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
252-450 1.82e-13

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: 72.14  E-value: 1.82e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  252 FFSGPYMVMTNLvwNGSRVTVKELNLPTHpHCSRLRLADLLiaeqehsSKLRHPYLLQLMAVCLSQDleKTRLVYERITI 331
Cdd:cd14065     5 FFGEVYKVTHRE--TGKVMVMKELKRFDE-QRSFLKEVKLM-------RRLSHPNILRFIGVCVKDN--KLNFITEYVNG 72
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  332 GTLFSVLHERRSQFPvlhMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIispgeaRLTNLEYMLESEDRGVQRDL- 410
Cdd:cd14065    73 GTLEELLKSMDEQLP---WSQRVSLAKDIASGMAYLHSKNIIHRDLNSKNCLV------REANRGRNAVVADFGLAREMp 143
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 319803120  411 ---TRVPLPTQLYN------WAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd14065   144 dekTKKPDRKKRLTvvgspyWMAPEMLRGESYDEKVDVFSFGIVLCEII 192
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
270-483 1.99e-13

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: 72.79  E-value: 1.99e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  270 VTVKELNLPTHPHCSRLRLADLLIAeqehsSKLRHPYLLQLMAVCLSQDLEktrLVYERITIGTLFSVLHERRSQfpvLH 349
Cdd:cd05110    39 VAIKILNETTGPKANVEFMDEALIM-----ASMDHPHLVRLLGVCLSPTIQ---LVTQLMPHGCLLDYVHEHKDN---IG 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  350 MEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqlyNWAAPEV 427
Cdd:cd05110   108 SQLLLNWCVQIAKGMMYLEERRLVHRDLAARNVLVKSPNHVKITDfgLARLLEGDEKEYNADGGKMPI-----KWMALEC 182
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  428 ILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKkavvsgNYLEADVRLPKP 483
Cdd:cd05110   183 IHYRKFTHQSDVWSYGVTIWELMTfGGKPYDGIPTREIP------DLLEKGERLPQP 233
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
292-499 2.88e-13

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: 71.43  E-value: 2.88e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFpvlHMEVIVHLLLQISDALRYLHFQG 371
Cdd:cd05114    46 FIEEAKVMMKLTHPKLVQLYGVCTQQ--KPIYIVTEFMENGCLLNYLRQRRGKL---SRDMLLSMCQDVCEGMEYLERNN 120
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 FIHRSLSSYAVHIISPGEARLTNL---EYMLEseDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQE 448
Cdd:cd05114   121 FIHRDLAARNCLVNDTGVVKVSDFgmtRYVLD--DQYTSSSGAKFPV-----KWSPPEVFNYSKFSSKSDVWSFGVLMWE 193
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 319803120  449 ILTD-DIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05114   194 VFTEgKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEVMYSCWHEKPEGR 245
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
270-483 3.40e-13

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: 71.68  E-value: 3.40e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  270 VTVKelnlpTHPHCSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQdleKTRLVYERITIGTLFSVLHERRSQFPVLh 349
Cdd:cd05056    37 VAVK-----TCKNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITEN---PVWIVMELAPLGELRSYLQVNKYSLDLA- 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  350 meVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDL--------TRVPLPTQlyn 421
Cdd:cd05056   108 --SLILYAYQLSTALAYLESKRFVHRDIAARNVLVSSPDCVKLG---------DFGLSRYMedesyykaSKGKLPIK--- 173
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319803120  422 WAAPEVILQKAATVKSDIYSFSMIMQEILTDDI-PWKGLDGSVVKKAVVSGNyleadvRLPKP 483
Cdd:cd05056   174 WMAPESINFRRFTSASDVWMFGVCMWEILMLGVkPFQGVKNNDVIGRIENGE------RLPMP 230
Ank_2 pfam12796
Ankyrin repeats (3 copies);
27-119 7.38e-13

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 65.52  E-value: 7.38e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    27 LHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGsDPNHRCfDGSTPVHAAAFSGNQWILS 106
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLEHA-DVNLKD-NGRTALHYAARSGHLEIVK 78
                           90
                   ....*....|...
gi 319803120   107 KLLDAGGDLRLHD 119
Cdd:pfam12796   79 LLLEKGADINVKD 91
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
292-499 7.58e-13

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: 70.36  E-value: 7.58e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFPvlhMEVIVHLLLQISDALRYLHFQG 371
Cdd:cd05112    46 FIEEAEVMMKLSHPKLVQLYGVCLEQ--APICLVFEFMEHGCLSDYLRTQRGLFS---AETLLGMCLDVCEGMAYLEEAS 120
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 FIHRSLS--------SYAVHIISPGEARLTnleymleSEDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFS 443
Cdd:cd05112   121 VIHRDLAarnclvgeNQVVKVSDFGMTRFV-------LDDQYTSSTGTKFPV-----KWSSPEVFSFSRYSSKSDVWSFG 188
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  444 MIMQEILTD-DIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05112   189 VLMWEVFSEgKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNHCWKERPEDR 245
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
266-463 7.72e-13

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: 70.24  E-value: 7.72e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLpthpHCSRLRLADLLIAEQEHSSKLRHPYLLQlmavCLSQDLEKT--RLVYERITIGTLFSVLHerrs 343
Cdd:cd06606    24 TGELMAVKEVEL----SGDSEEELEALEREIRILSSLKHPNIVR----YLGTERTENtlNIFLEYVPGGSLASLLK---- 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 QFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPLPTQLY--- 420
Cdd:cd06606    92 KFGKLPEPVVRKYTRQILEGLEYLHSNGIVHRDIKGANILVDSDGVVKLA---------DFGCAKRLAEIATGEGTKslr 162
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 319803120  421 ---NWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSV 463
Cdd:cd06606   163 gtpYWMAPEVIRGEGYGRAADIWSLGCTVIEMATGKPPWSELGNPV 208
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
253-490 7.90e-13

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: 70.29  E-value: 7.90e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  253 FSGPYMvmtnlvwnGSRVTVKELNLPThphcsrlrLADLLIAEQEHSSKLRHPYLLQLMAVCLSQDLektRLVYERITIG 332
Cdd:cd05083    23 LQGEYM--------GQKVAVKNIKCDV--------TAQAFLEETAVMTKLQHKNLVRLLGVILHNGL---YIVMELMSKG 83
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  333 TLFSVLHER-RSQFPVLHMeviVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEyMLESEDRGVqrDLT 411
Cdd:cd05083    84 NLVNFLRSRgRALVPVIQL---LQFSLDVAEGMEYLESKKLVHRDLAARNILVSEDGVAKISDFG-LAKVGSMGV--DNS 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  412 RVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKS 490
Cdd:cd05083   158 RLPV-----KWTAPEALKNKKFSSKSDVWSYGVLLWEVFSyGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVYSIMTS 232
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
294-472 8.77e-13

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: 69.99  E-value: 8.77e-13
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  294 AEQEHSSKLRHPYLLQLMAVCLsqDLEKTRLVYERITIGTLFSVLHERRSQfpVLHMEVIVHLLLQISDALRYLHFQG-- 371
Cdd:cd14060    31 KEAEILSVLSHRNIIQFYGAIL--EAPNYGIVTEYASYGSLFDYLNSNESE--EMDMDQIMTWATDIAKGMHYLHMEApv 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 -FIHRSLSSYAVHIISpgearltnlEYMLESEDRGVQR--DLTRVPLPTQLYNWAAPEVILQKAATVKSDIYSFSMIMQE 448
Cdd:cd14060   107 kVIHRDLKSRNVVIAA---------DGVLKICDFGASRfhSHTTHMSLVGTFPWMAPEVIQSLPVSETCDTYSYGVVLWE 177
                         170       180
                  ....*....|....*....|....
gi 319803120  449 ILTDDIPWKGLDGSVVKKAVVSGN 472
Cdd:cd14060   178 MLTREVPFKGLEGLQVAWLVVEKN 201
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
265-488 1.02e-12

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: 69.56  E-value: 1.02e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGS-RVTVKELNLPTHPHCSRLRLADLLiaeqehsSKLRHPYLLQLMAVcLSQdlEKTRLVYERITIGTLFSVLHERRS 343
Cdd:cd14203    16 WNGTtKVAIKTLKPGTMSPEAFLEEAQIM-------KKLRHDKLVQLYAV-VSE--EPIYIVTEFMSKGSLLDFLKDGEG 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 QFpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSS--------YAVHIISPGEARLTnleymleSEDRGVQRDLTRVPL 415
Cdd:cd14203    86 KY--LKLPQLVDMAAQIASGMAYIERMNYIHRDLRAanilvgdnLVCKIADFGLARLI-------EDNEYTARQGAKFPI 156
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 319803120  416 ptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDD-IPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIV 488
Cdd:cd14203   157 -----KWTAPEAALYGRFTIKSDVWSFGILLTELVTKGrVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELM 225
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
18-144 1.06e-12

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 70.37  E-value: 1.06e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   18 LRNDSLEAQLHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAA 97
Cdd:COG0666    49 LADALGALLLLAAALAGDLLVALLLLAAGADINAKDDGGNTLLHAAARNGDLEIVKLLLEAGADVNARDKDGETPLHLAA 128
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 319803120   98 FSGNQWILSKLLDAGGDLRLHDERGQNPKTWALTAGkerSTQIVEFM 144
Cdd:COG0666   129 YNGNLEIVKLLLEAGADVNAQDNDGNTPLHLAAANG---NLEIVKLL 172
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
270-487 1.81e-12

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: 69.34  E-value: 1.81e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  270 VTVKelNLPTHphCSRLRLADLLIaEQEHSSKLRHPYLLQLMAVCLSQdleKTRL-VYERITIGTLFSVLHERR---SQF 345
Cdd:cd05036    39 VAVK--TLPEL--CSEQDEMDFLM-EALIMSKFNHPNIVRCIGVCFQR---LPRFiLLELMAGGDLKSFLRENRprpEQP 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 PVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEymleseDRGVQRDLTRVP---------LP 416
Cdd:cd05036   111 SSLTMLDLLQLAQDVAKGCRYLEENHFIHRDIAARNCLLTCKGPGRVAKIG------DFGMARDIYRADyyrkggkamLP 184
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 319803120  417 TQlynWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDI 487
Cdd:cd05036   185 VK---WMPPEAFLDGIFTSKTDVWSFGVLLWEIFSlGYMPYPGKSNQEVMEFVTSGGRMDPPKNCPGPVYRI 253
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
264-499 1.83e-12

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: 68.92  E-value: 1.83e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNGSRVTVKELNlpthphcSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHER-R 342
Cdd:cd05039    26 DYRGQKVAVKCLK-------DDSTAAQAFLAEASVMTTLRHPNLVQLLGVVLEGN--GLYIVTEYMAKGSLVDYLRSRgR 96
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  343 SqfpVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRD----LTRVPLPTQ 418
Cdd:cd05039    97 A---VITRKDQLGFALDVCEGMEYLESKKFVHRDLAARNVLVSEDNVAKVS---------DFGLAKEassnQDGGKLPIK 164
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  419 lynWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQK 497
Cdd:cd05039   165 ---WTAPEALREKKFSTKSDVWSFGILLWEIYSfGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMKNCWELDPA 241

                  ..
gi 319803120  498 DR 499
Cdd:cd05039   242 KR 243
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
295-510 7.11e-12

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: 68.11  E-value: 7.11e-12
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLH------------ERRSQFPVLHMEVIVHLLLQISD 362
Cdd:cd05094    57 EAELLTNLQHDHIVKFYGVCGDGD--PLIMVFEYMKHGDLNKFLRahgpdamilvdgQPRQAKGELGLSQMLHIATQIAS 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  363 ALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDLT-----RVPLPTQL-YNWAAPEVILQKAATVK 436
Cdd:cd05094   135 GMVYLASQHFVHRDLATRNC---------LVGANLLVKIGDFGMSRDVYstdyyRVGGHTMLpIRWMPPESIMYRKFTTE 205
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 319803120  437 SDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVkSGIHVKQKDRTMNLQDIRYIL 510
Cdd:cd05094   206 SDVWSFGVILWEIFTyGKQPWFQLSNTEVIECITQGRVLERPRVCPKEVYDIM-LGCWQREPQQRLNIKEIYKIL 279
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
290-499 1.10e-11

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: 66.83  E-value: 1.10e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  290 DLLIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFpvlHMEVIVHLLLQISDALRYLHF 369
Cdd:cd05113    44 DEFIEEAKVMMNLSHEKLVQLYGVCTKQ--RPIFIITEYMANGCLLNYLREMRKRF---QTQQLLEMCKDVCEAMEYLES 118
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  370 QGFIHRSLSSYAVHIISPGEARLTNL---EYMLEseDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIM 446
Cdd:cd05113   119 KQFLHRDLAARNCLVNDQGVVKVSDFglsRYVLD--DEYTSSVGSKFPV-----RWSPPEVLMYSKFSSKSDVWAFGVLM 191
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....
gi 319803120  447 QEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05113   192 WEVYSlGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYTIMYSCWHEKADER 245
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
269-517 1.42e-11

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: 66.95  E-value: 1.42e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  269 RVTVKELNLPThphCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCL----SQDLEKTRLVYERITIGTLFS-VLHERRS 343
Cdd:cd05075    29 KVAVKTMKIAI---CTRSEMEDFL-SEAVCMKEFDHPNVMRLIGVCLqnteSEGYPSPVVILPFMKHGDLHSfLLYSRLG 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 QFPV-LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqly 420
Cdd:cd05075   105 DCPVyLPTQMLVKFMTDIASGMEYLSSKNFIHRDLAARNCMLNENMNVCVADfgLSKKIYNGDYYRQGRISKMPV----- 179
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  421 NWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05075   180 KWIAIESLADRVYTTKSDVWSFGVTMWEIATrGQTPYPGVENSEIYDYLRQGNRLKQPPDCLDGLYELMSSCWLLNPKDR 259
                         250
                  ....*....|....*...
gi 319803120  500 TmNLQDIRYILKNDLKDF 517
Cdd:cd05075   260 P-SFETLRCELEKILKDL 276
PK_eIF2AK_GCN2_rpt1 cd14012
Pseudokinase domain, repeat 1, of eukaryotic translation Initiation Factor 2-Alpha Kinase 4 or ...
300-489 1.54e-11

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: 66.23  E-value: 1.54e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVCLSQDLE----KTRLVYERITIGTLFSVLherrSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHR 375
Cdd:cd14012    53 KKLRHPNLVSYLAFSIERRGRsdgwKVYLLTEYAPGGSLSELL----DSVGSVPLDTARRWTLQLLEALEYLHRNGVVHK 128
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  376 SLSSYAVHIISP---GEARLTNLeymleSEDRGVQRDLTRVPLPT--QLYnWAAPEVILQ-KAATVKSDIYSFSMIMQEI 449
Cdd:cd14012   129 SLHAGNVLLDRDagtGIVKLTDY-----SLGKTLLDMCSRGSLDEfkQTY-WLPPELAQGsKSPTRKTDVWDLGLLFLQM 202
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 319803120  450 LTddipwkgldGSVVKKAVVSGNYLEADVRLPKPYYDIVK 489
Cdd:cd14012   203 LF---------GLDVLEKYTSPNPVLVSLDLSASLQDFLS 233
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
266-448 1.64e-11

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: 66.07  E-value: 1.64e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLpthphcSRLRLADLLIAEQEHSSKLRHPYLLQLmavcLSQDLEKTRL--VYERITIGTLFSVLHERRS 343
Cdd:cd05122    24 TGQIVAIKKINL------ESKEKKESILNEIAILKKCKHPNIVKY----YGSYLKKDELwiVMEFCSGGSLKDLLKNTNK 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 QFPVLHMEVIVHLLLQisdALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPLPTQLY--- 420
Cdd:cd05122    94 TLTEQQIAYVCKEVLK---GLEYLHSHGIIHRDIKAANILLTSDGEVKLI---------DFGLSAQLSDGKTRNTFVgtp 161
                         170       180
                  ....*....|....*....|....*...
gi 319803120  421 NWAAPEVILQKAATVKSDIYSFSMIMQE 448
Cdd:cd05122   162 YWMAPEVIQGKPYGFKADIWSLGITAIE 189
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
305-483 2.17e-11

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: 66.20  E-value: 2.17e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  305 PYLLQLMAVCLSQDLEktrLVYERITIGTLFSVLHERRSQfpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHI 384
Cdd:cd05109    69 PYVCRLLGICLTSTVQ---LVTQLMPYGCLLDYVRENKDR---IGSQDLLNWCVQIAKGMSYLEEVRLVHRDLAARNVLV 142
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  385 ISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDI-PWKGLDG 461
Cdd:cd05109   143 KSPNHVKITDfgLARLLDIDETEYHADGGKVPI-----KWMALESILHRRFTHQSDVWSYGVTVWELMTFGAkPYDGIPA 217
                         170       180
                  ....*....|....*....|..
gi 319803120  462 SVVKkavvsgNYLEADVRLPKP 483
Cdd:cd05109   218 REIP------DLLEKGERLPQP 233
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
265-488 9.66e-11

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: 64.29  E-value: 9.66e-11
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGSrVTVKELNLpthphcSRLRLADLLIAEQEHSS--KLRHPYLLQLMAVCLsqDLEKTRLVYERITIGTLFSVLHERR 342
Cdd:cd14063    21 WHGD-VAIKLLNI------DYLNEEQLEAFKEEVAAykNTRHDNLVLFMGACM--DPPHLAIVTSLCKGRTLYSLIHERK 91
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  343 SQFPvlhMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVhIISPGEARLTNLEYM-LESEDRGVQRDLT-RVPlptqlY 420
Cdd:cd14063    92 EKFD---FNKTVQIAQQICQGMGYLHAKGIIHKDLKSKNI-FLENGRVVITDFGLFsLSGLLQPGRREDTlVIP-----N 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  421 NWA---APEVI----------LQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNYLE-ADVRLPKPYYD 486
Cdd:cd14063   163 GWLcylAPEIIralspdldfeESLPFTKASDVYAFGTVWYELLAGRWPFKEQPAESIIWQVGCGKKQSlSQLDIGREVKD 242

                  ..
gi 319803120  487 IV 488
Cdd:cd14063   243 IL 244
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
320-514 1.17e-10

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: 64.22  E-value: 1.17e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  320 EKTRLVYERITIGTLFSVLHERRSQF------PVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISpgearlt 393
Cdd:cd05061    82 QPTLVVMELMAHGDLKSYLRSLRPEAennpgrPPPTLQEMIQMAAEIADGMAYLNAKKFVHRDLAARNCMVAH------- 154
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  394 nlEYMLESEDRGVQRDLTRVP---------LPTQlynWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSV 463
Cdd:cd05061   155 --DFTVKIGDFGMTRDIYETDyyrkggkglLPVR---WMAPESLKDGVFTTSSDMWSFGVVLWEITSlAEQPYQGLSNEQ 229
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|.
gi 319803120  464 VKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDRTMnLQDIRYILKNDL 514
Cdd:cd05061   230 VLKFVMDGGYLDQPDNCPERVTDLMRMCWQFNPKMRPT-FLEIVNLLKDDL 279
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
295-512 1.53e-10

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: 63.64  E-value: 1.53e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVL-----------HERRSQFPvLHMEVIVHLLLQISDA 363
Cdd:cd05049    58 EAELLTNLQHENIVKFYGVCTEGD--PLLMVFEYMEHGDLNKFLrshgpdaaflaSEDSAPGE-LTLSQLLHIAVQIASG 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  364 LRYLHFQGFIHRSLSSYAVHIispGEARLTNLEymleseDRGVQRDLT-----RVPLPTQL-YNWAAPEVILQKAATVKS 437
Cdd:cd05049   135 MVYLASQHFVHRDLATRNCLV---GTNLVVKIG------DFGMSRDIYstdyyRVGGHTMLpIRWMPPESILYRKFTTES 205
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319803120  438 DIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDRTmNLQDIRYILKN 512
Cdd:cd05049   206 DVWSFGVVLWEIFTyGKQPWFQLSNTEVIECITQGRLLQRPRTCPSEVYAVMLGCWKREPQQRL-NIKDIHKRLQE 280
PK_STRAD cd08216
Pseudokinase domain of STE20-related kinase adapter protein; The pseudokinase domain shows ...
266-441 2.32e-10

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: 63.85  E-value: 2.32e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLPTHPHcsrlrlADLLIAEQE--HSSKLRHPYLLqlmaVCLSQDLEKTRL--VYERITIGTLFSVLher 341
Cdd:cd08216    24 TNTLVAVKKINLESDSK------EDLKFLQQEilTSRQLQHPNIL----PYVTSFVVDNDLyvVTPLMAYGSCRDLL--- 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  342 RSQFPVLHMEVIVHLLLQ-ISDALRYLHFQGFIHRSLSsyAVHI-ISP-GEARLTNLEYMLESEDRGvQRDLTRVPLP-- 416
Cdd:cd08216    91 KTHFPEGLPELAIAFILRdVLNALEYIHSKGYIHRSVK--ASHIlISGdGKVVLSGLRYAYSMVKHG-KRQRVVHDFPks 167
                         170       180
                  ....*....|....*....|....*...
gi 319803120  417 -TQLYNWAAPEVILQKAA--TVKSDIYS 441
Cdd:cd08216   168 sEKNLPWLSPEVLQQNLLgyNEKSDIYS 195
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
300-451 2.69e-10

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: 63.12  E-value: 2.69e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVL--HERRSQFPV------LHMEVIVHLLLQISDALRYLHFQG 371
Cdd:cd05051    74 SQLKDPNIVRLLGVCTRD--EPLCMIVEYMENGDLNQFLqkHEAETQGASatnsktLSYGTLLYMATQIASGMKYLESLN 151
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 FIHRSLSSyavhiispgEARLTNLEYMLESEDRGVQRDL---------TRVPLPTQlynWAAPEVILQKAATVKSDIYSF 442
Cdd:cd05051   152 FVHRDLAT---------RNCLVGPNYTIKIADFGMSRNLysgdyyrieGRAVLPIR---WMAWESILLGKFTTKSDVWAF 219

                  ....*....
gi 319803120  443 SMIMQEILT 451
Cdd:cd05051   220 GVTLWEILT 228
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
265-498 4.20e-10

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: 62.39  E-value: 4.20e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNG-SRVTVKELNLPTHPHCSRLRLADLLiaeqehsSKLRHPYLLQLMAVClsqDLEKTRLVYERITIGTLFSVLHERRS 343
Cdd:cd05070    30 WNGnTKVAIKTLKPGTMSPESFLEEAQIM-------KKLKHDKLVQLYAVV---SEEPIYIVTEYMSKGSLLDFLKDGEG 99
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 QfpVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAV--------HIISPGEARLTnleymleSEDRGVQRDLTRVPL 415
Cdd:cd05070   100 R--ALKLPNLVDMAAQVAAGMAYIERMNYIHRDLRSANIlvgnglicKIADFGLARLI-------EDNEYTARQGAKFPI 170
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  416 ptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDD-IPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVksgIHV 494
Cdd:cd05070   171 -----KWTAPEAALYGRFTIKSDVWSFGILLTELVTKGrVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELM---IHC 242

                  ....
gi 319803120  495 KQKD 498
Cdd:cd05070   243 WKKD 246
STKc_MEKK1_plant cd06632
Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP) ...
266-461 4.34e-10

Catalytic domain of the Serine/Threonine Kinase, Plant Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of plant MAPK kinase kinases (MAPKKKs) including Arabidopsis thaliana MEKK1 and MAPKKK3. Arabidopsis thaliana MEKK1 activates MPK4, a MAPK that regulates systemic acquired resistance. MEKK1 also participates in the regulation of temperature-sensitive and tissue-specific cell death. 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 plant MEKK1 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: 270802 [Multi-domain]  Cd Length: 259  Bit Score: 62.03  E-value: 4.34e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLPTHPHCSRLRLADLliaEQEHS--SKLRHPYLLQLMAvclSQDLEKTRLVY-ERITIGTLFSVLHErr 342
Cdd:cd06632    24 TGDFFAVKEVSLVDDDKKSRESVKQL---EQEIAllSKLRHPNIVQYYG---TEREEDNLYIFlEYVPGGSIHKLLQR-- 95
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  343 sqFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPLPTQLYN- 421
Cdd:cd06632    96 --YGAFEEPVIRLYTRQILSGLAYLHSRNTVHRDIKGANILVDTNGVVKLA---------DFGMAKHVEAFSFAKSFKGs 164
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 319803120  422 --WAAPEVILQKAA--TVKSDIYSFSMIMQEILTDDIPWKGLDG 461
Cdd:cd06632   165 pyWMAPEVIMQKNSgyGLAVDIWSLGCTVLEMATGKPPWSQYEG 208
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
268-499 5.13e-10

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: 61.97  E-value: 5.13e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  268 SRVTVKELNLPTHPHCSRLRLADLLIAeqehsskLRHPYLLQLMAVCLSqdlEKTRLVYERITIGTLFSVLHE---RRSQ 344
Cdd:cd05073    36 TKVAVKTMKPGSMSVEAFLAEANVMKT-------LQHDKLVKLHAVVTK---EPIYIITEFMAKGSLLDFLKSdegSKQP 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  345 FPVLhmeviVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRG-VQRDLTRVPLptqlyNWA 423
Cdd:cd05073   106 LPKL-----IDFSAQIAEGMAFIEQRNYIHRDLRAANILVSASLVCKIADFGLARVIEDNEyTAREGAKFPI-----KWT 175
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  424 APEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05073   176 APEAINFGSFTIKSDVWSFGILLMEIVTyGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCWKNRPEER 252
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
295-506 8.13e-10

