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Conserved domains on  [gi|1844139561|ref|NP_001369727|]
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receptor tyrosine-protein kinase erbB-2 isoform t precursor [Homo sapiens]

Protein Classification

Recep_L_domain and FU domain-containing protein( domain architecture ID 12013639)

protein containing domains Recep_L_domain, FU, TM_ErbB2, and Protein Kinases, catalytic domain

Graphical summary

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List of domain hits

 Name Accession Description Interval E-value
PKc_like super family cl21453
Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the ...
 712-938 2.40e-163

Protein Kinases, catalytic domain; The protein kinase superfamily is mainly composed of the catalytic domains of serine/threonine-specific and tyrosine-specific protein kinases. It also includes RIO kinases, which are atypical serine protein kinases, aminoglycoside phosphotransferases, and choline kinases. These proteins catalyze the transfer of the gamma-phosphoryl group from ATP to hydroxyl groups in specific substrates such as serine, threonine, or tyrosine residues of proteins.


The actual alignment was detected with superfamily member cd05109:

Pssm-ID: 473864 [Multi-domain]  Cd Length: 279  Bit Score: 486.07  E-value: 2.40e-163
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  712 MRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 791
Cdd:cd05109      1 MRILKETELKKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA----------------------------------------- 830
Cdd:cd05109     81 STVQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAkgmsyleevrlvhrdlaarnvlvkspnhvkitdfglarlld 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 -----------KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 899
Cdd:cd05109    161 ideteyhadggKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 240

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  900 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 938
Cdd:cd05109    241 YMIMVKCWMIDSECRPRFRELVDEFSRMARDPSRFVVIQ 279
GF_recep_IV pfam14843
Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine ...
 511-643 3.82e-59

Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (pfam00757) regulates the binding of ligands to the receptor L domains (pfam01030).


:

Pssm-ID: 464344 [Multi-domain]  Cd Length: 132  Bit Score: 199.14  E-value: 3.82e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  511 CHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHY 590
Cdd:pfam14843    2 CDPLCSSEGCWGPGPDQCLSCRNFSRGGTCVESCNILQGEPREYVVNSTCVPCHPECLPQNGTATCSGPGADNCTKCAHF 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1844139561  591 KDPPFCVARCPSGVKPDLSymPIWKFPDEEGACQPCPINCTHSCVDLDDKGCP 643
Cdd:pfam14843   82 RDGPHCVSSCPSGVLGEND--LIWKYADANGVCQPCHPNCTQGCTGPGLTGCP 132
Furin-like pfam00757
Furin-like cysteine rich region;
189-338 2.00e-40

Furin-like cysteine rich region;


:

Pssm-ID: 395614 [Multi-domain]  Cd Length: 143  Bit Score: 146.04  E-value: 2.00e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  189 SRACHPCSPMCKGSRCWGesSEDCQsltrTVCAGGCA-RCKGPlpTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELH 267
Cdd:pfam00757    9 PGTMEKCHSCCNNGYCWG--PGHCQ----KVCPEQCKkRCTKP--GECCHEQCLGGCTGPNDSDCLACRHFNDEGTCVDQ 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139561  268 CpalvtyntdtfesmpnPEGRYTFGASCVTA--CP------YNYLSTDVGSCTLVCPLHNQEVtaEDGTQRCEKCSKPC 338
Cdd:pfam00757   81 C----------------PPGTYQFGWRCVTFkeCPkshlpgYNPLVIHNGECVRECPSGYTEV--ENNSRKCEPCEGLC 141
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
 52-173 2.40e-32

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


:

Pssm-ID: 460032  Cd Length: 112  Bit Score: 121.57  E-value: 2.40e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   52 GCQVVQGNLELTYLPTN---ASLSFLQDIQEVQGYVLIAH-NQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDplnntt 127
Cdd:pfam01030    1 NCTVIYGNLEITLIDENndsELLSFLSNVEEITGYLLIANtNLVSLSFLPNLRIIRGRNLFDDNYALYILDNPN------ 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139561  128 pvtgaspggLRELQLRSLTEILKGGVLIQRNPQLCYQDT-ILWKDIF 173
Cdd:pfam01030   75 ---------LTELGLPSLKEITSGGVYIHNNPKLCYTETeILWKLLL 112
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
 366-482 1.11e-20

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


:

Pssm-ID: 460032  Cd Length: 112  Bit Score: 88.44  E-value: 1.11e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  366 GCKKIFGSLAFLPESFDGDPasntaplqpEQLQVFETLEEITGYLYISAWPDSlpDLSVFQNLQVIRGRILHNGAYSLT- 444
Cdd:pfam01030    1 NCTVIYGNLEITLIDENNDS---------ELLSFLSNVEEITGYLLIANTNLV--SLSFLPNLRIIRGRNLFDDNYALYi 69

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1844139561  445 LQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHT-VPW 482
Cdd:pfam01030   70 LDNPNLTELGLPSLKEITSGGVYIHNNPKLCYTETeILW 108
TM_ErbB2 cd12094
Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the ...
 641-684 3.41e-07

Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. ErbB2 (HER2, 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 (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. It is 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. ErbB2 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 ErbB2-ErbB3 heterodimer being the most potent pair in mitogenic signaling. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of ErbB2 have been associated with increased breast cancer risk. ErbB2 plays an important role in cell development, proliferation, survival and motility. Overexpression of ErbB2 results in its activation and downstream signaling, even in the absence of ligand. ErbB2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. ErbB2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. ErbB2 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.


:

Pssm-ID: 213055  Cd Length: 44  Bit Score: 47.96  E-value: 3.41e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1844139561  641 GCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRK 684
Cdd:cd12094      1 GCPAEQRASPLTSIIAGVVGILLVVVLLVVFGILIKRRRQKIRK 44
 
Name Accession Description Interval E-value
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
 712-938 2.40e-163

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: 486.07  E-value: 2.40e-163
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  712 MRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 791
Cdd:cd05109      1 MRILKETELKKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA----------------------------------------- 830
Cdd:cd05109     81 STVQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAkgmsyleevrlvhrdlaarnvlvkspnhvkitdfglarlld 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 -----------KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 899
Cdd:cd05109    161 ideteyhadggKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 240

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  900 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 938
Cdd:cd05109    241 YMIMVKCWMIDSECRPRFRELVDEFSRMARDPSRFVVIQ 279
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
 720-924 2.30e-85

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: 277.84  E-value: 2.30e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVT 798
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLKGEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTqGEPLYIVT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  799 QLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA------------------------------------------------ 830
Cdd:pfam07714   81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAkgmeylesknfvhrdlaarnclvsenlvvkisdfglsrdiydddyyrk 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ----KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKC 906
Cdd:pfam07714  161 rgggKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQC 240

                          250
                   ....*....|....*...
gi 1844139561  907 WMIDSECRPRFRELVSEF 924
Cdd:pfam07714  241 WAYDPEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
 720-924 9.74e-82

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 267.86  E-value: 9.74e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   720 LRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVT 798
Cdd:smart00219    1 LTLGKKLGEGAFGEVYKGKLKGKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEpLYIVM 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   799 QLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA------------------------------------------------ 830
Cdd:smart00219   81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIArgmeylesknfihrdlaarnclvgenlvvkisdfglsrdlydddyyrk 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   831 ---KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCW 907
Cdd:smart00219  161 rggKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCW 240

                           250
                    ....*....|....*..
gi 1844139561   908 MIDSECRPRFRELVSEF 924
Cdd:smart00219  241 AEDPEDRPTFSELVEIL 257
GF_recep_IV pfam14843
Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine ...
 511-643 3.82e-59

Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (pfam00757) regulates the binding of ligands to the receptor L domains (pfam01030).


Pssm-ID: 464344 [Multi-domain]  Cd Length: 132  Bit Score: 199.14  E-value: 3.82e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  511 CHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHY 590
Cdd:pfam14843    2 CDPLCSSEGCWGPGPDQCLSCRNFSRGGTCVESCNILQGEPREYVVNSTCVPCHPECLPQNGTATCSGPGADNCTKCAHF 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1844139561  591 KDPPFCVARCPSGVKPDLSymPIWKFPDEEGACQPCPINCTHSCVDLDDKGCP 643
Cdd:pfam14843   82 RDGPHCVSSCPSGVLGEND--LIWKYADANGVCQPCHPNCTQGCTGPGLTGCP 132
Furin-like pfam00757
Furin-like cysteine rich region;
189-338 2.00e-40

Furin-like cysteine rich region;


Pssm-ID: 395614 [Multi-domain]  Cd Length: 143  Bit Score: 146.04  E-value: 2.00e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  189 SRACHPCSPMCKGSRCWGesSEDCQsltrTVCAGGCA-RCKGPlpTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELH 267
Cdd:pfam00757    9 PGTMEKCHSCCNNGYCWG--PGHCQ----KVCPEQCKkRCTKP--GECCHEQCLGGCTGPNDSDCLACRHFNDEGTCVDQ 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139561  268 CpalvtyntdtfesmpnPEGRYTFGASCVTA--CP------YNYLSTDVGSCTLVCPLHNQEVtaEDGTQRCEKCSKPC 338
Cdd:pfam00757   81 C----------------PPGTYQFGWRCVTFkeCPkshlpgYNPLVIHNGECVRECPSGYTEV--ENNSRKCEPCEGLC 141
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
 52-173 2.40e-32

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


Pssm-ID: 460032  Cd Length: 112  Bit Score: 121.57  E-value: 2.40e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   52 GCQVVQGNLELTYLPTN---ASLSFLQDIQEVQGYVLIAH-NQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDplnntt 127
Cdd:pfam01030    1 NCTVIYGNLEITLIDENndsELLSFLSNVEEITGYLLIANtNLVSLSFLPNLRIIRGRNLFDDNYALYILDNPN------ 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139561  128 pvtgaspggLRELQLRSLTEILKGGVLIQRNPQLCYQDT-ILWKDIF 173
Cdd:pfam01030   75 ---------LTELGLPSLKEITSGGVYIHNNPKLCYTETeILWKLLL 112
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
 366-482 1.11e-20

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


Pssm-ID: 460032  Cd Length: 112  Bit Score: 88.44  E-value: 1.11e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  366 GCKKIFGSLAFLPESFDGDPasntaplqpEQLQVFETLEEITGYLYISAWPDSlpDLSVFQNLQVIRGRILHNGAYSLT- 444
Cdd:pfam01030    1 NCTVIYGNLEITLIDENNDS---------ELLSFLSNVEEITGYLLIANTNLV--SLSFLPNLRIIRGRNLFDDNYALYi 69

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1844139561  445 LQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHT-VPW 482
Cdd:pfam01030   70 LDNPNLTELGLPSLKEITSGGVYIHNNPKLCYTETeILW 108
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
721-1123 2.08e-15

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 80.44  E-value: 2.08e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  721 RKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLREN--TSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LV 797
Cdd:COG0515     10 RILRLLGRGGMGVVYLARDLRLGR----PVALKVLRPElaADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPyLV 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPyGCLLDHVRENRGRLGSQDLLNWCMQIAKV------------PIK------------------------------ 835
Cdd:COG0515     86 MEYVE-GESLADLLRRRGPLPPAEALRILAQLAEAlaaahaagivhrDIKpanilltpdgrvklidfgiaralggatltq 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 ---------WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREipdLLEKGERLPQPPICTidvymimvkc 906
Cdd:COG0515    165 tgtvvgtpgYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAE---LLRAHLREPPPPPSE---------- 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  907 wmIDSECRPRFRELVsefSRM-ARDP-QRFvviQN-----EDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFF 979
Cdd:COG0515    231 --LRPDLPPALDAIV---LRAlAKDPeERY---QSaaelaAALRAVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA 302

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  980 CPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQR 1059
Cdd:COG0515    303 AAAAAAAAAAAAAAAAAAAAPAAAAAAAAAAAALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAA 382

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139561 1060 YSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSP 1123
Cdd:COG0515    383 AALAAAAAAAAAAAAAALAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLA 446
FU smart00261
Furin-like repeats;
557-603 1.07e-07

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 49.43  E-value: 1.07e-07
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*....
gi 1844139561   557 ARHCLPCHPECQpqngsvTCFGPEADQCVACAH--YKDPPFCVARCPSG 603
Cdd:smart00261    1 DGECKPCHPECA------TCTGPGPDDCTSCKHgfFLDGGKCVSECPPG 43
TM_ErbB2 cd12094
Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the ...
 641-684 3.41e-07

Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. ErbB2 (HER2, 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 (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. It is 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. ErbB2 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 ErbB2-ErbB3 heterodimer being the most potent pair in mitogenic signaling. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of ErbB2 have been associated with increased breast cancer risk. ErbB2 plays an important role in cell development, proliferation, survival and motility. Overexpression of ErbB2 results in its activation and downstream signaling, even in the absence of ligand. ErbB2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. ErbB2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. ErbB2 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.


Pssm-ID: 213055  Cd Length: 44  Bit Score: 47.96  E-value: 3.41e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1844139561  641 GCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRK 684
Cdd:cd12094      1 GCPAEQRASPLTSIIAGVVGILLVVVLLVVFGILIKRRRQKIRK 44
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
 235-280 3.10e-06

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 45.20  E-value: 3.10e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139561  235 CCHEQCAaGCTGPKHSDCLACLHFN--HSGICELHCPALVTYNTDTFE 280
Cdd:cd00064      1 PCHPSCA-TCTGPGPDQCTSCRHGFylDGGTCVSECPEGTYADTEGGV 47
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
 562-607 6.66e-06

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 44.43  E-value: 6.66e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139561  562 PCHPECQpqngsvTCFGPEADQCVACAH--YKDPPFCVARCPSGVKPD 607
Cdd:cd00064      1 PCHPSCA------TCTGPGPDQCTSCRHgfYLDGGTCVSECPEGTYAD 42
FU smart00261
Furin-like repeats;
235-270 9.71e-05

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 40.96  E-value: 9.71e-05
                            10        20        30
                    ....*....|....*....|....*....|....*...
gi 1844139561   235 CCHEQCAaGCTGPKHSDCLACLHFNH--SGICELHCPA 270
Cdd:smart00261    6 PCHPECA-TCTGPGPDDCTSCKHGFFldGGKCVSECPP 42
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
 836-944 2.54e-03

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 41.93  E-value: 2.54e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALESILRRRFTHQSDVWSYGVTVWELMTFgAKPYDGIPAREIPDLLEKGERLPQPpiCTIDVYM--IMVKCWMIDSEC 913
Cdd:PTZ00267   237 YLAPELWERKRYSKKADMWSLGVILYELLTL-HRPFKGPSQREIMQQVLYGKYDPFP--CPVSSGMkaLLDPLLSKNPAL 313

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1844139561  914 RPRFRELV-SEFSRMARDPQRFVVIQNEDLGP 944
Cdd:PTZ00267   314 RPTTQQLLhTEFLKYVANLFQDIVRHSETISP 345
 
Name Accession Description Interval E-value
PTKc_HER2 cd05109
Catalytic domain of the Protein Tyrosine Kinase, HER2; PTKs catalyze the transfer of the ...
 712-938 2.40e-163

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: 486.07  E-value: 2.40e-163
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  712 MRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 791
Cdd:cd05109      1 MRILKETELKKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVCRLLGICLT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA----------------------------------------- 830
Cdd:cd05109     81 STVQLVTQLMPYGCLLDYVRENKDRIGSQDLLNWCVQIAkgmsyleevrlvhrdlaarnvlvkspnhvkitdfglarlld 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 -----------KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 899
Cdd:cd05109    161 ideteyhadggKVPIKWMALESILHRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 240

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  900 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 938
Cdd:cd05109    241 YMIMVKCWMIDSECRPRFRELVDEFSRMARDPSRFVVIQ 279
PTKc_EGFR cd05108
Catalytic domain of the Protein Tyrosine Kinase, Epidermal Growth Factor Receptor; PTKs ...
 712-971 3.23e-155

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: 466.42  E-value: 3.23e-155
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  712 MRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 791
Cdd:cd05108      1 LRILKETEFKKIKVLGSGAFGTVYKGLWIPEGEKVKIPVAIKELREATSPKANKEILDEAYVMASVDNPHVCRLLGICLT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAK---------------------------------------- 831
Cdd:cd05108     81 STVQLITQLMPFGCLLDYVREHKDNIGSQYLLNWCVQIAKgmnyledrrlvhrdlaarnvlvktpqhvkitdfglakllg 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 899
Cdd:cd05108    161 aeekeyhaeggkVPIKWMALESILHRIYTHQSDVWSYGVTVWELMTFGSKPYDGIPASEISSILEKGERLPQPPICTIDV 240

                          250       260       270       280       290       300       310
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139561  900 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ-NEDLGPASPLDSTFYRSLLEDDDMGDLVDAEEY 971
Cdd:cd05108    241 YMIMVKCWMIDADSRPKFRELIIEFSKMARDPQRYLVIQgDERMHLPSPTDSNFYRALMDEEDMDDVVDADEY 313
PTKc_EGFR_like cd05057
Catalytic domain of Epidermal Growth Factor Receptor-like Protein Tyrosine Kinases; PTKs ...
 712-938 3.47e-153

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: 459.57  E-value: 3.47e-153
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  712 MRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 791
Cdd:cd05057      1 LRIVKETELEKGKVLGSGAFGTVYKGVWIPEGEKVKIPVAIKVLREETGPKANEEILDEAYVMASVDHPHLVRLLGICLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA----------------------------------------- 830
Cdd:cd05057     81 SQVQLITQLMPLGCLLDYVRNHRDNIGSQLLLNWCVQIAkgmsyleekrlvhrdlaarnvlvktpnhvkitdfglaklld 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 -----------KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 899
Cdd:cd05057    161 vdekeyhaeggKVPIKWMALESIQYRIYTHKSDVWSYGVTVWELMTFGAKPYEGIPAVEIPDLLEKGERLPQPPICTIDV 240

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  900 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 938
Cdd:cd05057    241 YMVLVKCWMIDAESRPTFKELANEFSKMARDPQRYLVIQ 279
PTKc_HER4 cd05110
Catalytic domain of the Protein Tyrosine Kinase, HER4; PTKs catalyze the transfer of the ...
 712-961 6.72e-124

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: 383.65  E-value: 6.72e-124
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  712 MRILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 791
Cdd:cd05110      1 LRILKETELKRVKVLGSGAFGTVYKGIWVPEGETVKIPVAIKILNETTGPKANVEFMDEALIMASMDHPHLVRLLGVCLS 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 STVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAK---------------------------------------- 831
Cdd:cd05110     81 PTIQLVTQLMPHGCLLDYVHEHKDNIGSQLLLNWCVQIAKgmmyleerrlvhrdlaarnvlvkspnhvkitdfglarlle 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDV 899
Cdd:cd05110    161 gdekeynadggkMPIKWMALECIHYRKFTHQSDVWSYGVTIWELMTFGGKPYDGIPTREIPDLLEKGERLPQPPICTIDV 240

                          250       260       270       280       290       300
                   ....*....|....*....|....*....|....*....|....*....|....*....|...
gi 1844139561  900 YMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQNED-LGPASPLDSTFYRSLLEDDD 961
Cdd:cd05110    241 YMVMVKCWMIDADSRPKFKELAAEFSRMARDPQRYLVIQGDDrMKLPSPNDSKFFQNLLDEED 303
PTK_HER3 cd05111
Pseudokinase domain of the Protein Tyrosine Kinase, HER3; HER3 (ErbB3) is a member of the EGFR ...
 713-938 1.95e-111

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: 349.64  E-value: 1.95e-111
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  713 RILKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS 792
Cdd:cd05111      2 RIFKETELRKLKVLGSGVFGTVHKGIWIPEGDSIKIPVAIKVIQDRSGRQSFQAVTDHMLAIGSLDHAYIVRLLGICPGA 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  793 TVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAK----------------------------------------- 831
Cdd:cd05111     82 SLQLVTQLLPLGSLLDHVRQHRGSLGPQLLLNWCVQIAKgmyyleehrmvhrnlaarnvllkspsqvqvadfgvadllyp 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -----------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVY 900
Cdd:cd05111    162 ddkkyfyseakTPIKWMALESIHFGKYTHQSDVWSYGVTVWEMMTFGAEPYAGMRLAEVPDLLEKGERLAQPQICTIDVY 241

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1844139561  901 MIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFVVIQ 938
Cdd:cd05111    242 MVMVKCWMIDENIRPTFKELANEFTRMARDPPRYLVIK 279
PK_Tyr_Ser-Thr pfam07714
Protein tyrosine and serine/threonine kinase; Protein phosphorylation, which plays a key role ...
 720-924 2.30e-85