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: 61.52  E-value: 8.13e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLherRSQFP--------------VLHMEVIVHLLLQI 360
Cdd:cd05092    57 EAELLTVLQHQHIVRFYGVC--TEGEPLIMVFEYMRHGDLNRFL---RSHGPdakildggegqapgQLTLGQMLQIASQI 131
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  361 SDALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDL---------TRVPLPTQlynWAAPEVILQK 431
Cdd:cd05092   132 ASGMVYLASLHFVHRDLATRNC---------LVGQGLVVKIGDFGMSRDIystdyyrvgGRTMLPIR---WMPPESILYR 199
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319803120  432 AATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKsGIHVKQKDRTMNLQDI 506
Cdd:cd05092   200 KFTTESDIWSFGVVLWEIFTyGKQPWYQLSNTEAIECITQGRELERPRTCPPEVYAIMQ-GCWQREPQQRHSIKDI 274
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
265-483 8.27e-10

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: 61.63  E-value: 8.27e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGS-RVTVKELNLPThphcsrlRLADLLIAEQEHSSKLRHPYLLQLMAVCLSqdlEKTRLVYERITIGTLFSVLHERRS 343
Cdd:cd05069    33 WNGTtKVAIKTLKPGT-------MMPEAFLQEAQIMKKLRHDKLVPLYAVVSE---EPIYIVTEFMGKGSLLDFLKEGDG 102
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 QFpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLEsEDRGVQRDLTRVPLptqlyN 421
Cdd:cd05069   103 KY--LKLPQLVDMAAQIADGMAYIERMNYIHRDLRAANILVGDNLVCKIADfgLARLIE-DNEYTARQGAKFPI-----K 174
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319803120  422 WAAPEVILQKAATVKSDIYSFSMIMQEILTDD-IPWKGLDGSVVKKAVVSGnyleadVRLPKP 483
Cdd:cd05069   175 WTAPEAALYGRFTIKSDVWSFGILLTELVTKGrVPYPGMVNREVLEQVERG------YRMPCP 231
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
295-512 8.78e-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: 61.59  E-value: 8.78e-10
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLF---------SVLHERRSQFPVLHMEVIVHLLLQISDALR 365
Cdd:cd05093    57 EAELLTNLQHEHIVKFYGVCVEGD--PLIMVFEYMKHGDLNkflrahgpdAVLMAEGNRPAELTQSQMLHIAQQIAAGMV 134
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  366 YLHFQGFIHRSLSSYAVHIispGEARLTNLEymleseDRGVQRDLT-----RVPLPTQL-YNWAAPEVILQKAATVKSDI 439
Cdd:cd05093   135 YLASQHFVHRDLATRNCLV---GENLLVKIG------DFGMSRDVYstdyyRVGGHTMLpIRWMPPESIMYRKFTTESDV 205
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....
gi 319803120  440 YSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVkSGIHVKQKDRTMNLQDIRYILKN 512
Cdd:cd05093   206 WSLGVVLWEIFTyGKQPWYQLSNNEVIECITQGRVLQRPRTCPKEVYDLM-LGCWQREPHMRLNIKEIHSLLQN 278
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
300-451 1.03e-09

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: 61.53  E-value: 1.03e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHER--RSQF------PVLHMEVIVHLLLQISDALRYLHFQG 371
Cdd:cd05097    72 SRLKNPNIIRLLGVCVSDD--PLCMITEYMENGDLNQFLSQReiESTFthanniPSVSIANLLYMAVQIASGMKYLASLN 149
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 FIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDL---------TRVPLPTQlynWAAPEVILQKAATVKSDIYSF 442
Cdd:cd05097   150 FVHRDLATRNC---------LVGNHYTIKIADFGMSRNLysgdyyriqGRAVLPIR---WMAWESILLGKFTTASDVWAF 217

                  ....*....
gi 319803120  443 SMIMQEILT 451
Cdd:cd05097   218 GVTLWEMFT 226
PKc_TESK cd14155
Catalytic domain of the Dual-specificity protein kinase, Testicular protein kinase; ...
301-450 1.63e-09

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: 60.18  E-value: 1.63e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRsqfpVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSY 380
Cdd:cd14155    44 RLSHPNILRFMGVCVHQG--QLHALTEYINGGNLEQLLDSNE----PLSWTVRVKLALDIARGLSYLHSKGIFHRDLTSK 117
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319803120  381 AVhIISPGEARLT------NLEYMLESEDRGVQRdLTRVPLPTqlynWAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd14155   118 NC-LIKRDENGYTavvgdfGLAEKIPDYSDGKEK-LAVVGSPY----WMAPEVLRGEPYNEKADVFSYGIILCEII 187
STKc_Mos cd13979
Catalytic domain of the Serine/Threonine kinase, Oocyte maturation factor Mos; STKs catalyze ...
267-469 2.22e-09

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: 60.09  E-value: 2.22e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNLPTHPHCSRlrlaDLLIAEQeHSSKLRHPYLLQLMAVCLSQDLEKTRLV-YERITIGTLFSVLHERRSQF 345
Cdd:cd13979    26 GETVAVKIVRRRRKNRASR----QSFWAEL-NAARLRHENIVRVLAAETGTDFASLGLIiMEYCGNGTLQQLIYEGSEPL 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 PVLHMeviVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLE-SEDRGVQRDLTRVplpTQLYNWAA 424
Cdd:cd13979   101 PLAHR---ILISLDIARALRFCHSHGIVHLDVKPANILISEQGVCKLCDFGCSVKlGEGNEVGTPRSHI---GGTYTYRA 174
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 319803120  425 PEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDgSVVKKAVV 469
Cdd:cd13979   175 PELLKGERVTPKADIYSFGITLWQMLTRELPYAGLR-QHVLYAVV 218
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
324-500 2.32e-09

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: 59.94  E-value: 2.32e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  324 LVYERITIGTLFSVLHERRSQFPVLHMeviVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLeymlesed 403
Cdd:cd05064    83 IVTEYMSNGALDSFLRKHEGQLVAGQL---MGMLPGLASGMKYLSEMGYVHKGLAAHKVLVNSDLVCKISGF-------- 151
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  404 RGVQRDLTRVPLPT----QLYNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADV 478
Cdd:cd05064   152 RRLQEDKSEAIYTTmsgkSPVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSyGERPYWDMSGQDVIKAVEDGFRLPAPR 231
                         170       180
                  ....*....|....*....|..
gi 319803120  479 RLPKPYYDIVksgIHVKQKDRT 500
Cdd:cd05064   232 NCPNLLHQLM---LDCWQKERG 250
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
270-483 2.67e-09

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: 59.69  E-value: 2.67e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  270 VTVKELnlptHPHCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFpvlH 349
Cdd:cd05033    35 VAIKTL----KSGYSDKQRLDFL-TEASIMGQFDHPNVIRLEGVVTKS--RPVMIVTEYMENGSLDKFLRENDGKF---T 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  350 MEVIVHLLLQISDALRYLHFQGFIHRSLSsyAVHIispgearLTNLEYMLESEDRGVQRDLtRVPLPTqlYN-------- 421
Cdd:cd05033   105 VTQLVGMLRGIASGMKYLSEMNYVHRDLA--ARNI-------LVNSDLVCKVSDFGLSRRL-EDSEAT--YTtkggkipi 172
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 319803120  422 -WAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGnyleadVRLPKP 483
Cdd:cd05033   173 rWTAPEAIAYRKFTSASDVWSFGIVMWEVMSyGERPYWDMSNQDVIKAVEDG------YRLPPP 230
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
264-517 3.39e-09

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: 59.52  E-value: 3.39e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNG-----SRVTVKELNLPTHPHCSRLRLADLLiaeqehsSKLRHPYLLQLMAVCLSqdlEKTRLVYERITIGTLFSVL 338
Cdd:cd05067    23 VWMGyynghTKVAIKSLKQGSMSPDAFLAEANLM-------KQLQHQRLVRLYAVVTQ---EPIYIITEYMENGSLVDFL 92
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  339 heRRSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLS------SYAVH--IISPGEARL-TNLEYmlesedrgVQRD 409
Cdd:cd05067    93 --KTPSGIKLTINKLLDMAAQIAEGMAFIEERNYIHRDLRaanilvSDTLSckIADFGLARLiEDNEY--------TARE 162
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  410 LTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAvvsgnyLEADVRLPKP----- 483
Cdd:cd05067   163 GAKFPI-----KWTAPEAINYGTFTIKSDVWSFGILLTEIVThGRIPYPGMTNPEVIQN------LERGYRMPRPdncpe 231
                         250       260       270
                  ....*....|....*....|....*....|....*.
gi 319803120  484 -YYDIVKSGIHVKQKDR-TMNLqdiryiLKNDLKDF 517
Cdd:cd05067   232 eLYQLMRLCWKERPEDRpTFEY------LRSVLEDF 261
STKc_CNK2-like cd08530
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii CNK2 and similar ...
324-499 3.72e-09

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: 59.33  E-value: 3.72e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  324 LVYERITIGTLFSVLHERRSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLeymlesed 403
Cdd:cd08530    76 IVMEYAPFGDLSKLISKRKKKRRLFPEDDIWRIFIQMLRGLKALHDQKILHRDLKSANILLSAGDLVKIGDL-------- 147
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  404 rGVQRDLTRVPLPTQ----LYnwAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNYleadVR 479
Cdd:cd08530   148 -GISKVLKKNLAKTQigtpLY--AAPEVWKGRPYDYKSDIWSLGCLLYEMATFRPPFEARTMQELRYKVCRGKF----PP 220
                         170       180
                  ....*....|....*....|....
gi 319803120  480 LPKPYYD----IVKSGIHVKQKDR 499
Cdd:cd08530   221 IPPVYSQdlqqIIRSLLQVNPKKR 244
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
253-460 4.07e-09

Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein Kinase Kinase Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. Members of this group include the MAPKKKs Schizosaccharomyces pombe Byr2, Saccharomyces cerevisiae and Cryptococcus neoformans Ste11, and related proteins. They contain an N-terminal SAM (sterile alpha-motif) domain, which mediates protein-protein interaction, and a C-terminal catalytic domain. 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 Byr2 is regulated by Ras1. It responds to pheromone signaling and controls mating through the MAPK pathway. Budding yeast Ste11 functions in MAPK cascades that regulate mating, high osmolarity glycerol, and filamentous growth responses. The Byr2 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: 270798 [Multi-domain]  Cd Length: 267  Bit Score: 59.47  E-value: 4.07e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  253 FSGPYMVMTNLvwNGSRVTVKELNLPTHPHCSRLRLADLLIAEQEHSSKLR---HPYLLQLMAVclSQDLEKTRLVYERI 329
Cdd:cd06628    13 FGSVYLGMNAS--SGELMAVKQVELPSVSAENKDRKKSMLDALQREIALLRelqHENIVQYLGS--SSDANHLNIFLEYV 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  330 TIGTLFSVLherrSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQ 407
Cdd:cd06628    89 PGGSVATLL----NNYGAFEESLVRNFVRQILKGLNYLHNRGIIHRDIKGANILVDNKGGIKISDfgISKKLEANSLSTK 164
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|...
gi 319803120  408 RDLTRVPLPTQLYnWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd06628   165 NNGARPSLQGSVF-WMAPEVVKQTSYTRKADIWSLGCLVVEMLTGTHPFPDCT 216
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
300-451 5.27e-09

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: 58.97  E-value: 5.27e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVCLsqDLEKTRLVYERITIGTLFSVLHERR---SQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRS 376
Cdd:cd05044    54 SNFKHPNILKLLGVCL--DNDPQYIILELMEGGDLLSYLRAARptaFTPPLLTLKDLLSICVDVAKGCVYLEDMHFVHRD 131
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  377 LSSYAVHIISPGEARLTnleymLESEDRGVQRDLTRVP---------LPTQlynWAAPEVILQKAATVKSDIYSFSMIMQ 447
Cdd:cd05044   132 LAARNCLVSSKDYRERV-----VKIGDFGLARDIYKNDyyrkegeglLPVR---WMAPESLVDGVFTTQSDVWAFGVLMW 203

                  ....
gi 319803120  448 EILT 451
Cdd:cd05044   204 EILT 207
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
266-460 6.28e-09

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: 58.39  E-value: 6.28e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLPTHPHCSRLRL---ADLLiaeqehsSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHeRR 342
Cdd:cd06627    24 TGEFVAIKQISLEKIPKSDLKSVmgeIDLL-------KKLNHPNIVKYIGSVKTKD--SLYIILEYVENGSLASIIK-KF 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  343 SQFPvlhmEVIVHLLL-QISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPLPTQLY- 420
Cdd:cd06627    94 GKFP----ESLVAVYIyQVLEGLAYLHEQGVIHRDIKGANILTTKDGLVKLA---------DFGVATKLNEVEKDENSVv 160
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|...
gi 319803120  421 ---NWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd06627   161 gtpYWMAPEVIEMSGVTTASDIWSVGCTVIELLTGNPPYYDLQ 203
STKc_PSKH1 cd14087
Catalytic domain of the Protein Serine/Threonine kinase H1; STKs catalyze the transfer of the ...
300-473 8.75e-09

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: 58.31  E-value: 8.75e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHER-----RSQFPVLHMevivhlllqISDALRYLHFQGFIH 374
Cdd:cd14087    52 RRVRHTNIIQLIEVFETKE--RVYMVMELATGGELFDRIIAKgsfteRDATRVLQM---------VLDGVKYLHGLGITH 120
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  375 RSLSSYAVHIISPG-EARLTNLEYMLESEDRGVQRDLTRVPLPTQLYnwAAPEVILQKAATVKSDIYSFSMIMQEILTDD 453
Cdd:cd14087   121 RDLKPENLLYYHPGpDSKIMITDFGLASTRKKGPNCLMKTTCGTPEY--IAPEILLRKPYTQSVDMWAVGVIAYILLSGT 198
                         170       180
                  ....*....|....*....|
gi 319803120  454 IPWKGLDGSVVKKAVVSGNY 473
Cdd:cd14087   199 MPFDDDNRTRLYRQILRAKY 218
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
304-499 9.73e-09

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: 58.09  E-value: 9.73e-09
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  304 HPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQfpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVH 383
Cdd:cd05085    52 HPNIVKLIGVCTQR--QPIYIVMELVPGGDFLSFLRKKKDE---LKTKQLVKFSLDAAAGMAYLESKNCIHRDLAARNCL 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  384 IISPGEARLTNLEyMLESEDRGV--QRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDI-PWKGLD 460
Cdd:cd05085   127 VGENNALKISDFG-MSRQEDDGVysSSGLKQIPI-----KWTAPEALNYGRYSSESDVWSFGILLWETFSLGVcPYPGMT 200
                         170       180       190
                  ....*....|....*....|....*....|....*....
gi 319803120  461 GSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05085   201 NQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNPENR 239
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
265-488 1.03e-08

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: 58.16  E-value: 1.03e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGS-RVTVKELNLPTHPhcsrlrlADLLIAEQEHSSKLRHPYLLQLMAVCLSqdlEKTRLVYERITIGTLFSVLHERRS 343
Cdd:cd05071    30 WNGTtRVAIKTLKPGTMS-------PEAFLQEAQVMKKLRHEKLVQLYAVVSE---EPIYIVTEYMSKGSLLDFLKGEMG 99
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 QFpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRG-VQRDLTRVPLptqlyNW 422
Cdd:cd05071   100 KY--LRLPQLVDMAAQIASGMAYVERMNYVHRDLRAANILVGENLVCKVADFGLARLIEDNEyTARQGAKFPI-----KW 172
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  423 AAPEVILQKAATVKSDIYSFSMIMQEILTDD-IPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIV 488
Cdd:cd05071   173 TAPEAALYGRFTIKSDVWSFGILLTELTTKGrVPYPGMVNREVLDQVERGYRMPCPPECPESLHDLM 239
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
292-451 1.08e-08

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: 58.44  E-value: 1.08e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKLRHPYLLQLMAVClSQDlEKTRLVYERITIGTLFSVLHERRSQFP--------------------VLHME 351
Cdd:cd05045    50 LLSEFNLLKQVNHPHVIKLYGAC-SQD-GPLLLIVEYAKYGSLRSFLRESRKVGPsylgsdgnrnssyldnpderALTMG 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  352 VIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqlyNWAAPEVIL 429
Cdd:cd05045   128 DLISFAWQISRGMQYLAEMKLVHRDLAARNVLVAEGRKMKISDfgLSRDVYEEDSYVKRSKGRIPV-----KWMAIESLF 202
                         170       180
                  ....*....|....*....|..
gi 319803120  430 QKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05045   203 DHIYTTQSDVWSFGVLLWEIVT 224
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
261-466 1.51e-08

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: 57.42  E-value: 1.51e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  261 TNLVWNGSRVTVKELNLPTHPHCSRLRLaDLLIAEQEhsskLRH----PYLLQLMavclsqDLEKTRLVYERITIGTLFS 336
Cdd:cd14043    17 TGVAYEGDWVWLKKFPGGSHTELRPSTK-NVFSKLRE----LRHenvnLFLGLFV------DCGILAIVSEHCSRGSLED 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  337 VLherRSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEY--MLESedrgvQRDLTRVP 414
Cdd:cd14043    86 LL---RNDDMKLDWMFKSSLLLDLIKGMRYLHHRGIVHGRLKSRNCVVDGRFVLKITDYGYneILEA-----QNLPLPEP 157
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 319803120  415 LPTQLYnWAAPEVI----LQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGS---VVKK 466
Cdd:cd14043   158 APEELL-WTAPELLrdprLERRGTFPGDVFSFAIIMQEVIVRGAPYCMLGLSpeeIIEK 215
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
301-512 1.61e-08

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: 57.43  E-value: 1.61e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVClsqdlekTR-----LVYERITIGTLFSVLHER-RSQFPVLhmeVIVHLLLQISDALRYLHFQGFIH 374
Cdd:cd05052    58 EIKHPNLVQLLGVC-------TReppfyIITEFMPYGNLLDYLRECnREELNAV---VLLYMATQIASAMEYLEKKNFIH 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  375 RSLSS--------YAVHIISPGEARLTnleymleSEDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIM 446
Cdd:cd05052   128 RDLAArnclvgenHLVKVADFGLSRLM-------TGDTYTAHAGAKFPI-----KWTAPESLAYNKFSIKSDVWAFGVLL 195
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  447 QEILTDDI-PWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDRTmNLQDIRYILKN 512
Cdd:cd05052   196 WEIATYGMsPYPGIDLSQVYELLEKGYRMERPEGCPPKVYELMRACWQWNPSDRP-SFAEIHQALET 261
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
302-525 2.18e-08

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: 57.27  E-value: 2.18e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  302 LRHPYLLQLMAVCLSQDLEktrLVYERITIGTLFSVLHERRSQfpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYA 381
Cdd:cd05111    66 LDHAYIVRLLGICPGASLQ---LVTQLLPLGSLLDHVRQHRGS---LGPQLLLNWCVQIAKGMYYLEEHRMVHRNLAARN 139
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  382 VHIISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDI-PWKG 458
Cdd:cd05111   140 VLLKSPSQVQVADfgVADLLYPDDKKYFYSEAKTPI-----KWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAePYAG 214
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  459 LDGSVVKkavvsgNYLEADVRLPKPYydIVKSGIHVKQKDRTMNLQDIRYILKNDLKDFTGAQRTQP 525
Cdd:cd05111   215 MRLAEVP------DLLEKGERLAQPQ--ICTIDVYMVMVKCWMIDENIRPTFKELANEFTRMARDPP 273
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
304-499 2.57e-08

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: 56.80  E-value: 2.57e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  304 HPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFPVLHMeviVHLLLQISDALRYLHFQGFIHRSLSSYAVh 383
Cdd:cd05066    64 HPNIIHLEGVVTRS--KPVMIVTEYMENGSLDAFLRKHDGQFTVIQL---VGMLRGIASGMKYLSDMGYVHRDLAARNI- 137
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  384 iispgearLTNLEYMLESEDRGVQRDLTRVP----------LPTQlynWAAPEVILQKAATVKSDIYSFSMIMQEILT-D 452
Cdd:cd05066   138 --------LVNSNLVCKVSDFGLSRVLEDDPeaayttrggkIPIR---WTAPEAIAYRKFTSASDVWSYGIVMWEVMSyG 206
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*..
gi 319803120  453 DIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVksgIHVKQKDR 499
Cdd:cd05066   207 ERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQLM---LDCWQKDR 250
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
277-458 2.85e-08

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: 56.69  E-value: 2.85e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  277 LPTHPHCSRLRLAdlLIAEQEHSSKLRHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLHerrSQFPVLHMEVIVHL 356
Cdd:cd13978    26 LHSSPNCIEERKA--LLKEAEKMERARHSYVLPLLGVC--VERRSLGLVMEYMENGSLKSLLE---REIQDVPWSLRFRI 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  357 LLQISDALRYLH--FQGFIHRSL--------SSYAVHIISPGEARLtnleYMLESedrGVQRDLTRVPLPTQLYnWAAPE 426
Cdd:cd13978    99 IHEIALGMNFLHnmDPPLLHHDLkpenilldNHFHVKISDFGLSKL----GMKSI---SANRRRGTENLGGTPI-YMAPE 170
                         170       180       190
                  ....*....|....*....|....*....|....
gi 319803120  427 VI--LQKAATVKSDIYSFSMIMQEILTDDIPWKG 458
Cdd:cd13978   171 AFddFNKKPTSKSDVYSFAIVIWAVLTRKEPFEN 204
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
276-458 3.01e-08

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: 56.85  E-value: 3.01e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  276 NLPTHPHCSRLRLADLL----IAEQEHS--SKLRHPYLLQLMAVCLsqdlEKTRLVYERITIGTLFSVL-HERRSQFPVL 348
Cdd:cd14000    35 NVPADTMLRHLRATDAMknfrLLRQELTvlSHLHHPSIVYLLGIGI----HPLMLVLELAPLGSLDHLLqQDSRSFASLG 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  349 HMeVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYmlesEDRGVQRDLTRVPLPTQ--LYNWAAPE 426
Cdd:cd14000   111 RT-LQQRIALQVADGLRYLHSAMIIYRDLKSHNVLVWTLYPNSAIIIKI----ADYGISRQCCRMGAKGSegTPGFRAPE 185
                         170       180       190
                  ....*....|....*....|....*....|...
gi 319803120  427 VILQKAA-TVKSDIYSFSMIMQEILTDDIPWKG 458
Cdd:cd14000   186 IARGNVIyNEKVDVFSFGMLLYEILSGGAPMVG 218
STKc_HAL4_like cd13994
Catalytic domain of Fungal Halotolerance protein 4-like Serine/Threonine kinases; STKs ...
267-484 3.37e-08

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: 56.55  E-value: 3.37e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNLPTHPHcSRLRLADLLIAEQEHSSKLRHPYLLQlmAVCLSQDLEKTR-LVYERITIGTLFSVLHERRSqf 345
Cdd:cd13994    20 GVLYAVKEYRRRDDES-KRKDYVKRLTSEYIISSKLHHPNIVK--VLDLCQDLHGKWcLVMEYCPGGDLFTLIEKADS-- 94
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 pVLHMEVIVhLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEymlESEDRGVQRDLTrVPLPTQLYN---W 422
Cdd:cd13994    95 -LSLEEKDC-FFKQILRGVAYLHSHGIAHRDLKPENILLDEDGVLKLTDFG---TAEVFGMPAEKE-SPMSAGLCGsepY 168
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 319803120  423 AAPEVILQKAATVKS-DIYSFSMIMQEILTDDIPWK--GLDGSVVKKAVVSGNYLEADVRLPKPY 484
Cdd:cd13994   169 MAPEVFTSGSYDGRAvDVWSCGIVLFALFTGRFPWRsaKKSDSAYKAYEKSGDFTNGPYEPIENL 233
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
265-499 3.96e-08

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: 56.25  E-value: 3.96e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGSrVTVKELNL--PThphcsrlrlADLLIA---EQEHSSKLRHPYLLQLMAVCLSQDLEktrLVYERITIGTLFSVLH 339
Cdd:cd14062    14 WHGD-VAVKKLNVtdPT---------PSQLQAfknEVAVLRKTRHVNILLFMGYMTKPQLA---IVTQWCEGSSLYKHLH 80
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  340 ERRSQFpvlHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTR------V 413
Cdd:cd14062    81 VLETKF---EMLQLIDIARQTAQGMDYLHAKNIIHRDLKSNNIFLHEDLTVKIG---------DFGLATVKTRwsgsqqF 148
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  414 PLPTQLYNWAAPEVILQKAA---TVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNYLEADVRL-----PKPYY 485
Cdd:cd14062   149 EQPTGSILWMAPEVIRMQDEnpySFQSDVYAFGIVLYELLTGQLPYSHINNRDQILFMVGRGYLRPDLSKvrsdtPKALR 228
                         250
                  ....*....|....
gi 319803120  486 DIVKSGIHVKQKDR 499
Cdd:cd14062   229 RLMEDCIKFQRDER 242
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
267-506 4.40e-08

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: 56.24  E-value: 4.40e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNlpthPHCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLSQDLEKTRLVYERITIGTLFSVLHERRSQfp 346
Cdd:cd05038    33 GEQVAVKSLQ----PSGEEQHMSDFK-REIEILRTLDHEYIVKYKGVCESPGRRSLRLIMEYLPSGSLRDYLQRHRDQ-- 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 vLHMEVIVHLLLQISDALRYLHFQGFIHRSL--------SSYAVHIISPGEARLTNL--EYMLESEDRgvqrdltrvPLP 416
Cdd:cd05038   106 -IDLKRLLLFASQICKGMEYLGSQRYIHRDLaarnilveSEDLVKISDFGLAKVLPEdkEYYYVKEPG---------ESP 175
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  417 TQlynWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSG--------NYLEADVRLPKP---- 483
Cdd:cd05038   176 IF---WYAPECLRESRFSSASDVWSFGVTLYELFTyGDPSQSPPALFLRMIGIAQGqmivtrllELLKSGERLPRPpscp 252
                         250       260
                  ....*....|....*....|....*..
gi 319803120  484 --YYDIVKSGIHVKQKDRTM--NLQDI 506
Cdd:cd05038   253 deVYDLMKECWEYEPQDRPSfsDLILI 279
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
295-451 4.67e-08

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: 56.23  E-value: 4.67e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTL--FSVLHERRSQFPV----------LHMEVIVHLLLQISD 362
Cdd:cd05048    58 EAELMSDLQHPNIVCLLGVCTKE--QPQCMLFEYMAHGDLheFLVRHSPHSDVGVssdddgtassLDQSDFLHIAIQIAA 135
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  363 ALRYLHFQGFIHRSLSSYAVHIispGEARLTNLEymleseDRGVQRD---------LTRVPLPTQlynWAAPEVILQKAA 433
Cdd:cd05048   136 GMEYLSSHHYVHRDLAARNCLV---GDGLTVKIS------DFGLSRDiyssdyyrvQSKSLLPVR---WMPPEAILYGKF 203
                         170
                  ....*....|....*...
gi 319803120  434 TVKSDIYSFSMIMQEILT 451
Cdd:cd05048   204 TTESDVWSFGVVLWEIFS 221
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
269-490 4.91e-08

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: 56.10  E-value: 4.91e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  269 RVTVKELNLPTHPHcsrlRLADLLIAEQEHSSKLRHPYLLQLMAVCL---SQDLEKTRLVYERITIGTLFS-VLHERRSQ 344
Cdd:cd14204    37 KVAVKTMKLDNFSQ----REIEEFLSEAACMKDFNHPNVIRLLGVCLevgSQRIPKPMVILPFMKYGDLHSfLLRSRLGS 112
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  345 FPV-LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqlyN 421
Cdd:cd14204   113 GPQhVPLQTLLKFMIDIALGMEYLSSRNFLHRDLAARNCMLRDDMTVCVADfgLSKKIYSGDYYRQGRIAKMPV-----K 187
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  422 WAAPEVILQKAATVKSDIYSFSMIMQEILTDDI-PWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKS 490
Cdd:cd14204   188 WIAVESLADRVYTVKSDVWAFGVTMWEIATRGMtPYPGVQNHEIYDYLLHGHRLKQPEDCLDELYDIMYS 257
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
267-451 6.38e-08

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: 55.79  E-value: 6.38e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNLPTHPHcsrlrLADLLiAEQEHSSKLRHPYLLQLMAVCLSQDLEKTRLVYERITIGTLFSVLHERRSQFP 346
Cdd:cd14205    33 GEVVAVKKLQHSTEEH-----LRDFE-REIEILKSLQHDNIVKYKGVCYSAGRRNLRLIMEYLPYGSLRDYLQKHKERID 106
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 vlHMEVIVHLLlQISDALRYLHFQGFIHRSLSSYAVhiispgearltnleyMLESEDRGVQRD--LTRV-PLPTQLYN-- 421
Cdd:cd14205   107 --HIKLLQYTS-QICKGMEYLGTKRYIHRDLATRNI---------------LVENENRVKIGDfgLTKVlPQDKEYYKvk 168
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 319803120  422 --------WAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd14205   169 epgespifWYAPESLTESKFSVASDVWSFGVVLYELFT 206
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
269-499 7.82e-08

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: 55.62  E-value: 7.82e-08
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  269 RVTVKELNLPThphCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLS----QDLEKTRLVYERITIGTLFS-VLHERRS 343
Cdd:cd05035    29 KVAVKTMKVDI---HTYSEIEEFL-SEAACMKDFDHPNVMRLIGVCFTasdlNKPPSPMVILPFMKHGDLHSyLLYSRLG 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 QFPV-LHMEVIVHLLLQISDALRYLHFQGFIHRSLSS--------YAVHIISPGEARltnleyMLESEDRGVQRDLTRVP 414
Cdd:cd05035   105 GLPEkLPLQTLLKFMVDIAKGMEYLSNRNFIHRDLAArncmldenMTVCVADFGLSR------KIYSGDYYRQGRISKMP 178
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  415 LptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIH 493
Cdd:cd05035   179 V-----KWIALESLADNVYTSKSDVWSFGVTMWEIATrGQTPYPGVENHEIYDYLRNGNRLKQPEDCLDEVYFLMYFCWT 253

                  ....*.
gi 319803120  494 VKQKDR 499
Cdd:cd05035   254 VDPKDR 259
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
300-450 1.14e-07

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: 55.33  E-value: 1.14e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERR---------------SQFPVLHMEVIVHLLLQISDAL 364
Cdd:cd05096    74 SRLKDPNIIRLLGVCVDED--PLCMITEYMENGDLNQFLSSHHlddkeengndavppaHCLPAISYSSLLHVALQIASGM 151
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  365 RYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDL---------TRVPLPTQlynWAAPEVILQKAATV 435
Cdd:cd05096   152 KYLSSLNFVHRDLATRNC---------LVGENLTIKIADFGMSRNLyagdyyriqGRAVLPIR---WMAWECILMGKFTT 219
                         170
                  ....*....|....*
gi 319803120  436 KSDIYSFSMIMQEIL 450
Cdd:cd05096   220 ASDVWAFGVTLWEIL 234
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
324-488 1.19e-07

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: 54.98  E-value: 1.19e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  324 LVYERITIGTLFSVLHERRSQFPVLHMeviVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLES 401
Cdd:cd05063    83 IITEYMENGALDKYLRDHDGEFSSYQL---VGMLRGIAAGMKYLSDMNYVHRDLAARNILVNSNLECKVSDfgLSRVLED 159
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  402 EDRGVQRDLT-RVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVR 479
Cdd:cd05063   160 DPEGTYTTSGgKIPI-----RWTAPEAIAYRKFTSASDVWSFGIVMWEVMSfGERPYWDMSNHEVMKAINDGFRLPAPMD 234

                  ....*....
gi 319803120  480 LPKPYYDIV 488
Cdd:cd05063   235 CPSAVYQLM 243
PHA02875 PHA02875
ankyrin repeat protein; Provisional
23-133 1.29e-07

ankyrin repeat protein; Provisional


Pssm-ID: 165206 [Multi-domain]  Cd Length: 413  Bit Score: 55.77  E-value: 1.29e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   23 LEAQLHEYVKQGNYVKVKKILKKGIYVDAV-NSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAAFSGN 101
Cdd:PHA02875   68 IESELHDAVEEGDVKAVEELLDLGKFADDVfYKDGMTPLHLATILKKLDIMKLLIARGADPDIPNTDKFSPLHLAVMMGD 147
                          90       100       110
                  ....*....|....*....|....*....|..
gi 319803120  102 QWILSKLLDAGGDLRLHDERGQNPKTWALTAG 133
Cdd:PHA02875  148 IKGIELLIDHKACLDIEDCCGCTPLIIAMAKG 179
PHA03100 PHA03100
ankyrin repeat protein; Provisional
27-114 1.48e-07

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 55.83  E-value: 1.48e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   27 LHEYVKqGNYVK---VKKILKKGIYVDAVNSL----------------GQTALFVAALLGLRKFVDVLVDYGSDPNHRCF 87
Cdd:PHA03100  145 LHLYLE-SNKIDlkiLKLLIDKGVDINAKNRVnyllsygvpinikdvyGFTPLHYAVYNNNPEFVKYLLDLGANPNLVNK 223
                          90       100
                  ....*....|....*....|....*..
gi 319803120   88 DGSTPVHAAAFSGNQWILSKLLDAGGD 114
Cdd:PHA03100  224 YGDTPLHIAILNNNKEIFKLLLNNGPS 250
STKc_LIMK cd14154
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase; STKs catalyze the transfer ...
302-450 1.53e-07

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: 54.44  E-value: 1.53e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  302 LRHPYLLQLMAVcLSQDlEKTRLVYERITIGTLFSVLHERRSQFPVLHMeviVHLLLQISDALRYLHFQGFIHRSLSSY- 380
Cdd:cd14154    47 LDHPNVLKFIGV-LYKD-KKLNLITEYIPGGTLKDVLKDMARPLPWAQR---VRFAKDIASGMAYLHSMNIIHRDLNSHn 121
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  381 -------AVHIISPGEARLTNLEYM-LESEDRGVQRDLTRVPLPTQLYN------WAAPEVILQKAATVKSDIYSFSMIM 446
Cdd:cd14154   122 clvredkTVVVADFGLARLIVEERLpSGNMSPSETLRHLKSPDRKKRYTvvgnpyWMAPEMLNGRSYDEKVDIFSFGIVL 201

                  ....
gi 319803120  447 QEIL 450
Cdd:cd14154   202 CEII 205
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
295-499 1.56e-07

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: 54.39  E-value: 1.56e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVL-----HERRSQFPVLHMEVIVHLLLQISDALRYLHF 369
Cdd:cd05046    58 ELDMFRKLSHKNVVRLLGLC--REAEPHYMILEYTDLGDLKQFLratksKDEKLKPPPLSTKQKVALCTQIALGMDHLSN 135
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  370 QGFIHRSL--------SSYAVHIISPGEARLT-NLEYMLESEdrgvqrdlTRVPLptqlyNWAAPEVILQKAATVKSDIY 440
Cdd:cd05046   136 ARFVHRDLaarnclvsSQREVKVSLLSLSKDVyNSEYYKLRN--------ALIPL-----RWLAPEAVQEDDFSTKSDVW 202
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|.
gi 319803120  441 SFSMIMQEILT-DDIPWKGL-DGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05046   203 SFGVLMWEVFTqGELPFYGLsDEEVLNRLQAGKLELPVPEGCPSRLYKLMTRCWAVNPKDR 263
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
304-512 2.02e-07

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: 54.15  E-value: 2.02e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  304 HPYLLQLMAVCLsQDLEKTRLVYERITI-----GTLFS-VLHERRSQFPV-LHMEVIVHLLLQISDALRYLHFQGFIHRS 376
Cdd:cd05074    70 HPNVIKLIGVSL-RSRAKGRLPIPMVILpfmkhGDLHTfLLMSRIGEEPFtLPLQTLVRFMIDIASGMEYLSSKNFIHRD 148
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  377 LSSYAVHIISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DD 453
Cdd:cd05074   149 LAARNCMLNENMTVCVADfgLSKKIYSGDYYRQGCASKLPV-----KWLALESLADNVYTTHSDVWAFGVTMWEIMTrGQ 223
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*....
gi 319803120  454 IPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDRTmNLQDIRYILKN 512
Cdd:cd05074   224 TPYAGVENSEIYNYLIKGNRLKQPPDCLEDVYELMCQCWSPEPKCRP-SFQHLRDQLEL 281
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
292-483 2.28e-07

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: 54.11  E-value: 2.28e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKLRHPYLLQLMAVclsqdLEKTR---LVYERITIGTLFSVLHERRSQFPVLHMeviVHLLLQISDALRYLH 368
Cdd:cd05065    52 FLSEASIMGQFDHPNIIHLEGV-----VTKSRpvmIITEFMENGALDSFLRQNDGQFTVIQL---VGMLRGIAAGMKYLS 123
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  369 FQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQR---DLTRVPLPTQLYN------WAAPEVILQKAATVKSDI 439
Cdd:cd05065   124 EMNYVHRDLAARNI---------LVNSNLVCKVSDFGLSRfleDDTSDPTYTSSLGgkipirWTAPEAIAYRKFTSASDV 194
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 319803120  440 YSFSMIMQEILT-DDIP-WKGLDGSVVkkavvsgNYLEADVRLPKP 483
Cdd:cd05065   195 WSYGIVMWEVMSyGERPyWDMSNQDVI-------NAIEQDYRLPPP 233
STKc_RIP2 cd14026
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 2; STKs catalyze ...
270-457 3.17e-07

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: 53.77  E-value: 3.17e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  270 VTVKELNLPThPHCSRLRlaDLLIAEQEHSSKLRHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLHeRRSQFPVLH 349
Cdd:cd14026    25 VAIKCLKLDS-PVGDSER--NCLLKEAEILHKARFSYILPILGIC--NEPEFLGIVTEYMTNGSLNELLH-EKDIYPDVA 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  350 MEVIVHLLLQISDALRYLHFQG--FIHRSLSS--------YAVHIISPGEARLTNLEYMLESEDRGVQRDLTRVPLPTQL 419
Cdd:cd14026    99 WPLRLRILYEIALGVNYLHNMSppLLHHDLKTqnilldgeFHVKIADFGLSKWRQLSISQSRSSKSAPEGGTIIYMPPEE 178
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 319803120  420 YNWAApevilQKAATVKSDIYSFSMIMQEILTDDIPWK 457
Cdd:cd14026   179 YEPSQ-----KRRASVKHDIYSYAIIMWEVLSRKIPFE 211
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
271-455 3.66e-07

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: 53.27  E-value: 3.66e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  271 TVKELNLPTHPHCSRLRLADLLIAEQEHS--------SKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERR 342
Cdd:cd14664     8 TVYKGVMPNGTLVAVKRLKGEGTQGGDHGfqaeiqtlGMIRHRNIVRLRGYCSNPT--TNLLVYEYMPNGSLGELLHSRP 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  343 SQFPVLHMEVIVHLLLQISDALRYLHFQG---FIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQRDLTRVplpt 417
Cdd:cd14664    86 ESQPPLDWETRQRIALGSARGLAYLHHDCsplIIHRDVKSNNILLDEEFEAHVADfgLAKLMDDKDSHVMSSVAGS---- 161
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 319803120  418 qlYNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIP 455
Cdd:cd14664   162 --YGYIAPEYAYTGKVSEKSDVYSYGVVLLELITGKRP 197
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
288-451 3.67e-07

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: 53.82  E-value: 3.67e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  288 LADLlIAEQEHSSKL-RHPYLLQLMAVClSQDLEKTRLVyERITIGTLFSVLHERRSQFPVLHMEV------------IV 354
Cdd:cd05099    61 LADL-ISEMELMKLIgKHKNIINLLGVC-TQEGPLYVIV-EYAAKGNLREFLRARRPPGPDYTFDItkvpeeqlsfkdLV 137
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  355 HLLLQISDALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDLTRVPLPTQLYN------WAAPEVI 428
Cdd:cd05099   138 SCAYQVARGMEYLESRRCIHRDLAARNV---------LVTEDNVMKIADFGLARGVHDIDYYKKTSNgrlpvkWMAPEAL 208
                         170       180
                  ....*....|....*....|...
gi 319803120  429 LQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05099   209 FDRVYTHQSDVWSFGILMWEIFT 231
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
268-451 3.77e-07

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: 53.58  E-value: 3.77e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  268 SRVTVKELNLPTHPHcsrlRLADLlIAEQEHSSKL-RHPYLLQLMAVClSQDlEKTRLVYERITIGTLFSVLHERRSQ-- 344
Cdd:cd05053    44 VTVAVKMLKDDATEK----DLSDL-VSEMEMMKMIgKHKNIINLLGAC-TQD-GPLYVVVEYASKGNLREFLRARRPPge 116
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  345 -----FPVLHMEV-----IVHLLLQISDALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDL---- 410
Cdd:cd05053   117 easpdDPRVPEEQltqkdLVSFAYQVARGMEYLASKKCIHRDLAARNV---------LVTEDNVMKIADFGLARDIhhid 187
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*.
gi 319803120  411 -----TRVPLPtqlYNWAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05053   188 yyrktTNGRLP---VKWMAPEALFDRVYTHQSDVWSFGVLLWEIFT 230
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
295-473 5.86e-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: 52.99  E-value: 5.86e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMavCLSQDLEKTRLVYERITIGTLFSVLHERRSqfpvLHMEVIVHLLLQISDALRYLHFQGFIH 374
Cdd:cd05581    51 EKEVLSRLAHPGIVKLY--YTFQDESKLYFVLEYAPNGDLLEYIRKYGS----LDEKCTRFYTAEIVLALEYLHSKGIIH 124
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  375 RSL--------SSYAVHIISPGEARLTNLEYMLESED------RGVQRDLTRVPLPTQLYnwAAPEVILQKAATVKSDIY 440
Cdd:cd05581   125 RDLkpenilldEDMHIKITDFGTAKVLGPDSSPESTKgdadsqIAYNQARAASFVGTAEY--VSPELLNEKPAGKSSDLW 202
                         170       180       190
                  ....*....|....*....|....*....|...
gi 319803120  441 SFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNY 473
Cdd:cd05581   203 ALGCIIYQMLTGKPPFRGSNEYLTFQKIVKLEY 235
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
303-499 6.77e-07

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: 52.45  E-value: 6.77e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  303 RHPYLLQLMAVCLsqDLEKTRLVYERITIGTLFSVLherRSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAV 382
Cdd:cd05041    51 DHPNIVKLIGVCV--QKQPIMIVMELVPGGSLLTFL---RKKGARLTVKQLLQMCLDAAAGMEYLESKNCIHRDLAARNC 125
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  383 HIISPGEARLTNLEyMLESEDRG---VQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKG 458
Cdd:cd05041   126 LVGENNVLKISDFG-MSREEEDGeytVSDGLKQIPI-----KWTAPEALNYGRYTSESDVWSFGILLWEIFSlGATPYPG 199
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 319803120  459 LDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05041   200 MSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYDPENR 240
STKc_IKK_beta cd14038
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
348-451 7.62e-07

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK) beta; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. IKKbeta is involved in the classical pathway of regulating Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. The classical pathway regulates the majority of genes activated by NF-kB including those encoding cytokines, chemokines, leukocyte adhesion molecules, and anti-apoptotic factors. It involves NEMO (NF-kB Essential MOdulator)- and IKKbeta-dependent phosphorylation and degradation of the Inhibitor of NF-kB (IkB), which liberates NF-kB dimers (typified by the p50-p65 heterodimer) from an inactive IkB/dimeric NF-kB complex, enabling them to migrate to the nucleus where they regulate gene transcription. The IKKbeta 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: 270940 [Multi-domain]  Cd Length: 290  Bit Score: 52.66  E-value: 7.62e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVhIISPGEARLTNleymlESEDRGVQRDLTRVPLPTQL---YNWAA 424
Cdd:cd14038    98 LREGAILTLLSDISSALRYLHENRIIHRDLKPENI-VLQQGEQRLIH-----KIIDLGYAKELDQGSLCTSFvgtLQYLA 171
                          90       100
                  ....*....|....*....|....*..
gi 319803120  425 PEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd14038   172 PELLEQQKYTVTVDYWSFGTLAFECIT 198
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
324-490 7.70e-07

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: 52.87  E-value: 7.70e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  324 LVYERITIGTLFSVLHERRSQFpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseD 403
Cdd:cd05055   116 VITEYCCYGDLLNFLRRKRESF--LTLEDLLSFSYQVAKGMAFLASKNCIHRDLAARNVLLTHGKIVKIC---------D 184
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  404 RGVQRDL-----------TRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDI-PWKGLD-GSVVKKAVVS 470
Cdd:cd05055   185 FGLARDImndsnyvvkgnARLPV-----KWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSnPYPGMPvDSKFYKLIKE 259
                         170       180
                  ....*....|....*....|
gi 319803120  471 GNYLEADVRLPKPYYDIVKS 490
Cdd:cd05055   260 GYRMAQPEHAPAEIYDIMKT 279
STKc_YSK4 cd06631
Catalytic domain of the Serine/Threonine Kinase, Yeast Sps1/Ste20-related Kinase 4; STKs ...
259-460 8.42e-07

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: 52.05  E-value: 8.42e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  259 VMTNLVWNGSRVTVKELNLPThphcsrlrlADLLIAEQEHS---------SKLRHPYLLQLMAVCLSQDLekTRLVYERI 329
Cdd:cd06631    17 VYCGLTSTGQLIAVKQVELDT---------SDKEKAEKEYEklqeevdllKTLKHVNIVGYLGTCLEDNV--VSIFMEFV 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  330 TIGTLFSVLherrSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN------LEYMLESed 403
Cdd:cd06631    86 PGGSIASIL----ARFGALEEPVFCRYTKQILEGVAYLHNNNVIHRDIKGNNIMLMPNGVIKLIDfgcakrLCINLSS-- 159
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  404 rGVQRDLTRVPLPTQLynWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd06631   160 -GSQSQLLKSMRGTPY--WMAPEVINETGHGRKSDIWSIGCTVFEMATGKPPWADMN 213
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
300-510 9.37e-07

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: 52.30  E-value: 9.37e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVL--HERRSQFPVLHMEVIV------HLLLQISDALRYLHFQG 371
Cdd:cd05095    74 SRLKDPNIIRLLAVCITDD--PLCMITEYMENGDLNQFLsrQQPEGQLALPSNALTVsysdlrFMAAQIASGMKYLSSLN 151
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 FIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDL---------TRVPLPTQLYNWaapEVILQKAATVKSDIYSF 442
Cdd:cd05095   152 FVHRDLATRNC---------LVGKNYTIKIADFGMSRNLysgdyyriqGRAVLPIRWMSW---ESILLGKFTTASDVWAF 219
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  443 SMIMQEILT--DDIPWKGL-DGSVVKKavvSGNYLEADVR---LPKP------YYDIVKSGIHVKQKDRTmNLQDIRYIL 510
Cdd:cd05095   220 GVTLWETLTfcREQPYSQLsDEQVIEN---TGEFFRDQGRqtyLPQPalcpdsVYKLMLSCWRRDTKDRP-SFQEIHTLL 295
STKc_LRRK2 cd14068
Catalytic domain of the Serine/Threonine Kinase, Leucine-Rich Repeat Kinase 2; STKs catalyze ...
264-451 9.74e-07

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: 51.88  E-value: 9.74e-07
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNGSRVTVKELNLPTHphcSRLRLADLLIAeqehsSKLRHPYLLQLMAVCLSQDLektrLVYERITIGTLFSVLHERRS 343
Cdd:cd14068    14 VYRGEDVAVKIFNKHTS---FRLLRQELVVL-----SHLHHPSLVALLAAGTAPRM----LVMELAPKGSLDALLQQDNA 81
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 QfpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISpgeaRLTNLEYMLESEDRGVQRDLTRVPLPTQLYN-- 421
Cdd:cd14068    82 S---LTRTLQHRIALHVADGLRYLHSAMIIYRDLKPHNVLLFT----LYPNCAIIAKIADYGIAQYCCRMGIKTSEGTpg 154
                         170       180       190
                  ....*....|....*....|....*....|.
gi 319803120  422 WAAPEVILQKAA-TVKSDIYSFSMIMQEILT 451
Cdd:cd14068   155 FRAPEVARGNVIyNQQADVYSFGLLLYDILT 185
STKc_PLK3 cd14189
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 3; STKs catalyze the ...
292-460 1.04e-06

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: 51.85  E-value: 1.04e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKLRHPYLLQLmavclSQDLEKTRLVYERITIGTLFSVLHERRSQFPVLHMEViVHLLLQISDALRYLHFQG 371
Cdd:cd14189    48 IVNEIELHRDLHHKHVVKF-----SHHFEDAENIYIFLELCSRKSLAHIWKARHTLLEPEV-RYYLKQIISGLKYLHLKG 121
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 FIHRSLSSYAVHIISPGEARLTN--LEYMLESEDrgvQRDLTRVPLPtqlyNWAAPEVILQKAATVKSDIYSFSMIMQEI 449
Cdd:cd14189   122 ILHRDLKLGNFFINENMELKVGDfgLAARLEPPE---QRKKTICGTP----NYLAPEVLLRQGHGPESDVWSLGCVMYTL 194
                         170
                  ....*....|.
gi 319803120  450 LTDDIPWKGLD 460
Cdd:cd14189   195 LCGNPPFETLD 205
STKc_CDK4 cd07863
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs ...
254-450 1.12e-06

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK4 partners with all three D-type cyclins (D1, D2, and D3) and is also regulated by INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein and plays a role in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the nucleus. CDK4 also shows kinase activity towards Smad3, a signal transducer of TGF-beta signaling which modulates transcription and plays a role in cell proliferation and apoptosis. CDK4 is inhibited by the p21 inhibitor and is specifically mutated in human melanoma. 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 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: 143368 [Multi-domain]  Cd Length: 288  Bit Score: 52.27  E-value: 1.12e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  254 SGPYMVMTNLvwngsRVTVKELNLPThphcSRLRLADLLiAEQEHsskLRHPYLLQLMAVCLS--QDLE-KTRLVYERIT 330
Cdd:cd07863    24 SGHFVALKSV-----RVQTNEDGLPL----STVREVALL-KRLEA---FDHPNIVRLMDVCATsrTDREtKVTLVFEHVD 90
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  331 iGTLFSVLHerRSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQR-- 408
Cdd:cd07863    91 -QDLRTYLD--KVPPPGLPAETIKDLMRQFLRGLDFLHANCIVHRDLKPENILVTSGGQVKLA---------DFGLARiy 158
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....
gi 319803120  409 --DLTRVPLPTQLYnWAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd07863   159 scQMALTPVVVTLW-YRAPEVLLQSTYATPVDMWSVGCIFAEMF 201
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
269-462 1.15e-06