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: 277.84  E-value: 2.30e-85
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVT 798
Cdd:pfam07714    1 LTLGEKLGEGAFGEVYKGTLKGEGENTKIKVAVKTLKEGADEEEREDFLEEASIMKKLDHPNIVKLLGVCTqGEPLYIVT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  799 QLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA------------------------------------------------ 830
Cdd:pfam07714   81 EYMPGGDLLDFLRKHKRKLTLKDLLSMALQIAkgmeylesknfvhrdlaarnclvsenlvvkisdfglsrdiydddyyrk 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ----KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKC 906
Cdd:pfam07714  161 rgggKLPIKWMAPESLKDGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEFLEDGYRLPQPENCPDELYDLMKQC 240

                          250
                   ....*....|....*...
gi 1844139561  907 WMIDSECRPRFRELVSEF 924
Cdd:pfam07714  241 WAYDPEDRPTFSELVEDL 258
TyrKc smart00219
Tyrosine kinase, catalytic domain; Phosphotransferases. Tyrosine-specific kinase subfamily.
 720-924 9.74e-82

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


Pssm-ID: 197581 [Multi-domain]  Cd Length: 257  Bit Score: 267.86  E-value: 9.74e-82
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   720 LRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVT 798
Cdd:smart00219    1 LTLGKKLGEGAFGEVYKGKLKGKGGKKKVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNVVKLLGVCTEEEpLYIVM 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   799 QLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA------------------------------------------------ 830
Cdd:smart00219   81 EYMEGGDLLSYLRKNRPKLSLSDLLSFALQIArgmeylesknfihrdlaarnclvgenlvvkisdfglsrdlydddyyrk 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   831 ---KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCW 907
Cdd:smart00219  161 rggKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEQPYPGMSNEEVLEYLKNGYRLPQPPNCPPELYDLMLQCW 240

                           250
                    ....*....|....*..
gi 1844139561   908 MIDSECRPRFRELVSEF 924
Cdd:smart00219  241 AEDPEDRPTFSELVEIL 257
STYKc smart00221
Protein kinase; unclassified specificity; Phosphotransferases. The specificity of this class ...
 720-924 2.55e-80

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: 264.03  E-value: 2.55e-80
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   720 LRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVT 798
Cdd:smart00221    1 LTLGKKLGEGAFGEVYKGTLKGKGDGKEVEVAVKTLKEDASEQQIEEFLREARIMRKLDHPNIVKLLGVCTEEEpLMIVM 80

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   799 QLMPYGCLLDHVRENRGR-LGSQDLLNWCMQIA----------------------------------------------- 830
Cdd:smart00221   81 EYMPGGDLLDYLRKNRPKeLSLSDLLSFALQIArgmeylesknfihrdlaarnclvgenlvvkisdfglsrdlydddyyk 160

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   831 ----KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKC 906
Cdd:smart00221  161 vkggKLPIRWMAPESLKEGKFTSKSDVWSFGVLLWEIFTLGEEPYPGMSNAEVLEYLKKGYRLPKPPNCPPELYKLMLQC 240

                           250
                    ....*....|....*...
gi 1844139561   907 WMIDSECRPRFRELVSEF 924
Cdd:smart00221  241 WAEDPEDRPTFSELVEIL 258
PTKc cd00192
Catalytic domain of Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 724-924 2.63e-75

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: 250.15  E-value: 2.63e-75
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIpDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMP 802
Cdd:cd00192      1 KKLGEGAFGEVYKGKLK-GGDGKTVDVAVKTLKEDASESERKDFLKEARVMKKLGHPNVVRLLGVCTEEePLYLVMEYME 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCLLDHVRENR--------GRLGSQDLLNWCMQIA-------------------------------------------- 830
Cdd:cd00192     80 GGDLLDFLRKSRpvfpspepSTLSLKDLLSFAIQIAkgmeylaskkfvhrdlaarnclvgedlvvkisdfglsrdiyddd 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 --------KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMI 902
Cdd:cd00192    160 yyrkktggKLPIRWMAPESLKDGIFTSKSDVWSFGVLLWEIFTLGATPYPGLSNEEVLEYLRKGYRLPKPENCPDELYEL 239

                          250       260
                   ....*....|....*....|..
gi 1844139561  903 MVKCWMIDSECRPRFRELVSEF 924
Cdd:cd00192    240 MLSCWQLDPEDRPTFSELVERL 261
GF_recep_IV pfam14843
Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine ...
 511-643 3.82e-59

Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (pfam00757) regulates the binding of ligands to the receptor L domains (pfam01030).


Pssm-ID: 464344 [Multi-domain]  Cd Length: 132  Bit Score: 199.14  E-value: 3.82e-59
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  511 CHQLCARGHCWGPGPTQCVNCSQFLRGQECVEECRVLQGLPREYVNARHCLPCHPECQPQNGSVTCFGPEADQCVACAHY 590
Cdd:pfam14843    2 CDPLCSSEGCWGPGPDQCLSCRNFSRGGTCVESCNILQGEPREYVVNSTCVPCHPECLPQNGTATCSGPGADNCTKCAHF 81

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|...
gi 1844139561  591 KDPPFCVARCPSGVKPDLSymPIWKFPDEEGACQPCPINCTHSCVDLDDKGCP 643
Cdd:pfam14843   82 RDGPHCVSSCPSGVLGEND--LIWKYADANGVCQPCHPNCTQGCTGPGLTGCP 132
PTKc_Syk_like cd05060
Catalytic domain of Spleen Tyrosine Kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 726-932 1.21e-56

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: 196.80  E-value: 1.21e-56
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIPDGeNVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGC 805
Cdd:cd05060      3 LGHGNFGSVRKGVYLMKS-GKEVEVAVKTLKQEHEKAGKKEFLREASVMAQLDHPCIVRLIGVCKGEPLMLVMELAPLGP 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  806 LLDHVRENRgRLGSQDLLNWCMQIA-----------------------------------------------------KV 832
Cdd:cd05060     82 LLKYLKKRR-EIPVSDLKELAHQVAmgmayleskhfvhrdlaarnvllvnrhqakisdfgmsralgagsdyyrattagRW 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd05060    161 PLKWYAPECINYGKFSSKSDVWSYGVTLWEAFSYGAKPYGEMKGPEVIAMLESGERLPRPEECPQEIYSIMLSCWKYRPE 240

                          250       260
                   ....*....|....*....|
gi 1844139561  913 CRPRFRELVsefSRMARDPQ 932
Cdd:cd05060    241 DRPTFSELE---STFRRDPE 257
PTKc_FAK cd05056
Catalytic domain of the Protein Tyrosine Kinase, Focal Adhesion Kinase; PTKs catalyze the ...
 724-925 1.61e-50

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: 179.93  E-value: 1.61e-50
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIpDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPY 803
Cdd:cd05056     12 RCIGEGQFGDVYQGVYM-SPENEKIAVAVKTCKNCTSPSVREKFLQEAYIMRQFDHPHIVKLIGVITENPVWIVMELAPL 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  804 GCLLDHVRENRGRLGSQDLLNWCMQIA---------------------------------------------------KV 832
Cdd:cd05056     91 GELRSYLQVNKYSLDLASLILYAYQLStalayleskrfvhrdiaarnvlvsspdcvklgdfglsrymedesyykaskgKL 170

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd05056    171 PIKWMAPESINFRRFTSASDVWMFGVCMWEILMLGVKPFQGVKNNDVIGRIENGERLPMPPNCPPTLYSLMTKCWAYDPS 250

                          250
                   ....*....|...
gi 1844139561  913 CRPRFRELVSEFS 925
Cdd:cd05056    251 KRPRFTELKAQLS 263
PTKc_Ack_like cd05040
Catalytic domain of the Protein Tyrosine Kinase, Activated Cdc42-associated kinase; PTKs ...
 724-925 1.53e-47

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: 170.60  E-value: 1.53e-47
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWI-PDGEnvKIPVAIKVLREN--TSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQL 800
Cdd:cd05040      1 EKLGDGSFGVVRRGEWTtPSGK--VIQVAVKCLKSDvlSQPNAMDDFLKEVNAMHSLDHPNLIRLYGVVLSSPLMMVTEL 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  801 MPYGCLLDHVRENRGRLGSQDLLNWCMQIA-------------------------------------------------- 830
Cdd:cd05040     79 APLGSLLDRLRKDQGHFLISTLCDYAVQIAngmayleskrfihrdlaarnillaskdkvkigdfglmralpqnedhyvmq 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ---KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEK-GERLPQPPICTIDVYMIMVKC 906
Cdd:cd05040    159 ehrKVPFAWCAPESLKTRKFSHASDVWMFGVTLWEMFTYGEEPWLGLNGSQILEKIDKeGERLERPDDCPQDIYNVMLQC 238

                          250
                   ....*....|....*....
gi 1844139561  907 WMIDSECRPRFRELVSEFS 925
Cdd:cd05040    239 WAHKPADRPTFVALRDFLP 257
PTKc_FGFR cd05053
Catalytic domain of the Protein Tyrosine Kinases, Fibroblast Growth Factor Receptors; PTKs ...
 715-927 9.21e-45

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: 164.13  E-value: 9.21e-45
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  715 LKETELRKVKVLGSGAFGTVYKG--IWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLT 791
Cdd:cd05053      9 LPRDRLTLGKPLGEGAFGQVVKAeaVGLDNKPNEVVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKhKNIINLLGACTQ 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 S-TVQLVTQLMPYGCLLDHVRENR---------------GRLGSQDLLNWCMQIAK------------------------ 831
Cdd:cd05053     89 DgPLYVVVEYASKGNLREFLRARRppgeeaspddprvpeEQLTQKDLVSFAYQVARgmeylaskkcihrdlaarnvlvte 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ----------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLL 883
Cdd:cd05053    169 dnvmkiadfglardihhidyyrkttngrLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKLL 248

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1844139561  884 EKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05053    249 KEGHRMEKPQNCTQELYMLMRDCWHEVPSQRPTFKQLVEDLDRI 292
PTKc_Src_like cd05034
Catalytic domain of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
 724-924 9.68e-44

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: 159.37  E-value: 9.68e-44
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLM 801
Cdd:cd05034      1 KKLGAGQFGEVWMGVW-----NGTTKVAVKTLKPGTmSPEA---FLQEAQIMKKLRHDKLVQLYAVCSDEEpIYIVTELM 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVRENRGR-LGSQDLLNWCMQIA-------------------------------------------------- 830
Cdd:cd05034     73 SKGSLLDYLRTGEGRaLRLPQLIDMAAQIAsgmaylesrnyihrdlaarnilvgennvckvadfglarlieddeytareg 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 -KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMI 909
Cdd:cd05034    153 aKFPIKWTAPEAALYGRFTIKSDVWSFGILLYEIVTYGRVPYPGMTNREVLEQVERGYRMPKPPGCPDELYDIMLQCWKK 232

                          250
                   ....*....|....*
gi 1844139561  910 DSECRPRFRELVSEF 924
Cdd:cd05034    233 EPEERPTFEYLQSFL 247
PTKc_Tec_like cd05059
Catalytic domain of Tec-like Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 719-922 1.27e-42

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: 156.45  E-value: 1.27e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWIPdgenvKIPVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLV 797
Cdd:cd05059      5 ELTFLKELGSGQFGVVHLGKWRG-----KIDVAIKMIKEGS--MSEDDFIEEAKVMMKLSHPKLVQLYGVCTKqRPIFIV 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCLLDHVRENRGRLGSQDLLNWCMQI------------------------------------------------ 829
Cdd:cd05059     78 TEYMANGCLLNYLRERRGKFQTEQLLEMCKDVceameylesngfihrdlaarnclvgeqnvvkvsdfglaryvlddeyts 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 ---AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKC 906
Cdd:cd05059    158 svgTKFPVKWSPPEVFMYSKFSSKSDVWSFGVLMWEVFSEGKMPYERFSNSEVVEHISQGYRLYRPHLAPTEVYTIMYSC 237

                          250
                   ....*....|....*.
gi 1844139561  907 WMIDSECRPRFRELVS 922
Cdd:cd05059    238 WHEKPEERPTFKILLS 253
PTKc_EphR cd05033
Catalytic domain of Ephrin Receptor Protein Tyrosine Kinases; PTKs catalyze the transfer of ...
 723-927 2.26e-42

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: 155.99  E-value: 2.26e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  723 VKVLGSGAFGTVYKGIWIPDGENVkIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLM 801
Cdd:cd05033      9 EKVIGGGEFGEVCSGSLKLPGKKE-IDVAIKTLKSGYSDKQRLDFLTEASIMGQFDHPNVIRLEGVVTkSRPVMIVTEYM 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVRENRGRLGSQDLLNWCMQIA--------------------------------------------------- 830
Cdd:cd05033     88 ENGSLDKFLRENDGKFTVTQLVGMLRGIAsgmkylsemnyvhrdlaarnilvnsdlvckvsdfglsrrledseatyttkg 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 -KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMI 909
Cdd:cd05033    168 gKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSYGERPYWDMSNQDVIKAVEDGYRLPPPMDCPSALYQLMLDCWQK 247

                          250
                   ....*....|....*...
gi 1844139561  910 DSECRPRFRELVSEFSRM 927
Cdd:cd05033    248 DRNERPTFSQIVSTLDKM 265
PTKc_Csk_like cd05039
Catalytic domain of C-terminal Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 715-926 6.34e-42

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: 154.43  E-value: 6.34e-42
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  715 LKETELRKVKVLGSGAFGTVYKGIWipdgENVKipVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLT-ST 793
Cdd:cd05039      3 INKKDLKLGELIGKGEFGDVMLGDY----RGQK--VAVKCLKDDS--TAAQAFLAEASVMTTLRHPNLVQLLGVVLEgNG 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  794 VQLVTQLMPYGCLLDHVReNRGR--LGSQDLLNWCMQI-----------------------------AKV---------- 832
Cdd:cd05039     75 LYIVTEYMAKGSLVDYLR-SRGRavITRKDQLGFALDVcegmeyleskkfvhrdlaarnvlvsednvAKVsdfglakeas 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 --------PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMV 904
Cdd:cd05039    154 snqdggklPIKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPHVEKGYRMEAPEGCPPEVYKVMK 233

                          250       260
                   ....*....|....*....|..
gi 1844139561  905 KCWMIDSECRPRFRELVSEFSR 926
Cdd:cd05039    234 NCWELDPAKRPTFKQLREKLEH 255
PTKc_c-ros cd05044
Catalytic domain of the Protein Tyrosine Kinase, C-ros; PTKs catalyze the transfer of the ...
 724-918 1.09e-41

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: 154.11  E-value: 1.09e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIW--IPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQL 800
Cdd:cd05044      1 KFLGSGAFGEVFEGTAkdILGDGSGETKVAVKTLRKGATDQEKAEFLKEAHLMSNFKHPNILKLLGVCLdNDPQYIILEL 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  801 MPYGCLLDHVRENR------GRLGSQDLLNWCMQIAK------------------------------------------- 831
Cdd:cd05044     81 MEGGDLLSYLRAARptaftpPLLTLKDLLSICVDVAKgcvyledmhfvhrdlaarnclvsskdyrervvkigdfglardi 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYdgiPAR---EIPDLLEKGERLPQPPIC 895
Cdd:cd05044    161 ykndyyrkegeglLPVRWMAPESLVDGVFTTQSDVWAFGVLMWEILTLGQQPY---PARnnlEVLHFVRAGGRLDQPDNC 237

                          250       260
                   ....*....|....*....|...
gi 1844139561  896 TIDVYMIMVKCWMIDSECRPRFR 918
Cdd:cd05044    238 PDDLYELMLRCWSTDPEERPSFA 260
PTKc_Jak_rpt2 cd05038
Catalytic (repeat 2) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak subfamily ...
 720-928 4.44e-41

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: 152.92  E-value: 4.44e-41
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIC---LTSTVQL 796
Cdd:cd05038      6 LKFIKQLGEGHFGSVELCRYDPLGDNTGEQVAVKSLQPSGEEQHMSDFKREIEILRTLDHEYIVKYKGVCespGRRSLRL 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  797 VTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAK--------------------------------------------- 831
Cdd:cd05038     86 IMEYLPSGSLRDYLQRHRDQIDLKRLLLFASQICKgmeylgsqryihrdlaarnilvesedlvkisdfglakvlpedkey 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 --------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYD--GIPAREIP------------DLLEKGERL 889
Cdd:cd05038    166 yyvkepgeSPIFWYAPECLRESRFSSASDVWSFGVTLYELFTYGDPSQSppALFLRMIGiaqgqmivtrllELLKSGERL 245

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  890 PQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMA 928
Cdd:cd05038    246 PRPPSCPDEVYDLMKECWEYEPQDRPSFSDLILIIDRLR 284
PTKc_Frk_like cd05068
Catalytic domain of Fyn-related kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 718-920 1.11e-40

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: 151.41  E-value: 1.11e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  718 TELRKVKVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENT-SPKankEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQ 795
Cdd:cd05068      8 KSLKLLRKLGSGQFGEVWEGLW-----NNTTPVAVKTLKPGTmDPE---DFLREAQIMKKLRHPKLIQLYAVCtLEEPIY 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  796 LVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIA--------------------------------------------- 830
Cdd:cd05068     80 IITELMKHGSLLEYLQGKGRSLQLPQLIDMAAQVAsgmaylesqnyihrdlaarnvlvgennickvadfglarvikvede 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 -------KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIM 903
Cdd:cd05068    160 yearegaKFPIKWTAPEAANYNRFSIKSDVWSFGILLTEIVTYGRIPYPGMTNAEVLQQVERGYRMPCPPNCPPQLYDIM 239

                          250
                   ....*....|....*..
gi 1844139561  904 VKCWMIDSECRPRFREL 920
Cdd:cd05068    240 LECWKADPMERPTFETL 256
Furin-like pfam00757
Furin-like cysteine rich region;
189-338 2.00e-40

Furin-like cysteine rich region;


Pssm-ID: 395614 [Multi-domain]  Cd Length: 143  Bit Score: 146.04  E-value: 2.00e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  189 SRACHPCSPMCKGSRCWGesSEDCQsltrTVCAGGCA-RCKGPlpTDCCHEQCAAGCTGPKHSDCLACLHFNHSGICELH 267
Cdd:pfam00757    9 PGTMEKCHSCCNNGYCWG--PGHCQ----KVCPEQCKkRCTKP--GECCHEQCLGGCTGPNDSDCLACRHFNDEGTCVDQ 80

                           90       100       110       120       130       140       150
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....
gi 1844139561  268 CpalvtyntdtfesmpnPEGRYTFGASCVTA--CP------YNYLSTDVGSCTLVCPLHNQEVtaEDGTQRCEKCSKPC 338
Cdd:pfam00757   81 C----------------PPGTYQFGWRCVTFkeCPkshlpgYNPLVIHNGECVRECPSGYTEV--ENNSRKCEPCEGLC 141
PTKc_Abl cd05052
Catalytic domain of the Protein Tyrosine Kinase, Abelson kinase; PTKs catalyze the transfer of ...
 726-927 7.46e-40

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: 148.72  E-value: 7.46e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWipdgENVKIPVAIKVLRENTSPKanKEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQLVTQLMPYG 804
Cdd:cd05052     14 LGGGQYGEVYEGVW----KKYNLTVAVKTLKEDTMEV--EEFLKEAAVMKEIKHPNLVQLLGVCtREPPFYIITEFMPYG 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRE-NRGRLGSQDLLNWCMQI---------------------------------------------------AKV 832
Cdd:cd05052     88 NLLDYLREcNREELNAVVLLYMATQIasameylekknfihrdlaarnclvgenhlvkvadfglsrlmtgdtytahagAKF 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd05052    168 PIKWTAPESLAYNKFSIKSDVWAFGVLLWEIATYGMSPYPGIDLSQVYELLEKGYRMERPEGCPPKVYELMRACWQWNPS 247

                          250
                   ....*....|....*
gi 1844139561  913 CRPRFRELVSEFSRM 927
Cdd:cd05052    248 DRPSFAEIHQALETM 262
PTKc_Met_Ron cd05058
Catalytic domain of the Protein Tyrosine Kinases, Met and Ron; PTKs catalyze the transfer of ...
 724-925 8.98e-40

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: 148.39  E-value: 8.98e-40
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIpDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS--TVQLVTQLM 801
Cdd:cd05058      1 EVIGKGHFGCVYHGTLI-DSDGQKIHCAVKSLNRITDIEEVEQFLKEGIIMKDFSHPNVLSLLGICLPSegSPLVVLPYM 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVRENRGRLGSQDLLNWCMQIAK-------------------------------------------------- 831
Cdd:cd05058     80 KHGDLRNFIRSETHNPTVKDLIGFGLQVAKgmeylaskkfvhrdlaarncmldesftvkvadfglardiydkeyysvhnh 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ----VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCW 907
Cdd:cd05058    160 tgakLPVKWMALESLQTQKFTTKSDVWSFGVLLWELMTRGAPPYPDVDSFDITVYLLQGRRLLQPEYCPDPLYEVMLSCW 239