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: 51.71  E-value: 1.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  269 RVTVKELNlPTHPHCSR--LRLADLLiaeqehsSKLRHPYLLQLMAVCLSQDlekTRLVYERITIGTLFSVLHERRSQFP 346
Cdd:cd05037    32 EVLLKVLD-SDHRDISEsfFETASLM-------SQISHKHLVKLYGVCVADE---NIMVQEYVRYGPLDKYLRRMGNNVP 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 VLHMEVIVHlllQISDALRYLHFQGFIHRSLSSYAVHIispgeARLTNLEYMLESE--DRGVQRDLTRVPLPTQLYNWAA 424
Cdd:cd05037   101 LSWKLQVAK---QLASALHYLEDKKLIHGNVRGRNILL-----AREGLDGYPPFIKlsDPGVPITVLSREERVDRIPWIA 172
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|.
gi 319803120  425 PEVI--LQKAATVKSDIYSFSMIMQEILTD-DIPWKGLDGS 462
Cdd:cd05037   173 PECLrnLQANLTIAADKWSFGTTLWEICSGgEEPLSALSSQ 213
STKc_PAK2 cd06655
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the ...
267-456 1.22e-06

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK2 plays a role in pro-apoptotic signaling. It is cleaved and activated by caspases leading to morphological changes during apoptosis. PAK2 is also activated in response to a variety of stresses including DNA damage, hyperosmolarity, serum starvation, and contact inhibition, and may play a role in coordinating the stress response. PAK2 also contributes to cancer cell invasion through a mechanism distinct from that of PAK1. It 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: 132986 [Multi-domain]  Cd Length: 296  Bit Score: 52.03  E-value: 1.22e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNLPTHPHcsrlrlADLLIAEQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHErrsqfP 346
Cdd:cd06655    44 GQEVAIKQINLQKQPK------KELIINEILVMKELKNPNIVNFLDSFLVGD--ELFVVMEYLAGGSLTDVVTE-----T 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 VLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDlTRVPLPTqlynWAAPE 426
Cdd:cd06655   111 CMDEAQIAAVCRECLQALEFLHANQVIHRDIKSDNVLLGMDGSVKLTDFGFCAQITPEQSKRS-TMVGTPY----WMAPE 185
                         170       180       190
                  ....*....|....*....|....*....|
gi 319803120  427 VILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06655   186 VVTRKAYGPKVDIWSLGIMAIEMVEGEPPY 215
ANKYR COG0666
Ankyrin repeat [Signal transduction mechanisms];
27-124 1.48e-06

Ankyrin repeat [Signal transduction mechanisms];


Pssm-ID: 440430 [Multi-domain]  Cd Length: 289  Bit Score: 51.88  E-value: 1.48e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   27 LHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAAFSGNQWILS 106
Cdd:COG0666   190 LHLAAENGHLEIVKLLLEAGADVNAKDNDGKTALDLAAENGNLEIVKLLLEAGADLNAKDKDGLTALLLAAAAGAALIVK 269
                          90
                  ....*....|....*...
gi 319803120  107 KLLDAGGDLRLHDERGQN 124
Cdd:COG0666   270 LLLLALLLLAAALLDLLT 287
STKc_AMPK-like cd14003
Catalytic domain of AMP-activated protein kinase-like Serine/Threonine Kinases; STKs catalyze ...
292-473 1.73e-06

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: 50.98  E-value: 1.73e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRsqfpVLHmEVIVHLLL-QISDALRYLHFQ 370
Cdd:cd14003    46 IKREIEIMKLLNHPNIIKLYEVIETEN--KIYLVMEYASGGELFDYIVNNG----RLS-EDEARRFFqQLISAVDYCHSN 118
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  371 GFIHRSL--------SSYAVHIISPGEARLTNLEYMLEsedrgvqrdlTRVPLPtqlyNWAAPEVIL-QKAATVKSDIYS 441
Cdd:cd14003   119 GIVHRDLklenilldKNGNLKIIDFGLSNEFRGGSLLK----------TFCGTP----AYAAPEVLLgRKYDGPKADVWS 184
                         170       180       190
                  ....*....|....*....|....*....|..
gi 319803120  442 FSMIMQEILTDDIPWKGLDGSVVKKAVVSGNY 473
Cdd:cd14003   185 LGVILYAMLTGYLPFDDDNDSKLFRKILKGKY 216
STKc_PAK_II cd06648
Catalytic domain of the Serine/Threonine Kinase, Group II p21-activated kinase; STKs catalyze ...
267-456 2.38e-06

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: 50.90  E-value: 2.38e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNLpTHPHCSRLRLADLLIAEQEHssklrHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRsqfp 346
Cdd:cd06648    32 GRQVAVKKMDL-RKQQRRELLFNEVVIMRDYQ-----HPNIVEMYSSYLVGD--ELWVVMEFLEGGALTDIVTHTR---- 99
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 vLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLE-SEDRGVQRDLTRVPLptqlynWAAP 425
Cdd:cd06648   100 -MNEEQIATVCRAVLKALSFLHSQGVIHRDIKSDSILLTSDGRVKLSDFGFCAQvSKEVPRRKSLVGTPY------WMAP 172
                         170       180       190
                  ....*....|....*....|....*....|.
gi 319803120  426 EVILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06648   173 EVISRLPYGTEVDIWSLGIMVIEMVDGEPPY 203
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
356-456 2.55e-06

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: 50.85  E-value: 2.55e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  356 LLLQISDALRYLHFQGFI-HRSLSSYAVHIISPGEARLTNL---EYMLESEDRgvqrDLTRVPLPTQLYnWAAPEVI--- 428
Cdd:cd13992   102 FIKDIVKGMNYLHSSSIGyHGRLKSSNCLVDSRWVVKLTDFglrNLLEEQTNH----QLDEDAQHKKLL-WTAPELLrgs 176
                          90       100
                  ....*....|....*....|....*....
gi 319803120  429 -LQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd13992   177 lLEVRGTQKGDVYSFAIILYEILFRSDPF 205
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
302-450 2.60e-06

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: 50.72  E-value: 2.60e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  302 LRHPYLLQLMAVcLSQDlEKTRLVYERITIGTLFSVLHERRSQFPVLHMeviVHLLLQISDALRYLHFQGFIHRSLSSY- 380
Cdd:cd14221    47 LEHPNVLKFIGV-LYKD-KRLNFITEYIKGGTLRGIIKSMDSHYPWSQR---VSFAKDIASGMAYLHSMNIIHRDLNSHn 121
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  381 -------AVHIISPGEARL-----TNLEYMLESEDRGVQRDLTRVPLPTqlynWAAPEVILQKAATVKSDIYSFSMIMQE 448
Cdd:cd14221   122 clvrenkSVVVADFGLARLmvdekTQPEGLRSLKKPDRKKRYTVVGNPY----WMAPEMINGRSYDEKVDVFSFGIVLCE 197

                  ..
gi 319803120  449 IL 450
Cdd:cd14221   198 II 199
STKc_Nek10 cd08528
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase ...
292-473 2.77e-06

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: 50.58  E-value: 2.77e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQehsskLRHPYLLQLMAVCLSQDleKTRLVYERI---TIGTLFSVLHERRSQFPvlhMEVIVHLLLQISDALRYLH 368
Cdd:cd08528    61 IIKEQ-----LRHPNIVRYYKTFLEND--RLYIVMELIegaPLGEHFSSLKEKNEHFT---EDRIWNIFVQMVLALRYLH 130
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  369 FQ-GFIHRSLSSYAVHIispGEA-RLTNLEYMLESEDRGVQRDLTRVpLPTQLYnwAAPEVILQKAATVKSDIYSFSMIM 446
Cdd:cd08528   131 KEkQIVHRDLKPNNIML---GEDdKVTITDFGLAKQKGPESSKMTSV-VGTILY--SCPEIVQNEPYGEKADIWALGCIL 204
                         170       180
                  ....*....|....*....|....*..
gi 319803120  447 QEILTDDIPWKGLDGSVVKKAVVSGNY 473
Cdd:cd08528   205 YQMCTLQPPFYSTNMLTLATKIVEAEY 231
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
282-451 3.15e-06

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: 50.53  E-value: 3.15e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  282 HCSRLRLADLLiaeQEhSSKLR---HPYLLQLMAVClSQDLEKTRLVYERITIGTLFSVLHERR---SQFP-VLHMEVIV 354
Cdd:cd05043    45 HASEIQVTMLL---QE-SSLLYglsHQNLLPILHVC-IEDGEKPMVLYPYMNWGNLKLFLQQCRlseANNPqALSTQQLV 119
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  355 HLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLtrvpLPTQlYN-----------WA 423
Cdd:cd05043   120 HMALQIACGMSYLHRRGVIHKDIAARNCVIDDELQVKIT---------DNALSRDL----FPMD-YHclgdnenrpikWM 185
                         170       180
                  ....*....|....*....|....*...
gi 319803120  424 APEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05043   186 SLESLVNKEYSSASDVWSFGVLLWELMT 213
PKc_LIMK_like_unk cd14156
Catalytic domain of an unknown subfamily of LIM domain kinase-like protein kinases; PKs ...
292-510 4.12e-06

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: 49.82  E-value: 4.12e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLheRRSQFPvLHMEVIVHLLLQISDALRYLHFQG 371
Cdd:cd14156    35 IVREISLLQKLSHPNIVRYLGICVKD--EKLHPILEYVSGGCLEELL--AREELP-LSWREKVELACDISRGMVYLHSKN 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 FIHRSLSSYAVHI-ISPG--EARLTnleymleseDRGVQRDLTRVPL--PTQLYN------WAAPEVILQKAATVKSDIY 440
Cdd:cd14156   110 IYHRDLNSKNCLIrVTPRgrEAVVT---------DFGLAREVGEMPAndPERKLSlvgsafWMAPEMLRGEPYDRKVDVF 180
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  441 SFSMIMQEILT------DDIPWK---GLDGSVVKKAVVSgnyleadvrLPKPYYDIVKSGIHVKQKDRTM------NLQD 505
Cdd:cd14156   181 SFGIVLCEILAripadpEVLPRTgdfGLDVQAFKEMVPG---------CPEPFLDLAASCCRMDAFKRPSfaelldELED 251

                  ....*
gi 319803120  506 IRYIL 510
Cdd:cd14156   252 IAETL 256
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
332-450 4.26e-06

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: 49.98  E-value: 4.26e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  332 GTLFSVLHERRSQFPVLHmEVIVHLLLQISDALRYLHFQGFIHRSL---------SSYAVHIISPGEAR----LTNLEYM 398
Cdd:cd13996    89 GTLRDWIDRRNSSSKNDR-KLALELFKQILKGVSYIHSKGIVHRDLkpsnifldnDDLQVKIGDFGLATsignQKRELNN 167
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|..
gi 319803120  399 LESEDRGVQRDLTRVpLPTQLYnwAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd13996   168 LNNNNNGNTSNNSVG-IGTPLY--ASPEQLDGENYNEKADIYSLGIILFEML 216
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
266-456 4.30e-06

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK6 may play a role in stress responses through its activation by the mitogen-activated protein kinase (MAPK) p38 and MAPK kinase 6 (MKK6) pathway. PAK6 is highly expressed in the brain. It is not required for viability, but together with PAK5, it is required for normal levels of locomotion and activity, and for learning and memory. Increased expression of PAK6 is found in primary and metastatic prostate cancer. PAK6 may play a role in the regulation of motility. PAK6 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 STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 270821 [Multi-domain]  Cd Length: 297  Bit Score: 50.37  E-value: 4.30e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLpthphcSRLRLADLLIAEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRsqf 345
Cdd:cd06659    45 SGRQVAVKMMDL------RKQQRRELLFNEVVIMRDYQHPNVVEMYKSYLVG--EELWVLMEYLQGGALTDIVSQTR--- 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 pvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLE-SEDRGVQRDLTRVPLptqlynWAA 424
Cdd:cd06659   114 --LNEEQIATVCEAVLQALAYLHSQGVIHRDIKSDSILLTLDGRVKLSDFGFCAQiSKDVPKRKSLVGTPY------WMA 185
                         170       180       190
                  ....*....|....*....|....*....|..
gi 319803120  425 PEVILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06659   186 PEVISRCPYGTEVDIWSLGIMVIEMVDGEPPY 217
Pkinase pfam00069
Protein kinase domain;
301-499 4.44e-06

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 49.55  E-value: 4.44e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   301 KLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRsqfpVLHMEVIVHLLLQISDALRYLHfqgfihrSLSSY 380
Cdd:pfam00069   54 KLNHPNIVRLYDAFEDKD--NLYLVLEYVEGGSLFDLLSEKG----AFSEREAKFIMKQILEGLESGS-------SLTTF 120
                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   381 AVhiispgearltnleymlesedrgvqrdlTRvplptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:pfam00069  121 VG----------------------------TP--------WYMAPEVLGGNPYGPKVDVWSLGCILYELLTGKPPFPGIN 164
                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 319803120   461 GSVVKKAVVSGNYLEADV--RLPKPYYDIVKSGIHVKQKDR 499
Cdd:pfam00069  165 GNEIYELIIDQPYAFPELpsNLSEEAKDLLKKLLKKDPSKR 205
STKc_16 cd13986
Catalytic domain of Serine/Threonine Kinase 16; STKs catalyze the transfer of the ...
295-499 4.87e-06

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: 49.99  E-value: 4.87e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAVCLSQDLEKTRLVY---ERITIGTLFSVLHERRSQFPVLHMEVIVHLLLQISDALRYLH--- 368
Cdd:cd13986    47 EIENYRLFNHPNILRLLDSQIVKEAGGKKEVYlllPYYKRGSLQDEIERRLVKGTFFPEDRILHIFLGICRGLKAMHepe 126
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  369 FQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDLTRvplptQLYNWA---------APEVILQKAATV---K 436
Cdd:cd13986   127 LVPYAHRDIKPGNVLLSEDDEPILMDLGSMNPARIEIEGRREAL-----ALQDWAaehctmpyrAPELFDVKSHCTideK 201
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319803120  437 SDIYSF-----SMIMQEILTDDIPWKGldGSvVKKAVVSGNYLEADvrlpKPYY-----DIVKSGIHVKQKDR 499
Cdd:cd13986   202 TDIWSLgctlyALMYGESPFERIFQKG--DS-LALAVLSGNYSFPD----NSRYseelhQLVKSMLVVNPAER 267
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
358-485 5.61e-06

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: 49.78  E-value: 5.61e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  358 LQISDALRYLHFQGFIHRSLS--------SYAVHIISPGEARltnleYMLESEDRGVQRDlTRVPLPTQlynWAAPEVIL 429
Cdd:cd05058   105 LQVAKGMEYLASKKFVHRDLAarncmldeSFTVKVADFGLAR-----DIYDKEYYSVHNH-TGAKLPVK---WMALESLQ 175
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  430 QKAATVKSDIYSFSMIMQEILTDDI-PWKGLDGSVVKkavvsgNYLEADVRLPKPYY 485
Cdd:cd05058   176 TQKFTTKSDVWSFGVLLWELMTRGApPYPDVDSFDIT------VYLLQGRRLLQPEY 226
STKc_PAK_I cd06647
Catalytic domain of the Serine/Threonine Kinase, Group I p21-activated kinase; STKs catalyze ...
264-456 6.42e-06

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: 49.54  E-value: 6.42e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNGSRVTVKELNLPTHPHcsrlrlADLLIAEQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHErrs 343
Cdd:cd06647    29 VATGQEVAIKQMNLQQQPK------KELIINEILVMRENKNPNIVNYLDSYLVGD--ELWVVMEYLAGGSLTDVVTE--- 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 qfPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDlTRVPLPTqlynWA 423
Cdd:cd06647    98 --TCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRS-TMVGTPY----WM 170
                         170       180       190
                  ....*....|....*....|....*....|...
gi 319803120  424 APEVILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06647   171 APEVVTRKAYGPKVDIWSLGIMAIEMVEGEPPY 203
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
288-499 6.61e-06

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: 50.01  E-value: 6.61e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  288 LADLlIAEQEHSSKL-RHPYLLQLMAVClSQDlEKTRLVYERITIGTLFSVLHERR----------SQFPVLHMEV--IV 354
Cdd:cd05101    73 LSDL-VSEMEMMKMIgKHKNIINLLGAC-TQD-GPLYVIVEYASKGNLREYLRARRppgmeysydiNRVPEEQMTFkdLV 149
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  355 HLLLQISDALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDLTRVPLPTQLYN------WAAPEVI 428
Cdd:cd05101   150 SCTYQLARGMEYLASQKCIHRDLAARNV---------LVTENNVMKIADFGLARDINNIDYYKKTTNgrlpvkWMAPEAL 220
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 319803120  429 LQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05101   221 FDRVYTHQSDVWSFGVLMWEIFTlGGSPYPGIPVEELFKLLKEGHRMDKPANCTNELYMMMRDCWHAVPSQR 292
Ank_2 pfam12796
Ankyrin repeats (3 copies);
60-143 7.80e-06

Ankyrin repeats (3 copies);


Pssm-ID: 463710 [Multi-domain]  Cd Length: 91  Bit Score: 45.88  E-value: 7.80e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    60 LFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAAFSGNQWILSKLLDaGGDLRLhDERGQNPKTWALTAGkerSTQ 139
Cdd:pfam12796    1 LHLAAKNGNLELVKLLLENGADANLQDKNGRTALHLAAKNGHLEIVKLLLE-HADVNL-KDNGRTALHYAARSG---HLE 75

                   ....
gi 319803120   140 IVEF 143
Cdd:pfam12796   76 IVKL 79
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
266-460 8.84e-06

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: 48.77  E-value: 8.84e-06
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLPTHPHCSRLRLADLLiaeQEHSSKLRHPYLLQLMAVCLSQDLEKTRLVYERITIgTLFSVLHERRSQF 345
Cdd:cd05118    23 TGEKVAIKKIKNDFRHPKAALREIKLL---KHLNDVEGHPNIVKLLDVFEHRGGNHLCLVFELMGM-NLYELIKDYPRGL 98
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 PVLHMEVIVHLLLQisdALRYLHFQGFIHR---------SLSSYAVHIISPGEARLTNLEYMLESedrgVQrdltrvplp 416
Cdd:cd05118    99 PLDLIKSYLYQLLQ---ALDFLHSNGIIHRdlkpeniliNLELGQLKLADFGLARSFTSPPYTPY----VA--------- 162
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 319803120  417 TQLYNwaAPEVILQ-KAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd05118   163 TRWYR--APEVLLGaKPYGSSIDIWSLGCILAELLTGRPLFPGDS 205
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
292-451 1.02e-05

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: 49.24  E-value: 1.02e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKL-RHPYLLQLMAVClSQDlEKTRLVYERITIGTLFSVLHERR----------SQFPVLHMEV--IVHLLL 358
Cdd:cd05098    65 LISEMEMMKMIgKHKNIINLLGAC-TQD-GPLYVIVEYASKGNLREYLQARRppgmeycynpSHNPEEQLSSkdLVSCAY 142
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  359 QISDALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDLTRVPLPTQLYN------WAAPEVILQKA 432
Cdd:cd05098   143 QVARGMEYLASKKCIHRDLAARNV---------LVTEDNVMKIADFGLARDIHHIDYYKKTTNgrlpvkWMAPEALFDRI 213
                         170
                  ....*....|....*....
gi 319803120  433 ATVKSDIYSFSMIMQEILT 451
Cdd:cd05098   214 YTHQSDVWSFGVLLWEIFT 232
STKc_PAK5 cd06658
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the ...
266-456 1.24e-05

Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 5; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PAK5 is mainly expressed in the brain. It is not required for viability, but together with PAK6, it is required for normal levels of locomotion and activity, and for learning and memory. PAK5 cooperates with Inca (induced in neural crest by AP2) in the regulation of cell adhesion and cytoskeletal organization in the embryo and in neural crest cells during craniofacial development. PAK5 may also play a role in controlling the signaling of Raf-1, an effector of Ras, at the mitochondria. PAK5 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 STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132989 [Multi-domain]  Cd Length: 292  Bit Score: 48.88  E-value: 1.24e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLPTHPHcSRLRLADLLIAEQEHSSKLRHPYLLQLMAvclsqdlEKTRLVYERITIGTLFSVLHERRsqf 345
Cdd:cd06658    46 TGKQVAVKKMDLRKQQR-RELLFNEVVIMRDYHHENVVDMYNSYLVG-------DELWVVMEFLEGGALTDIVTHTR--- 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 pvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLE-SEDRGVQRDLTRVPLptqlynWAA 424
Cdd:cd06658   115 --MNEEQIATVCLSVLRALSYLHNQGVIHRDIKSDSILLTSDGRIKLSDFGFCAQvSKEVPKRKSLVGTPY------WMA 186
                         170       180       190
                  ....*....|....*....|....*....|..
gi 319803120  425 PEVILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06658   187 PEVISRLPYGTEVDIWSLGIMVIEMIDGEPPY 218
STKc_CAMK cd05117
The catalytic domain of CAMK family Serine/Threonine Kinases; STKs catalyze the transfer of ...
301-473 1.25e-05

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: 48.63  E-value: 1.25e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVclSQDLEKTRLVYERITIGTLFSVLHERRSqFPvlhmEVIV-HLLLQISDALRYLHFQGFIHRSL-- 377
Cdd:cd05117    55 RLDHPNIVKLYEV--FEDDKNLYLVMELCTGGELFDRIVKKGS-FS----EREAaKIMKQILSAVAYLHSQGIVHRDLkp 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  378 ---------SSYAVHIISPGEARLTNLEYMLEsedrgvqrdlTRVplPTQLYnwAAPEVILQKAATVKSDIYSFSMIMQE 448
Cdd:cd05117   128 enillaskdPDSPIKIIDFGLAKIFEEGEKLK----------TVC--GTPYY--VAPEVLKGKGYGKKCDIWSLGVILYI 193
                         170       180
                  ....*....|....*....|....*
gi 319803120  449 ILTDDIPWKGLDGSVVKKAVVSGNY 473
Cdd:cd05117   194 LLCGYPPFYGETEQELFEKILKGKY 218
PK_STRAD_alpha cd08227
Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain ...
353-459 1.29e-05

Pseudokinase domain of STE20-related kinase adapter protein alpha; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity. 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. A mutation which results in a truncation of a C-terminal part of the human STRAD-alpha pseudokinase domain and disrupts its association with LKB1, leads to PMSE (polyhydramnios, megalencephaly, symptomatic epilepsy) syndrome. Several splice variants of STRAD-alpha exist which exhibit different effects on the localization and activation of LKB1. 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. The STRAD alpha 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: 173767 [Multi-domain]  Cd Length: 327  Bit Score: 49.17  E-value: 1.29e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  353 IVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGvQRDLTRVPLP---TQLYNWAAPEVIL 429
Cdd:cd08227   103 IAYILQGVLKALDYIHHMGYVHRSVKASHILISVDGKVYLSGLRSNLSMINHG-QRLRVVHDFPkysVKVLPWLSPEVLQ 181
                          90       100       110
                  ....*....|....*....|....*....|..
gi 319803120  430 Q--KAATVKSDIYSFSMIMQEILTDDIPWKGL 459
Cdd:cd08227   182 QnlQGYDAKSDIYSVGITACELANGHVPFKDM 213
PK_STRAD_beta cd08226
Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain ...
267-459 1.31e-05

Pseudokinase domain of STE20-related kinase adapter protein beta; The pseudokinase domain shows similarity to protein kinases but lacks crucial residues for catalytic activity.STRAD-beta is also referred to as ALS2CR2 (Amyotrophic lateral sclerosis 2 chromosomal region candidate gene 2 protein), since the human gene encoding it is located within the juvenile ALS2 critical region on chromosome 2q33-q34. It is not linked to the development of ALS2. 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. The STRAD-beta 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: 270864 [Multi-domain]  Cd Length: 328  Bit Score: 49.10  E-value: 1.31e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNLPThphCSRLRLaDLLIAEQEHSSKLRHPYLLQLMAVclsqdlektrlvyerITIGTLFSVL-------- 338
Cdd:cd08226    25 GTLVTVKITNLDN---CSEEHL-KALQNEVVLSHFFRHPNIMTHWTV---------------FTEGSWLWVIspfmaygs 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  339 --HERRSQFPV-LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYmLESEDRGVQRDLTRVPL 415
Cdd:cd08226    86 arGLLKTYFPEgMNEALIGNILYGAIKALNYLHQNGCIHRSVKASHILISGDGLVSLSGLSH-LYSMVTNGQRSKVVYDF 164
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*....
gi 319803120  416 P---TQLYNWAAPEVILQK--AATVKSDIYSFSMIMQEILTDDIPWKGL 459
Cdd:cd08226   165 PqfsTSVLPWLSPELLRQDlhGYNVKSDIYSVGITACELARGQVPFQDM 213
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
320-473 1.33e-05

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 49.63  E-value: 1.33e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  320 EKTRLVYERITIGTLFSVLHER-RSQFPVLHMEVIVhLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYM 398
Cdd:PTZ00267  138 DKLLLIMEYGSGGDLNKQIKQRlKEHLPFQEYEVGL-LFYQIVLALDEVHSRKMMHRDLKSANIFLMPTGIIKLGDFGFS 216
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 319803120  399 LESEDrGVQRDLTRVPLPTQLYnwAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNY 473
Cdd:PTZ00267  217 KQYSD-SVSLDVASSFCGTPYY--LAPELWERKRYSKKADMWSLGVILYELLTLHRPFKGPSQREIMQQVLYGKY 288
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
348-460 1.56e-05

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: 48.40  E-value: 1.56e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRvplpTQLYN------ 421
Cdd:cd06609    95 LDETYIAFILREVLLGLEYLHSEGKIHRDIKAANILLSEEGDVKLA---------DFGVSGQLTS----TMSKRntfvgt 161
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|.
gi 319803120  422 --WAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd06609   162 pfWMAPEVIKQSGYDEKADIWSLGITAIELAKGEPPLSDLH 202
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
348-460 1.58e-05

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: 48.24  E-value: 1.58e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 LHMEVIVHLLLQisdALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGV-----QRDLTRVPLPTQLYnW 422
Cdd:cd06917   101 RYIAVIMREVLV---ALKFIHKDGIIHRDIKAANILVTNTGNVKLC---------DFGVaaslnQNSSKRSTFVGTPY-W 167
                          90       100       110
                  ....*....|....*....|....*....|....*....
gi 319803120  423 AAPEVILQ-KAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd06917   168 MAPEVITEgKYYDTKADIWSLGITTYEMATGNPPYSDVD 206
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
304-483 1.63e-05

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: 48.00  E-value: 1.63e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  304 HPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLherRSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVH 383
Cdd:cd05084    53 HPNIVRLIGVCTQK--QPIYIVMELVQGGDFLTFL---RTEGPRLKVKELIRMVENAAAGMEYLESKHCIHRDLAARNCL 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  384 IISPGEARLTNLEYMLESEDrGVQRD---LTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGL 459
Cdd:cd05084   128 VTEKNVLKISDFGMSREEED-GVYAAtggMKQIPV-----KWTAPEALNYGRYSSESDVWSFGILLWETFSlGAVPYANL 201
                         170       180
                  ....*....|....*....|....
gi 319803120  460 DGSVVKKAVvsgnylEADVRLPKP 483
Cdd:cd05084   202 SNQQTREAV------EQGVRLPCP 219
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
320-509 1.99e-05

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: 48.11  E-value: 1.99e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  320 EKTRLVYERITIGTLFSVLHERRSQF---PVLH---MEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLT 393
Cdd:cd05062    82 QPTLVIMELMTRGDLKSYLRSLRPEMennPVQAppsLKKMIQMAGEIADGMAYLNANKFVHRDLAARNCMVAEDFTVKIG 161
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  394 NLEYMLESEDRGVQRDLTRVPLPTQlynWAAPEVILQKAATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGN 472
Cdd:cd05062   162 DFGMTRDIYETDYYRKGGKGLLPVR---WMSPESLKDGVFTTYSDVWSFGVVLWEIATlAEQPYQGMSNEQVLRFVMEGG 238
                         170       180       190
                  ....*....|....*....|....*....|....*..
gi 319803120  473 YLEADVRLPKPYYDIVKSGIHVKQKDRTMNLQDIRYI 509
Cdd:cd05062   239 LLDKPDNCPDMLFELMRMCWQYNPKMRPSFLEIISSI 275
STKc_MAST_like cd05579
Catalytic domain of Microtubule-associated serine/threonine (MAST) kinase-like proteins; STKs ...
292-456 2.04e-05

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: 47.98  E-value: 2.04e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKLRHPYLLQLmaVCLSQDLEKTRLVYERITIGTLFSVLHerrsQFPVLHMEVIVHLLLQISDALRYLHFQG 371
Cdd:cd05579    40 VLAERNILSQAQNPFVVKL--YYSFQGKKNLYLVMEYLPGGDLYSLLE----NVGALDEDVARIYIAEIVLALEYLHSHG 113
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  372 FIHRSLSSYAVHIISPGEARLTN--LEYMlesedrGVQRDLTRVPLPTQLYN--------------WAAPEVILQKAATV 435
Cdd:cd05579   114 IIHRDLKPDNILIDANGHLKLTDfgLSKV------GLVRRQIKLSIQKKSNGapekedrrivgtpdYLAPEILLGQGHGK 187
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 319803120  436 KSD-------IYSF------------SMIMQEILTDDIPW 456
Cdd:cd05579   188 TVDwwslgviLYEFlvgippfhaetpEEIFQNILNGKIEW 227
STKc_Aurora cd14007
Catalytic domain of the Serine/Threonine kinase, Aurora kinase; STKs catalyze the transfer of ...
300-473 2.15e-05

Catalytic domain of the Serine/Threonine kinase, Aurora 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. Yeast contains only one Aurora kinase while most higher eukaryotes have two. 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. Aurora-B is most active at the transition during metaphase to the end of mitosis. It is critical for accurate chromosomal segregation, cytokinesis, protein localization to the centrosome and kinetochore, correct microtubule-kinetochore attachments, and regulation of the mitotic checkpoint. Aurora-C is mainly expressed in meiotically dividing cells; it was originally discovered in mice as a testis-specific STK called Aie1. Both Aurora-B and -C are chromosomal passenger proteins that can form complexes with INCENP and survivin, and they may have redundant cellular functions. 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: 270909 [Multi-domain]  Cd Length: 253  Bit Score: 47.85  E-value: 2.15e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLhERRSQFPvlhmEVIV-HLLLQISDALRYLHFQGFIHRSLS 378
Cdd:cd14007    55 SHLRHPNILRLYGYF--EDKKRIYLILEYAPNGELYKEL-KKQKRFD----EKEAaKYIYQLALALDYLHSKNIIHRDIK 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  379 -----------------SYAVHIisPGEARLT---NLEYMlesedrgvqrdltrvplptqlynwaAPEVILQKAATVKSD 438
Cdd:cd14007   128 penillgsngelkladfGWSVHA--PSNRRKTfcgTLDYL-------------------------PPEMVEGKEYDYKVD 180
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 319803120  439 IYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNY 473
Cdd:cd14007   181 IWSLGVLCYELLVGKPPFESKSHQETYKRIQNVDI 215
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
324-450 2.16e-05

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: 47.59  E-value: 2.16e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  324 LVYERITIGTLFSVLHERRSQFPVLHMEVIVHLLLQisdALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEY--MLES 401
Cdd:cd06614    73 VVMEYMDGGSLTDIITQNPVRMNESQIAYVCREVLQ---GLEYLHSQNVIHRDIKSDNILLSKDGSVKLADFGFaaQLTK 149
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*....
gi 319803120  402 EdrgVQRDLTRVPLPtqlYnWAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd06614   150 E---KSKRNSVVGTP---Y-WMAPEVIKRKDYGPKVDIWSLGIMCIEMA 191
PHA03095 PHA03095
ankyrin-like protein; Provisional
27-125 2.21e-05

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 48.87  E-value: 2.21e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   27 LHEYVKQGNyVKVKKI----LKKGIYVDAVNSLGQTALFVAALLGLR-KFVDVLVDYGSDPNHRCFDGSTPVHA--AAFS 99
Cdd:PHA03095   51 LHLYLHYSS-EKVKDIvrllLEAGADVNAPERCGFTPLHLYLYNATTlDVIKLLIKAGADVNAKDKVGRTPLHVylSGFN 129
                          90       100
                  ....*....|....*....|....*.
gi 319803120  100 GNQWILSKLLDAGGDLRLHDERGQNP 125
Cdd:PHA03095  130 INPKVIRLLLRKGADVNALDLYGMTP 155
STKc_MLCK1 cd14191
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze ...
302-458 3.28e-05

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK1 (or MYLK1) phosphorylates myosin regulatory light chain and controls the contraction of smooth muscles. 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 followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site; a long MLCK1 containing six additional Ig-like domains at the N-terminus compared to the short MLCK1; and the C-terminal Ig module which results in the expression of telokin in phasic smooth muscles, leading to Ca2+ desensitization by cyclic nucleotides of smooth muscle force. MLCK1 is also responsible for myosin regulatory light chain phosphorylation in nonmuscle cells and may play a role in regulating myosin II ATPase activity. The MLCK1 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: 271093 [Multi-domain]  Cd Length: 259  Bit Score: 47.31  E-value: 3.28e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  302 LRHPYLLQlmavCLSQDLEKTR--LVYERITIGTLFSVLHERrsQFPVLHMEVIVHLLlQISDALRYLHFQGFIHRSLSS 379
Cdd:cd14191    56 LHHPKLVQ----CVDAFEEKANivMVLEMVSGGELFERIIDE--DFELTERECIKYMR-QISEGVEYIHKQGIVHLDLKP 128
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  380 YAVHIISPGEARLTNLEYMLES--EDRGVQRDLTRVPlptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWK 457
Cdd:cd14191   129 ENIMCVNKTGTKIKLIDFGLARrlENAGSLKVLFGTP------EFVAPEVINYEPIGYATDMWSIGVICYILVSGLSPFM 202

                  .
gi 319803120  458 G 458
Cdd:cd14191   203 G 203
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
348-451 4.12e-05

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: 47.69  E-value: 4.12e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSY--------AVHIISPGEAR--LTNLEYmlesedrgVQRDLTRVPLpt 417
Cdd:cd14207   177 LTMEDLISYSFQVARGMEFLSSRKCIHRDLAARnillsennVVKICDFGLARdiYKNPDY--------VRKGDARLPL-- 246
                          90       100       110
                  ....*....|....*....|....*....|....
gi 319803120  418 qlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd14207   247 ---KWMAPESIFDKIYSTKSDVWSYGVLLWEIFS 277
STKc_PAK1 cd06654
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 1; STKs catalyze the ...
264-456 4.18e-05

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: 47.41  E-value: 4.18e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  264 VWNGSRVTVKELNLPTHPHcSRLRLADLLIAEQEhssklRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHErrs 343
Cdd:cd06654    42 VATGQEVAIRQMNLQQQPK-KELIINEILVMREN-----KNPNIVNYLDSYLVGD--ELWVVMEYLAGGSLTDVVTE--- 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 qfPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDlTRVPLPTqlynWA 423
Cdd:cd06654   111 --TCMDEGQIAAVCRECLQALEFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRS-TMVGTPY----WM 183
                         170       180       190
                  ....*....|....*....|....*....|...
gi 319803120  424 APEVILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06654   184 APEVVTRKAYGPKVDIWSLGIMAIEMIEGEPPY 216
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
267-451 4.64e-05

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: 47.23  E-value: 4.64e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNlpthPHCSRLRLADLLiAEQEHSSKLRHPYLLQLMAVCLSQDLEKTRLVYERITIGTLFSVLHERRSQfp 346
Cdd:cd05079    33 GEQVAVKSLK----PESGGNHIADLK-KEIEILRNLYHENIVKYKGICTEDGGNGIKLIMEFLPSGSLKEYLPRNKNK-- 105
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 vLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAV-----HIISPGEARLT-----NLEYMLESEDrgvqrdltrvpLP 416
Cdd:cd05079   106 -INLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVlveseHQVKIGDFGLTkaietDKEYYTVKDD-----------LD 173
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 319803120  417 TQLYnWAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05079   174 SPVF-WYAPECLIQSKFYIASDVWSFGVTLYELLT 207
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
347-451 5.17e-05

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: 47.28  E-value: 5.17e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 VLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDLTRVP---------LPT 417
Cdd:cd05103   175 FLTLEDLICYSFQVAKGMEFLASRKCIHRDLAARNI---------LLSENNVVKICDFGLARDIYKDPdyvrkgdarLPL 245
                          90       100       110
                  ....*....|....*....|....*....|....
gi 319803120  418 QlynWAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05103   246 K---WMAPETIFDRVYTIQSDVWSFGVLLWEIFS 276
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
265-459 5.60e-05

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: 46.33  E-value: 5.60e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGSRVTVKELNLPthpHCSRLRLADLliaeQEHSSKLR---HPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLHEr 341
Cdd:cd14057    16 WQGNDIVAKILKVR---DVTTRISRDF----NEEYPRLRifsHPNVLPVLGAC--NSPPNLVVISQYMPYGSLYNVLHE- 85
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  342 RSQFPVLHMEViVHLLLQISDALRYLH-FQGFIHR-SLSSYAVHIISPGEARLTNLEYMLESEDRGvqrdltrvplptQL 419
Cdd:cd14057    86 GTGVVVDQSQA-VKFALDIARGMAFLHtLEPLIPRhHLNSKHVMIDEDMTARINMADVKFSFQEPG------------KM 152
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|....*
gi 319803120  420 YN--WAAPEVILQKAATVK---SDIYSFSMIMQEILTDDIPWKGL 459
Cdd:cd14057   153 YNpaWMAPEALQKKPEDINrrsADMWSFAILLWELVTREVPFADL 197
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
300-451 6.23e-05

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: 46.55  E-value: 6.23e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFPV------------LHMEVIVHLLLQISDALRYL 367
Cdd:cd05091    64 SRLQHPNIVCLLGVVTKE--QPMSMIFSYCSHGDLHEFLVMRSPHSDVgstdddktvkstLEPADFLHIVTQIAAGMEYL 141
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  368 HFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDLTRVPLPTQlynWAAPEVILQKAATVKSDIYSFSMIMQ 447
Cdd:cd05091   142 SSHHVVHKDLATRNVLVFDKLNVKISDLGLFREVYAADYYKLMGNSLLPIR---WMSPEAIMYGKFSIDSDIWSYGVVLW 218

                  ....
gi 319803120  448 EILT 451
Cdd:cd05091   219 EVFS 222
STKc_PAK3 cd06656
Catalytic domain of the Protein Serine/Threonine Kinase, p21-activated kinase 3; Serine ...
267-456 6.33e-05

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: 46.64  E-value: 6.33e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNLPTHPHcSRLRLADLLIAEQEhssklRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHErrsqfP 346
Cdd:cd06656    44 GQEVAIKQMNLQQQPK-KELIINEILVMREN-----KNPNIVNYLDSYLVGD--ELWVVMEYLAGGSLTDVVTE-----T 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 VLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDlTRVPLPTqlynWAAPE 426
Cdd:cd06656   111 CMDEGQIAAVCRECLQALDFLHSNQVIHRDIKSDNILLGMDGSVKLTDFGFCAQITPEQSKRS-TMVGTPY----WMAPE 185
                         170       180       190
                  ....*....|....*....|....*....|
gi 319803120  427 VILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06656   186 VVTRKAYGPKVDIWSLGIMAIEMVEGEPPY 215
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
303-489 6.58e-05

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: 46.57  E-value: 6.58e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  303 RHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLHERR------------SQFPVLHMEVIVHLLLQISDALRYLHFQ 370
Cdd:cd05047    54 HHPNIINLLGAC--EHRGYLYLAIEYAPHGNLLDFLRKSRvletdpafaianSTASTLSSQQLLHFAADVARGMDYLSQK 131
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  371 GFIHRSLSSYAVHIISPGEARLTNLEyMLESEDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd05047   132 QFIHRDLAARNILVGENYVAKIADFG-LSRGQEVYVKKTMGRLPV-----RWMAIESLNYSVYTTNSDVWSYGVLLWEIV 205
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 319803120  451 T-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVK 489
Cdd:cd05047   206 SlGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDEVYDLMR 245
STKc_LIMK2 cd14222
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 2; STKs catalyze the ...
279-450 6.63e-05

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: 46.48  E-value: 6.63e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  279 THPHCSRLRLADLLIAEQEHSSK-----------LRHPYLLQLMAVcLSQDlEKTRLVYERITIGTLFSVLHERRSqFPv 347
Cdd:cd14222    13 THKATGKVMVMKELIRCDEETQKtfltevkvmrsLDHPNVLKFIGV-LYKD-KRLNLLTEFIEGGTLKDFLRADDP-FP- 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 lhMEVIVHLLLQISDALRYLHFQGFIHRSLSSY--------AVHIISPGEARLTNLEYMLESEDRGVQRDLT-----RVP 414
Cdd:cd14222    89 --WQQKVSFAKGIASGMAYLHSMSIIHRDLNSHnclikldkTVVVADFGLSRLIVEEKKKPPPDKPTTKKRTlrkndRKK 166
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 319803120  415 LPTQLYN--WAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd14222   167 RYTVVGNpyWMAPEMLNGKSYDEKVDIFSFGIVLCEII 204
STKc_p38 cd07851
Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs ...
342-460 9.54e-05

Catalytic domain of the Serine/Threonine Kinase, p38 Mitogen-Activated Protein Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38 kinases are mitogen-activated protein kinases (MAPKs), serving as important mediators of cellular responses to extracellular signals. They function in the regulation of the cell cycle, cell development, cell differentiation, senescence, tumorigenesis, apoptosis, pain development and pain progression, and immune responses. p38 kinases 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. p38 substrates include other protein kinases and factors that regulate transcription, nuclear export, mRNA stability and translation. p38 kinases are drug targets for the inflammatory diseases psoriasis, rheumatoid arthritis, and chronic pulmonary disease. Vertebrates contain four isoforms of p38, named alpha, beta, gamma, and delta, which show varying substrate specificity and expression patterns. p38alpha and p38beta are ubiquitously expressed, p38gamma is predominantly found in skeletal muscle, and p38delta is found in the heart, lung, testis, pancreas, and small intestine. The p38 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: 143356 [Multi-domain]  Cd Length: 343  Bit Score: 46.52  E-value: 9.54e-05
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  342 RSQfpVLHMEVIVHLLLQISDALRYLHFQGFIHRSL--SSYAVH------IISPGEARLTnleymlESEDRG-VQrdlTR 412
Cdd:cd07851   111 KCQ--KLSDDHIQFLVYQILRGLKYIHSAGIIHRDLkpSNLAVNedcelkILDFGLARHT------DDEMTGyVA---TR 179
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|
gi 319803120  413 vplptqlynW-AAPEVILQKAATVKS-DIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd07851   180 ---------WyRAPEIMLNWMHYNQTvDIWSVGCIMAELLTGKTLFPGSD 220
PHA02988 PHA02988
hypothetical protein; Provisional
434-510 9.89e-05

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 45.89  E-value: 9.89e-05
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 319803120  434 TVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNY-LEADVRLPKPYYDIVKSGIHvKQKDRTMNLQDIRYIL 510
Cdd:PHA02988  200 TIKDDIYSLGVVLWEIFTGKIPFENLTTKEIYDLIINKNNsLKLPLDCPLEIKCIVEACTS-HDSIKRPNIKEILYNL 276
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
353-490 1.01e-04

Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. STK25 is also called Ste20/oxidant stress response kinase 1 (SOK1) or yeast Sps1/Ste20-related kinase 1 (YSK1). It is localized in the Golgi apparatus through its interaction with the Golgi matrix protein GM130. It may be involved in the regulation of cell migration and polarization. STK25 binds and phosphorylates CCM3 (cerebral cavernous malformation 3), also called PCD10 (programmed cell death 10), and may play a role in apoptosis. Human STK25 is a candidate gene responsible for pseudopseudohypoparathyroidism (PPHP), a disease that shares features with the Albright hereditary osteodystrophy (AHO) phenotype. The STK25 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: 270810 [Multi-domain]  Cd Length: 277  Bit Score: 45.82  E-value: 1.01e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  353 IVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDlTRVPLPTqlynWAAPEVILQKA 432
Cdd:cd06642   103 IATILREILKGLDYLHSERKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRN-TFVGTPF----WMAPEVIKQSA 177
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 319803120  433 ATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKS 490
Cdd:cd06642   178 YDFKADIWSLGITAIELAKGEPPNSDLHPMRVLFLIPKNSPPTLEGQHSKPFKEFVEA 235
STKc_NUAK cd14073
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze ...
295-377 1.04e-04

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK1, also called ARK5 (AMPK-related protein kinase 5), regulates cell proliferation and displays tumor suppression through direct interaction and phosphorylation of p53. It is also involved in cell senescence and motility. High NUAK1 expression is associated with invasiveness of nonsmall cell lung cancer (NSCLC) and breast cancer cells. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. The NUAK 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: 270975 [Multi-domain]  Cd Length: 254  Bit Score: 45.84  E-value: 1.04e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRSqfpvLHMEVIVHLLLQISDALRYLHFQGFIH 374
Cdd:cd14073    51 EIEIMSSLNHPHIIRIYEVFENKD--KIVIVMEYASGGELYDYISERRR----LPEREARRIFRQIVSAVHYCHKNGVVH 124

                  ...
gi 319803120  375 RSL 377
Cdd:cd14073   125 RDL 127
PHA03095 PHA03095
ankyrin-like protein; Provisional
19-130 1.09e-04

ankyrin-like protein; Provisional


Pssm-ID: 222980 [Multi-domain]  Cd Length: 471  Bit Score: 46.56  E-value: 1.09e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   19 RNDSLEAQLHEYVKQgNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDV--LVDYGSDPNHRCFDGSTPVHAA 96
Cdd:PHA03095  186 RFRSLLHHHLQSFKP-RARIVRELIRAGCDPAATDMLGNTPLHSMATGSSCKRSLVlpLLIAGISINARNRYGQTPLHYA 264
                          90       100       110
                  ....*....|....*....|....*....|....
gi 319803120   97 AFSGNQWILSKLLDAGGDLRLHDERGQNPKTWAL 130
Cdd:PHA03095  265 AVFNNPRACRRLIALGADINAVSSDGNTPLSLMV 298
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
268-490 1.12e-04

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: 45.66  E-value: 1.12e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  268 SRVTVKELNLPTHPhcsrlRLADLLIAEQEHSSKLRHPYLLQlmavCLSQDLEKTR--LVYERITIGTLFSVLH-ERRSQ 344
Cdd:cd05042    23 AQVVVKELKASANP-----KEQDTFLKEGQPYRILQHPNILQ----CLGQCVEAIPylLVMEFCDLGDLKAYLRsEREHE 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  345 FPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptqlyNW 422
Cdd:cd05042    94 RGDSDTRTLQRMACEVAAGLAHLHKLNFVHSDLALRNCLLTSDLTVKIGDygLAHSRYKEDYIETDDKLWFPL-----RW 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  423 AAPEVI-------LQKAATVKSDIYSFSMIMQEILTDDI-PWKGLDGSVVKKAVVSgnylEADVRLPKP---------YY 485
Cdd:cd05042   169 TAPELVtefhdrlLVVDQTKYSNIWSLGVTLWELFENGAqPYSNLSDLDVLAQVVR----EQDTKLPKPqlelpysdrWY 244

                  ....*
gi 319803120  486 DIVKS 490
Cdd:cd05042   245 EVLQF 249
PKc_TOPK cd14001
Catalytic domain of the Dual-specificity protein kinase, Lymphokine-activated killer ...
333-455 1.17e-04

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: 45.85  E-value: 1.17e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  333 TLFSVLHERRSQ----FPVlhmEVIVHLLLQISDALRYLHFQGFI-HRSLSSYAVHIISPGEA-RLTnleymleseDRGV 406
Cdd:cd14001    91 SLNDLIEERYEAglgpFPA---ATILKVALSIARALEYLHNEKKIlHGDIKSGNVLIKGDFESvKLC---------DFGV 158
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*...
gi 319803120  407 ----QRDLTRVPLPTQLY----NWAAPEVILQKAA-TVKSDIYSFSMIMQEILTDDIP 455
Cdd:cd14001   159 slplTENLEVDSDPKAQYvgtePWKAKEALEEGGViTDKADIFAYGLVLWEMMTLSVP 216
STKc_Mnk2 cd14173
Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase ...
278-462 1.19e-04

Catalytic domain of the Serine/Threonine kinase, Mitogen-activated protein kinase signal-integrating kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAPK signal-integrating kinases (Mnks) are MAPK-activated protein kinases and is comprised by a group of four proteins, produced by alternative splicing from two genes (Mnk1 and Mnk2). The isoforms of Mnk1 (1a/1b) and Mnk2 (2a/2b) differ at their C-termini, with the a-form having a longer C-terminus containing a MAPK-binding region. All Mnks contain a catalytic kinase domain and a polybasic region at the N-terminus which binds importin and the eukaryotic initiation factor eIF4G. The best characterized Mnk substrate is eIF4G, whose phosphorylation may promote the export of certain mRNAs from the nucleus. Mnk also phosphorylate substrates that bind to AU-rich elements that regulate mRNA stability and translation. Mnks have also been implicated in tyrosine kinase receptor signaling, inflammation, and cell prolieration or survival. The Mnk 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: 271075 [Multi-domain]  Cd Length: 288  Bit Score: 45.79  E-value: 1.19e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  278 PTHPHCSRLRLADLLIAEQEHSSklrhpyLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRsQFPVLHMEVIVHll 357
Cdd:cd14173    39 PGHSRSRVFREVEMLYQCQGHRN------VLELIEFFEEED--KFYLVFEKMRGGSILSHIHRRR-HFNELEASVVVQ-- 107
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  358 lQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNL-EYMLESEDRgVQRDLTRVPLPTQLY-----NWAAPEVI--L 429
Cdd:cd14173   108 -DIASALDFLHNKGIAHRDLKPENILCEHPNQVSPVKIcDFDLGSGIK-LNSDCSPISTPELLTpcgsaEYMAPEVVeaF 185
                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 319803120  430 QKAATV---KSDIYSFSMIMQEILTDDIPWKGLDGS 462
Cdd:cd14173   186 NEEASIydkRCDLWSLGVILYIMLSGYPPFVGRCGS 221
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
302-451 1.22e-04