                          250
                   ....*....|....*...
gi 1844139561  908 MIDSECRPRFRELVSEFS 925
Cdd:cd05058    240 HPKPEMRPTFSELVSRIS 257
PTKc_InsR_like cd05032
Catalytic domain of Insulin Receptor-like Protein Tyrosine Kinases; PTKs catalyze the transfer ...
 726-922 2.90e-38

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: 144.79  E-value: 2.90e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIW--IPDGEnVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVT-QLMP 802
Cdd:cd05032     14 LGQGSFGMVYEGLAkgVVKGE-PETRVAIKTVNENASMRERIEFLNEASVMKEFNCHHVVRLLGVVSTGQPTLVVmELMA 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCLLDHVRENR---------GRLGSQDLLNWCMQIAK------------------------------------------ 831
Cdd:cd05032     93 KGDLKSYLRSRRpeaennpglGPPTLQKFIQMAAEIADgmaylaakkfvhrdlaarncmvaedltvkigdfgmtrdiyet 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ----------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYM 901
Cdd:cd05032    173 dyyrkggkglLPVRWMAPESLKDGVFTTKSDVWSFGVVLWEMATLAEQPYQGLSNEEVLKFVIDGGHLDLPENCPDKLLE 252

                          250       260
                   ....*....|....*....|.
gi 1844139561  902 IMVKCWMIDSECRPRFRELVS 922
Cdd:cd05032    253 LMRMCWQYNPKMRPTFLEIVS 273
PTKc_Fes_like cd05041
Catalytic domain of Fes-like Protein Tyrosine Kinases; Protein Tyrosine Kinase (PTK) family; ...
 726-923 4.18e-38

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: 143.35  E-value: 4.18e-38
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIPDGenvkIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPYG 804
Cdd:cd05041      3 IGRGNFGDVYRGVLKPDN----TEVAVKTCRETLPPDLKRKFLQEARILKQYDHPNIVKLIGVCVqKQPIMIVMELVPGG 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRGRLGSQDLLNWCMQIA----------------------------------------------------KV 832
Cdd:cd05041     79 SLLTFLRKKGARLTVKQLLQMCLDAAagmeyleskncihrdlaarnclvgennvlkisdfgmsreeedgeytvsdglkQI 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd05041    159 PIKWTAPEALNYGRYTSESDVWSFGILLWEIFSLGATPYPGMSNQQTREQIESGYRMPAPELCPEAVYRLMLQCWAYDPE 238

                          250
                   ....*....|.
gi 1844139561  913 CRPRFRELVSE 923
Cdd:cd05041    239 NRPSFSEIYNE 249
PTKc_Mer cd14204
Catalytic Domain of the Protein Tyrosine Kinase, Mer; PTKs catalyze the transfer of the ...
 724-920 4.82e-37

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: 141.23  E-value: 4.82e-37
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKG-IWIPDGENVKipVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ------ 795
Cdd:cd14204     13 KVLGEGEFGSVMEGeLQQPDGTNHK--VAVKTMKlDNFSQREIEEFLSEAACMKDFNHPNVIRLLGVCLEVGSQripkpm 90

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  796 LVTQLMPYGCLldHVRENRGRLGS-------QDLLNW-------------------------CM---------------- 827
Cdd:cd14204     91 VILPFMKYGDL--HSFLLRSRLGSgpqhvplQTLLKFmidialgmeylssrnflhrdlaarnCMlrddmtvcvadfglsk 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  828 -----------QIAKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICT 896
Cdd:cd14204    169 kiysgdyyrqgRIAKMPVKWIAVESLADRVYTVKSDVWAFGVTMWEIATRGMTPYPGVQNHEIYDYLLHGHRLKQPEDCL 248

                          250       260
                   ....*....|....*....|....
gi 1844139561  897 IDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd14204    249 DELYDIMYSCWRSDPTDRPTFTQL 272
PTKc_TAM cd05035
Catalytic Domain of TAM (Tyro3, Axl, Mer) Protein Tyrosine Kinases; PTKs catalyze the transfer ...
 724-927 4.80e-36

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: 138.05  E-value: 4.80e-36
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKG-IWIPDGENVKipVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ------ 795
Cdd:cd05035      5 KILGEGEFGSVMEAqLKQDDGSQLK--VAVKTMKvDIHTYSEIEEFLSEAACMKDFDHPNVMRLIGVCFTASDLnkppsp 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  796 -LVTQLMPYG-----CLLDHVRENRGRLGSQDLLNW-------------------------CM----------------- 827
Cdd:cd05035     83 mVILPFMKHGdlhsyLLYSRLGGLPEKLPLQTLLKFmvdiakgmeylsnrnfihrdlaarnCMldenmtvcvadfglsrk 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  828 ----------QIAKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTI 897
Cdd:cd05035    163 iysgdyyrqgRISKMPVKWIALESLADNVYTSKSDVWSFGVTMWEIATRGQTPYPGVENHEIYDYLRNGNRLKQPEDCLD 242

                          250       260       270
                   ....*....|....*....|....*....|
gi 1844139561  898 DVYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05035    243 EVYFLMYFCWTVDPKDRPTFTKLREVLENI 272
STKc_MAP3K-like cd13999
Catalytic domain of Mitogen-Activated Protein Kinase (MAPK) Kinase Kinase-like Serine ...
 726-924 1.05e-35

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: 136.13  E-value: 1.05e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIpdgenvKIPVAIKVLRENTSPKAN-KEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPY 803
Cdd:cd13999      1 IGSGSFGEVYKGKWR------GTDVAIKKLKVEDDNDELlKEFRREVSILSKLRHPNIVQFIGACLSpPPLCIVTEYMPG 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  804 GCLLDHVRENRGRLGSQDLLNWCMQIAK-------VPI------------------------------------------ 834
Cdd:cd13999     75 GSLYDLLHKKKIPLSWSLRLKIALDIARgmnylhsPPIihrdlkslnilldenftvkiadfglsriknsttekmtgvvgt 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  835 -KWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLL-EKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd13999    155 pRWMAPEVLRGEPYTEKADVYSFGIVLWELLT-GEVPFKELSPIQIAAAVvQKGLRPPIPPDCPPELSKLIKRCWNEDPE 233

                          250
                   ....*....|..
gi 1844139561  913 CRPRFRELVSEF 924
Cdd:cd13999    234 KRPSFSEIVKRL 245
PTKc_Srm_Brk cd05148
Catalytic domain of the Protein Tyrosine Kinases, Src-related kinase lacking C-terminal ...
 719-925 1.41e-35

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: 136.41  E-value: 1.41e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENTSPKAnKEILDEAYVMAGVGSPYVSRLLGIC-LTSTVQLV 797
Cdd:cd05148      7 EFTLERKLGSGYFGEVWEGLW-----KNRVRVAIKILKSDDLLKQ-QDFQKEVQALKRLRHKHLISLFAVCsVGEPVYII 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCLLDHVRENRGR-LGSQDLLNWCMQIA---------------------------------------------- 830
Cdd:cd05148     81 TELMEKGSLLAFLRSPEGQvLPVASLIDMACQVAegmayleeqnsihrdlaarnilvgedlvckvadfglarlikedvyl 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ----KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKC 906
Cdd:cd05148    161 ssdkKIPYKWTAPEAASHGTFSTKSDVWSFGILLYEMFTYGQVPYPGMNNHEVYDQITAGYRMPCPAKCPQEIYKIMLEC 240

                          250
                   ....*....|....*....
gi 1844139561  907 WMIDSECRPRFRELVSEFS 925
Cdd:cd05148    241 WAAEPEDRPSFKALREELD 259
PTKc_Itk cd05112
Catalytic domain of the Protein Tyrosine Kinase, Interleukin-2-inducible T-cell Kinase; PTKs ...
 718-925 1.50e-35

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: 136.23  E-value: 1.50e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  718 TELRKVKVLGSGAFGTVYKGIWIPDGEnvkipVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQL 796
Cdd:cd05112      4 SELTFVQEIGSGQFGLVHLGYWLNKDK-----VAIKTIREGA--MSEEDFIEEAEVMMKLSHPKLVQLYGVCLEQApICL 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  797 VTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQI----------------------------------------------- 829
Cdd:cd05112     77 VFEFMEHGCLSDYLRTQRGLFSAETLLGMCLDVcegmayleeasvihrdlaarnclvgenqvvkvsdfgmtrfvlddqyt 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 ----AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVK 905
Cdd:cd05112    157 sstgTKFPVKWSSPEVFSFSRYSSKSDVWSFGVLMWEVFSEGKIPYENRSNSEVVEDINAGFRLYKPRLASTHVYEIMNH 236

                          250       260
                   ....*....|....*....|
gi 1844139561  906 CWMIDSECRPRFRELVSEFS 925
Cdd:cd05112    237 CWKERPEDRPSFSLLLRQLA 256
PTKc_EphR_B cd05065
Catalytic domain of the Protein Tyrosine Kinases, Class EphB Ephrin Receptors; PTKs catalyze ...
 724-927 1.55e-35

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: 136.54  E-value: 1.55e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIPDGENvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMP 802
Cdd:cd05065     10 EVIGAGEFGEVCRGRLKLPGKR-EIFVAIKTLKSGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTKSRpVMIITEFME 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCLLDHVRENRGRLGSQDLLNWCMQIA---------------------------------------------------- 830
Cdd:cd05065     89 NGALDSFLRQNDGQFTVIQLVGMLRGIAagmkylsemnyvhrdlaarnilvnsnlvckvsdfglsrfleddtsdptytss 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ---KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCW 907
Cdd:cd05065    169 lggKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWDMSNQDVINAIEQDYRLPPPMDCPTALHQLMLDCW 248

                          250       260
                   ....*....|....*....|
gi 1844139561  908 MIDSECRPRFRELVSEFSRM 927
Cdd:cd05065    249 QKDRNLRPKFGQIVNTLDKM 268
PTKc_RET cd05045
Catalytic domain of the Protein Tyrosine Kinase, REarranged during Transfection protein; PTKs ...
 724-927 5.31e-35

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: 135.86  E-value: 5.31e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIP-DGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLM 801
Cdd:cd05045      6 KTLGEGEFGKVVKATAFRlKGRAGYTTVAVKMLKENASSSELRDLLSEFNLLKQVNHPHVIKLYGACSQDgPLLLIVEYA 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVRENR----GRLGS-------------------QDLLNWCMQIAK--------------------------- 831
Cdd:cd05045     86 KYGSLRSFLRESRkvgpSYLGSdgnrnssyldnpderaltmGDLISFAWQISRgmqylaemklvhrdlaarnvlvaegrk 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKG 886
Cdd:cd05045    166 mkisdfglsrdvyeedsyvkrskgrIPVKWMAIESLFDHIYTTQSDVWSFGVLLWEIVTLGGNPYPGIAPERLFNLLKTG 245

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|.
gi 1844139561  887 ERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05045    246 YRMERPENCSEEMYNLMLTCWKQEPDKRPTFADISKELEKM 286
PTKc_Syk cd05116
Catalytic domain of the Protein Tyrosine Kinase, Spleen tyrosine kinase; PTKs catalyze the ...
 726-917 5.52e-35

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: 134.70  E-value: 5.52e-35
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWipDGENVKIPVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYG 804
Cdd:cd05116      3 LGSGNFGTVKKGYY--QMKKVVKTVAVKILKnEANDPALKDELLREANVMQQLDNPYIVRMIGICEAESWMLVMEMAELG 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRG----------------------------RLGSQDLLNWCMQIAKV------------------------ 832
Cdd:cd05116     81 PLNKFLQKNRHvteknitelvhqvsmgmkyleesnfvhrDLAARNVLLVTQHYAKIsdfglskalradenyykaqthgkw 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd05116    161 PVKWYAPECMNYYKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVTQMIEKGERMECPAGCPPEMYDLMKLCWTYDVD 240


                   ....*
gi 1844139561  913 CRPRF 917
Cdd:cd05116    241 ERPGF 245
PTKc_EphR_A2 cd05063
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A2; PTKs catalyze the ...
 722-927 1.22e-34

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: 133.95  E-value: 1.22e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  722 KVKVLGSGAFGTVYKGIWIPDGENvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQL 800
Cdd:cd05063      9 KQKVIGAGEFGEVFRGILKMPGRK-EVAVAIKTLKPGYTEKQRQDFLSEASIMGQFSHHNIIRLEGVVTKfKPAMIITEY 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  801 MPYGCLLDHVRENRGRLGSQDLLNWCMQIA-------------------------------------------------- 830
Cdd:cd05063     88 MENGALDKYLRDHDGEFSSYQLVGMLRGIAagmkylsdmnyvhrdlaarnilvnsnleckvsdfglsrvleddpegtytt 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ---KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCW 907
Cdd:cd05063    168 sggKIPIRWTAPEAIAYRKFTSASDVWSFGIVMWEVMSFGERPYWDMSNHEVMKAINDGFRLPAPMDCPSAVYQLMLQCW 247

                          250       260
                   ....*....|....*....|
gi 1844139561  908 MIDSECRPRFRELVSEFSRM 927
Cdd:cd05063    248 QQDRARRPRFVDIVNLLDKL 267
PTKc_ALK_LTK cd05036
Catalytic domain of the Protein Tyrosine Kinases, Anaplastic Lymphoma Kinase and Leukocyte ...
 720-917 1.33e-34

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: 134.05  E-value: 1.33e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWIP-DGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQL-V 797
Cdd:cd05036      8 LTLIRALGQGAFGEVYEGTVSGmPGDPSPLQVAVKTLPELCSEQDEMDFLMEALIMSKFNHPNIVRCIGVCFQRLPRFiL 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCLLDHVRENRGRLGS------QDLLNWCMQIAK---------------------------------------- 831
Cdd:cd05036     88 LELMAGGDLKSFLRENRPRPEQpssltmLDLLQLAQDVAKgcryleenhfihrdiaarnclltckgpgrvakigdfgmar 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ---------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICT 896
Cdd:cd05036    168 diyradyyrkggkamLPVKWMPPEAFLDGIFTSKTDVWSFGVLLWEIFSLGYMPYPGKSNQEVMEFVTSGGRMDPPKNCP 247

                          250       260
                   ....*....|....*....|.
gi 1844139561  897 IDVYMIMVKCWMIDSECRPRF 917
Cdd:cd05036    248 GPVYRIMTQCWQHIPEDRPNF 268
PTKc_Zap-70 cd05115
Catalytic domain of the Protein Tyrosine Kinase, Zeta-chain-associated protein of 70kDa; PTKs ...
 726-917 3.77e-34

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: 132.38  E-value: 3.77e-34
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWipDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYGC 805
Cdd:cd05115     12 LGSGNFGCVKKGVY--KMRKKQIDVAIKVLKQGNEKAVRDEMMREAQIMHQLDNPYIVRMIGVCEAEALMLVMEMASGGP 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  806 LLDHVRENRGRLGSQDLLNWCMQIA-----------------------------------------------------KV 832
Cdd:cd05115     90 LNKFLSGKKDEITVSNVVELMHQVSmgmkyleeknfvhrdlaarnvllvnqhyakisdfglskalgaddsyykarsagKW 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd05115    170 PLKWYAPECINFRKFSSRSDVWSYGVTMWEAFSYGQKPYKKMKGPEVMSFIEQGKRMDCPAECPPEMYALMSDCWIYKWE 249


                   ....*
gi 1844139561  913 CRPRF 917
Cdd:cd05115    250 DRPNF 254
PTKc_Ror cd05048
Catalytic Domain of the Protein Tyrosine Kinases, Receptor tyrosine kinase-like Orphan ...
 720-920 1.71e-33

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: 130.96  E-value: 1.71e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKG-IWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LV 797
Cdd:cd05048      7 VRFLEELGEGAFGKVYKGeLLGPSSEESAISVAIKTLKENASPKTQQDFRREAELMSDLQHPNIVCLLGVCTKEQPQcML 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCL---------------LDHVRENRGRLGSQDLLNWCMQIAK------------------------------- 831
Cdd:cd05048     87 FEYMAHGDLheflvrhsphsdvgvSSDDDGTASSLDQSDFLHIAIQIAAgmeylsshhyvhrdlaarnclvgdgltvkis 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ---------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLP 890
Cdd:cd05048    167 dfglsrdiyssdyyrvqskslLPVRWMPPEAILYGKFTTESDVWSFGVVLWEIFSYGLQPYYGYSNQEVIEMIRSRQLLP 246

                          250       260       270
                   ....*....|....*....|....*....|
gi 1844139561  891 QPPICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05048    247 CPEDCPARVYSLMVECWHEIPSRRPRFKEI 276
PTKc_Axl cd05075
Catalytic domain of the Protein Tyrosine Kinase, Axl; PTKs catalyze the transfer of the ...
 724-930 8.32e-33

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: 128.97  E-value: 8.32e-33
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIPDGENVKipVAIKVLRENTSPKANKE-ILDEAYVMAGVGSPYVSRLLGICLTSTVQ------- 795
Cdd:cd05075      6 KTLGEGEFGSVMEGQLNQDDSVLK--VAVKTMKIAICTRSEMEdFLSEAVCMKEFDHPNVMRLIGVCLQNTESegypspv 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  796 LVTQLMPYGCLldHVRENRGRLG-------SQDLLNW-------------------------CM---------------- 827
Cdd:cd05075     84 VILPFMKHGDL--HSFLLYSRLGdcpvylpTQMLVKFmtdiasgmeylssknfihrdlaarnCMlnenmnvcvadfglsk 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  828 -----------QIAKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICT 896
Cdd:cd05075    162 kiyngdyyrqgRISKMPVKWIAIESLADRVYTTKSDVWSFGVTMWEIATRGQTPYPGVENSEIYDYLRQGNRLKQPPDCL 241

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1844139561  897 IDVYMIMVKCWMIDSECRPRFRELVSEFSRMARD 930
Cdd:cd05075    242 DGLYELMSSCWLLNPKDRPSFETLRCELEKILKD 275
PTKc_Csk cd05082
Catalytic domain of the Protein Tyrosine Kinase, C-terminal Src kinase; PTKs catalyze the ...
 715-920 1.18e-32

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: 127.79  E-value: 1.18e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  715 LKETELRKVKVLGSGAFGTVYKGiwipDGENVKipVAIKVLRENTSPKAnkeILDEAYVMAGVGSPYVSRLLGICL--TS 792
Cdd:cd05082      3 LNMKELKLLQTIGKGEFGDVMLG----DYRGNK--VAVKCIKNDATAQA---FLAEASVMTQLRHSNLVQLLGVIVeeKG 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  793 TVQLVTQLMPYGCLLDHVReNRGR--LGSQDLLNWCMQI----------------------------------------- 829
Cdd:cd05082     74 GLYIVTEYMAKGSLVDYLR-SRGRsvLGGDCLLKFSLDVceameylegnnfvhrdlaarnvlvsednvakvsdfgltkea 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 ------AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIM 903
Cdd:cd05082    153 sstqdtGKLPVKWTAPEALREKKFSTKSDVWSFGILLWEIYSFGRVPYPRIPLKDVVPRVEKGYKMDAPDGCPPAVYDVM 232

                          250
                   ....*....|....*..
gi 1844139561  904 VKCWMIDSECRPRFREL 920
Cdd:cd05082    233 KNCWHLDAAMRPSFLQL 249
PTKc_Tyro3 cd05074
Catalytic domain of the Protein Tyrosine Kinase, Tyro3; PTKs catalyze the transfer of the ...
 714-924 2.19e-32

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: 127.73  E-value: 2.19e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  714 ILKETELRKVKVLGSGAFGTVYKG-IWIPDGENVKipVAIKVLRENTSPKAN-KEILDEAYVMAGVGSPYVSRLLGICLT 791
Cdd:cd05074      5 LIQEQQFTLGRMLGKGEFGSVREAqLKSEDGSFQK--VAVKMLKADIFSSSDiEEFLREAACMKEFDHPNVIKLIGVSLR 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 STVQ-------LVTQLMPYG-----CLLDHVRENRGRLGSQDLLNWCMQIA----------------------------- 830
Cdd:cd05074     83 SRAKgrlpipmVILPFMKHGdlhtfLLMSRIGEEPFTLPLQTLVRFMIDIAsgmeylssknfihrdlaarncmlnenmtv 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 -----------------------KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGE 887
Cdd:cd05074    163 cvadfglskkiysgdyyrqgcasKLPVKWLALESLADNVYTTHSDVWAFGVTMWEIMTRGQTPYAGVENSEIYNYLIKGN 242

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1844139561  888 RLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEF 924
Cdd:cd05074    243 RLKQPPDCLEDVYELMCQCWSPEPKCRPSFQHLRDQL 279
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
 52-173 2.40e-32