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: 45.65  E-value: 1.22e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  302 LRHPYLLQLMAVCLSQDLEKTRLVYERITIGTLFSVLHERRSQFPVlhmeviVHLLL---QISDALRYLHFQGFIHRSLS 378
Cdd:cd05081    62 LHSDFIVKYRGVSYGPGRRSLRLVMEYLPSGCLRDFLQRHRARLDA------SRLLLyssQICKGMEYLGSRRCVHRDLA 135
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319803120  379 SYAVHIISPGEARLTNL---EYMLESEDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05081   136 ARNILVESEAHVKIADFglaKLLPLDKDYYVVREPGQSPI-----FWYAPESLSDNIFSRQSDVWSFGVVLYELFT 206
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
301-501 1.24e-04

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: 45.79  E-value: 1.24e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVCLSQDLEktrLVYERITIGTLFSVLHERRSQFpvlHMEVIVHLLLQISDALRYLHFQGFIHRSLSSY 380
Cdd:cd14149    64 KTRHVNILLFMGYMTKDNLA---IVTQWCEGSSLYKHLHVQETKF---QMFQLIDIARQTAQGMDYLHAKNIIHRDMKSN 137
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  381 AVHIISPGEARLTNLEY-MLESEDRGVQRdltrVPLPTQLYNWAAPEVILQK---AATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd14149   138 NIFLHEGLTVKIGDFGLaTVKSRWSGSQQ----VEQPTGSILWMAPEVIRMQdnnPFSFQSDVYSYGIVLYELMTGELPY 213
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 319803120  457 KGLDGSVVKKAVVSGNYLEADV-----RLPKPYYDIVKSGIHVKQKDRTM 501
Cdd:cd14149   214 SHINNRDQIIFMVGRGYASPDLsklykNCPKAMKRLVADCIKKVKEERPL 263
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
268-490 1.25e-04

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: 45.71  E-value: 1.25e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  268 SRVTVKELNLPTHPHCSRLrladlLIAEQEHSSKLRHPYLLQLMAVCLsqDLEKTRLVYERITIGTLFSVLHERRS---- 343
Cdd:cd14206    25 AQVVVKELRVSAGPLEQRK-----FISEAQPYRSLQHPNILQCLGLCT--ETIPFLLIMEFCQLGDLKRYLRAQRKadgm 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  344 --QFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDRGVQRDLTRVPLptql 419
Cdd:cd14206    98 tpDLPTRDLRTLQRMAYEITLGLLHLHKNNYIHSDLALRNCLLTSDLTVRIGDygLSHNNYKEDYYLTPDRLWIPL---- 173
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  420 yNWAAPEVILQKAATV-------KSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLE-ADVRLPKPY----YD 486
Cdd:cd14206   174 -RWVAPELLDELHGNLivvdqskESNVWSLGVTIWELFEfGAQPYRHLSDEEVLTFVVREQQMKlAKPRLKLPYadywYE 252

                  ....
gi 319803120  487 IVKS 490
Cdd:cd14206   253 IMQS 256
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
72-147 1.26e-04

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 46.43  E-value: 1.26e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319803120   72 VDVLVDYGSDPNHRCFDGSTPVHAAAFSGNQWILSKLLDAGGDLRLHDERGQNPKTwalTAGKERSTQIVEFMQRC 147
Cdd:PTZ00322   98 ARILLTGGADPNCRDYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLE---LAEENGFREVVQLLSRH 170
STKc_LKB1 cd14119
Catalytic domain of the Serine/Threonine kinase, Liver Kinase B1; STKs catalyze the transfer ...
301-412 1.32e-04

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: 45.33  E-value: 1.32e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVCLSQDLEKTRLVYERITIGTLFSVLHERRSQFPVLHMEvivHLLLQISDALRYLHFQGFIHRSlssy 380
Cdd:cd14119    50 RLNHRNVIKLVDVLYNEEKQKLYMVMEYCVGGLQEMLDSAPDKRLPIWQAH---GYFVQLIDGLEYLHSQGIIHKD---- 122
                          90       100       110
                  ....*....|....*....|....*....|..
gi 319803120  381 avhiISPGEARLTNlEYMLESEDRGVQRDLTR 412
Cdd:cd14119   123 ----IKPGNLLLTT-DGTLKISDFGVAEALDL 149
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
292-499 1.38e-04

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: 45.78  E-value: 1.38e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  292 LIAEQEHSSKL-RHPYLLQLMAVClSQDLEKTRLVyERITIGTLFSVLHERRS----------QFP--VLHMEVIVHLLL 358
Cdd:cd05100    64 LVSEMEMMKMIgKHKNIINLLGAC-TQDGPLYVLV-EYASKGNLREYLRARRPpgmdysfdtcKLPeeQLTFKDLVSCAY 141
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  359 QISDALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDLTRVPLPTQLYN------WAAPEVILQKA 432
Cdd:cd05100   142 QVARGMEYLASQKCIHRDLAARNV---------LVTEDNVMKIADFGLARDVHNIDYYKKTTNgrlpvkWMAPEALFDRV 212
                         170       180       190       200       210       220
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 319803120  433 ATVKSDIYSFSMIMQEILT-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVKSGIHVKQKDR 499
Cdd:cd05100   213 YTHQSDVWSFGVLLWEIFTlGGSPYPGIPVEELFKLLKEGHRMDKPANCTHELYMIMRECWHAVPSQR 280
STKc_Aurora-A cd14116
Catalytic domain of the Serine/Threonine kinase, Aurora-A kinase; STKs catalyze the transfer ...
295-457 1.44e-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: 45.33  E-value: 1.44e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAvcLSQDLEKTRLVYERITIGTLFSVLhERRSQFPVLHMEVIVhllLQISDALRYLHFQGFIH 374
Cdd:cd14116    55 EVEIQSHLRHPNILRLYG--YFHDATRVYLILEYAPLGTVYREL-QKLSKFDEQRTATYI---TELANALSYCHSKRVIH 128
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  375 RSLSSYAVHIISPGEARLTNLEYMLESEDRgvqrdlTRVPLPTQLyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDI 454
Cdd:cd14116   129 RDIKPENLLLGSAGELKIADFGWSVHAPSS------RRTTLCGTL-DYLPPEMIEGRMHDEKVDLWSLGVLCYEFLVGKP 201

                  ...
gi 319803120  455 PWK 457
Cdd:cd14116   202 PFE 204
PHA03100 PHA03100
ankyrin repeat protein; Provisional
27-143 1.54e-04

ankyrin repeat protein; Provisional


Pssm-ID: 222984 [Multi-domain]  Cd Length: 422  Bit Score: 45.81  E-value: 1.54e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   27 LHEYVKQGNYVKVKKILKKGIYVD--AVNSLGQTALFVAALLGL---RKFVDVLVDYGSDPNHRCFDGSTPVHAAAF--S 99
Cdd:PHA03100   39 LYLAKEARNIDVVKILLDNGADINssTKNNSTPLHYLSNIKYNLtdvKEIVKLLLEYGANVNAPDNNGITPLLYAISkkS 118
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 319803120  100 GNQWILSKLLDAGGDLRLHDERGQNPKTWALTaGKERSTQIVEF 143
Cdd:PHA03100  119 NSYSIVEYLLDNGANVNIKNSDGENLLHLYLE-SNKIDLKILKL 161
STKc_OSR1_SPAK cd06610
Catalytic domain of the Serine/Threonine Kinases, Oxidative stress response kinase and ...
336-456 1.67e-04

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: 45.04  E-value: 1.67e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  336 SVLHERRSQFP--VLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNL---EYMLESEDRGVQRDL 410
Cdd:cd06610    85 SLLDIMKSSYPrgGLDEAIIATVLKEVLKGLEYLHSNGQIHRDVKAGNILLGEDGSVKIADFgvsASLATGGDRTRKVRK 164
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*..
gi 319803120  411 TRVPLPTqlynWAAPEVILQ-KAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06610   165 TFVGTPC----WMAPEVMEQvRGYDFKADIWSFGITAIELATGAAPY 207
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
343-451 1.74e-04

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: 45.77  E-value: 1.74e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  343 SQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIIspgEARLTNLEymleseDRGVQRDLTR---------- 412
Cdd:cd05107   231 NESPALSYMDLVGFSYQVANGMEFLASKNCVHRDLAARNVLIC---EGKLVKIC------DFGLARDIMRdsnyiskgst 301
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|
gi 319803120  413 -VPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05107   302 fLPL-----KWMAPESIFNNLYTTLSDVWSFGILLWEIFT 336
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
295-488 1.83e-04

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: 45.00  E-value: 1.83e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHS--SKLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFPV-------------LHMEVIVHLLLQ 359
Cdd:cd05090    55 QQEASlmTELHHPNIVCLLGVVTQE--QPVCMLFEFMNQGDLHEFLIMRSPHSDVgcssdedgtvkssLDHGDFLHIAIQ 132
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  360 ISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDLTRVPLPTQlynWAAPEVILQKAATVKSDI 439
Cdd:cd05090   133 IAAGMEYLSSHFFVHKDLAARNILVGEQLHVKISDLGLSREIYSSDYYRVQNKSLLPIR---WMPPEAIMYGKFSSDSDI 209
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|
gi 319803120  440 YSFSMIMQEILTDDI-PWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIV 488
Cdd:cd05090   210 WSFGVVLWEIFSFGLqPYYGFSNQEVIEMVRKRQLLPCSEDCPPRMYSLM 259
STKc_MST4 cd06640
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs ...
353-455 1.97e-04

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 4; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST4 is sometimes referred to as MASK (MST3 and SOK1-related kinase). It plays a role in mitogen-activated protein kinase (MAPK) signaling during cytoskeletal rearrangement, morphogenesis, and apoptosis. It influences cell growth and transformation by modulating the extracellular signal-regulated kinase (ERK) pathway. MST4 may also play a role in tumor formation and progression. It localizes in the Golgi apparatus by interacting with the Golgi matrix protein GM130 and may play a role in cell migration. The MST4 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: 132971 [Multi-domain]  Cd Length: 277  Bit Score: 45.04  E-value: 1.97e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  353 IVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDlTRVPLPTqlynWAAPEVILQKA 432
Cdd:cd06640   103 IATMLKEILKGLDYLHSEKKIHRDIKAANVLLSEQGDVKLADFGVAGQLTDTQIKRN-TFVGTPF----WMAPEVIQQSA 177
                          90       100
                  ....*....|....*....|...
gi 319803120  433 ATVKSDIYSFSMIMQEILTDDIP 455
Cdd:cd06640   178 YDSKADIWSLGITAIELAKGEPP 200
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
353-455 2.07e-04

Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MST3 phosphorylates the STK NDR and may play a role in cell cycle progression and cell morphology. It may also regulate paxillin and consequently, cell migration. MST3 is present in human placenta, where it plays an essential role in the oxidative stress-induced apoptosis of trophoblasts in normal spontaneous delivery. Dysregulation of trophoblast apoptosis may result in pregnancy complications such as preeclampsia and intrauterine growth retardation. The MST3 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: 270809 [Multi-domain]  Cd Length: 277  Bit Score: 45.06  E-value: 2.07e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  353 IVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRD-LTRVPLptqlynWAAPEVILQK 431
Cdd:cd06641   103 IATILREILKGLDYLHSEKKIHRDIKAANVLLSEHGEVKLADFGVAGQLTDTQIKRN*FVGTPF------WMAPEVIKQS 176
                          90       100
                  ....*....|....*....|....
gi 319803120  432 AATVKSDIYSFSMIMQEILTDDIP 455
Cdd:cd06641   177 AYDSKADIWSLGITAIELARGEPP 200
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
279-457 2.07e-04

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: 44.80  E-value: 2.07e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  279 THPHCSRLRLAdlLIAEQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLheRRSQFPvlhMEVIVHLLL 358
Cdd:cd14027    27 TGPNCIEHNEA--LLEEGKMMNRLRHSRVVKLLGVILEEG--KYSLVMEYMEKGNLMHVL--KKVSVP---LSVKGRIIL 97
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  359 QISDALRYLHFQGFIHRSL--------SSYAVHIISPGEA------RLTNLEYMLESEDRGVQRDLTrvplPTQLYnwAA 424
Cdd:cd14027    98 EIIEGMAYLHGKGVIHKDLkpenilvdNDFHIKIADLGLAsfkmwsKLTKEEHNEQREVDGTAKKNA----GTLYY--MA 171
                         170       180       190
                  ....*....|....*....|....*....|....*
gi 319803120  425 PEVI--LQKAATVKSDIYSFSMIMQEILTDDIPWK 457
Cdd:cd14027   172 PEHLndVNAKPTEKSDVYSFAIVLWAIFANKEPYE 206
STKc_LKB1_CaMKK cd14008
Catalytic domain of the Serine/Threonine kinases, Liver Kinase B1, Calmodulin Dependent ...
301-375 2.16e-04

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: 44.85  E-value: 2.16e-04
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 319803120  301 KLRHPYLLQLMAVCLSQDLEKTRLVYERITIGTLFSVLHERRSqfPVLHMEVIVHLLLQISDALRYLHFQGFIHR 375
Cdd:cd14008    60 KLDHPNIVRLYEVIDDPESDKLYLVLEYCEGGPVMELDSGDRV--PPLPEETARKYFRDLVLGLEYLHENGIVHR 132
STKc_p38gamma cd07880
Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase ...
339-460 2.35e-04

Catalytic domain of the Serine/Threonine Kinase, p38gamma Mitogen-Activated Protein Kinase (also called MAPK12); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. p38gamma/MAPK12 is predominantly expressed in skeletal muscle. Unlike p38alpha and p38beta, p38gamma is insensitive to pyridinylimidazoles. It displays an antagonizing function compared to p38alpha. p38gamma inhibits, while p38alpha stimulates, c-Jun phosphorylation and AP-1 mediated transcription. p38gamma also plays a role in the signaling between Ras and the estrogen receptor and has been implicated to increase cell invasion and breast cancer progression. In Xenopus, p38gamma is critical in the meiotic maturation of oocytes. p38 kinases are 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 p38gamma 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: 143385 [Multi-domain]  Cd Length: 343  Bit Score: 45.33  E-value: 2.35e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  339 HERRSQfpvlhmEVIVHLLLQISDALRYLHFQGFIHRSLssyavhiiSPGEARLtNLEYMLESEDRGVQRDLTRVPLPTQ 418
Cdd:cd07880   112 HEKLSE------DRIQFLVYQMLKGLKYIHAAGIIHRDL--------KPGNLAV-NEDCELKILDFGLARQTDSEMTGYV 176
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....
gi 319803120  419 LYNW-AAPEVILQ-KAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd07880   177 VTRWyRAPEVILNwMHYTQTVDIWSVGCIMAEMLTGKPLFKGHD 220
STKc_JNK2 cd07876
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase 2; STKs catalyze the ...
347-460 2.61e-04

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: 45.02  E-value: 2.61e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 VLHMEV----IVHLLLQISDALRYLHFQGFIHRSLSSyaVHIISPGEARLTNLEYMLEsedRGVQRDLTRVPLPTQLYnW 422
Cdd:cd07876   115 VIHMELdherMSYLLYQMLCGIKHLHSAGIIHRDLKP--SNIVVKSDCTLKILDFGLA---RTACTNFMMTPYVVTRY-Y 188
                          90       100       110
                  ....*....|....*....|....*....|....*...
gi 319803120  423 AAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd07876   189 RAPEVILGMGYKENVDIWSVGCIMGELVKGSVIFQGTD 226
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
265-501 2.81e-04

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: 44.62  E-value: 2.81e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  265 WNGSrVTVKELNLpTHPHCSRLRLadlLIAEQEHSSKLRHPYLLQLMAVclsqdleKTRLVYERITI----GTLFSVLHE 340
Cdd:cd14150    21 WHGD-VAVKILKV-TEPTPEQLQA---FKNEMQVLRKTRHVNILLFMGF-------MTRPNFAIITQwcegSSLYRHLHV 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  341 RRSQFPVLHMeviVHLLLQISDALRYLHFQGFIHRSLSSYAVHI-----ISPGEARLTNleymLESEDRGVQrdltRVPL 415
Cdd:cd14150    89 TETRFDTMQL---IDVARQTAQGMDYLHAKNIIHRDLKSNNIFLhegltVKIGDFGLAT----VKTRWSGSQ----QVEQ 157
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  416 PTQLYNWAAPEVI-LQKAA--TVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNYLEADV-----RLPKPYYDI 487
Cdd:cd14150   158 PSGSILWMAPEVIrMQDTNpySFQSDVYAYGVVLYELMSGTLPYSNINNRDQIIFMVGRGYLSPDLsklssNCPKAMKRL 237
                         250
                  ....*....|....
gi 319803120  488 VKSGIHVKQKDRTM 501
Cdd:cd14150   238 LIDCLKFKREERPL 251
STKc_MAP3K8 cd13995
Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) ...
284-456 2.87e-04

Catalytic domain of the Serine/Threonine kinase, Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase 8; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MAP3K8 is also called Tumor progression locus 2 (Tpl2) or Cancer Osaka thyroid (Cot), and was first identified as a proto-oncogene in T-cell lymphoma induced by MoMuL virus and in breast carcinoma induced by MMTV. Activated MAP3K8 induces various MAPK pathways including Extracellular Regulated Kinase (ERK) 1/2, c-Jun N-terminal kinase (JNK), and p38. It plays a pivotal role in innate immunity, linking Toll-like receptors to the production of TNF and the activation of ERK in macrophages. It is also required in interleukin-1beta production and is critical in host defense against Gram-positive bacteria. 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 MAP3K8 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: 270897 [Multi-domain]  Cd Length: 256  Bit Score: 44.23  E-value: 2.87e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  284 SRLRLADLLI-------AEQEHSSKLRHPYLLQLMAVCLSQdlEKTRLVYEritIGTLFSVLHERRSQFPVLHMEVIvHL 356
Cdd:cd13995    28 TKKRMACKLIpveqfkpSDVEIQACFRHENIAELYGALLWE--ETVHLFME---AGEGGSVLEKLESCGPMREFEII-WV 101
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  357 LLQISDALRYLHFQGFIHRSLSSYAVHIISpGEARLTNLEYMLE-SEDRGVQRDLTrvplPTQLYnwAAPEVILQKAATV 435
Cdd:cd13995   102 TKHVLKGLDFLHSKNIIHHDIKPSNIVFMS-TKAVLVDFGLSVQmTEDVYVPKDLR----GTEIY--MSPEVILCRGHNT 174
                         170       180
                  ....*....|....*....|.
gi 319803120  436 KSDIYSFSMIMQEILTDDIPW 456
Cdd:cd13995   175 KADIYSLGATIIHMQTGSPPW 195
STKc_MEKK2 cd06652
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular ...
267-456 3.17e-04

Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein (MAP)/Extracellular signal-Regulated Kinase (ERK) Kinase Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MEKK2 is a MAPK kinase kinase (MAPKKK or MKKK), that phosphorylates and activates the MAPK kinase MEK5 (or MKK5), which in turn phosphorylates and activates ERK5. The ERK5 cascade plays roles in promoting cell proliferation, differentiation, neuronal survival, and neuroprotection. MEKK2 also activates ERK1/2, c-Jun N-terminal kinase (JNK) and p38 through their respective MAPKKs MEK1/2, JNK-activating kinase 2 (JNKK2), and MKK3/6. MEKK2 plays roles in T cell receptor signaling, immune synapse formation, cytokine gene expression, as well as in EGF and FGF receptor signaling. The MEKK2 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: 270818 [Multi-domain]  Cd Length: 264  Bit Score: 44.26  E-value: 3.17e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  267 GSRVTVKELNL-PTHPHCSRLrlADLLIAEQEHSSKLRHPYLLQLMAvCLSQDLEKTRLVYERITIGtlfSVLHERRSQF 345
Cdd:cd06652    27 GRELAVKQVQFdPESPETSKE--VNALECEIQLLKNLLHERIVQYYG-CLRDPQERTLSIFMEYMPG---GSIKDQLKSY 100
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 PVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPLP-------TQ 418
Cdd:cd06652   101 GALTENVTRKYTRQILEGVHYLHSNMIVHRDIKGANILRDSVGNVKLG---------DFGASKRLQTICLSgtgmksvTG 171
                         170       180       190
                  ....*....|....*....|....*....|....*...
gi 319803120  419 LYNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06652   172 TPYWMSPEVISGEGYGRKADIWSVGCTVVEMLTEKPPW 209
PHA02874 PHA02874
ankyrin repeat protein; Provisional
7-141 4.35e-04

ankyrin repeat protein; Provisional


Pssm-ID: 165205 [Multi-domain]  Cd Length: 434  Bit Score: 44.57  E-value: 4.35e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120    7 LPVPCpvqlgtLRNDSleaqlheyvkqgnyvkVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRC 86
Cdd:PHA02874   97 LPIPC------IEKDM----------------IKTILDCGIDVNIKDAELKTFLHYAIKKGDLESIKMLFEYGADVNIED 154
                          90       100       110       120       130
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 319803120   87 FDGSTPVHAAAFSGNQWILSKLLDAGGDLRLHDERGQNPKTWALTAGKERSTQIV 141
Cdd:PHA02874  155 DNGCYPIHIAIKHNFFDIIKLLLEKGAYANVKDNNGESPLHNAAEYGDYACIKLL 209
STKc_JNK cd07850
Catalytic domain of the Serine/Threonine Kinase, c-Jun N-terminal Kinase; STKs catalyze the ...
347-460 5.03e-04

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: 43.94  E-value: 5.03e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  347 VLHMEV----IVHLLLQISDALRYLHFQGFIHRSL--------SSYAVHIISPGEARLTNLEYMLESEdrgvqrdltrvp 414
Cdd:cd07850    94 VIQMDLdherMSYLLYQMLCGIKHLHSAGIIHRDLkpsnivvkSDCTLKILDFGLARTAGTSFMMTPY------------ 161
                          90       100       110       120
                  ....*....|....*....|....*....|....*....|....*.
gi 319803120  415 LPTQLYNwaAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLD 460
Cdd:cd07850   162 VVTRYYR--APEVILGMGYKENVDIWSVGCIMGEMIRGTVLFPGTD 205
STKc_Unc-89_rpt2 cd14112
Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated ...
289-458 5.11e-04

Catalytic kinase domain, second repeat, of the Giant Serine/Threonine Kinase Uncoordinated protein 89; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The nematode Unc-89 gene, through alternative promoter use and splicing, encodes at least six major isoforms (Unc-89A to Unc-89F) of giant muscle proteins that are homologs for the vetebrate obscurin. In flies, five isoforms of Unc-89 have been detected: four in the muscles of adult flies (two in the indirect flight muscle and two in other muscles) and another isoform in the larva. Unc-89 in nematodes is required for normal muscle cell architecture. In flies, it is necessary for the development of a symmetrical sarcomere in the flight muscles. Unc-89 proteins contain several adhesion and signaling domains including multiple copies of the immunoglobulin (Ig) domain, as well as fibronectin type III (FN3), SH3, RhoGEF, and PH domains. The nematode Unc-89 isoforms D, C, D, and F contain two kinase domain with B and F having two complete kinase domains while the first repeat of C and D are partial domains. Homology modeling suggests that the first kinase repeat of Unc-89 may be catalytically inactive, a pseudokinase, while the second kinase repeat may be active. The Unc-89 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: 271014 [Multi-domain]  Cd Length: 259  Bit Score: 43.67  E-value: 5.11e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  289 ADLLIAEQEHSSKLRHPYLLQLMAVclSQDLEKTRLVYERI--TIGTLFSVLHERRSQfpvlhmeVIVHLLLQISDALRY 366
Cdd:cd14112    44 ASEAVREFESLRTLQHENVQRLIAA--FKPSNFAYLVMEKLqeDVFTRFSSNDYYSEE-------QVATTVRQILDALHY 114
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  367 LHFQGFIH----------RSLSSYAVHIISPGEARLTNLEYMlesedrgvqrdltrVPLPTQLyNWAAPEVILQKA-ATV 435
Cdd:cd14112   115 LHFKGIAHldvqpdnimfQSVRSWQVKLVDFGRAQKVSKLGK--------------VPVDGDT-DWASPEFHNPETpITV 179
                         170       180
                  ....*....|....*....|...
gi 319803120  436 KSDIYSFSMIMQEILTDDIPWKG 458
Cdd:cd14112   180 QSDIWGLGVLTFCLLSGFHPFTS 202
STKc_IRAK4 cd14158
Catalytic domain of the Serine/Threonine kinase, Interleukin-1 Receptor Associated Kinase 4; ...
300-451 5.29e-04