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


Pssm-ID: 460032  Cd Length: 112  Bit Score: 121.57  E-value: 2.40e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   52 GCQVVQGNLELTYLPTN---ASLSFLQDIQEVQGYVLIAH-NQVRQVPLQRLRIVRGTQLFEDNYALAVLDNGDplnntt 127
Cdd:pfam01030    1 NCTVIYGNLEITLIDENndsELLSFLSNVEEITGYLLIANtNLVSLSFLPNLRIIRGRNLFDDNYALYILDNPN------ 74

                           90       100       110       120
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139561  128 pvtgaspggLRELQLRSLTEILKGGVLIQRNPQLCYQDT-ILWKDIF 173
Cdd:pfam01030   75 ---------LTELGLPSLKEITSGGVYIHNNPKLCYTETeILWKLLL 112
PTKc_Src_Fyn_like cd14203
Catalytic domain of a subset of Src kinase-like Protein Tyrosine Kinases; PTKs catalyze the ...
 724-922 2.81e-32

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: 126.57  E-value: 2.81e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMP 802
Cdd:cd14203      1 VKLGQGCFGEVWMGTW-----NGTTKVAIKTLKPGTmSPEA---FLEEAQIMKKLRHDKLVQLYAVVSEEPIYIVTEFMS 72

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCLLDHVRENRGR-LGSQDLLNWCMQIA--------------------------------------------------- 830
Cdd:cd14203     73 KGSLLDFLKDGEGKyLKLPQLVDMAAQIAsgmayiermnyihrdlraanilvgdnlvckiadfglarliedneytarqga 152

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMID 910
Cdd:cd14203    153 KFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPPGCPESLHELMCQCWRKD 232

                          250
                   ....*....|..
gi 1844139561  911 SECRPRFRELVS 922
Cdd:cd14203    233 PEERPTFEYLQS 244
PTKc_Tec_Rlk cd05114
Catalytic domain of the Protein Tyrosine Kinases, Tyrosine kinase expressed in hepatocellular ...
 715-928 3.21e-32

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: 126.51  E-value: 3.21e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  715 LKETELRKVKVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLTST- 793
Cdd:cd05114      1 INPSELTFMKELGSGLFGVVRLGKW-----RAQYKVAIKAIREGA--MSEEDFIEEAKVMMKLTHPKLVQLYGVCTQQKp 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  794 VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQI-------------------------------------------- 829
Cdd:cd05114     74 IYIVTEFMENGCLLNYLRQRRGKLSRDMLLSMCQDVcegmeylernnfihrdlaarnclvndtgvvkvsdfgmtryvldd 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 -------AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMI 902
Cdd:cd05114    154 qytsssgAKFPVKWSPPEVFNYSKFSSKSDVWSFGVLMWEVFTEGKMPFESKSNYEVVEMVSRGHRLYRPKLASKSVYEV 233

                          250       260
                   ....*....|....*....|....*.
gi 1844139561  903 MVKCWMIDSECRPRFRELVSEFSRMA 928
Cdd:cd05114    234 MYSCWHEKPEGRPTFADLLRTITEIA 259
PTKc_DDR cd05051
Catalytic domain of the Protein Tyrosine Kinases, Discoidin Domain Receptors; PTKs catalyze ...
 717-920 3.28e-32

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: 127.84  E-value: 3.28e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  717 ETELRKVKVLGSGAFGTV---------------YKGIWIPDGENVkipVAIKVLRENTSPKANKEILDEAYVMAGVGSPY 781
Cdd:cd05051      4 REKLEFVEKLGEGQFGEVhlceanglsdltsddFIGNDNKDEPVL---VAVKMLRPDASKNAREDFLKEVKIMSQLKDPN 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  782 VSRLLGICLTS-TVQLVTQLMPYG----CLLDHVRE-------NRGRLGSQDLLNWCMQIAK------------------ 831
Cdd:cd05051     81 IVRLLGVCTRDePLCMIVEYMENGdlnqFLQKHEAEtqgasatNSKTLSYGTLLYMATQIASgmkyleslnfvhrdlatr 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ----------------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFG-AKPYDGIPA 876
Cdd:cd05051    161 nclvgpnytikiadfgmsrnlysgdyyriegravLPIRWMAWESILLGKFTTKSDVWAFGVTLWEILTLCkEQPYEHLTD 240

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1844139561  877 RE-IPDLLEK----GER--LPQPPICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05051    241 EQvIENAGEFfrddGMEvyLSRPPNCPKEIYELMLECWRRDEEDRPTFREI 291
PTKc_Fer cd05085
Catalytic domain of the Protein Tyrosine Kinase, Fer; Protein Tyrosine Kinase (PTK) family; ...
 724-925 4.69e-32

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: 125.89  E-value: 4.69e-32
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIwIPDgenvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMP 802
Cdd:cd05085      2 ELLGKGNFGEVYKGT-LKD----KTPVAVKTCKEDLPQELKIKFLSEARILKQYDHPNIVKLIGVCTQrQPIYIVMELVP 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCLLDHVRENRGRLGSQDLLNWCMQIA---------------------------------------------------K 831
Cdd:cd05085     77 GGDFLSFLRKKKDELKTKQLVKFSLDAAagmayleskncihrdlaarnclvgennalkisdfgmsrqeddgvysssglkQ 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDS 911
Cdd:cd05085    157 IPIKWTAPEALNYGRYSSESDVWSFGILLWETFSLGVCPYPGMTNQQAREQVEKGYRMSAPQRCPEDIYKIMQRCWDYNP 236

                          250
                   ....*....|....
gi 1844139561  912 ECRPRFRELVSEFS 925
Cdd:cd05085    237 ENRPKFSELQKELA 250
PTKc_EphR_A cd05066
Catalytic domain of the Protein Tyrosine Kinases, Class EphA Ephrin Receptors; PTKs catalyze ...
 724-927 1.20e-31

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: 125.36  E-value: 1.20e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIPDGENvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMP 802
Cdd:cd05066     10 KVIGAGEFGEVCSGRLKLPGKR-EIPVAIKTLKAGYTEKQRRDFLSEASIMGQFDHPNIIHLEGVVTRSKpVMIVTEYME 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCLLDHVRENRGRLGSQDLLNWCMQIA---------------------------------------------------- 830
Cdd:cd05066     89 NGSLDAFLRKHDGQFTVIQLVGMLRGIAsgmkylsdmgyvhrdlaarnilvnsnlvckvsdfglsrvleddpeaayttrg 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 -KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMI 909
Cdd:cd05066    169 gKIPIRWTAPEAIAYRKFTSASDVWSYGIVMWEVMSYGERPYWEMSNQDVIKAIEEGYRLPAPMDCPAALHQLMLDCWQK 248

                          250
                   ....*....|....*...
gi 1844139561  910 DSECRPRFRELVSEFSRM 927
Cdd:cd05066    249 DRNERPKFEQIVSILDKL 266
PTKc_PDGFR cd05055
Catalytic domain of the Protein Tyrosine Kinases, Platelet Derived Growth Factor Receptors; ...
 724-928 1.52e-31

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: 126.06  E-value: 1.52e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIPDG-ENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPY-VSRLLGIC-LTSTVQLVTQL 800
Cdd:cd05055     41 KTLGAGAFGKVVEATAYGLSkSDAVMKVAVKMLKPTAHSSEREALMSELKIMSHLGNHEnIVNLLGACtIGGPILVITEY 120

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  801 MPYGCLLDHVRENRGR-LGSQDLLNWCMQIAK------------------------------------------------ 831
Cdd:cd05055    121 CCYGDLLNFLRRKRESfLTLEDLLSFSYQVAKgmaflaskncihrdlaarnvllthgkivkicdfglardimndsnyvvk 200

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ----VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPARE-IPDLLEKGERLPQPPICTIDVYMIMVKC 906
Cdd:cd05055    201 gnarLPVKWMAPESIFNCVYTFESDVWSYGILLWEIFSLGSNPYPGMPVDSkFYKLIKEGYRMAQPEHAPAEIYDIMKTC 280

                          250       260
                   ....*....|....*....|..
gi 1844139561  907 WMIDSECRPRFRELVSEFSRMA 928
Cdd:cd05055    281 WDADPLKRPTFKQIVQLIGKQL 302
PTKc_Btk_Bmx cd05113
Catalytic domain of the Protein Tyrosine Kinases, Bruton's tyrosine kinase and Bone marrow ...
 715-922 3.20e-31

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: 123.45  E-value: 3.20e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  715 LKETELRKVKVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLTS-T 793
Cdd:cd05113      1 IDPKDLTFLKELGTGQFGVVKYGKW-----RGQYDVAIKMIKEGS--MSEDEFIEEAKVMMNLSHEKLVQLYGVCTKQrP 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  794 VQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQI-------------------------------------------- 829
Cdd:cd05113     74 IFIITEYMANGCLLNYLREMRKRFQTQQLLEMCKDVceameyleskqflhrdlaarnclvndqgvvkvsdfglsryvldd 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 -------AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMI 902
Cdd:cd05113    154 eytssvgSKFPVRWSPPEVLMYSKFSSKSDVWAFGVLMWEVYSLGKMPYERFTNSETVEHVSQGLRLYRPHLASEKVYTI 233

                          250       260
                   ....*....|....*....|
gi 1844139561  903 MVKCWMIDSECRPRFRELVS 922
Cdd:cd05113    234 MYSCWHEKADERPTFKILLS 253
PTKc_FGFR4 cd05099
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 4; PTKs ...
 724-927 4.85e-31

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: 124.69  E-value: 4.85e-31
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYK----GIwIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLTS-TVQLV 797
Cdd:cd05099     18 KPLGEGCFGQVVRaeayGI-DKSRPDQTVTVAVKMLKDNATDKDLADLISEMELMKLIGKhKNIINLLGVCTQEgPLYVI 96

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCLLDHVRENR---------------GRLGSQDLLNWCMQIAK------------------------------- 831
Cdd:cd05099     97 VEYAAKGNLREFLRARRppgpdytfditkvpeEQLSFKDLVSCAYQVARgmeylesrrcihrdlaarnvlvtednvmkia 176

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ---------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLP 890
Cdd:cd05099    177 dfglargvhdidyykktsngrLPVKWMAPEALFDRVYTHQSDVWSFGILMWEIFTLGGSPYPGIPVEELFKLLREGHRMD 256

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1844139561  891 QPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05099    257 KPSNCTHELYMLMRECWHAVPTQRPTFKQLVEALDKV 293
PTKc_Lck_Blk cd05067
Catalytic domain of the Protein Tyrosine Kinases, Lymphocyte-specific kinase and Blk; PTKs ...
 720-922 3.16e-30

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: 121.15  E-value: 3.16e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVT 798
Cdd:cd05067      9 LKLVERLGAGQFGEVWMGYY-----NGHTKVAIKSLKQGSmSPDA---FLAEANLMKQLQHQRLVRLYAVVTQEPIYIIT 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  799 QLMPYGCLLDHVRENRG-RLGSQDLLNWCMQI------------------------------------------------ 829
Cdd:cd05067     81 EYMENGSLVDFLKTPSGiKLTINKLLDMAAQIaegmafieernyihrdlraanilvsdtlsckiadfglarliedneyta 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 ---AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKC 906
Cdd:cd05067    161 regAKFPIKWTAPEAINYGTFTIKSDVWSFGILLTEIVTHGRIPYPGMTNPEVIQNLERGYRMPRPDNCPEELYQLMRLC 240

                          250
                   ....*....|....*.
gi 1844139561  907 WMIDSECRPRFRELVS 922
Cdd:cd05067    241 WKERPEDRPTFEYLRS 256
PTKc_Chk cd05083
Catalytic domain of the Protein Tyrosine Kinase, Csk homologous kinase; PTKs catalyze the ...
 724-927 4.05e-30

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: 120.36  E-value: 4.05e-30
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGiwipdgENVKIPVAIKVLRENTSPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPY 803
Cdd:cd05083     12 EIIGEGEFGAVLQG------EYMGQKVAVKNIKCDVTAQA---FLEETAVMTKLQHKNLVRLLGVILHNGLYIVMELMSK 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  804 GCLLDHVReNRGR--LGSQDLLNWCMQIA-----------------------------------------------KVPI 834
Cdd:cd05083     83 GNLVNFLR-SRGRalVPVIQLLQFSLDVAegmeyleskklvhrdlaarnilvsedgvakisdfglakvgsmgvdnsRLPV 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  835 KWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECR 914
Cdd:cd05083    162 KWTAPEALKNKKFSSKSDVWSYGVLLWEVFSYGRAPYPKMSVKEVKEAVEKGYRMEPPEGCPPDVYSIMTSCWEAEPGKR 241

                          250
                   ....*....|...
gi 1844139561  915 PRFRELVSEFSRM 927
Cdd:cd05083    242 PSFKKLREKLEKE 254
PTK_Ryk cd05043
Pseudokinase domain of Ryk (Receptor related to tyrosine kinase); Ryk is a receptor tyr kinase ...
 725-922 1.72e-29

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: 119.48  E-value: 1.72e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  725 VLGSGAFGTVYKGIWIpDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIC--LTSTVQLVTQLMP 802
Cdd:cd05043     13 LLQEGTFGRIFHGILR-DEKGKEEEVLVKTVKDHASEIQVTMLLQESSLLYGLSHQNLLPILHVCieDGEKPMVLYPYMN 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCL------LDHVRENRGR-LGSQDLLNWCMQIAKV------------------------------------------- 832
Cdd:cd05043     92 WGNLklflqqCRLSEANNPQaLSTQQLVHMALQIACGmsylhrrgvihkdiaarncviddelqvkitdnalsrdlfpmdy 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 ---------PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIM 903
Cdd:cd05043    172 hclgdnenrPIKWMSLESLVNKEYSSASDVWSFGVLLWELMTLGQTPYVEIDPFEMAAYLKDGYRLAQPINCPDELFAVM 251

                          250
                   ....*....|....*....
gi 1844139561  904 VKCWMIDSECRPRFRELVS 922
Cdd:cd05043    252 ACCWALDPEERPSFQQLVQ 270
PTKc_FGFR2 cd05101
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 2; PTKs ...
 724-927 2.41e-29

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: 119.73  E-value: 2.41e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYK----GIwipDGENVK--IPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLTS-TVQ 795
Cdd:cd05101     30 KPLGEGCFGQVVMaeavGI---DKDKPKeaVTVAVKMLKDDATEKDLSDLVSEMEMMKMIGKhKNIINLLGACTQDgPLY 106

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  796 LVTQLMPYGCLLDHVRENR---------------GRLGSQDLLNWCMQIAK----------------------------- 831
Cdd:cd05101    107 VIVEYASKGNLREYLRARRppgmeysydinrvpeEQMTFKDLVSCTYQLARgmeylasqkcihrdlaarnvlvtennvmk 186

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -----------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGER 888
Cdd:cd05101    187 iadfglardinnidyykkttngrLPVKWMAPEALFDRVYTHQSDVWSFGVLMWEIFTLGGSPYPGIPVEELFKLLKEGHR 266

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  889 LPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05101    267 MDKPANCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRI 305
PTKc_FGFR3 cd05100
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 3; PTKs ...
 715-927 5.27e-29

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: 119.36  E-value: 5.27e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  715 LKETELRKVKVLGSGAFGTVYKGIWI---PDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICL 790
Cdd:cd05100      9 LSRTRLTLGKPLGEGCFGQVVMAEAIgidKDKPNKPVTVAVKMLKDDATDKDLSDLVSEMEMMKMIGKhKNIINLLGACT 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  791 TS-TVQLVTQLMPYGCLLDHVRENR---------------GRLGSQDLLNWCMQIAK----------------------- 831
Cdd:cd05100     89 QDgPLYVLVEYASKGNLREYLRARRppgmdysfdtcklpeEQLTFKDLVSCAYQVARgmeylasqkcihrdlaarnvlvt 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -----------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDL 882
Cdd:cd05100    169 ednvmkiadfglardvhnidyykkttngrLPVKWMAPEALFDRVYTHQSDVWSFGVLLWEIFTLGGSPYPGIPVEELFKL 248

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*
gi 1844139561  883 LEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05100    249 LKEGHRMDKPANCTHELYMIMRECWHAVPSQRPTFKQLVEDLDRV 293
PTKc_FGFR1 cd05098
Catalytic domain of the Protein Tyrosine Kinase, Fibroblast Growth Factor Receptor 1; PTKs ...
 724-927 9.37e-29

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: 117.81  E-value: 9.37e-29
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWI---PDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLTS-TVQLVT 798
Cdd:cd05098     19 KPLGEGCFGQVVLAEAIgldKDKPNRVTKVAVKMLKSDATEKDLSDLISEMEMMKMIGKhKNIINLLGACTQDgPLYVIV 98

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  799 QLMPYGCLLDHVRENR---------------GRLGSQDLLNWCMQIAK-------------------------------- 831
Cdd:cd05098     99 EYASKGNLREYLQARRppgmeycynpshnpeEQLSSKDLVSCAYQVARgmeylaskkcihrdlaarnvlvtednvmkiad 178

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 --------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQ 891
Cdd:cd05098    179 fglardihhidyykkttngrLPVKWMAPEALFDRIYTHQSDVWSFGVLLWEIFTLGGSPYPGVPVEELFKLLKEGHRMDK 258

                          250       260       270
                   ....*....|....*....|....*....|....*.
gi 1844139561  892 PPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05098    259 PSNCTNELYMMMRDCWHAVPSQRPTFKQLVEDLDRI 294
PTKc_Trk cd05049
Catalytic domain of the Protein Tyrosine Kinases, Tropomyosin Related Kinases; PTKs catalyze ...
 723-920 2.40e-28

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: 116.03  E-value: 2.40e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  723 VKVLGSGAFGTVYKGI---WIPDGEnvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVT 798
Cdd:cd05049     10 KRELGEGAFGKVFLGEcynLEPEQD--KMLVAVKTLKDASSPDARKDFEREAELLTNLQHENIVKFYGVCTEGdPLLMVF 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  799 QLMPYGCLLDHVREN-------------RGRLGSQDLLNWCMQIAK---------------------------------- 831
Cdd:cd05049     88 EYMEHGDLNKFLRSHgpdaaflasedsaPGELTLSQLLHIAVQIASgmvylasqhfvhrdlatrnclvgtnlvvkigdfg 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPP 893
Cdd:cd05049    168 msrdiystdyyrvgghtmLPIRWMPPESILYRKFTTESDVWSFGVVLWEIFTYGKQPWFQLSNTEVIECITQGRLLQRPR 247

                          250       260
                   ....*....|....*....|....*..
gi 1844139561  894 ICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05049    248 TCPSEVYAVMLGCWKREPQQRLNIKDI 274
Pkinase pfam00069
Protein kinase domain;
720-922 6.02e-28

Protein kinase domain;


Pssm-ID: 459660 [Multi-domain]  Cd Length: 217  Bit Score: 112.72  E-value: 6.02e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLV 797
Cdd:pfam00069    1 YEVLRKLGSGSFGTVYKAKHRDTGK----IVAIKKIKkEKIKKKKDKNILREIKILKKLNHPNIVRLYDAFEDKDnLYLV 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCLLDHVRENrGRLGSQDLLNWCMQIAKVpIK-------------WMALESILRRRFTHQSDVWSYGVTVWELM 864
Cdd:pfam00069   77 LEYVEGGSLFDLLSEK-GAFSEREAKFIMKQILEG-LEsgsslttfvgtpwYMAPEVLGGNPYGPKVDVWSLGCILYELL 154

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  865 TfGAKPYDGIPAREIP--DLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVS 922
Cdd:pfam00069  155 T-GKPPFPGINGNEIYelIIDQPYAFPELPSNLSEEAKDLLKKLLKKDPSKRLTATQALQ 213
PTKc_Fyn cd05070
Catalytic domain of the Protein Tyrosine Kinase, Fyn; PTKs catalyze the transfer of the ...
 720-932 6.70e-28

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: 114.40  E-value: 6.70e-28
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVT 798
Cdd:cd05070     11 LQLIKRLGNGQFGEVWMGTW-----NGNTKVAIKTLKPGTmSPES---FLEEAQIMKKLKHDKLVQLYAVVSEEPIYIVT 82

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  799 QLMPYGCLLDHVRENRGR-LGSQDLLNWCMQIA----------------------------------------------- 830
Cdd:cd05070     83 EYMSKGSLLDFLKDGEGRaLKLPNLVDMAAQVAagmayiermnyihrdlrsanilvgnglickiadfglarliedneyta 162

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ----KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKC 906
Cdd:cd05070    163 rqgaKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMNNREVLEQVERGYRMPCPQDCPISLHELMIHC 242

                          250       260
                   ....*....|....*....|....*...
gi 1844139561  907 WMIDSECRPRFRELVS--EFSRMARDPQ 932
Cdd:cd05070    243 WKKDPEERPTFEYLQGflEDYFTATEPQ 270
PTKc_Tie cd05047
Catalytic domain of Tie Protein Tyrosine Kinases; PTKs catalyze the transfer of the ...
 725-927 1.36e-27