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: 43.64  E-value: 5.29e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLMAvcLSQDLEKTRLVYERITIGTLFSVLHERRSQFPVlhmevIVHLLLQI----SDALRYLHFQGFIHR 375
Cdd:cd14158    69 AKCQHENLVELLG--YSCDGPQLCLVYTYMPNGSLLDRLACLNDTPPL-----SWHMRCKIaqgtANGINYLHENNHIHR 141
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319803120  376 SLSSYAVHIISPGEARLTNLEYMLESEdRGVQRDLTRVPLPTQLYnwAAPEViLQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd14158   142 DIKSANILLDETFVPKISDFGLARASE-KFSQTIMTERIVGTTAY--MAPEA-LRGEITPKSDIFSFGVVLLEIIT 213
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
348-451 5.37e-04

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: 43.63  E-value: 5.37e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDL-----------TRVPLp 416
Cdd:cd05054   135 LTLEDLICYSFQVARGMEFLASRKCIHRDLAARNI---------LLSENNVVKICDFGLARDIykdpdyvrkgdARLPL- 204
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 319803120  417 tqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05054   205 ----KWMAPESIFDKVYTTQSDVWSFGVLLWEIFS 235
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
300-484 5.81e-04

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: 43.55  E-value: 5.81e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  300 SKLRHPYLLQLmavcLSQDLEKTRL--VYERITIGTLFSVLHERRSQfpVLHMEVIVHLLLQISDALRYLHFQGFIHRSL 377
Cdd:cd08529    54 SKLNSPYVIKY----YDSFVDKGKLniVMEYAENGDLHSLIKSQRGR--PLPEDQIWKFFIQTLLGLSHLHSKKILHRDI 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  378 SSYAVHIISPGEARLTNLeymlesedrGVQRDL--------TRVPLPTQLynwaAPEVILQKAATVKSDIYSFSMIMQEI 449
Cdd:cd08529   128 KSMNIFLDKGDNVKIGDL---------GVAKILsdttnfaqTIVGTPYYL----SPELCEDKPYNEKSDVWALGCVLYEL 194
                         170       180       190
                  ....*....|....*....|....*....|....*.
gi 319803120  450 LTDDIPWKGLD-GSVVKKaVVSGNYLEadvrLPKPY 484
Cdd:cd08529   195 CTGKHPFEAQNqGALILK-IVRGKYPP----ISASY 225
STKc_PAK4 cd06657
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 4; STKs catalyze the ...
348-456 5.99e-04

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: 43.47  E-value: 5.99e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESeDRGVQRDLTRVPLPTqlynWAAPEV 427
Cdd:cd06657   113 MNEEQIAAVCLAVLKALSVLHAQGVIHRDIKSDSILLTHDGRVKLSDFGFCAQV-SKEVPRRKSLVGTPY----WMAPEL 187
                          90       100
                  ....*....|....*....|....*....
gi 319803120  428 ILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd06657   188 ISRLPYGPEVDIWSLGIMVIEMVDGEPPY 216
PTKc_Wee1_fungi cd14052
Catalytic domain of the Protein Tyrosine Kinases, Fungal Wee1 proteins; PTKs catalyze the ...
253-459 6.19e-04

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: 43.56  E-value: 6.19e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  253 FSGPYMVmTNLVWNGSRVTVKELNLPTHPHCSRLRLADLLIAEQEHSSKlRHPYLLQLMAVCLSQDleKTRLVYERITIG 332
Cdd:cd14052    13 FSQVYKV-SERVPTGKVYAVKKLKPNYAGAKDRLRRLEEVSILRELTLD-GHDNIVQLIDSWEYHG--HLYIQTELCENG 88
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  333 TLFSVLHERrSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEyMLES--EDRGVQRDL 410
Cdd:cd14052    89 SLDVFLSEL-GLLGRLDEFRVWKILVELSLGLRFIHDHHFVHLDLKPANVLITFEGTLKIGDFG-MATVwpLIRGIEREG 166
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*
gi 319803120  411 TRVPLptqlynwaAPEVILQKAATVKSDIYSFSMIMQEI-----LTDD-IPWKGL 459
Cdd:cd14052   167 DREYI--------APEILSEHMYDKPADIFSLGLILLEAaanvvLPDNgDAWQKL 213
STKc_RSK2_C cd14176
C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called ...
356-508 7.13e-04

C-terminal catalytic domain of the Serine/Threonine Kinase, Ribosomal S6 kinase 2 (also called 90kDa ribosomal protein S6 kinase 3 or Ribosomal protein S6 kinase alpha-3); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. RSK2 is also called p90RSK3, RPS6KA3, S6K-alpha-3, or MAPK-activated protein kinase 1b (MAPKAPK-1b). RSK2 is expressed highly in the regions of the brain with high synaptic activity. It plays a role in the maintenance and consolidation of excitatory synapses. It is a specific modulator of phospholipase D in calcium-regulated exocytosis. Mutations in the RSK2 gene, RPS6KA3, cause Coffin-Lowry syndrome (CLS), a rare syndromic form of X-linked mental retardation characterized by growth and psychomotor retardation and skeletal abnormalities. RSK2 is one of four RSK isoforms (RSK1-4) from distinct genes present in vertebrates. RSKs contain an N-terminal kinase domain (NTD) from the AGC family and a C-terminal kinase domain (CTD) from the CAMK family. They are activated by signaling inputs from extracellular regulated kinase (ERK) and phosphoinositide dependent kinase 1 (PDK1). ERK phosphorylates and activates the CTD of RSK, serving as a docking site for PDK1, which phosphorylates and activates the NTD, which in turn phosphorylates all known RSK substrates. RSKs act as downstream effectors of mitogen-activated protein kinase (MAPK) and play key roles in mitogen-activated cell growth, differentiation, and survival. The RSK2 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: 271078 [Multi-domain]  Cd Length: 339  Bit Score: 43.47  E-value: 7.13e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  356 LLLQISDALRYLHFQGFIHRSLSSYAVHII----SPGEARLTNLEYmleSEDRGVQRDLTRVPLPTQlyNWAAPEVILQK 431
Cdd:cd14176   118 VLFTITKTVEYLHAQGVVHRDLKPSNILYVdesgNPESIRICDFGF---AKQLRAENGLLMTPCYTA--NFVAPEVLERQ 192
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  432 AATVKSDIYSFSMIMQEILT---------DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKpyyDIVKSGIHVKQKDRTMN 502
Cdd:cd14176   193 GYDAACDIWSLGVLLYTMLTgytpfangpDDTPEEILARIGSGKFSLSGGYWNSVSDTAK---DLVSKMLHVDPHQRLTA 269

                  ....*.
gi 319803120  503 LQDIRY 508
Cdd:cd14176   270 ALVLRH 275
STKc_Yank1 cd05578
Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the ...
283-506 7.44e-04

Catalytic domain of the Serine/Threonine Kinase, Yank1; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily contains uncharacterized STKs with similarity to the human protein designated as Yank1 or STK32A. The Yank1 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: 270730 [Multi-domain]  Cd Length: 257  Bit Score: 43.01  E-value: 7.44e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  283 CSRLRLADLLIAEQEHSSKLRHPYLLQLmavCLS-QDLEKTRLVYERITIGTL-FSVLHERRsqfpvLHMEVIVHLLLQI 360
Cdd:cd05578    38 CIEKDSVRNVLNELEILQELEHPFLVNL---WYSfQDEEDMYMVVDLLLGGDLrYHLQQKVK-----FSEETVKFYICEI 109
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  361 SDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPLPTQLYN---WAAPEVILQKAATVKS 437
Cdd:cd05578   110 VLALDYLHSKNIIHRDIKPDNILLDEQGHVHIT---------DFNIATKLTDGTLATSTSGtkpYMAPEVFMRAGYSFAV 180
                         170       180       190       200       210       220       230
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319803120  438 DIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSgnYLEADVRLP----KPYYDIVKSGIHVKQKDRTMNLQDI 506
Cdd:cd05578   181 DWWSLGVTAYEMLRGKRPYEIHSRTSIEEIRAK--FETASVLYPagwsEEAIDLINKLLERDPQKRLGDLSDL 251
STKc_MAST cd05609
Catalytic domain of the Protein Serine/Threonine Kinase, Microtubule-associated serine ...
363-488 8.39e-04

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: 43.16  E-value: 8.39e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  363 ALRYLHFQGFIHRSLSSYAVHIISPGEARL--------------TNL-EYMLESEDRGVQrDLTRVPLPtqlyNWAAPEV 427
Cdd:cd05609   112 ALEYLHSYGIVHRDLKPDNLLITSMGHIKLtdfglskiglmsltTNLyEGHIEKDTREFL-DKQVCGTP----EYIAPEV 186
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319803120  428 ILQKAATVKSDIYSFSMIMQEILTDDIPWKG-----LDGSVVKKAVVsgnYLEADVRLPKPYYDIV 488
Cdd:cd05609   187 ILRQGYGKPVDWWAMGIILYEFLVGCVPFFGdtpeeLFGQVISDEIE---WPEGDDALPDDAQDLI 249
STKc_PLK4 cd14186
Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; STKs catalyze the ...
295-473 8.46e-04

Catalytic domain of the Serine/Threonine Kinase, Polo-like kinase 4; 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. PLK4, also called SAK or STK18, is structurally different from other PLKs in that it contains only one polo box that can form two adjacent polo boxes and a functional PDB by homodimerization. It is required for late mitotic progression, cell survival, and embryonic development. It localizes to centrosomes and is required for centriole duplication and chromosomal stability. Overexpression of PLK4 may be associated with colon tumors. The PLK4 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: 271088 [Multi-domain]  Cd Length: 256  Bit Score: 42.93  E-value: 8.46e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAvcLSQDLEKTRLVYERITIGTLFSVLHERRSQFPvlhMEVIVHLLLQISDALRYLHFQGFIH 374
Cdd:cd14186    51 EVEIHCQLKHPSILELYN--YFEDSNYVYLVLEMCHNGEMSRYLKNRKKPFT---EDEARHFMHQIVTGMLYLHSHGILH 125
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  375 RSLSsyavhiispgearLTNL----EYMLESEDRGVQrdlTRVPLPTQLY-------NWAAPEVILQKAATVKSDIYSFS 443
Cdd:cd14186   126 RDLT-------------LSNLlltrNMNIKIADFGLA---TQLKMPHEKHftmcgtpNYISPEIATRSAHGLESDVWSLG 189
                         170       180       190
                  ....*....|....*....|....*....|...
gi 319803120  444 MIMQEILTDDIPWkglDGSVVKKA---VVSGNY 473
Cdd:cd14186   190 CMFYTLLVGRPPF---DTDTVKNTlnkVVLADY 219
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
302-451 9.09e-04

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: 42.96  E-value: 9.09e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  302 LRHPYLLQLMAVCLSQDLEKTRLVYERITIGTLFSVLHERRsqfpvLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYA 381
Cdd:cd05080    63 LYHENIVKYKGCCSEQGGKSLQLIMEYVPLGSLRDYLPKHS-----IGLAQLLLFAQQICEGMAYLHSQHYIHRDLAARN 137
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  382 VhiispgearLTNLEYMLESEDRGVQRdltRVPLPTQLYN----------WAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05080   138 V---------LLDNDRLVKIGDFGLAK---AVPEGHEYYRvredgdspvfWYAPECLKEYKFYYASDVWSFGVTLYELLT 205
STKc_Chk2 cd14084
Catalytic domain of the Serine/Threonine kinase, Cell cycle Checkpoint Kinase 2; STKs catalyze ...
268-473 9.78e-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: 42.77  E-value: 9.78e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  268 SRVTVKELNLPTHPHCSRLRLADLLIAEQEHS--SKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSvlherRSQF 345
Cdd:cd14084    32 KKVAIKIINKRKFTIGSRREINKPRNIETEIEilKKLSHPCIIKIEDFFDAED--DYYIVLELMEGGELFD-----RVVS 104
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  346 PVLHMEVIVHLLL-QISDALRYLHFQGFIHRSLSSYAVHIISPGE---ARLTNLEYMLESEDRGVQRDLTRVPLptqlyn 421
Cdd:cd14084   105 NKRLKEAICKLYFyQMLLAVKYLHSNGIIHRDLKPENVLLSSQEEeclIKITDFGLSKILGETSLMKTLCGTPT------ 178
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|....*.
gi 319803120  422 WAAPEVIL---QKAATVKSDIYSFSMIMQEILTDDIPWKG-LDGSVVKKAVVSGNY 473
Cdd:cd14084   179 YLAPEVLRsfgTEGYTRAVDCWSLGVILFICLSGYPPFSEeYTQMSLKEQILSGKY 234
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
266-514 9.87e-04

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: 42.84  E-value: 9.87e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  266 NGSRVTVKELNLpthphcSRLRLADLLIAEQEHS--SKLRHPYLLQLMAVCLsqdlEKTRL--VYERITIGTLFSVLHER 341
Cdd:cd08215    24 DGKLYVLKEIDL------SNMSEKEREEALNEVKllSKLKHPNIVKYYESFE----ENGKLciVMEYADGGDLAQKIKKQ 93
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  342 RSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDrgvqrDLTRVPLPTQL 419
Cdd:cd08215    94 KKKGQPFPEEQILDWFVQICLALKYLHSRKILHRDLKTQNIFLTKDGVVKLGDfgISKVLESTT-----DLAKTVVGTPY 168
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  420 YnwAAPEVILQKAATVKSDIYSFSMIMQEILT-------DDIPwkgldgSVVKKaVVSGNYleadVRLPKPY----YDIV 488
Cdd:cd08215   169 Y--LSPELCENKPYNYKSDIWALGCVLYELCTlkhpfeaNNLP------ALVYK-IVKGQY----PPIPSQYsselRDLV 235
                         250       260
                  ....*....|....*....|....*.
gi 319803120  489 KSGIHVKQKDRTmnlqDIRYILKNDL 514
Cdd:cd08215   236 NSMLQKDPEKRP----SANEILSSPF 257
STKc_CaMKI cd14083
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
301-445 9.95e-04

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I; 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. In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. 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. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI 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: 270985 [Multi-domain]  Cd Length: 259  Bit Score: 42.74  E-value: 9.95e-04
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVclSQDLEKTRLVYERITIGTLFSVLHERRSqfpvlHMEV-IVHLLLQISDALRYLHFQGFIHRSLSS 379
Cdd:cd14083    57 KIKHPNIVQLLDI--YESKSHLYLVMELVTGGELFDRIVEKGS-----YTEKdASHLIRQVLEAVDYLHSLGIVHRDLKP 129
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 319803120  380 YAVHIISPGEarltNLEYML------ESEDRGVQRDLTRVPlptqlyNWAAPEVILQKAATVKSDIYSFSMI 445
Cdd:cd14083   130 ENLLYYSPDE----DSKIMIsdfglsKMEDSGVMSTACGTP------GYVAPEVLAQKPYGKAVDCWSIGVI 191
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
348-451 1.02e-03

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: 43.04  E-value: 1.02e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVhiispgearLTNLEYMLESEDRGVQRDLTRVP---------LPTQ 418
Cdd:cd05102   169 LTMEDLICYSFQVARGMEFLASRKCIHRDLAARNI---------LLSENNVVKICDFGLARDIYKDPdyvrkgsarLPLK 239
                          90       100       110
                  ....*....|....*....|....*....|...
gi 319803120  419 lynWAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05102   240 ---WMAPESIFDKVYTTQSDVWSFGVLLWEIFS 269
Ank_4 pfam13637
Ankyrin repeats (many copies);
58-101 1.05e-03

Ankyrin repeats (many copies);


Pssm-ID: 372654 [Multi-domain]  Cd Length: 54  Bit Score: 38.41  E-value: 1.05e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 319803120    58 TALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAAFSGN 101
Cdd:pfam13637    3 TALHAAAASGHLELLRLLLEKGADINAVDGNGETALHFAASNGN 46
STKc_CaMKI_gamma cd14166
Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase ...
324-486 1.15e-03

Catalytic domain of the Serine/Threonine kinase, Calcium/calmodulin-dependent protein kinase Type I gamma; 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. The CaMK family includes CaMKI, CaMKII, CaMKIV, and CaMK kinase (CaMKK). In vertebrates, there are four CaMKI proteins encoded by different genes (alpha, beta, gamma, and delta), each producing at least one variant. CaMKs contain an N-terminal catalytic domain and a C-terminal regulatory domain that harbors a CaM binding site. 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. In addition, they may be involved in osteoclast differentiation and bone resorption. The CaMKI-gamma 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: 271068 [Multi-domain]  Cd Length: 285  Bit Score: 42.67  E-value: 1.15e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  324 LVYERITIGTLFSVLHERrSQFPVLHMEVIVHlllQISDALRYLHFQGFIHRSLSSYAVHIISPGE-ARLTNLEYMLES- 401
Cdd:cd14166    77 LVMQLVSGGELFDRILER-GVYTEKDASRVIN---QVLSAVKYLHENGIVHRDLKPENLLYLTPDEnSKIMITDFGLSKm 152
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  402 EDRGVQRDLTRVPlptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNYleadvRLP 481
Cdd:cd14166   153 EQNGIMSTACGTP------GYVAPEVLAQKPYSKAVDCWSIGVITYILLCGYPPFYEETESRLFEKIKEGYY-----EFE 221

                  ....*
gi 319803120  482 KPYYD 486
Cdd:cd14166   222 SPFWD 226
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
303-461 1.19e-03

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: 42.81  E-value: 1.19e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  303 RHPYLLQLMAVCLSQDLEKTrLVYERITIGTLFSVLHERrSQFPVlhmEVIVHLLLQISDALRYLHFQ-GFIHRSLSSYA 381
Cdd:cd06620    61 HSPYIVSFYGAFLNENNNII-ICMEYMDCGSLDKILKKK-GPFPE---EVLGKIAVAVLEGLTYLYNVhRIIHRDIKPSN 135
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  382 VHIISPGEARLTnleymleseDRGVQRDL------TRVPLPTqlynWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIP 455
Cdd:cd06620   136 ILVNSKGQIKLC---------DFGVSGELinsiadTFVGTST----YMSPERIQGGKYSVKSDVWSLGLSIIELALGEFP 202

                  ....*.
gi 319803120  456 WKGLDG 461
Cdd:cd06620   203 FAGSND 208
PHA02874 PHA02874
ankyrin repeat protein; Provisional
27-130 1.43e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165205 [Multi-domain]  Cd Length: 434  Bit Score: 43.03  E-value: 1.43e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   27 LHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAAFSGNQWIls 106
Cdd:PHA02874  161 IHIAIKHNFFDIIKLLLEKGAYANVKDNNGESPLHNAAEYGDYACIKLLIDHGNHIMNKCKNGFTPLHNAIIHNRSAI-- 238
                          90       100
                  ....*....|....*....|....
gi 319803120  107 KLLDAGGDLRLHDERGQNPKTWAL 130
Cdd:PHA02874  239 ELLINNASINDQDIDGSTPLHHAI 262
STKc_CDK6 cd07862
Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs ...
293-450 1.43e-03

Catalytic domain of the Serine/Threonine Kinase, Cyclin-Dependent protein Kinase 6; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CDK6 is regulated by D-type cyclins and INK4 inhibitors. It is active towards the retinoblastoma (pRb) protein, implicating it to function in regulating the early G1 phase of the cell cycle. It is expressed ubiquitously and is localized in the cytoplasm. It is also present in the ruffling edge of spreading fibroblasts and may play a role in cell spreading. It binds to the p21 inhibitor without any effect on its own activity and it is overexpressed in squamous cell carcinomas and neuroblastomas. CDK6 has also been shown to inhibit cell differentiation in many cell types. 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 CDK6 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: 270846 [Multi-domain]  Cd Length: 290  Bit Score: 42.33  E-value: 1.43e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  293 IAEQEHSSKLRHPYLLQLMAVCL--SQDLE-KTRLVYERITiGTLFSVLHerRSQFPVLHMEVIVHLLLQISDALRYLHF 369
Cdd:cd07862    52 VAVLRHLETFEHPNVVRLFDVCTvsRTDREtKLTLVFEHVD-QDLTTYLD--KVPEPGVPTETIKDMMFQLLRGLDFLHS 128
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  370 QGFIHRSLSSYAVHIISPGEARLTNLEYmleSEDRGVQRDLTRVpLPTQLYNwaAPEVILQKAATVKSDIYSFSMIMQEI 449
Cdd:cd07862   129 HRVVHRDLKPQNILVTSSGQIKLADFGL---ARIYSFQMALTSV-VVTLWYR--APEVLLQSSYATPVDLWSVGCIFAEM 202

                  .
gi 319803120  450 L 450
Cdd:cd07862   203 F 203
STKc_EIF2AK3_PERK cd14048
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
352-450 1.77e-03

Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor 2-Alpha Kinase 3 or PKR-like Endoplasmic Reticulum Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PERK (or EIF2AK3) is a type-I ER transmembrane protein containing a luminal domain bound with the chaperone BiP under unstressed conditions and a cytoplasmic catalytic kinase domain. In response to the accumulation of misfolded or unfolded proteins in the ER, PERK is activated through the release of BiP, allowing it to dimerize and autophosphorylate. It functions as the central regulator of translational control during the Unfolded Protein Response (UPR) pathway. In addition to the eIF-2 alpha subunit, PERK also phosphorylates Nrf2, a leucine zipper transcription factor which regulates cellular redox status and promotes cell survival during the UPR. EIF2AKs phosphorylate the alpha subunit of eIF-2, resulting in the downregulation of protein synthesis. The PERK 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: 270950 [Multi-domain]  Cd Length: 281  Bit Score: 42.17  E-value: 1.77e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  352 VIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEyMLESEDRGVQRDLTRVPLP----------TQLYn 421
Cdd:cd14048   119 VCLNIFKQIASAVEYLHSKGLIHRDLKPSNVFFSLDDVVKVGDFG-LVTAMDQGEPEQTVLTPMPayakhtgqvgTRLY- 196
                          90       100
                  ....*....|....*....|....*....
gi 319803120  422 wAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd14048   197 -MSPEQIHGNQYSEKVDIFALGLILFELI 224
STKc_NUAK2 cd14161
Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs ...
295-483 1.78e-03

Catalytic domain of the Serine/Threonine Kinase, novel (nua) kinase family NUAK 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. NUAK proteins are classified as AMP-activated protein kinase (AMPK)-related kinases, which like AMPK are activated by the major tumor suppressor LKB1. Vertebrates contain two NUAK proteins, called NUAK1 and NUAK2. NUAK2, also called SNARK (Sucrose, non-fermenting 1/AMP-activated protein kinase-related kinase), is involved in energy metabolism. It is activated by hyperosmotic stress, DNA damage, and nutrients such as glucose and glutamine. NUAK2-knockout mice develop obesity, altered serum lipid profiles, hyperinsulinaemia, hyperglycaemia, and impaired glucose tolerance. NUAK2 is implicated in regulating actin stress fiber assembly through its association with myosin phosphatase Rho-interacting protein (MRIP), which leads to an increase in myosin regulatory light chain (MLC) phosphorylation. It is also associated with tumor growth, migration, and oncogenicity of melanoma cells. The NUAK2 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: 271063 [Multi-domain]  Cd Length: 255  Bit Score: 41.86  E-value: 1.78e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  295 EQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRsqfPVLHMEViVHLLLQISDALRYLHFQGFIH 374
Cdd:cd14161    52 EIEIMSSLNHPHIISVYEVFENSS--KIVIVMEYASRGDLYDYISERQ---RLSELEA-RHFFRQIVSAVHYCHANGIVH 125
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  375 RSLSSYAVHIISPGEARLTNLEYM-LESEDRGVQrDLTRVPLptqlynWAAPEVILQKAAT-VKSDIYSFSMIMQEILTD 452
Cdd:cd14161   126 RDLKLENILLDANGNIKIADFGLSnLYNQDKFLQ-TYCGSPL------YASPEIVNGRPYIgPEVDSWSLGVLLYILVHG 198
                         170       180       190
                  ....*....|....*....|....*....|.
gi 319803120  453 DIPWKGLDGSVVKKAVVSGNYLEAdvrlPKP 483
Cdd:cd14161   199 TMPFDGHDYKILVKQISSGAYREP----TKP 225
STKc_MLCK cd14103
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase; STKs catalyze the ...
301-445 2.29e-03

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: 41.44  E-value: 2.29e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVclsqdLEKTR---LVYERITIGTLF-------SVLHERRSqfpvlhmeviVHLLLQISDALRYLHFQ 370
Cdd:cd14103    46 QLRHPRLLQLYDA-----FETPRemvLVMEYVAGGELFervvdddFELTERDC----------ILFMRQICEGVQYMHKQ 110
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  371 GFIHRSL----------SSYAVHIISPGEARLTNleymlesedrgvQRDLTRVPLPTQlyNWAAPEVILQKAATVKSDIY 440
Cdd:cd14103   111 GILHLDLkpenilcvsrTGNQIKIIDFGLARKYD------------PDKKLKVLFGTP--EFVAPEVVNYEPISYATDMW 176

                  ....*
gi 319803120  441 SFSMI 445
Cdd:cd14103   177 SVGVI 181
STKc_CDK4_6_like cd07838
Catalytic domain of Cyclin-Dependent protein Kinase 4 and 6-like Serine/Threonine Kinases; ...
304-449 2.46e-03