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: 113.60  E-value: 1.36e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  725 VLGSGAFGTVYKGIWIPDGenVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLT-STVQLVTQLMP 802
Cdd:cd05047      2 VIGEGNFGQVLKARIKKDG--LRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHhPNIINLLGACEHrGYLYLAIEYAP 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCLLDHVRENR---------------GRLGSQDLLNWCMQIA------------------------------------- 830
Cdd:cd05047     80 HGNLLDFLRKSRvletdpafaianstaSTLSSQQLLHFAADVArgmdylsqkqfihrdlaarnilvgenyvakiadfgls 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ------------KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTID 898
Cdd:cd05047    160 rgqevyvkktmgRLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRLEKPLNCDDE 239

                          250       260
                   ....*....|....*....|....*....
gi 1844139561  899 VYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05047    240 VYDLMRQCWREKPYERPSFAQILVSLNRM 268
PTKc_EphR_A10 cd05064
Catalytic domain of the Protein Tyrosine Kinase, Ephrin Receptor A10; PTKs catalyze the ...
 724-927 2.91e-27

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: 112.32  E-value: 2.91e-27
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGiWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMP 802
Cdd:cd05064     11 RILGTGRFGELCRG-CLKLPSKRELPVAIHTLRAGCSDKQRRGFLAEALTLGQFDHSNIVRLEGVITRgNTMMIVTEYMS 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCLLDHVRENRGRLGSQDLLNWCMQIA---------------------------------------------------K 831
Cdd:cd05064     90 NGALDSFLRKHEGQLVAGQLMGMLPGLAsgmkylsemgyvhkglaahkvlvnsdlvckisgfrrlqedkseaiyttmsgK 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDS 911
Cdd:cd05064    170 SPVLWAAPEAIQYHHFSSASDVWSFGIVMWEVMSYGERPYWDMSGQDVIKAVEDGFRLPAPRNCPNLLHQLMLDCWQKER 249

                          250
                   ....*....|....*.
gi 1844139561  912 ECRPRFRELVSEFSRM 927
Cdd:cd05064    250 GERPRFSQIHSILSKM 265
PTKc_Tie1 cd05089
Catalytic domain of the Protein Tyrosine Kinase, Tie1; Protein Tyrosine Kinase (PTK) family; ...
 725-935 2.73e-26

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: 110.47  E-value: 2.73e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  725 VLGSGAFGTVYKGIWIPDGEnvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGICLT-STVQLVTQLMP 802
Cdd:cd05089      9 VIGEGNFGQVIKAMIKKDGL--KMNAAIKMLKEFASENDHRDFAGELEVLCKLGHhPNIINLLGACENrGYLYIAIEYAP 86

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  803 YGCLLDHVRENR---------------GRLGSQDLLNWCMQIAK------------------------------------ 831
Cdd:cd05089     87 YGNLLDFLRKSRvletdpafakehgtaSTLTSQQLLQFASDVAKgmqylsekqfihrdlaarnvlvgenlvskiadfgls 166

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTID 898
Cdd:cd05089    167 rgeevyvkktmgrLPVRWMAIESLNYSVYTTKSDVWSFGVLLWEIVSLGGTPYCGMTCAELYEKLPQGYRMEKPRNCDDE 246

                          250       260       270
                   ....*....|....*....|....*....|....*..
gi 1844139561  899 VYMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFV 935
Cdd:cd05089    247 VYELMRQCWRDRPYERPPFSQISVQLSRMLEARKAYV 283
PTKc_Fes cd05084
Catalytic domain of the Protein Tyrosine Kinase, Fes; PTKs catalyze the transfer of the ...
 726-917 5.62e-26

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: 108.48  E-value: 5.62e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIPDgenvKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYG 804
Cdd:cd05084      4 IGRGNFGEVFSGRLRAD----NTPVAVKSCRETLPPDLKAKFLQEARILKQYSHPNIVRLIGVCTQKQpIYIVMELVQGG 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRGRLGSQDLLNWCMQIA----------------------------------------------------KV 832
Cdd:cd05084     80 DFLTFLRTEGPRLKVKELIRMVENAAagmeyleskhcihrdlaarnclvteknvlkisdfgmsreeedgvyaatggmkQI 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd05084    160 PVKWTAPEALNYGRYSSESDVWSFGILLWETFSLGAVPYANLSNQQTREAVEQGVRLPCPENCPDEVYRLMEQCWEYDPR 239


                   ....*
gi 1844139561  913 CRPRF 917
Cdd:cd05084    240 KRPSF 244
PTKc_Lyn cd05072
Catalytic domain of the Protein Tyrosine Kinase, Lyn; PTKs catalyze the transfer of the ...
 720-922 6.00e-26

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: 108.98  E-value: 6.00e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVT 798
Cdd:cd05072      9 IKLVKKLGAGQFGEVWMGYY-----NNSTKVAVKTLKPGT--MSVQAFLEEANLMKTLQHDKLVRLYAVVTkEEPIYIIT 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  799 QLMPYGCLLDHVRENRG-RLGSQDLLNWCMQIA----------------------------------------------- 830
Cdd:cd05072     82 EYMAKGSLLDFLKSDEGgKVLLPKLIDFSAQIAegmayierknyihrdlraanvlvseslmckiadfglarviedneyta 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ----KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKC 906
Cdd:cd05072    162 regaKFPIKWTAPEAINFGSFTIKSDVWSFGILLYEIVTYGKIPYPGMSNSDVMSALQRGYRMPRMENCPDELYDIMKTC 241

                          250
                   ....*....|....*.
gi 1844139561  907 WMIDSECRPRFRELVS 922
Cdd:cd05072    242 WKEKAEERPTFDYLQS 257
PTKc_VEGFR cd05054
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
 720-925 6.58e-26

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: 109.50  E-value: 6.58e-26
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYK----GIwipDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPY-VSRLLGICLTSTV 794
Cdd:cd05054      9 LKLGKPLGRGAFGKVIQasafGI---DKSATCRTVAVKMLKEGATASEHKALMTELKILIHIGHHLnVVNLLGACTKPGG 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  795 QL--VTQLMPYGCLLDHVRENR-------------------------GRLGSQDLLNWCMQIAK---------------- 831
Cdd:cd05054     86 PLmvIVEFCKFGNLSNYLRSKReefvpyrdkgardveeeedddelykEPLTLEDLICYSFQVARgmeflasrkcihrdla 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ------------------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIP 875
Cdd:cd05054    166 arnillsennvvkicdfglardiykdpdyvrkgdarLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQ 245

                          250       260       270       280       290
                   ....*....|....*....|....*....|....*....|....*....|.
gi 1844139561  876 A-REIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFS 925
Cdd:cd05054    246 MdEEFCRRLKEGTRMRAPEYTTPEIYQIMLDCWHGEPKERPTFSELVEKLG 296
PTKc_Jak3_rpt2 cd05081
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 3; PTKs catalyze the ...
 716-920 1.82e-25

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: 107.67  E-value: 1.82e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  716 KETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTsPKANKEILDEAYVMAGVGSPYVSRLLGICLTS--- 792
Cdd:cd05081      2 EERHLKYISQLGKGNFGSVELCRYDPLGDNTGALVAVKQLQHSG-PDQQRDFQREIQILKALHSDFIVKYRGVSYGPgrr 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  793 TVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAK----------------------------------------- 831
Cdd:cd05081     81 SLRLVMEYLPSGCLRDFLQRHRARLDASRLLLYSSQICKgmeylgsrrcvhrdlaarnilveseahvkiadfglakllpl 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAK-------------PYDGIPAR-EIPDLLEK 885
Cdd:cd05081    161 dkdyyvvrepgqSPIFWYAPESLSDNIFSRQSDVWSFGVVLYELFTYCDKscspsaeflrmmgCERDVPALcRLLELLEE 240

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1844139561  886 GERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05081    241 GQRLPAPPACPAEVHELMKLCWAPSPQDRPSFSAL 275
PTKc_Src cd05071
Catalytic domain of the Protein Tyrosine Kinase, Src; PTKs catalyze the transfer of the ...
 714-920 4.96e-25

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: 106.31  E-value: 4.96e-25
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  714 ILKETELRKVKvLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTS 792
Cdd:cd05071      6 IPRESLRLEVK-LGQGCFGEVWMGTW-----NGTTRVAIKTLKPGTmSPEA---FLQEAQVMKKLRHEKLVQLYAVVSEE 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  793 TVQLVTQLMPYGCLLDHVRENRGR-LGSQDLLNWCMQIA----------------------------------------- 830
Cdd:cd05071     77 PIYIVTEYMSKGSLLDFLKGEMGKyLRLPQLVDMAAQIAsgmayvermnyvhrdlraanilvgenlvckvadfglarlie 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ----------KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVY 900
Cdd:cd05071    157 dneytarqgaKFPIKWTAPEAALYGRFTIKSDVWSFGILLTELTTKGRVPYPGMVNREVLDQVERGYRMPCPPECPESLH 236

                          250       260
                   ....*....|....*....|
gi 1844139561  901 MIMVKCWMIDSECRPRFREL 920
Cdd:cd05071    237 DLMCQCWRKEPEERPTFEYL 256
PTKc_Musk cd05050
Catalytic domain of the Protein Tyrosine Kinase, Muscle-specific kinase; PTKs catalyze the ...
 720-920 3.27e-24

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


Pssm-ID: 133181 [Multi-domain]  Cd Length: 288  Bit Score: 104.14  E-value: 3.27e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYK----GIwIPDGENVKipVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIC-LTSTV 794
Cdd:cd05050      7 IEYVRDIGQGAFGRVFQarapGL-LPYEPFTM--VAVKMLKEEASADMQADFQREAALMAEFDHPNIVKLLGVCaVGKPM 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  795 QLVTQLMPYGCLLDHVR---------------------ENRGRLGSQDLLNWCMQIAK---------------------- 831
Cdd:cd05050     84 CLLFEYMAYGDLNEFLRhrspraqcslshstssarkcgLNPLPLSCTEQLCIAKQVAAgmaylserkfvhrdlatrnclv 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ------------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPD 881
Cdd:cd05050    164 genmvvkiadfglsrniysadyykasendaIPIRWMPPESIFYNRYTTESDVWAYGVVLWEIFSYGMQPYYGMAHEEVIY 243

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  882 LLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05050    244 YVRDGNVLSCPDNCPLELYNLMRLCWSKLPSDRPSFASI 282
PTKc_InsR cd05061
Catalytic domain of the Protein Tyrosine Kinase, Insulin Receptor; PTKs catalyze the transfer ...
 723-921 3.95e-24

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: 103.90  E-value: 3.95e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  723 VKVLGSGAFGTVYKGIW--IPDGEnVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVT-Q 799
Cdd:cd05061     11 LRELGQGSFGMVYEGNArdIIKGE-AETRVAVKTVNESASLRERIEFLNEASVMKGFTCHHVVRLLGVVSKGQPTLVVmE 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  800 LMPYGCLLDHVR-------ENRGRLGS--QDLLNWCMQIAK--------------------------------------- 831
Cdd:cd05061     90 LMAHGDLKSYLRslrpeaeNNPGRPPPtlQEMIQMAAEIADgmaylnakkfvhrdlaarncmvahdftvkigdfgmtrdi 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTID 898
Cdd:cd05061    170 yetdyyrkggkglLPVRWMAPESLKDGVFTTSSDMWSFGVVLWEITSLAEQPYQGLSNEQVLKFVMDGGYLDQPDNCPER 249

                          250       260
                   ....*....|....*....|...
gi 1844139561  899 VYMIMVKCWMIDSECRPRFRELV 921
Cdd:cd05061    250 VTDLMRMCWQFNPKMRPTFLEIV 272
PTKc_Yes cd05069
Catalytic domain of the Protein Tyrosine Kinase, Yes; PTKs catalyze the transfer of the ...
 726-932 6.27e-24

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: 103.23  E-value: 6.27e-24
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENT-SPKAnkeILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYG 804
Cdd:cd05069     20 LGQGCFGEVWMGTW-----NGTTKVAIKTLKPGTmMPEA---FLQEAQIMKKLRHDKLVPLYAVVSEEPIYIVTEFMGKG 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRGR-LGSQDLLNWCMQIA---------------------------------------------------KV 832
Cdd:cd05069     92 SLLDFLKEGDGKyLKLPQLVDMAAQIAdgmayiermnyihrdlraanilvgdnlvckiadfglarliedneytarqgaKF 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd05069    172 PIKWTAPEAALYGRFTIKSDVWSFGILLTELVTKGRVPYPGMVNREVLEQVERGYRMPCPQGCPESLHELMKLCWKKDPD 251

                          250       260
                   ....*....|....*....|..
gi 1844139561  913 CRPRFRELVS--EFSRMARDPQ 932
Cdd:cd05069    252 ERPTFEYIQSflEDYFTATEPQ 273
S_TKc smart00220
Serine/Threonine protein kinases, catalytic domain; Phosphotransferases. Serine or ...
 721-920 1.57e-23

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


Pssm-ID: 214567 [Multi-domain]  Cd Length: 254  Bit Score: 101.07  E-value: 1.57e-23
                            10        20        30        40        50        60        70        80
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   721 RKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQ 799
Cdd:smart00220    2 EILEKLGEGSFGKVYLARDKKTGK----LVAIKVIKKKKIKKDRERILREIKILKKLKHPNIVRLYDVFEDEDkLYLVME 77

                            90       100       110       120       130       140       150       160
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   800 LMPYGCLLDHVREnRGRLGSQDLLNWCMQIAKV-------------------------PIK------------------- 835
Cdd:smart00220   78 YCEGGDLFDLLKK-RGRLSEDEARFYLRQILSAleylhskgivhrdlkpenilldedgHVKladfglarqldpgeklttf 156

                           170       180       190       200       210       220       230       240
                    ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561   836 -----WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGI-PAREIPDLLEKGERLPQPPICTI--DVYMIMVKCW 907
Cdd:smart00220  157 vgtpeYMAPEVLLGKGYGKAVDIWSLGVILYELLT-GKPPFPGDdQLLELFKKIGKPKPPFPPPEWDIspEAKDLIRKLL 235

                           250
                    ....*....|...
gi 1844139561   908 MIDSECRPRFREL 920
Cdd:smart00220  236 VKDPEKRLTAEEA 248
PTKc_Ror1 cd05090
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
 718-920 1.68e-23

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: 102.01  E-value: 1.68e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  718 TELRKVKVLGSGAFGTVYKG-IWIPDGENVKIpVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIclTSTVQL 796
Cdd:cd05090      5 SAVRFMEELGECAFGKIYKGhLYLPGMDHAQL-VAIKTLKDYNNPQQWNEFQQEASLMTELHHPNIVCLLGV--VTQEQP 81

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  797 VTQLMPY-------------------GCLLDHVRENRGRLGSQDLLNWCMQIAK-------------------------- 831
Cdd:cd05090     82 VCMLFEFmnqgdlheflimrsphsdvGCSSDEDGTVKSSLDHGDFLHIAIQIAAgmeylsshffvhkdlaarnilvgeql 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 --------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEK 885
Cdd:cd05090    162 hvkisdlglsreiyssdyyrvqnkslLPIRWMPPEAIMYGKFSSDSDIWSFGVVLWEIFSFGLQPYYGFSNQEVIEMVRK 241

                          250       260       270
                   ....*....|....*....|....*....|....*
gi 1844139561  886 GERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05090    242 RQLLPCSEDCPPRMYSLMTECWQEIPSRRPRFKDI 276
PTKc_Hck cd05073
Catalytic domain of the Protein Tyrosine Kinase, Hematopoietic cell kinase; PTKs catalyze the ...
 720-922 1.87e-23

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: 101.26  E-value: 1.87e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWipdgeNVKIPVAIKVLRENTspKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQ 799
Cdd:cd05073     13 LKLEKKLGAGQFGEVWMATY-----NKHTKVAVKTMKPGS--MSVEAFLAEANVMKTLQHDKLVKLHAVVTKEPIYIITE 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  800 LMPYGCLLDHVRENRG-RLGSQDLLNWCMQIA------------------------------------------------ 830
Cdd:cd05073     86 FMAKGSLLDFLKSDEGsKQPLPKLIDFSAQIAegmafieqrnyihrdlraanilvsaslvckiadfglarviedneytar 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  831 ---KVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVYMIMVKCW 907
Cdd:cd05073    166 egaKFPIKWTAPEAINFGSFTIKSDVWSFGILLMEIVTYGRIPYPGMSNPEVIRALERGYRMPRPENCPEELYNIMMRCW 245

                          250
                   ....*....|....*
gi 1844139561  908 MIDSECRPRFRELVS 922
Cdd:cd05073    246 KNRPEERPTFEYIQS 260
PTK_CCK4 cd05046
Pseudokinase domain of the Protein Tyrosine Kinase, Colon Carcinoma Kinase 4; CCK4, also ...
 714-925 1.94e-23

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: 101.39  E-value: 1.94e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  714 ILKETELRKVKVLGSGAFGTVYKG-IWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-T 791
Cdd:cd05046      1 AFPRSNLQEITTLGRGEFGEVFLAkAKGIEEEGGETLVLVKALQKTKDENLQSEFRRELDMFRKLSHKNVVRLLGLCReA 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 STVQLVTQLMPYGCLLDHVRENRGR--------LGSQDLLNWCMQIAK-------------------------------- 831
Cdd:cd05046     81 EPHYMILEYTDLGDLKQFLRATKSKdeklkpppLSTKQKVALCTQIALgmdhlsnarfvhrdlaarnclvssqrevkvsl 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGE-RLPQ 891
Cdd:cd05046    161 lslskdvynseyyklrnalIPLRWLAPEAVQEDDFSTKSDVWSFGVLMWEVFTQGELPFYGLSDEEVLNRLQAGKlELPV 240

                          250       260       270
                   ....*....|....*....|....*....|....
gi 1844139561  892 PPICTIDVYMIMVKCWMIDSECRPRFRELVSEFS 925
Cdd:cd05046    241 PEGCPSRLYKLMTRCWAVNPKDRPSFSELVSALG 274
PTKc_VEGFR1 cd14207
Catalytic domain of the Protein Tyrosine Kinases, Vascular Endothelial Growth Factor Receptors; ...
 830-921 4.34e-23

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: 102.00  E-value: 4.34e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPARE-IPDLLEKGERLPQPPICTIDVYMIMVKCWM 908
Cdd:cd14207    242 ARLPLKWMAPESIFDKIYSTKSDVWSYGVLLWEIFSLGASPYPGVQIDEdFCSKLKEGIRMRAPEFATSEIYQIMLDCWQ 321

                           90
                   ....*....|...
gi 1844139561  909 IDSECRPRFRELV 921
Cdd:cd14207    322 GDPNERPRFSELV 334
PTKc_Jak2_rpt2 cd14205
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 2; PTKs catalyze the ...
 715-920 7.41e-23

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: 100.09  E-value: 7.41e-23
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  715 LKETELRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKAnKEILDEAYVMAGVGSPYVSRLLGICLTS-- 792
Cdd:cd14205      1 FEERHLKFLQQLGKGNFGSVEMCRYDPLQDNTGEVVAVKKLQHSTEEHL-RDFEREIEILKSLQHDNIVKYKGVCYSAgr 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  793 -TVQLVTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAK---------------------------------------- 831
Cdd:cd14205     80 rNLRLIMEYLPYGSLRDYLQKHKERIDHIKLLQYTSQICKgmeylgtkryihrdlatrnilvenenrvkigdfgltkvlp 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGiPAR----------------EIPDL 882
Cdd:cd14205    160 qdkeyykvkepgeSPIFWYAPESLTESKFSVASDVWSFGVVLYELFTYIEKSKSP-PAEfmrmigndkqgqmivfHLIEL 238

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1844139561  883 LEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd14205    239 LKNNGRLPRPDGCPDEIYMIMTECWNNNVNQRPSFRDL 276
PTKc_Tie2 cd05088
Catalytic domain of the Protein Tyrosine Kinase, Tie2; PTKs catalyze the transfer of the ...
 714-935 1.15e-22

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


Pssm-ID: 133219 [Multi-domain]  Cd Length: 303  Bit Score: 100.07  E-value: 1.15e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  714 ILKETELRKVKVLGSGAFGTVYKGIWIPDGenVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGS-PYVSRLLGIC-LT 791
Cdd:cd05088      3 VLEWNDIKFQDVIGEGNFGQVLKARIKKDG--LRMDAAIKRMKEYASKDDHRDFAGELEVLCKLGHhPNIINLLGACeHR 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  792 STVQLVTQLMPYGCLLDHVRENR---------------GRLGSQDLLNWCMQIAK------------------------- 831
Cdd:cd05088     81 GYLYLAIEYAPHGNLLDFLRKSRvletdpafaianstaSTLSSQQLLHFAADVARgmdylsqkqfihrdlaarnilvgen 160