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: 41.49  E-value: 2.46e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  304 HPYLLQLMAVCLSQDLEKTRLVYeritigTLFSVLHERRSQF------PVLHMEVIVHLLLQISDALRYLHFQGFIHRSL 377
Cdd:cd07838    60 HPNVVRLLDVCHGPRTDRELKLT------LVFEHVDQDLATYldkcpkPGLPPETIKDLMRQLLRGLDFLHSHRIVHRDL 133
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 319803120  378 SSYAVHIISPGEARLTnleymleseDRGVQRDLT-RVPLPTQLYN-W-AAPEVILQK--AATVksDIYSFSMIMQEI 449
Cdd:cd07838   134 KPQNILVTSDGQVKLA---------DFGLARIYSfEMALTSVVVTlWyRAPEVLLQSsyATPV--DMWSVGCIFAEL 199
PHA03207 PHA03207
serine/threonine kinase US3; Provisional
340-479 2.54e-03

serine/threonine kinase US3; Provisional


Pssm-ID: 165473 [Multi-domain]  Cd Length: 392  Bit Score: 42.14  E-value: 2.54e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  340 ERRSQFPVLHMEVIVHLLLQisdALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDLTRVPLPTQL 419
Cdd:PHA03207  177 DRSGPLPLEQAITIQRRLLE---ALAYLHGRGIIHRDVKTENIFLDEPENAVLG---------DFGAACKLDAHPDTPQC 244
                          90       100       110       120       130       140
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 319803120  420 YNWA------APEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGldgsvvKKAVVSGNYLEADVR 479
Cdd:PHA03207  245 YGWSgtletnSPELLALDPYCAKTDIWSAGLVLFEMSVKNVTLFG------KQVKSSSSQLRSIIR 304
PHA02876 PHA02876
ankyrin repeat protein; Provisional
19-115 2.58e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165207 [Multi-domain]  Cd Length: 682  Bit Score: 42.36  E-value: 2.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   19 RNDSLEAQLHEYVKQG-NYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRK-FVDVLVDYGSDPNHRCFDGSTPVHAA 96
Cdd:PHA02876  303 KNIKGETPLYLMAKNGyDTENIRTLIMLGADVNAADRLYITPLHQASTLDRNKdIVITLLELGANVNARDYCDKTPIHYA 382
                          90
                  ....*....|....*....
gi 319803120   97 AFSGNQWILSKLLDAGGDL 115
Cdd:PHA02876  383 AVRNNVVIINTLLDYGADI 401
PHA02874 PHA02874
ankyrin repeat protein; Provisional
18-125 2.81e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165205 [Multi-domain]  Cd Length: 434  Bit Score: 41.87  E-value: 2.81e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   18 LRNDSLEAQLHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGlRKFVDVLVDYGSdPNHRCFDGSTPVH-AA 96
Cdd:PHA02874  185 VKDNNGESPLHNAAEYGDYACIKLLIDHGNHIMNKCKNGFTPLHNAIIHN-RSAIELLINNAS-INDQDIDGSTPLHhAI 262
                          90       100
                  ....*....|....*....|....*....
gi 319803120   97 AFSGNQWILSKLLDAGGDLRLHDERGQNP 125
Cdd:PHA02874  263 NPPCDIDIIDILLYHKADISIKDNKGENP 291
STKc_ULK2 cd14201
Catalytic domain of the Serine/Threonine kinase, Unc-51-like kinase 2; STKs catalyze the ...
348-458 2.96e-03

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: 41.15  E-value: 2.96e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDLTRVPLPTQLYN---WAA 424
Cdd:cd14201   102 LSEDTIRVFLQQIAAAMRILHSKGIIHRDLKPQNILLSYASRKKSSVSGIRIKIADFGFARYLQSNMMAATLCGspmYMA 181
                          90       100       110
                  ....*....|....*....|....*....|....
gi 319803120  425 PEVILQKAATVKSDIYSFSMIMQEILTDDIPWKG 458
Cdd:cd14201   182 PEVIMSQHYDAKADLWSIGTVIYQCLVGKPPFQA 215
STKc_MLCK2 cd14190
Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze ...
290-473 3.16e-03

Catalytic domain of the Serine/Threonine Kinase, Myosin Light Chain Kinase 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. MLCK2 (or MYLK2) phosphorylates myosin regulatory light chain and controls the contraction of skeletal muscles. MLCK2 contains a single kinase domain near the C-terminus followed by a regulatory segment containing an autoinhibitory Ca2+/calmodulin binding site. The MLCK2 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: 271092 [Multi-domain]  Cd Length: 261  Bit Score: 41.06  E-value: 3.16e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  290 DLLIAEQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRSQFPVLHMEVIVHlllQISDALRYLHF 369
Cdd:cd14190    46 EMVLLEIQVMNQLNHRNLIQLYEAIETPN--EIVLFMEYVEGGELFERIVDEDYHLTEVDAMVFVR---QICEGIQFMHQ 120
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  370 QGFIHRSL----------SSYAVHIISPGEARLTNLEYMLesedrgvqrdltRVPLPTQlyNWAAPEVILQKAATVKSDI 439
Cdd:cd14190   121 MRVLHLDLkpenilcvnrTGHQVKIIDFGLARRYNPREKL------------KVNFGTP--EFLSPEVVNYDQVSFPTDM 186
                         170       180       190
                  ....*....|....*....|....*....|....
gi 319803120  440 YSFSMIMQEILTDDIPWKGLDGSVVKKAVVSGNY 473
Cdd:cd14190   187 WSMGVITYMLLSGLSPFLGDDDTETLNNVLMGNW 220
STKc_SLK_like cd06611
Catalytic domain of Ste20-Like Kinase-like Serine/Threonine Kinases; STKs catalyze the ...
288-449 3.27e-03

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: 41.27  E-value: 3.27e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  288 LADLLIaEQEHSSKLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRSQFPVLHMEVIVHlllQISDALRYL 367
Cdd:cd06611    46 LEDFMV-EIDILSECKHPNIVGLYEAYFYEN--KLWILIEFCDGGALDSIMLELERGLTEPQIRYVCR---QMLEALNFL 119
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  368 HFQGFIHRSLSSYAVHIISPGEARLTN--LEYMLESEDrgvQRDLTRVPLPtqlyNWAAPEVIL-----QKAATVKSDIY 440
Cdd:cd06611   120 HSHKVIHRDLKAGNILLTLDGDVKLADfgVSAKNKSTL---QKRDTFIGTP----YWMAPEVVAcetfkDNPYDYKADIW 192

                  ....*....
gi 319803120  441 SFSMIMQEI 449
Cdd:cd06611   193 SLGITLIEL 201
TRPV5-6 cd22192
Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and ...
55-144 3.58e-03

Transient Receptor Potential channel, Vanilloid subfamily (TRPV), types 5 and 6; TRPV5 and TRPV6 (TRPV5/6) are two homologous members within the vanilloid subfamily of the transient receptor potential (TRP) family. TRPV5 and TRPV6 show only 30-40% homology with other members of the TRP family and have unique properties that differentiates them from other TRP channels. They mediate calcium uptake in epithelia and their expression is dramatically increased in numerous types of cancer. The structure of TRPV5/6 shows the typical topology features of all TRP family members, such as six transmembrane regions, a short hydrophobic stretch between transmembrane segments 5 and 6, which is predicted to form the Ca2+ pore, and large intracellular N- and C-terminal domains. The N-terminal domain of TRPV5/6 contains three ankyrin repeats. This structural element is present in several proteins and plays a role in protein-protein interactions. The N- and C-terminal tails of TRPV5/6 each contain an internal PDZ motif which can function as part of a molecular scaffold via interaction with PDZ-domain containing proteins. A major difference between the properties of TRPV5 and TRPV6 is in their tissue distribution: TRPV5 is predominantly expressed in the distal convoluted tubules (DCT) and connecting tubules (CNT) of the kidney, with limited expression in extrarenal tissues. In contrast, TRPV6 has a broader expression pattern such as expression in the intestine, kidney, placenta, epididymis, exocrine tissues, and a few other tissues.


Pssm-ID: 411976 [Multi-domain]  Cd Length: 609  Bit Score: 41.92  E-value: 3.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   55 LGQTALFVAALLGLRKFVDVLVDYGSD--------------PNHRCFDGSTPVHAAAFSGNQWILSKLLDAGGDLRLHDE 120
Cdd:cd22192    88 QGETALHIAVVNQNLNLVRELIARGADvvspratgtffrpgPKNLIYYGEHPLSFAACVGNEEIVRLLIEHGADIRAQDS 167
                          90       100
                  ....*....|....*....|....*
gi 319803120  121 RGQNP-KTWALTAGKERSTQIVEFM 144
Cdd:cd22192   168 LGNTVlHILVLQPNKTFACQMYDLI 192
STKc_PKD cd14082
Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer ...
301-456 4.39e-03

Catalytic domain of the Serine/Threonine kinase, Protein Kinase D; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. PKDs are important regulators of many intracellular signaling pathways such as ERK and JNK, and cellular processes including the organization of the trans-Golgi network, membrane trafficking, cell proliferation, migration, and apoptosis. They contain N-terminal cysteine-rich zinc binding C1 (PKC conserved region 1), central PH (Pleckstrin Homology), and C-terminal catalytic kinase domains. Mammals harbor three types of PKDs: PKD1 (or PKCmu), PKD2, and PKD3 (or PKCnu). PKDs are activated in a PKC-dependent manner by many agents including diacylglycerol (DAG), PDGF, neuropeptides, oxidative stress, and tumor-promoting phorbol esters, among others. The PKD 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: 270984 [Multi-domain]  Cd Length: 260  Bit Score: 40.86  E-value: 4.39e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVCLSQdlEKTRLVYERITIGTLFSVLHERRSQFPvlhMEVIVHLLLQISDALRYLHFQGFIHRSLSSY 380
Cdd:cd14082    58 QLSHPGVVNLECMFETP--ERVFVVMEKLHGDMLEMILSSEKGRLP---ERITKFLVTQILVALRYLHSKNIVHCDLKPE 132
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 319803120  381 AVHIISPG---EARLTNLEYMLESEDRGVQRDLTRVPLptqlynWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPW 456
Cdd:cd14082   133 NVLLASAEpfpQVKLCDFGFARIIGEKSFRRSVVGTPA------YLAPEVLRNKGYNRSLDMWSVGVIIYVSLSGTFPF 205
STKc_CASK cd14094
Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein ...
302-473 4.80e-03

Catalytic domain of the Serine/Threonine Kinase, Calcium/calmodulin-dependent serine protein kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. CASK belongs to the MAGUK (membrane-associated guanylate kinase) protein family, which functions as multiple domain adaptor proteins and is characterized by the presence of a core of three domains: PDZ, SH3, and guanylate kinase (GuK). The enzymatically inactive GuK domain in MAGUK proteins mediates protein-protein interactions and associates intramolecularly with the SH3 domain. In addition, CASK contains a catalytic kinase and two L27 domains. It is highly expressed in the nervous system and plays roles in synaptic protein targeting, neural development, and regulation of gene expression. Binding partners include parkin (a Parkinson's disease molecule), neurexin (adhesion molecule), syndecans, calcium channel proteins, CINAP (nucleosome assembly protein), transcription factor Tbr-1, and the cytoplasmic adaptor proteins Mint1, Veli/mLIN-7/MALS, SAP97, caskin, and CIP98. Deletion or mutations in the CASK gene have been implicated in X-linked mental retardation. The CASK 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: 270996 [Multi-domain]  Cd Length: 300  Bit Score: 40.99  E-value: 4.80e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  302 LRHPYLLQLMAVCLSQDLekTRLVYERITIGTL-FSVLHERRSQFpVLHMEVIVHLLLQISDALRYLHFQGFIHRSLSSY 380
Cdd:cd14094    62 LKHPHIVELLETYSSDGM--LYMVFEFMDGADLcFEIVKRADAGF-VYSEAVASHYMRQILEALRYCHDNNIIHRDVKPH 138
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  381 AVHIISPGEARLTNLEYMlesedrGVQRDLT--------RVPLPtqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILTD 452
Cdd:cd14094   139 CVLLASKENSAPVKLGGF------GVAIQLGesglvaggRVGTP----HFMAPEVVKREPYGKPVDVWGCGVILFILLSG 208
                         170       180
                  ....*....|....*....|.
gi 319803120  453 DIPWKGlDGSVVKKAVVSGNY 473
Cdd:cd14094   209 CLPFYG-TKERLFEGIIKGKY 228
STKc_Pat1_like cd13993
Catalytic domain of Fungal Pat1-like Serine/Threonine kinases; STKs catalyze the transfer of ...
303-377 5.19e-03

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: 40.41  E-value: 5.19e-03
                          10        20        30        40        50        60        70
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*
gi 319803120  303 RHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLHERRsqFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSL 377
Cdd:cd13993    63 RHPNIITLHDVF--ETEVAIYIVLEYCPNGDLFEAITENR--IYVGKTELIKNVFLQLIDAVKHCHSLGIYHRDI 133
STKc_DCKL cd14095
Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called ...
301-499 5.33e-03

Catalytic domain of the Serine/Threonine Kinase, Doublecortin-like kinase (also called Doublecortin-like and CAM kinase-like); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. DCKL (or DCAMKL) proteins belong to the doublecortin (DCX) family of proteins which are involved in neuronal migration, neurogenesis, and eye receptor development, among others. Family members typically contain tandem doublecortin (DCX) domains at the N-terminus; DCX domains can bind microtubules and serve as protein-interaction platforms. In addition, DCKL proteins contain a C-terminal kinase domain with similarity to CAMKs. They are involved in the regulation of cAMP signaling. Vertebrates contain three DCKL proteins (DCKL1-3); DCKL1 and 2 also contain a serine, threonine, and proline rich domain (SP), while DCKL3 contains only a single DCX domain instead of tandem domains. The DCKL 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: 270997 [Multi-domain]  Cd Length: 258  Bit Score: 40.39  E-value: 5.33e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVCLSQDleKTRLVYERITIGTLFSVLHERRsQFPVLHMEVIVHLLLQisdALRYLHFQGFIHRSL--S 378
Cdd:cd14095    54 RVKHPNIVQLIEEYDTDT--ELYLVMELVKGGDLFDAITSST-KFTERDASRMVTDLAQ---ALKYLHSLSIVHRDIkpE 127
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  379 SYAVHIISPGEARLTNLEYMLESEdrgVQRDLTRV-PLPTqlynWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWK 457
Cdd:cd14095   128 NLLVVEHEDGSKSLKLADFGLATE---VKEPLFTVcGTPT----YVAPEILAETGYGLKVDIWAAGVITYILLCGFPPFR 200
                         170       180       190       200       210
                  ....*....|....*....|....*....|....*....|....*....|..
gi 319803120  458 GLDGS--VVKKAVVSGNYleadvRLPKPYYDIVKSG--------IHVKQKDR 499
Cdd:cd14095   201 SPDRDqeELFDLILAGEF-----EFLSPYWDNISDSakdlisrmLVVDPEKR 247
STKc_Rad53_Cds1 cd14098
Catalytic domain of the yeast Serine/Threonine Kinases, Rad53 and Cds1; STKs catalyze the ...
301-475 5.63e-03

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: 40.54  E-value: 5.63e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  301 KLRHPYLLQLMAVclSQDLEKTRLVYERITIGTLFSVLherrSQFPVLHMEVIVHLLLQISDALRYLHFQGFIHRSL--- 377
Cdd:cd14098    57 SLEHPGIVRLIDW--YEDDQHIYLVMEYVEGGDLMDFI----MAWGAIPEQHARELTKQILEAMAYTHSMGITHRDLkpe 130
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  378 -------SSYAVHIISPGEARLTNLEYMLEsedrgvqrdlTRVPLPTQLynwaAPEVILQKAATV------KSDIYSFSM 444
Cdd:cd14098   131 nilitqdDPVIVKISDFGLAKVIHTGTFLV----------TFCGTMAYL----APEILMSKEQNLqggysnLVDMWSVGC 196
                         170       180       190
                  ....*....|....*....|....*....|.
gi 319803120  445 IMQEILTDDIPWKGLDGSVVKKAVVSGNYLE 475
Cdd:cd14098   197 LVYVMLTGALPFDGSSQLPVEKRIRKGRYTQ 227
PTZ00322 PTZ00322
6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional
23-109 7.58e-03

6-phosphofructo-2-kinase/fructose-2,6-biphosphatase; Provisional


Pssm-ID: 140343 [Multi-domain]  Cd Length: 664  Bit Score: 40.65  E-value: 7.58e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   23 LEAQLHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAAFSGNQ 102
Cdd:PTZ00322   82 LTVELCQLAASGDAVGARILLTGGADPNCRDYDGRTPLHIACANGHVQVVRVLLEFGADPTLLDKDGKTPLELAEENGFR 161

                  ....*..
gi 319803120  103 WILSKLL 109
Cdd:PTZ00322  162 EVVQLLS 168
PHA02876 PHA02876
ankyrin repeat protein; Provisional
20-119 8.00e-03

ankyrin repeat protein; Provisional


Pssm-ID: 165207 [Multi-domain]  Cd Length: 682  Bit Score: 40.82  E-value: 8.00e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120   20 NDSLE--AQLHEYVKQGNYVKVKKILKKGIYVDAVNSLGQTALFVAALLGLRKFVDVLVDYGSDPNHRCFDGSTPVHAAA 97
Cdd:PHA02876  140 NESIEymKLIKERIQQDELLIAEMLLEGGADVNAKDIYCITPIHYAAERGNAKMVNLLLSYGADVNIIALDDLSVLECAV 219
                          90       100
                  ....*....|....*....|..
gi 319803120   98 FSGNQWILSKLLDAGGDLRLHD 119
Cdd:PHA02876  220 DSKNIDTIKAIIDNRSNINKND 241
STKc_MLCK-like cd14006
Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs ...
302-441 8.23e-03

Catalytic kinase domain of Myosin Light Chain Kinase-like Serine/Threonine Kinases; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This family is composed of MLCKs and related MLCK-like kinase domains from giant STKs such as titin, obscurin, SPEG, Unc-89, Trio, kalirin, and Twitchin. Also included in this family are Death-Associated Protein Kinases (DAPKs) and Death-associated protein kinase-Related Apoptosis-inducing protein Kinase (DRAKs). MLCK phosphorylates myosin regulatory light chain and controls the contraction of all muscle types. Titin, obscurin, Twitchin, and SPEG are muscle proteins involved in the contractile apparatus. The giant STKs are multidomain proteins containing immunoglobulin (Ig), fibronectin type III (FN3), SH3, RhoGEF, PH and kinase domains. Titin, obscurin, Twitchin, and SPEG contain many Ig domain repeats at the N-terminus, while Trio and Kalirin contain spectrin-like repeats. The MLCK-like 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: 270908 [Multi-domain]  Cd Length: 247  Bit Score: 39.94  E-value: 8.23e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  302 LRHPYLLQLMAVclsqdLEKTR---LVYERITIGTLFSVLHERRSqfpVLHMEVIVHLLlQISDALRYLHFQGFIHRSL- 377
Cdd:cd14006    46 LQHPRIIQLHEA-----YESPTelvLILELCSGGELLDRLAERGS---LSEEEVRTYMR-QLLEGLQYLHNHHILHLDLk 116
                          90       100       110       120       130       140       150
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 319803120  378 ---------SSYAVHIISPGEARLTNleymlesedrgvQRDLTRVPLPTQLYnwAAPEVILQKAATVKSDIYS 441
Cdd:cd14006   117 penilladrPSPQIKIIDFGLARKLN------------PGEELKEIFGTPEF--VAPEIVNGEPVSLATDMWS 175
STKc_TTBK cd14017
Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the ...
341-496 8.62e-03

Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. TTBK is a neuron-specific kinase that phosphorylates the microtubule-associated protein tau and promotes its aggregation. Higher vertebrates contain two TTBK proteins, TTBK1 and TTBK2, both of which have been implicated in neurodegeneration. TTBK1 has been linked to Alzheimer's disease (AD) while TTBK2 is associated with spinocerebellar ataxia type 11 (SCA11). Both AD and SCA11 patients show the presence of neurofibrillary tangles in the brain. The Drosophila TTBK homolog, Asator, is an essential protein that localizes to the mitotic spindle during mitosis and may be involved in regulating microtubule dynamics and function. The TTBK 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: 270919 [Multi-domain]  Cd Length: 263  Bit Score: 39.93  E-value: 8.62e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  341 RRSQFP-VLHMEVIVHLLLQISDALRYLHFQGFIHRSL--SSYAVHiISPGEARLTnleYMLeseDRGVQR-------DL 410
Cdd:cd14017    86 RRSQPRgKFSVSTTLRLGIQILKAIEDIHEVGFLHRDVkpSNFAIG-RGPSDERTV---YIL---DFGLARqytnkdgEV 158
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  411 TRVPLPTQLY----NWAAPEVILQKAATVKSDIYSFSMIMQEILTDDIPWKGLDG----SVVKKAVVSGNYLEadvRLPK 482
Cdd:cd14017   159 ERPPRNAAGFrgtvRYASVNAHRNKEQGRRDDLWSWFYMLIEFVTGQLPWRKLKDkeevGKMKEKIDHEELLK---GLPK 235
                         170
                  ....*....|....
gi 319803120  483 PYYDIVKsgiHVKQ 496
Cdd:cd14017   236 EFFQILK---HIRS 246
STKc_IKK cd13989
Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase ...
353-451 8.79e-03

Catalytic domain of the Serine/Threonine kinase, Inhibitor of Nuclear Factor-KappaB Kinase (IKK); STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. The IKK complex functions as a master regulator of Nuclear Factor-KappaB (NF-kB) proteins, a family of transcription factors which are critical in many cellular functions including inflammatory responses, immune development, cell survival, and cell proliferation, among others. It is composed of two kinases, IKKalpha and IKKbeta, and the regulatory subunit IKKgamma or NEMO (NF-kB Essential MOdulator). IKKs facilitate the release of NF-kB dimers from an inactive state, allowing them to migrate to the nucleus where they regulate gene transcription. There are two IKK pathways that regulate NF-kB signaling, called the classical (involving IKKbeta and NEMO) and non-canonical (involving IKKalpha) pathways. The classical pathway regulates the majority of genes activated by NF-kB. The IKK 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: 270891 [Multi-domain]  Cd Length: 289  Bit Score: 40.12  E-value: 8.79e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  353 IVHLLLQISDALRYLHFQGFIHRSLSSYAVhIISPGEARLTnleYMLesEDRGVQRDLTRVPLPTQL---YNWAAPEVIL 429
Cdd:cd13989   104 VRTLLSDISSAISYLHENRIIHRDLKPENI-VLQQGGGRVI---YKL--IDLGYAKELDQGSLCTSFvgtLQYLAPELFE 177
                          90       100
                  ....*....|....*....|..
gi 319803120  430 QKAATVKSDIYSFSMIMQEILT 451
Cdd:cd13989   178 SKKYTCTVDYWSFGTLAFECIT 199
STKc_Rim15_like cd05611
Catalytic domain of fungal Rim15-like Protein Serine/Threonine Kinases; STKs catalyze the ...
363-451 9.64e-03

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: 39.77  E-value: 9.64e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  363 ALRYLHFQGFIHRSLSSYAVHIISPGEARLTNLEYMLESEDRGVQRDLTRVPlptqlyNWAAPEVILQKAATVKSDIYSF 442
Cdd:cd05611   109 GVEDLHQRGIIHRDIKPENLLIDQTGHLKLTDFGLSRNGLEKRHNKKFVGTP------DYLAPETILGVGDDKMSDWWSL 182

                  ....*....
gi 319803120  443 SMIMQEILT 451
Cdd:cd05611   183 GCVIFEFLF 191
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
303-489 9.68e-03

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: 39.98  E-value: 9.68e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  303 RHPYLLQLMAVClsQDLEKTRLVYERITIGTLFSVLHERR------------SQFPVLHMEVIVHLLLQISDALRYLHFQ 370
Cdd:cd05089    61 HHPNIINLLGAC--ENRGYLYIAIEYAPYGNLLDFLRKSRvletdpafakehGTASTLTSQQLLQFASDVAKGMQYLSEK 138
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  371 GFIHRSLSSYAVHIISPGEARLTNLEyMLESEDRGVQRDLTRVPLptqlyNWAAPEVILQKAATVKSDIYSFSMIMQEIL 450
Cdd:cd05089   139 QFIHRDLAARNVLVGENLVSKIADFG-LSRGEEVYVKKTMGRLPV-----RWMAIESLNYSVYTTKSDVWSFGVLLWEIV 212
                         170       180       190       200
                  ....*....|....*....|....*....|....*....|
gi 319803120  451 T-DDIPWKGLDGSVVKKAVVSGNYLEADVRLPKPYYDIVK 489
Cdd:cd05089   213 SlGGTPYCGMTCAELYEKLPQGYRMEKPRNCDDEVYELMR 252
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
348-451 9.90e-03

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: 40.21  E-value: 9.90e-03
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 319803120  348 LHMEVIVHLLLQISDALRYLHFQGFIHRSLSSYAVHIISPGEARLTnleymleseDRGVQRDL-----------TRVPLp 416
Cdd:cd05106   209 LDLDDLLRFSSQVAQGMDFLASKNCIHRDVAARNVLLTDGRVAKIC---------DFGLARDImndsnyvvkgnARLPV- 278
                          90       100       110
                  ....*....|....*....|....*....|....*
gi 319803120  417 tqlyNWAAPEVILQKAATVKSDIYSFSMIMQEILT 451
Cdd:cd05106   279 ----KWMAPESIFDCVYTVQSDVWSYGILLWEIFS 309
 
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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