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGE 887
Cdd:cd05088    161 yvakiadfglsrgqevyvkktmgrLPVRWMAIESLNYSVYTTNSDVWSYGVLLWEIVSLGGTPYCGMTCAELYEKLPQGY 240

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139561  888 RLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMARDPQRFV 935
Cdd:cd05088    241 RLEKPLNCDDEVYDLMRQCWREKPYERPSFAQILVSLNRMLEERKTYV 288
PTKc_DDR2 cd05095
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 2; PTKs catalyze ...
 726-920 4.34e-22

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: 98.14  E-value: 4.34e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVY------------KGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST 793
Cdd:cd05095     13 LGEGQFGEVHlceaegmekfmdKDFALEVSENQPVLVAVKMLRADANKNARNDFLKEIKIMSRLKDPNIIRLLAVCITDD 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  794 -VQLVTQLMPYG----CLLDHVRENRGRLGSQDLL---------------------------------------NWCMQI 829
Cdd:cd05095     93 pLCMITEYMENGdlnqFLSRQQPEGQLALPSNALTvsysdlrfmaaqiasgmkylsslnfvhrdlatrnclvgkNYTIKI 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 AK--------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTF-GAKPYDGIPAREIPD-----LL 883
Cdd:cd05095    173 ADfgmsrnlysgdyyriqgravLPIRWMSWESILLGKFTTASDVWAFGVTLWETLTFcREQPYSQLSDEQVIEntgefFR 252

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  884 EKGER--LPQPPICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05095    253 DQGRQtyLPQPALCPDSVYKLMLSCWRRDTKDRPSFQEI 291
PTKc_VEGFR3 cd05102
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 3; ...
 830-921 5.89e-22

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: 98.51  E-value: 5.89e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPARE-IPDLLEKGERLPQPPICTIDVYMIMVKCWM 908
Cdd:cd05102    234 ARLPLKWMAPESIFDKVYTTQSDVWSFGVLLWEIFSLGASPYPGVQINEeFCQRLKDGTRMRAPEYATPEIYRIMLSCWH 313

                           90
                   ....*....|...
gi 1844139561  909 IDSECRPRFRELV 921
Cdd:cd05102    314 GDPKERPTFSDLV 326
PTKc_Jak1_rpt2 cd05079
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Janus kinase 1; PTKs catalyze the ...
 720-927 7.88e-22

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: 96.92  E-value: 7.88e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT---STVQL 796
Cdd:cd05079      6 LKRIRDLGEGHFGKVELCRYDPEGDNTGEQVAVKSLKPESGGNHIADLKKEIEILRNLYHENIVKYKGICTEdggNGIKL 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  797 VTQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAK--------------------------------------------- 831
Cdd:cd05079     86 IMEFLPSGSLKEYLPRNKNKINLKQQLKYAVQICKgmdylgsrqyvhrdlaarnvlvesehqvkigdfgltkaietdkey 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 --------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAK-------------PYDG-IPAREIPDLLEKGERL 889
Cdd:cd05079    166 ytvkddldSPVFWYAPECLIQSKFYIASDVWSFGVTLYELLTYCDSesspmtlflkmigPTHGqMTVTRLVRVLEEGKRL 245

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1844139561  890 PQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05079    246 PRPPNCPEEVYQLMRKCWEFQPSKRTTFQNLIEGFEAI 283
PTKc_VEGFR2 cd05103
Catalytic domain of the Protein Tyrosine Kinase, Vascular Endothelial Growth Factor Receptor 2; ...
 830-921 9.02e-22

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: 98.13  E-value: 9.02e-22
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPA-REIPDLLEKGERLPQPPICTIDVYMIMVKCWM 908
Cdd:cd05103    241 ARLPLKWMAPETIFDRVYTIQSDVWSFGVLLWEIFSLGASPYPGVKIdEEFCRRLKEGTRMRAPDYTTPEMYQTMLDCWH 320

                           90
                   ....*....|...
gi 1844139561  909 IDSECRPRFRELV 921
Cdd:cd05103    321 GEPSQRPTFSELV 333
PKc cd00180
Catalytic domain of Protein Kinases; PKs catalyze the transfer of the gamma-phosphoryl group ...
 726-922 2.51e-21

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: 93.87  E-value: 2.51e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIPDGEnvkiPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYG 804
Cdd:cd00180      1 LGKGSFGKVYKARDKETGK----KVAVKVIPKEKLKKLLEELLREIEILKKLNHPNIVKLYDVFETEnFLYLVMEYCEGG 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRGRLGSQDLLNWCMQIAK----------------------------------------------------V 832
Cdd:cd00180     77 SLKDLLKENKGPLSEEEALSILRQLLSaleylhsngiihrdlkpenilldsdgtvkladfglakdldsddsllkttggtT 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRRFTHQSDVWSYGVTVWELmtfgakpydgipaREIPDLLEkgerlpqppictidvymimvKCWMIDSE 912
Cdd:cd00180    157 PPYYAPPELLGGRYYGPKVDIWSLGVILYEL-------------EELKDLIR--------------------RMLQYDPK 203

                          250
                   ....*....|
gi 1844139561  913 CRPRFRELVS 922
Cdd:cd00180    204 KRPSAKELLE 213
PTKc_DDR_like cd05097
Catalytic domain of Discoidin Domain Receptor-like Protein Tyrosine Kinases; PTKs catalyze the ...
 719-920 5.95e-21

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: 94.66  E-value: 5.95e-21
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTV----------YKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGI 788
Cdd:cd05097      6 QLRLKEKLGEGQFGEVhlceaeglaeFLGEGAPEFDGQPVLVAVKMLRADVTKTARNDFLKEIKIMSRLKNPNIIRLLGV 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  789 CLTST-VQLVTQLMPYGCLLDHV--RENRGRL---------GSQDLLNWCMQIAK------------------------- 831
Cdd:cd05097     86 CVSDDpLCMITEYMENGDLNQFLsqREIESTFthannipsvSIANLLYMAVQIASgmkylaslnfvhrdlatrnclvgnh 165

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ---------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTF-GAKPYDGIPAREIPD-- 881
Cdd:cd05097    166 ytikiadfgmsrnlysgdyyriqgravLPIRWMAWESILLGKFTTASDVWAFGVTLWEMFTLcKEQPYSLLSDEQVIEnt 245

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....
gi 1844139561  882 ---LLEKGER--LPQPPICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05097    246 gefFRNQGRQiyLSQTPLCPSPVFKLMMRCWSRDIKDRPTFNKI 289
Recep_L_domain pfam01030
Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. ...
 366-482 1.11e-20

Receptor L domain; The L domains from these receptors make up the bilobal ligand binding site. Each L domain consists of a single-stranded right hand beta-helix. This Pfam entry is missing the first 50 amino acid residues of the domain.


Pssm-ID: 460032  Cd Length: 112  Bit Score: 88.44  E-value: 1.11e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  366 GCKKIFGSLAFLPESFDGDPasntaplqpEQLQVFETLEEITGYLYISAWPDSlpDLSVFQNLQVIRGRILHNGAYSLT- 444
Cdd:pfam01030    1 NCTVIYGNLEITLIDENNDS---------ELLSFLSNVEEITGYLLIANTNLV--SLSFLPNLRIIRGRNLFDDNYALYi 69

                           90       100       110
                   ....*....|....*....|....*....|....*....
gi 1844139561  445 LQGLGISWLGLRSLRELGSGLALIHHNTHLCFVHT-VPW 482
Cdd:pfam01030   70 LDNPNLTELGLPSLKEITSGGVYIHNNPKLCYTETeILW 108
PTKc_TrkA cd05092
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase A; PTKs catalyze ...
 726-926 1.24e-20

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: 93.49  E-value: 1.24e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIW---IPDGEnvKIPVAIKVLRENTSpKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLM 801
Cdd:cd05092     13 LGEGAFGKVFLAEChnlLPEQD--KMLVAVKALKEATE-SARQDFQREAELLTVLQHQHIVRFYGVCTEGEpLIMVFEYM 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVREN--------------RGRLGSQDLLNWCMQIAK------------------------------------ 831
Cdd:cd05092     90 RHGDLNRFLRSHgpdakildggegqaPGQLTLGQMLQIASQIASgmvylaslhfvhrdlatrnclvgqglvvkigdfgms 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ----------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPIC 895
Cdd:cd05092    170 rdiystdyyrvggrtmLPIRWMPPESILYRKFTTESDIWSFGVVLWEIFTYGKQPWYQLSNTEAIECITQGRELERPRTC 249

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1844139561  896 TIDVYMIMVKCWMIDSECRPRFRELVSEFSR 926
Cdd:cd05092    250 PPEVYAIMQGCWQREPQQRHSIKDIHSRLQA 280
PTKc_Tyk2_rpt2 cd05080
Catalytic (repeat 2) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2; PTKs catalyze ...
 720-927 4.46e-20

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: 91.88  E-value: 4.46e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  720 LRKVKVLGSGAFGTVYKGIWIPDGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT---STVQL 796
Cdd:cd05080      6 LKKIRDLGEGHFGKVSLYCYDPTNDGTGEMVAVKALKADCGPQHRSGWKQEIDILKTLYHENIVKYKGCCSEqggKSLQL 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  797 VTQLMPYGCLLDHVRENRgrLGSQDLLNWCMQIAK--------------------------------------------- 831
Cdd:cd05080     86 IMEYVPLGSLRDYLPKHS--IGLAQLLLFAQQICEgmaylhsqhyihrdlaarnvlldndrlvkigdfglakavpeghey 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 --------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFgAKPYDGIPAR---------------EIPDLLEKGER 888
Cdd:cd05080    164 yrvredgdSPVFWYAPECLKEYKFYYASDVWSFGVTLYELLTH-CDSSQSPPTKflemigiaqgqmtvvRLIELLERGER 242

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  889 LPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd05080    243 LPCPDKCPQEVYHLMKNCWETEASFRPTFENLIPILKTV 281
PTKc_PDGFR_beta cd05107
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor beta; ...
 832-927 4.75e-20

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: 93.92  E-value: 4.75e-20
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPARE-IPDLLEKGERLPQPPICTIDVYMIMVKCWMID 910
Cdd:cd05107    303 LPLKWMAPESIFNNLYTTLSDVWSFGILLWEIFTLGGTPYPELPMNEqFYNAIKRGYRMAKPAHASDEIYEIMQKCWEEK 382

                           90
                   ....*....|....*..
gi 1844139561  911 SECRPRFRELVSEFSRM 927
Cdd:cd05107    383 FEIRPDFSQLVHLVGDL 399
PTKc_Ror2 cd05091
Catalytic domain of the Protein Tyrosine Kinase, Receptor tyrosine kinase-like Orphan Receptor ...
 716-920 1.34e-19

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: 90.46  E-value: 1.34e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  716 KETELRKVKV---LGSGAFGTVYKG--IWIPDGENVKIpVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGIcl 790
Cdd:cd05091      1 KEINLSAVRFmeeLGEDRFGKVYKGhlFGTAPGEQTQA-VAIKTLKDKAEGPLREEFRHEAMLRSRLQHPNIVCLLGV-- 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  791 TSTVQLVTQLMPYGCLLD-H----VRENRGRLGSQD-------------LLNWCMQIAK--------------------- 831
Cdd:cd05091     78 VTKEQPMSMIFSYCSHGDlHeflvMRSPHSDVGSTDddktvkstlepadFLHIVTQIAAgmeylsshhvvhkdlatrnvl 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -------------------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIP 880
Cdd:cd05091    158 vfdklnvkisdlglfrevyaadyyklmgnslLPIRWMSPEAIMYGKFSIDSDIWSYGVVLWEVFSYGLQPYCGYSNQDVI 237

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|
gi 1844139561  881 DLLEKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05091    238 EMIRNRQVLPCPDDCPAWVYTLMLECWNEFPSRRPRFKDI 277
PTKc_CSF-1R cd05106
Catalytic domain of the Protein Tyrosine Kinase, Colony-Stimulating Factor-1 Receptor; PTKs ...
 830-929 2.54e-19

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: 91.44  E-value: 2.54e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPA-REIPDLLEKGERLPQPPICTIDVYMIMVKCWM 908
Cdd:cd05106    274 ARLPVKWMAPESIFDCVYTVQSDVWSYGILLWEIFSLGKSPYPGILVnSKFYKMVKRGYQMSRPDFAPPEIYSIMKMCWN 353

                           90       100
                   ....*....|....*....|.
gi 1844139561  909 IDSECRPRFRELVSEFSRMAR 929
Cdd:cd05106    354 LEPTERPTFSQISQLIQRQLG 374
PTKc_Kit cd05104
Catalytic domain of the Protein Tyrosine Kinase, Kit; PTKs catalyze the transfer of the ...
 830-921 4.12e-19

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


Pssm-ID: 270682 [Multi-domain]  Cd Length: 375  Bit Score: 90.73  E-value: 4.12e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  830 AKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPA-REIPDLLEKGERLPQPPICTIDVYMIMVKCWM 908
Cdd:cd05104    276 ARLPVKWMAPESIFECVYTFESDVWSYGILLWEIFSLGSSPYPGMPVdSKFYKMIKEGYRMDSPEFAPSEMYDIMRSCWD 355

                           90
                   ....*....|...
gi 1844139561  909 IDSECRPRFRELV 921
Cdd:cd05104    356 ADPLKRPTFKQIV 368
PTKc_IGF-1R cd05062
Catalytic domain of the Protein Tyrosine Kinase, Insulin-like Growth Factor-1 Receptor; PTKs ...
 726-922 4.94e-19

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: 88.55  E-value: 4.94e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIW---IPDGENVKipVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLV-TQLM 801
Cdd:cd05062     14 LGQGSFGMVYEGIAkgvVKDEPETR--VAIKTVNEAASMRERIEFLNEASVMKEFNCHHVVRLLGVVSQGQPTLViMELM 91

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVRE---------------------------------NRGRLGSQDLLNWCMQIAK----------------- 831
Cdd:cd05062     92 TRGDLKSYLRSlrpemennpvqappslkkmiqmageiadgmaylNANKFVHRDLAARNCMVAEdftvkigdfgmtrdiye 171

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -----------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIDVY 900
Cdd:cd05062    172 tdyyrkggkglLPVRWMSPESLKDGVFTTYSDVWSFGVVLWEIATLAEQPYQGMSNEQVLRFVMEGGLLDKPDNCPDMLF 251

                          250       260
                   ....*....|....*....|..
gi 1844139561  901 MIMVKCWMIDSECRPRFRELVS 922
Cdd:cd05062    252 ELMRMCWQYNPKMRPSFLEIIS 273
STKc_MLTK cd14060
Catalytic domain of the Serine/Threonine Kinase, Mixed lineage kinase-Like mitogen-activated ...
 727-927 5.41e-19

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: 87.71  E-value: 5.41e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  727 GSGAFGTVYKGIWIPDGENVkipvAIKvlrentspKANKeILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPYGC 805
Cdd:cd14060      2 GGGSFGSVYRAIWVSQDKEV----AVK--------KLLK-IEKEAEILSVLSHRNIIQFYGAILEApNYGIVTEYASYGS 68

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  806 LLDHVRENRG-RLGSQDLLNWCMQIAK--------VPIK----------------------------------------- 835
Cdd:cd14060     69 LFDYLNSNESeEMDMDQIMTWATDIAKgmhylhmeAPVKvihrdlksrnvviaadgvlkicdfgasrfhshtthmslvgt 148

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 --WMALESILRRRFTHQSDVWSYGVTVWELMTFGAkPYDGIPAREIPDLL-EKGERLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd14060    149 fpWMAPEVIQSLPVSETCDTYSYGVVLWEMLTREV-PFKGLEGLQVAWLVvEKNERPTIPSSCPRSFAELMRRCWEADVK 227

                          250
                   ....*....|....*
gi 1844139561  913 CRPRFRELVSEFSRM 927
Cdd:cd14060    228 ERPSFKQIIGILESM 242
PTKc_PDGFR_alpha cd05105
Catalytic domain of the Protein Tyrosine Kinase, Platelet Derived Growth Factor Receptor alpha; ...
 832-920 8.33e-19

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


Pssm-ID: 173653 [Multi-domain]  Cd Length: 400  Bit Score: 90.08  E-value: 8.33e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDG-IPAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMID 910
Cdd:cd05105    301 LPVKWMAPESIFDNLYTTLSDVWSYGILLWEIFSLGGTPYPGmIVDSTFYNKIKSGYRMAKPDHATQEVYDIMVKCWNSE 380

                           90
                   ....*....|
gi 1844139561  911 SECRPRFREL 920
Cdd:cd05105    381 PEKRPSFLHL 390
STKc_MLK1 cd14145
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 1; STKs catalyze the ...
 718-925 9.98e-19

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


Pssm-ID: 271047 [Multi-domain]  Cd Length: 270  Bit Score: 87.79  E-value: 9.98e-19
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  718 TELRKVKVLGSGAFGTVYKGIWIPDgenvkiPVAIKVLRENTSPKANKEILD---EAYVMAGVGSPYVSRLLGICLTSTV 794
Cdd:cd14145      6 SELVLEEIIGIGGFGKVYRAIWIGD------EVAVKAARHDPDEDISQTIENvrqEAKLFAMLKHPNIIALRGVCLKEPN 79

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  795 QLVTQLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAK----------VPI------------------------------ 834
Cdd:cd14145     80 LCLVMEFARGGPLNRVLSGK-RIPPDILVNWAVQIARgmnylhceaiVPVihrdlkssnililekvengdlsnkilkitd 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  835 -------------------KWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLPQPPI 894
Cdd:cd14145    159 fglarewhrttkmsaagtyAWMAPEVIRSSMFSKGSDVWSYGVLLWELLT-GEVPFRGIDGLAVAYGVAMNKlSLPIPST 237

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1844139561  895 CTIDVYMIMVKCWMIDSECRPRFRELVSEFS 925
Cdd:cd14145    238 CPEPFARLMEDCWNPDPHSRPPFTNILDQLT 268
PTKc_DDR1 cd05096
Catalytic domain of the Protein Tyrosine Kinase, Discoidin Domain Receptor 1; PTKs catalyze ...
 750-920 1.84e-18

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: 87.68  E-value: 1.84e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  750 VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPYGCL--------LDHVRENRGRLGSQ 820
Cdd:cd05096     49 VAVKILRPDANKNARNDFLKEVKILSRLKDPNIIRLLGVCVDEDpLCMITEYMENGDLnqflsshhLDDKEENGNDAVPP 128

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  821 D----------LLNWCMQIAK----------------------------------------------------VPIKWMA 838
Cdd:cd05096    129 AhclpaisyssLLHVALQIASgmkylsslnfvhrdlatrnclvgenltikiadfgmsrnlyagdyyriqgravLPIRWMA 208

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  839 LESILRRRFTHQSDVWSYGVTVWE-LMTFGAKPYDGIPAREIPD-----LLEKGER--LPQPPICTIDVYMIMVKCWMID 910
Cdd:cd05096    209 WECILMGKFTTASDVWAFGVTLWEiLMLCKEQPYGELTDEQVIEnagefFRDQGRQvyLFRPPPCPQGLYELMLQCWSRD 288

                          250
                   ....*....|
gi 1844139561  911 SECRPRFREL 920
Cdd:cd05096    289 CRERPSFSDI 298
STKc_MLK cd14061
Catalytic domain of the Serine/Threonine Kinases, Mixed Lineage Kinases; STKs catalyze the ...
 725-927 2.36e-18

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: 86.29  E-value: 2.36e-18
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  725 VLGSGAFGTVYKGIWipDGENVkipvAIKVLR---ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVtql 800
Cdd:cd14061      1 VIGVGGFGKVYRGIW--RGEEV----AVKAARqdpDEDISVTLENVRQEARLFWMLRHPNIIALRGVCLqPPNLCLV--- 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  801 MPY--GCLLDHVRENRgRLGSQDLLNWCMQIAK----------VPI---------------------------------- 834
Cdd:cd14061     72 MEYarGGALNRVLAGR-KIPPHVLVDWAIQIARgmnylhneapVPIihrdlkssnilileaienedlenktlkitdfgla 150

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  835 ---------------KWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIP-DLLEKGERLPQPPICTID 898
Cdd:cd14061    151 rewhkttrmsaagtyAWMAPEVIKSSTFSKASDVWSYGVLLWELLT-GEVPYKGIDGLAVAyGVAVNKLTLPIPSTCPEP 229

                          250       260
                   ....*....|....*....|....*....
gi 1844139561  899 VYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd14061    230 FAQLMKDCWQPDPHDRPSFADILKQLENI 258
PTKc_TrkC cd05094
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase C; PTKs catalyze ...
 726-920 1.73e-17

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: 84.29  E-value: 1.73e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYkgiwIPDGENV-----KIPVAIKVLRENTSpKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQ 799
Cdd:cd05094     13 LGEGAFGKVF----LAECYNLsptkdKMLVAVKTLKDPTL-AARKDFQREAELLTNLQHDHIVKFYGVCGDGDpLIMVFE 87

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  800 LMPYGCLLDHVR---------------ENRGRLGSQDLLNWCMQIAK--------------------------------- 831
Cdd:cd05094     88 YMKHGDLNKFLRahgpdamilvdgqprQAKGELGLSQMLHIATQIASgmvylasqhfvhrdlatrnclvganllvkigdf 167

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 -------------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQP 892
Cdd:cd05094    168 gmsrdvystdyyrvgghtmLPIRWMPPESIMYRKFTTESDVWSFGVILWEIFTYGKQPWFQLSNTEVIECITQGRVLERP 247

                          250       260
                   ....*....|....*....|....*...
gi 1844139561  893 PICTIDVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd05094    248 RVCPKEVYDIMLGCWQREPQQRLNIKEI 275
PTKc_TrkB cd05093
Catalytic domain of the Protein Tyrosine Kinase, Tropomyosin Related Kinase B; PTKs catalyze ...
 726-929 2.55e-17

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: 83.94  E-value: 2.55e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGI---WIPDGEnvKIPVAIKVLREnTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLM 801
Cdd:cd05093     13 LGEGAFGKVFLAEcynLCPEQD--KILVAVKTLKD-ASDNARKDFHREAELLTNLQHEHIVKFYGVCVEGDpLIMVFEYM 89

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVR------------ENRGRLGSQDLLNWCMQIAK-------------------------------------- 831
Cdd:cd05093     90 KHGDLNKFLRahgpdavlmaegNRPAELTQSQMLHIAQQIAAgmvylasqhfvhrdlatrnclvgenllvkigdfgmsrd 169

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 --------------VPIKWMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTI 897
Cdd:cd05093    170 vystdyyrvgghtmLPIRWMPPESIMYRKFTTESDVWSLGVVLWEIFTYGKQPWYQLSNNEVIECITQGRVLQRPRTCPK 249

                          250       260       270
                   ....*....|....*....|....*....|..
gi 1844139561  898 DVYMIMVKCWMIDSECRPRFRELVSEFSRMAR 929
Cdd:cd05093    250 EVYDLMLGCWQREPHMRLNIKEIHSLLQNLAK 281
STKc_MLK3 cd14147
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 3; STKs catalyze the ...
 719-927 4.87e-17

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: 82.77  E-value: 4.87e-17
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWipDGENVKIPVAIKVLRENTSPKAnKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVT 798
Cdd:cd14147      4 ELRLEEVIGIGGFGKVYRGSW--RGELVAVKAARQDPDEDISVTA-ESVRQEARLFAMLAHPNIIALKAVCLEEPNLCLV 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  799 QLMPYGCLLDHVRENRgRLGSQDLLNWCMQIAK----------VPI---------------------------------- 834
Cdd:cd14147     81 MEYAAGGPLSRALAGR-RVPPHVLVNWAVQIARgmhylhcealVPVihrdlksnnilllqpienddmehktlkitdfgla 159

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  835 ---------------KWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLPQPPICTID 898
Cdd:cd14147    160 rewhkttqmsaagtyAWMAPEVIKASTFSKGSDVWSFGVLLWELLT-GEVPYRGIDCLAVAYGVAVNKlTLPIPSTCPEP 238

                          250       260
                   ....*....|....*....|....*....
gi 1844139561  899 VYMIMVKCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd14147    239 FAQLMADCWAQDPHRRPDFASILQQLEAL 267
STKc_TAK1 cd14058
Catalytic domain of the Serine/Threonine Kinase, Transforming Growth Factor beta Activated ...
 726-922 1.17e-16

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: 80.94  E-value: 1.17e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWipdgenVKIPVAIKVLrENTSPKanKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYG 804
Cdd:cd14058      1 VGRGSFGVVCKARW------RNQIVAVKII-ESESEK--KAFEVEVRQLSRVDHPNIIKLYGACSNqKPVCLVMEYAEGG 71

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLD--HVRENRGRLGSQDLLNWCMQIAKV----------PI-------------------------------------- 834
Cdd:cd14058     72 SLYNvlHGKEPKPIYTAAHAMSWALQCAKGvaylhsmkpkALihrdlkppnllltnggtvlkicdfgtacdisthmtnnk 151

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  835 ---KWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGI--PAREIPDLLEKGERLPQPPICTIDVYMIMVKCWMI 909
Cdd:cd14058    152 gsaAWMAPEVFEGSKYSEKCDVFSWGIILWEVIT-RRKPFDHIggPAFRIMWAVHNGERPPLIKNCPKPIESLMTRCWSK 230

                          250
                   ....*....|...
gi 1844139561  910 DSECRPRFRELVS 922
Cdd:cd14058    231 DPEKRPSMKEIVK 243
STKc_MLK4 cd14146
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 4; STKs catalyze the ...
 725-925 5.50e-16

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: 79.70  E-value: 5.50e-16
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  725 VLGSGAFGTVYKGIWipDGENVKIPVAIKVLRENTSPKANkEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLVTQLMPY 803
Cdd:cd14146      1 IIGVGGFGKVYRATW--KGQEVAVKAARQDPDEDIKATAE-SVRQEAKLFSMLRHPNIIKLEGVCLEEpNLCLVMEFARG 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  804 GCL---------LDHVRENRgRLGSQDLLNWCMQIAK----------VPI------------------------------ 834
Cdd:cd14146     78 GTLnralaaanaAPGPRRAR-RIPPHILVNWAVQIARgmlylheeavVPIlhrdlkssnilllekiehddicnktlkitd 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  835 -------------------KWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLPQPPI 894
Cdd:cd14146    157 fglarewhrttkmsaagtyAWMAPEVIKSSLFSKGSDIWSYGVLLWELLT-GEVPYRGIDGLAVAYGVAVNKlTLPIPST 235

                          250       260       270
                   ....*....|....*....|....*....|.
gi 1844139561  895 CTIDVYMIMVKCWMIDSECRPRFRELVSEFS 925
Cdd:cd14146    236 CPEPFAKLMKECWEQDPHIRPSFALILEQLT 266
STKc_MLK2 cd14148
Catalytic domain of the Serine/Threonine Kinase, Mixed Lineage Kinase 2; STKs catalyze the ...
 725-917 1.19e-15

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: 78.10  E-value: 1.19e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  725 VLGSGAFGTVYKGIWipDGENVkipvAIKVLRENTSPKAN---KEILDEAYVMAGVGSPYVSRLLGICLTstvqlvtqlM 801
Cdd:cd14148      1 IIGVGGFGKVYKGLW--RGEEV----AVKAARQDPDEDIAvtaENVRQEARLFWMLQHPNIIALRGVCLN---------P 65

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCL-LDHVRE---NRGRLGSQD----LLNWCMQIAK----------VPI----------------------------- 834
Cdd:cd14148     66 PHLCLvMEYARGgalNRALAGKKVpphvLVNWAVQIARgmnylhneaiVPIihrdlkssnililepienddlsgktlkit 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  835 --------------------KWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE-RLPQPP 893
Cdd:cd14148    146 dfglarewhkttkmsaagtyAWMAPEVIRLSLFSKSSDVWSFGVLLWELLT-GEVPYREIDALAVAYGVAMNKlTLPIPS 224

                          250       260
                   ....*....|....*....|....
gi 1844139561  894 ICTIDVYMIMVKCWMIDSECRPRF 917
Cdd:cd14148    225 TCPEPFARLLEECWDPDPHGRPDF 248
SPS1 COG0515
Serine/threonine protein kinase [Signal transduction mechanisms];
721-1123 2.08e-15

Serine/threonine protein kinase [Signal transduction mechanisms];


Pssm-ID: 440281 [Multi-domain]  Cd Length: 482  Bit Score: 80.44  E-value: 2.08e-15
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  721 RKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLREN--TSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LV 797
Cdd:COG0515     10 RILRLLGRGGMGVVYLARDLRLGR----PVALKVLRPElaADPEARERFRREARALARLNHPNIVRVYDVGEEDGRPyLV 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPyGCLLDHVRENRGRLGSQDLLNWCMQIAKV------------PIK------------------------------ 835
Cdd:COG0515     86 MEYVE-GESLADLLRRRGPLPPAEALRILAQLAEAlaaahaagivhrDIKpanilltpdgrvklidfgiaralggatltq 164

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 ---------WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREipdLLEKGERLPQPPICTidvymimvkc 906
Cdd:COG0515    165 tgtvvgtpgYMAPEQARGEPVDPRSDVYSLGVTLYELLT-GRPPFDGDSPAE---LLRAHLREPPPPPSE---------- 230

                          250       260       270       280       290       300       310       320
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  907 wmIDSECRPRFRELVsefSRM-ARDP-QRFvviQN-----EDLGPASPLDSTFYRSLLEDDDMGDLVDAEEYLVPQQGFF 979
Cdd:COG0515    231 --LRPDLPPALDAIV---LRAlAKDPeERY---QSaaelaAALRAVLRSLAAAAAAAAAAAAAAAAAAAAAAAAAAAAAA 302

                          330       340       350       360       370       380       390       400
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  980 CPDPAPGAGGMVHHRHRSSSTRSGGGDLTLGLEPSEEEAPRSPLAPSEGAGSDVFDGDLGMGAAKGLQSLPTHDPSPLQR 1059
Cdd:COG0515    303 AAAAAAAAAAAAAAAAAAAAPAAAAAAAAAAAALAAAAAAAAAAAAAALLAAAAALAAAAAAAAAAAAAAAAAAAAAAAA 382

                          410       420       430       440       450       460
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139561 1060 YSEDPTVPLPSETDGYVAPLTCSPQPEYVNQPDVRPQPPSPREGPLPAARPAGATLERPKTLSP 1123
Cdd:COG0515    383 AALAAAAAAAAAAAAAALAAAAAAAAAAAAAAAAAAALAAAAAAAAAAAAAAAAAAAAAARLLA 446
STKc_MAP3K12_13 cd14059
Catalytic domain of the Serine/Threonine Kinases, Mitogen-Activated Protein Kinase Kinase ...
 726-922 8.28e-14

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: 72.53  E-value: 8.28e-14
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWipDGENVkipvAIKVLRENtspkanKEIldEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPYG 804
Cdd:cd14059      1 LGSGAQGAVFLGKF--RGEEV----AVKKVRDE------KET--DIKHLRKLNHPNIIKFKGVCTQAPCYcILMEYCPYG 66

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRgRLGSQDLLNWCMQIA----------------KVP---------------------------------IK 835
Cdd:cd14059     67 QLYEVLRAGR-EITPSLLVDWSKQIAsgmnylhlhkiihrdlKSPnvlvtyndvlkisdfgtskelsekstkmsfagtVA 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIpdLLEKGE---RLPQPPICTIDVYMIMVKCWMIDSE 912
Cdd:cd14059    146 WMAPEVIRNEPCSEKVDIWSFGVVLWELLT-GEIPYKDVDSSAI--IWGVGSnslQLPVPSTCPDGFKLLMKQCWNSKPR 222

                          250
                   ....*....|
gi 1844139561  913 CRPRFRELVS 922
Cdd:cd14059    223 NRPSFRQILM 232
STKc_RIP cd13978
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein; STKs catalyze ...
 726-919 6.38e-13

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: 70.17  E-value: 6.38e-13
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIwipdGENVKIPVAIKVLRENTS-PKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLVTQLMPY 803
Cdd:cd13978      1 LGSGGFGTVSKAR----HVSWFGMVAIKCLHSSPNcIEERKALLKEAEKMERARHSYVLPLLGVCVeRRSLGLVMEYMEN 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  804 GCL---LDHVREN-----RGRLGSQ------------------D------LLN--------------WCMQIAKVP---- 833
Cdd:cd13978     77 GSLkslLEREIQDvpwslRFRIIHEialgmnflhnmdppllhhDlkpeniLLDnhfhvkisdfglskLGMKSISANrrrg 156

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  834 -------IKWMALESI--LRRRFTHQSDVWSYGVTVWELMTfGAKPYDGipAREIpdLLE-----KGERLPQPPICTIDV 899
Cdd:cd13978    157 tenlggtPIYMAPEAFddFNKKPTSKSDVYSFAIVIWAVLT-RKEPFEN--AINP--LLImqivsKGDRPSLDDIGRLKQ 231

                          250       260
                   ....*....|....*....|....*..
gi 1844139561  900 YM-------IMVKCWMIDSECRPRFRE 919
Cdd:cd13978    232 IEnvqelisLMIRCWDGNPDARPTFLE 258
STKc_PknB_like cd14014
Catalytic domain of bacterial Serine/Threonine kinases, PknB and similar proteins; STKs ...
 721-894 3.20e-11

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: 65.30  E-value: 3.20e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  721 RKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLRENTS--PKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LV 797
Cdd:cd14014      3 RLVRLLGRGGMGEVYRARDTLLGR----PVAIKVLRPELAedEEFRERFLREARALARLSHPNIVRVYDVGEDDGRPyIV 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPyGCLLDHVRENRGRLGSQDLLNWCMQIAKV---------------P----------IK----------------- 835
Cdd:cd14014     79 MEYVE-GGSLADLLRERGPLPPREALRILAQIADAlaaahragivhrdikPanilltedgrVKltdfgiaralgdsgltq 157

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139561  836 ---------WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGERLPQPPI 894
Cdd:cd14014    158 tgsvlgtpaYMAPEQARGGPVDPRSDIYSLGVVLYELLT-GRPPFDGDSPAAVLAKHLQEAPPPPSPL 224
PKc_STE cd05122
Catalytic domain of STE family Protein Kinases; PKs catalyze the transfer of the ...
 719-871 5.34e-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: 64.53  E-value: 5.34e-11
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLRENTSPKaNKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLV 797
Cdd:cd05122      1 LFEILEKIGKGGFGVVYKARHKKTGQ----IVAIKKINLESKEK-KESILNEIAILKKCKHPNIVKYYGSYLKkDELWIV 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCLLDHVRENRGRLGSQD------------------------------LLN-----------WCMQIAKVPIK- 835
Cdd:cd05122     76 MEFCSGGSLKDLLKNTNKTLTEQQiayvckevlkgleylhshgiihrdikaaniLLTsdgevklidfgLSAQLSDGKTRn 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|...
gi 1844139561  836 -------WMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPY 871
Cdd:cd05122    156 tfvgtpyWMAPEVIQGKPYGFKADIWSLGITAIE-MAEGKPPY 197
STKc_MAPKKK cd06606
Catalytic domain of the Serine/Threonine Kinase, Mitogen-Activated Protein Kinase Kinase ...
 719-871 4.70e-10

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: 61.77  E-value: 4.70e-10
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWIPDGENvkipVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQL 796
Cdd:cd06606      1 RWKKGELLGKGSFGSVYLALNLDTGEL----MAVKEVElSGDSEEELEALEREIRILSSLKHPNIVRYLGTERTeNTLNI 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  797 VTQLMPYGCLLDHVRENRG----------------------------------------------------RLGSQDLLN 824
Cdd:cd06606     77 FLEYVPGGSLASLLKKFGKlpepvvrkytrqilegleylhsngivhrdikganilvdsdgvvkladfgcakRLAEIATGE 156

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139561  825 WCMQIAKVPIkWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPY 871
Cdd:cd06606    157 GTKSLRGTPY-WMAPEVIRGEGYGRAADIWSLGCTVIEMAT-GKPPW 201
PTKc_Aatyk1 cd05087
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 1; PTKs ...
 832-920 4.95e-09

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


Pssm-ID: 270670 [Multi-domain]  Cd Length: 271  Bit Score: 58.85  E-value: 4.95e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 VPIKWMALE-------SILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIP--DLLEKGERLPQP--PICTIDV- 899
Cdd:cd05087    166 VPLRWIAPElvdevhgNLLVVDQTKQSNVWSLGVTIWELFELGNQPYRHYSDRQVLtyTVREQQLKLPKPqlKLSLAERw 245

                           90       100
                   ....*....|....*....|.
gi 1844139561  900 YMIMVKCWMiDSECRPRFREL 920
Cdd:cd05087    246 YEVMQFCWL-QPEQRPTAEEV 265
PKc_TNNI3K cd14064
Catalytic domain of the Dual-specificity protein kinase, TNNI3-interacting kinase; ...
 726-921 8.30e-09

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: 57.92  E-value: 8.30e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWipdgeNVKIpVAIKVLRENT-SPKANKEIL-DEAYVMAGVGSPYVSRLLGICLTSTVQ--LVTQLM 801
Cdd:cd14064      1 IGSGSFGKVYKGRC-----RNKI-VAIKRYRANTyCSKSDVDMFcREVSILCRLNHPCVIQFVGACLDDPSQfaIVTQYV 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVRENRGRLGSQDLLNWCMQIAK---------VPI-------------------------------------- 834
Cdd:cd14064     75 SGGSLFSLLHEQKRVIDLQSKLIIAVDVAKgmeylhnltQPIihrdlnshnillyedghavvadfgesrflqsldednmt 154

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  835 ------KWMALESILR-RRFTHQSDVWSYGVTVWELMTfGAKPYDGI-PAREIPDLLEKGERLPQP-----PICTidvym 901
Cdd:cd14064    155 kqpgnlRWMAPEVFTQcTRYSIKADVFSYALCLWELLT-GEIPFAHLkPAAAAADMAYHHIRPPIGysipkPISS----- 228

                          250       260
                   ....*....|....*....|
gi 1844139561  902 IMVKCWMIDSECRPRFRELV 921
Cdd:cd14064    229 LLMRGWNAEPESRPSFVEIV 248
STKc_IRAK cd14066
Catalytic domain of the Serine/Threonine kinases, Interleukin-1 Receptor Associated Kinases ...
 726-872 9.93e-09

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: 57.67  E-value: 9.93e-09
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWiPDGenvkIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPYG 804
Cdd:cd14066      1 IGSGGFGTVYKGVL-ENG----TVVAVKRLNEMNCAASKKEFLTELEMLGRLRHPNLVRLLGYCLESDEKlLVYEYMPNG 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRGR--LGSQDLLNWCMQIAK-----------------------------VP-------------------- 833
Cdd:cd14066     76 SLEDRLHCHKGSppLPWPQRLKIAKGIARgleylheecpppiihgdikssnilldedfEPkltdfglarlippsesvskt 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1844139561  834 ------IKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYD 872
Cdd:cd14066    156 savkgtIGYLAPEYIRTGRVSTKSDVYSFGVVLLELLT-GKPAVD 199
Furin-like pfam00757
Furin-like cysteine rich region;
502-603 1.03e-08

Furin-like cysteine rich region;


Pssm-ID: 395614 [Multi-domain]  Cd Length: 143  Bit Score: 55.13  E-value: 1.03e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  502 DECVGEGLACHQLCARGHCWGPGptQC-VNCSQflrgqECVEECRvlqglpreyvNARHClpCHPECQpqnGSvtCFGPE 580
Cdd:pfam00757    6 DVCPGTMEKCHSCCNNGYCWGPG--HCqKVCPE-----QCKKRCT----------KPGEC--CHEQCL---GG--CTGPN 61

                           90       100
                   ....*....|....*....|...
gi 1844139561  581 ADQCVACAHYKDPPFCVARCPSG 603
Cdd:pfam00757   62 DSDCLACRHFNDEGTCVDQCPPG 84
PTK_Jak_rpt1 cd05037
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinases, Janus kinases; The Jak ...
 726-923 1.05e-08

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: 57.49  E-value: 1.05e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIP--DGENVKIPVAIKVLRENTSPKAnKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPY 803
Cdd:cd05037      7 LGQGTFTNIYDGILREvgDGRVQEVEVLLKVLDSDHRDIS-ESFFETASLMSQISHKHLVKLYGVCVADENIMVQEYVRY 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  804 GCLLDHVRENRGRLGsqdlLNWCMQIAK---------------------------------------------------- 831
Cdd:cd05037     86 GPLDKYLRRMGNNVP----LSWKLQVAKqlasalhyledkklihgnvrgrnillaregldgyppfiklsdpgvpitvlsr 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 ----VPIKWMALE--SILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPICTIdvYMIMVK 905
Cdd:cd05037    162 eervDRIPWIAPEclRNLQANLTIAADKWSFGTTLWEICSGGEEPLSALSSQEKLQFYEDQHQLPAPDCAEL--AELIMQ 239

                          250
                   ....*....|....*...
gi 1844139561  906 CWMIDSECRPRFRELVSE 923
Cdd:cd05037    240 CWTYEPTKRPSFRAILRD 257
PKc_MAPKK cd06605
Catalytic domain of the dual-specificity Protein Kinase, Mitogen-Activated Protein Kinase ...
 719-920 3.56e-08

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


Pssm-ID: 270782 [Multi-domain]  Cd Length: 265  Bit Score: 56.20  E-value: 3.56e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWIPDGenvkIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQLV 797
Cdd:cd06605      2 DLEYLGELGEGNGGVVSKVRHRPSG----QIMAVKVIRLEIDEALQKQILRELDVLHKCNSPYIVGFYGAFYSEGdISIC 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCL-------------------------LDHVRENRGRLG-----SQDLLNWCMQI---------------AKV 832
Cdd:cd06605     78 MEYMDGGSLdkilkevgriperilgkiavavvkgLIYLHEKHKIIHrdvkpSNILVNSRGQVklcdfgvsgqlvdslAKT 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PI---KWMALESILRRRFTHQSDVWSYGVTVWELMT--FGAKPYDGIPAREIPDLL-----EKGERLPQPPIcTIDVYMI 902
Cdd:cd06605    158 FVgtrSYMAPERISGGKYTVKSDIWSLGLSLVELATgrFPYPPPNAKPSMMIFELLsyivdEPPPLLPSGKF-SPDFQDF 236

                          250
                   ....*....|....*...
gi 1844139561  903 MVKCWMIDSECRPRFREL 920
Cdd:cd06605    237 VSQCLQKDPTERPSYKEL 254
PKc_MAPKK_plant_like cd06623
Catalytic domain of Plant dual-specificity Mitogen-Activated Protein Kinase Kinases and ...
 719-922 7.43e-08

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


Pssm-ID: 132954 [Multi-domain]  Cd Length: 264  Bit Score: 54.91  E-value: 7.43e-08
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTS-TVQLV 797
Cdd:cd06623      2 DLERVKVLGQGSSGVVYKVRHKPTGK----IYALKKIHVDGDEEFRKQLLRELKTLRSCESPYVVKCYGAFYKEgEISIV 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCLLDHVRENR-------GRLGSQ-----------------D------LLNWCMQ-------IAKV-------- 832
Cdd:cd06623     78 LEYMDGGSLADLLKKVGkipepvlAYIARQilkgldylhtkrhiihrDikpsnlLINSKGEvkiadfgISKVlentldqc 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 -----PIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLE---KGERLPQPPI-CTIDVYMIM 903
Cdd:cd06623    158 ntfvgTVTYMSPERIQGESYSYAADIWSLGLTLLECAL-GKFPFLPPGQPSFFELMQaicDGPPPSLPAEeFSPEFRDFI 236

                          250
                   ....*....|....*....
gi 1844139561  904 VKCWMIDSECRPRFRELVS 922
Cdd:cd06623    237 SACLQKDPKKRPSAAELLQ 255
FU smart00261
Furin-like repeats;
557-603 1.07e-07

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 49.43  E-value: 1.07e-07
                            10        20        30        40
                    ....*....|....*....|....*....|....*....|....*....
gi 1844139561   557 ARHCLPCHPECQpqngsvTCFGPEADQCVACAH--YKDPPFCVARCPSG 603
Cdd:smart00261    1 DGECKPCHPECA------TCTGPGPDDCTSCKHgfFLDGGKCVSECPPG 43
PTKc_Aatyk3 cd14206
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinase 3; PTKs ...
 832-920 1.11e-07

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: 54.57  E-value: 1.11e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 VPIKWMALE-------SILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERL----PQPPICTIDV- 899
Cdd:cd14206    171 IPLRWVAPElldelhgNLIVVDQSKESNVWSLGVTIWELFEFGAQPYRHLSDEEVLTFVVREQQMklakPRLKLPYADYw 250

                           90       100
                   ....*....|....*....|.
gi 1844139561  900 YMIMVKCWMIDSEcRPRFREL 920
Cdd:cd14206    251 YEIMQSCWLPPSQ-RPSVEEL 270
STKc_A-Raf cd14150
Catalytic domain of the Serine/Threonine Kinase, A-Raf (Rapidly Accelerated Fibrosarcoma) ...
 719-929 1.14e-07

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: 54.64  E-value: 1.14e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWIPDgenvkipVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLV 797
Cdd:cd14150      1 EVSMLKRIGTGSFGTVFRGKWHGD-------VAVKILKvTEPTPEQLQAFKNEMQVLRKTRHVNILLFMGFMTRPNFAII 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCLLDHVRENRGRLGSQDLLNWCMQIAKV--------------------------------------------- 832
Cdd:cd14150     74 TQWCEGSSLYRHLHVTETRFDTMQLIDVARQTAQGmdylhakniihrdlksnniflhegltvkigdfglatvktrwsgsq 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 -------PIKWMALESILRRR---FTHQSDVWSYGVTVWELMTfGAKPYDGIPARE-----------IPDLLEKGERLPQ 891
Cdd:cd14150    154 qveqpsgSILWMAPEVIRMQDtnpYSFQSDVYAYGVVLYELMS-GTLPYSNINNRDqiifmvgrgylSPDLSKLSSNCPK 232

                          250       260       270
                   ....*....|....*....|....*....|....*...
gi 1844139561  892 PpictidVYMIMVKCWMIDSECRPRFRELVSEFSRMAR 929
Cdd:cd14150    233 A------MKRLLIDCLKFKREERPLFPQILVSIELLQR 264
STKc_B-Raf cd14151
Catalytic domain of the Serine/Threonine Kinase, B-Raf (Rapidly Accelerated Fibrosarcoma) ...
 726-930 2.05e-07

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


Pssm-ID: 271053 [Multi-domain]  Cd Length: 274  Bit Score: 53.91  E-value: 2.05e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIPDgenvkipVAIKVLRENT-SPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYG 804
Cdd:cd14151     16 IGSGSFGTVYKGKWHGD-------VAVKMLNVTApTPQQLQAFKNEVGVLRKTRHVNILLFMGYSTKPQLAIVTQWCEGS 88

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRGRLGSQDLLNWCMQIAKV---------------------------------------------------- 832
Cdd:cd14151     89 SLYHHLHIIETKFEMIKLIDIARQTAQGmdylhaksiihrdlksnniflhedltvkigdfglatvksrwsgshqfeqlsg 168

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESIL---RRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAR-EIPDLLEKGERLPQ----PPICTIDVYMIMV 904
Cdd:cd14151    169 SILWMAPEVIRmqdKNPYSFQSDVYAFGIVLYELMT-GQLPYSNINNRdQIIFMVGRGYLSPDlskvRSNCPKAMKRLMA 247

                          250       260
                   ....*....|....*....|....*.
gi 1844139561  905 KCWMIDSECRPRFRELVSEFSRMARD 930
Cdd:cd14151    248 ECLKKKRDERPLFPQILASIELLARS 273
STKc_MST1_2 cd06612
Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; ...
 717-876 2.12e-07

Catalytic domain of the Serine/Threonine Kinases, Mammalian STe20-like protein kinase 1 and 2; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. This subfamily is composed of MST1, MST2, and related proteins including Drosophila Hippo and Dictyostelium discoideum Krs1 (kinase responsive to stress 1). MST1/2 and Hippo are involved in a conserved pathway that governs cell contact inhibition, organ size control, and tumor development. MST1 activates the mitogen-activated protein kinases (MAPKs) p38 and c-Jun N-terminal kinase (JNK) through MKK7 and MEKK1 by acting as a MAPK kinase kinase kinase. Activation of JNK by MST1 leads to caspase activation and apoptosis. MST1 has also been implicated in cell proliferation and differentiation. Krs1 may regulate cell growth arrest and apoptosis in response to cellular stress. The MST1/2 subfamily is part of a larger superfamily that includes the catalytic domains of other STKs, protein tyrosine kinases, RIO kinases, aminoglycoside phosphotransferase, choline kinase, and phosphoinositide 3-kinase.


Pssm-ID: 132943 [Multi-domain]  Cd Length: 256  Bit Score: 53.42  E-value: 2.12e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  717 ETELRKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLRENTSpkaNKEILDEAYVMAGVGSPYVSRLLGICLTSTVQL 796
Cdd:cd06612      2 EEVFDILEKLGEGSYGSVYKAIHKETGQ----VVAIKVVPVEED---LQEIIKEISILKQCDSPYIVKYYGSYFKNTDLW 74

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  797 VtqLMPY---GCLLDHVRENRGRLGSQdllnwcmQIAKV-------------------PIK------------------- 835
Cdd:cd06612     75 I--VMEYcgaGSVSDIMKITNKTLTEE-------EIAAIlyqtlkgleylhsnkkihrDIKagnillneegqakladfgv 145

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 -------------------WMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPYDGIPA 876
Cdd:cd06612    146 sgqltdtmakrntvigtpfWMAPEVIQEIGYNNKADIWSLGITAIE-MAEGKPPYSDIHP 204
TM_ErbB2 cd12094
Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the ...
 641-684 3.41e-07

Transmembrane domain of ErbB2, a Protein Tyrosine Kinase; PTKs catalyze the transfer of the gamma-phosphoryl group from ATP to tyrosine (tyr) residues in protein substrates. ErbB2 (HER2, 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 (TM) helix, and a cytoplasmic region with a tyr kinase domain and a regulatory C-terminal tail. It is 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. ErbB2 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 ErbB2-ErbB3 heterodimer being the most potent pair in mitogenic signaling. The TM domain not only serves as a membrane anchor, but also plays an important role in receptor dimerization and optimal activation. Mutations in the TM domain of ErbB2 have been associated with increased breast cancer risk. ErbB2 plays an important role in cell development, proliferation, survival and motility. Overexpression of ErbB2 results in its activation and downstream signaling, even in the absence of ligand. ErbB2 overexpression, mainly due to gene amplification, has been shown in a variety of human cancers. Its role in breast cancer is especially well-documented. ErbB2 is up-regulated in about 25% of breast tumors and is associated with increases in tumor aggressiveness, recurrence and mortality. ErbB2 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.


Pssm-ID: 213055  Cd Length: 44  Bit Score: 47.96  E-value: 3.41e-07
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....
gi 1844139561  641 GCPAEQRASPLTSIISAVVGILLVVVLGVVFGILIKRRQQKIRK 684
Cdd:cd12094      1 GCPAEQRASPLTSIIAGVVGILLVVVLLVVFGILIKRRRQKIRK 44
STKc_Raf cd14062
Catalytic domain of the Serine/Threonine Kinases, Raf (Rapidly Accelerated Fibrosarcoma) ...
 726-920 3.51e-07

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: 52.78  E-value: 3.51e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWipDGenvkiPVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYG 804
Cdd:cd14062      1 IGSGSFGTVYKGRW--HG-----DVAVKKLNvTDPTPSQLQAFKNEVAVLRKTRHVNILLFMGYMTKPQLAIVTQWCEGS 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRGRLGSQDLLNWCMQIA---------------------------KVPIK---------------------- 835
Cdd:cd14062     74 SLYKHLHVLETKFEMLQLIDIARQTAqgmdylhakniihrdlksnniflhedlTVKIGdfglatvktrwsgsqqfeqptg 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 ---WMALESIlRRR----FTHQSDVWSYGVTVWELMTfGAKPYDGIPAREI-----------PDLLEKGERLPQPpicti 897
Cdd:cd14062    154 silWMAPEVI-RMQdenpYSFQSDVYAFGIVLYELLT-GQLPYSHINNRDQilfmvgrgylrPDLSKVRSDTPKA----- 226

                          250       260
                   ....*....|....*....|...
gi 1844139561  898 dVYMIMVKCWMIDSECRPRFREL 920
Cdd:cd14062    227 -LRRLMEDCIKFQRDERPLFPQI 248
PK_KSR cd14063
Pseudokinase domain of Kinase Suppressor of Ras; The pseudokinase domain shows similarity to ...
 719-929 5.21e-07

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: 52.74  E-value: 5.21e-07
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWipDGEnvkipVAIKVLRENTspkaNKEILDEAY---VMAGVGSPY--VSRLLGICLT-S 792
Cdd:cd14063      1 ELEIKEVIGKGRFGRVHRGRW--HGD-----VAIKLLNIDY----LNEEQLEAFkeeVAAYKNTRHdnLVLFMGACMDpP 69

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  793 TVQLVTQLMPYGCLLDHVRENRGRLGsqdlLNWCMQIA------------------------------KVPIKWMALESI 842
Cdd:cd14063     70 HLAIVTSLCKGRTLYSLIHERKEKFD----FNKTVQIAqqicqgmgylhakgiihkdlkskniflengRVVITDFGLFSL 145

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  843 LR-----RR---------------------------------FTHQSDVWSYGvTVW-ELMTfGAKPYDGIPAREIPDLL 883
Cdd:cd14063    146 SGllqpgRRedtlvipngwlcylapeiiralspdldfeeslpFTKASDVYAFG-TVWyELLA-GRWPFKEQPAESIIWQV 223

                          250       260       270       280
                   ....*....|....*....|....*....|....*....|....*..
gi 1844139561  884 EKGERLPQPPI-CTIDVYMIMVKCWMIDSECRPRFRELVSEFSRMAR 929
Cdd:cd14063    224 GCGKKQSLSQLdIGREVKDILMQCWAYDPEKRPTFSDLLRMLERLPK 270
STKc_Cdc7_like cd06627
Catalytic domain of Cell division control protein 7-like Serine/Threonine Kinases; STKs ...
 726-922 1.27e-06

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: 51.07  E-value: 1.27e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIPDGENVkipvAIKVLRENTSPKAN-KEILDEAYVMAGVGSPYVSRLLGICLTST-VQLVTQLMPY 803
Cdd:cd06627      8 IGRGAFGSVYKGLNLNTGEFV----AIKQISLEKIPKSDlKSVMGEIDLLKKLNHPNIVKYIGSVKTKDsLYIILEYVEN 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  804 GCLLDHVRENrGRLGsQDLLNWCM-QIAK----------------------------------VPIK------------- 835
Cdd:cd06627     84 GSLASIIKKF-GKFP-ESLVAVYIyQVLEglaylheqgvihrdikganilttkdglvkladfgVATKlnevekdensvvg 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 ---WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPY---DGIPA--REIPDllekgERLPQPPICTIDVYMIMVKCW 907
Cdd:cd06627    162 tpyWMAPEVIEMSGVTTASDIWSVGCTVIELLT-GNPPYydlQPMAAlfRIVQD-----DHPPLPENISPELRDFLLQCF 235

                          250
                   ....*....|....*
gi 1844139561  908 MIDSECRPRFRELVS 922
Cdd:cd06627    236 QKDPTLRPSAKELLK 250
STK_BAK1_like cd14664
Catalytic domain of the Serine/Threonine Kinase, BRI1 associated kinase 1 and related STKs; ...
 726-872 2.00e-06

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: 50.96  E-value: 2.00e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIwIPDGENvkipVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQ-LVTQLMPYG 804
Cdd:cd14664      1 IGRGGAGTVYKGV-MPNGTL----VAVKRLKGEGTQGGDHGFQAEIQTLGMIRHRNIVRLRGYCSNPTTNlLVYEYMPNG 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CL-------------LDHVRENRGRLGS--------------------------------------------QDLLNWCM 827
Cdd:cd14664     76 SLgellhsrpesqppLDWETRQRIALGSarglaylhhdcspliihrdvksnnilldeefeahvadfglaklmDDKDSHVM 155

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|....*
gi 1844139561  828 QIAKVPIKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYD 872
Cdd:cd14664    156 SSVAGSYGYIAPEYAYTGKVSEKSDVYSYGVVLLELIT-GKRPFD 199
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
 235-280 3.10e-06

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 45.20  E-value: 3.10e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139561  235 CCHEQCAaGCTGPKHSDCLACLHFN--HSGICELHCPALVTYNTDTFE 280
Cdd:cd00064      1 PCHPSCA-TCTGPGPDQCTSCRHGFylDGGTCVSECPEGTYADTEGGV 47
PTKc_Aatyk cd05042
Catalytic domain of the Protein Tyrosine Kinases, Apoptosis-associated tyrosine kinases; PTKs ...
 832-920 3.21e-06

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: 50.28  E-value: 3.21e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 VPIKWMALESI--LRRRF-----THQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLL--EKGERLPQPPI---CTIDV 899
Cdd:cd05042    164 FPLRWTAPELVteFHDRLlvvdqTKYSNIWSLGVTLWELFENGAQPYSNLSDLDVLAQVvrEQDTKLPKPQLelpYSDRW 243

                           90       100
                   ....*....|....*....|.
gi 1844139561  900 YMIMVKCWMiDSECRPRFREL 920
Cdd:cd05042    244 YEVLQFCWL-SPEQRPAAEDV 263
STKc_RIP1 cd14027
Catalytic domain of the Serine/Threonine kinase, Receptor Interacting Protein 1; STKs catalyze ...
 836-924 5.82e-06

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: 49.42  E-value: 5.82e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALESI--LRRRFTHQSDVWSYGVTVWELMTfGAKPY-DGIPAREIPDLLEKGERlPQ----PPICTIDVYMIMVKCWM 908
Cdd:cd14027    169 YMAPEHLndVNAKPTEKSDVYSFAIVLWAIFA-NKEPYeNAINEDQIIMCIKSGNR-PDvddiTEYCPREIIDLMKLCWE 246

                           90
                   ....*....|....*.
gi 1844139561  909 IDSECRPRFRELVSEF 924
Cdd:cd14027    247 ANPEARPTFPGIEEKF 262
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
 562-607 6.66e-06

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 44.43  E-value: 6.66e-06
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|....*...
gi 1844139561  562 PCHPECQpqngsvTCFGPEADQCVACAH--YKDPPFCVARCPSGVKPD 607
Cdd:cd00064      1 PCHPSCA------TCTGPGPDQCTSCRHgfYLDGGTCVSECPEGTYAD 42
STKc_C-Raf cd14149
Catalytic domain of the Serine/Threonine Kinase, C-Raf (Rapidly Accelerated Fibrosarcoma) ...
 726-922 9.63e-06

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: 48.87  E-value: 9.63e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIPDgenvkipVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPYG 804
Cdd:cd14149     20 IGSGSFGTVYKGKWHGD-------VAVKILKvVDPTPEQFQAFRNEVAVLRKTRHVNILLFMGYMTKDNLAIVTQWCEGS 92

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CLLDHVRENRGRLGSQDLLNWCMQIAKV---------------------------------------------------- 832
Cdd:cd14149     93 SLYKHLHVQETKFQMFQLIDIARQTAQGmdylhakniihrdmksnniflhegltvkigdfglatvksrwsgsqqveqptg 172

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  833 PIKWMALESILRRR---FTHQSDVWSYGVTVWELMTfGAKPYDGIPARE-----------IPDLLEKGERLPQPpictid 898
Cdd:cd14149    173 SILWMAPEVIRMQDnnpFSFQSDVYSYGIVLYELMT-GELPYSHINNRDqiifmvgrgyaSPDLSKLYKNCPKA------ 245

                          250       260
                   ....*....|....*....|....
gi 1844139561  899 VYMIMVKCWMIDSECRPRFRELVS 922
Cdd:cd14149    246 MKRLVADCIKKVKEERPLFPQILS 269
PTK_Jak3_rpt1 cd14208
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 3; Jak3 is ...
 726-925 9.72e-06

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


Pssm-ID: 271110 [Multi-domain]  Cd Length: 260  Bit Score: 48.75  E-value: 9.72e-06
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIW--IPDGENVKIPVAIKVLrENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVTQLMPY 803
Cdd:cd14208      7 LGKGSFTKIYRGLRtdEEDDERCETEVLLKVM-DPTHGNCQESFLEAASIMSQISHKHLVLLHGVCVGKDSIMVQEFVCH 85

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  804 GCLLDHVRENrgrlGSQDLL--NWCMQIAK--------------------------------------------VPIKWM 837
Cdd:cd14208     86 GALDLYLKKQ----QQKGPVaiSWKLQVVKqlayalnyledkqlvhgnvsakkvllsregdkgsppfiklsdpgVSIKVL 161

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  838 ALESILRR-------------RFTHQSDVWSYGVTVWELMTFGAKPYDGI-PAREIpDLLEKGERLPQPPicTIDVYMIM 903
Cdd:cd14208    162 DEELLAERipwvapeclsdpqNLALEADKWGFGATLWEIFSGGHMPLSALdPSKKL-QFYNDRKQLPAPH--WIELASLI 238

                          250       260
                   ....*....|....*....|..
gi 1844139561  904 VKCWMIDSECRPRFRELVSEFS 925
Cdd:cd14208    239 QQCMSYNPLLRPSFRAIIRDLN 260
STKc_PAK cd06614
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase; STKs catalyze the ...
 724-871 1.87e-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: 1.87e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIPDGENVkipvAIKVLRENtspKANKE-ILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLM 801
Cdd:cd06614      6 EKIGEGASGEVYKATDRATGKEV----AIKKMRLR---KQNKElIINEILIMKECKHPNIVDYYDSYLVgDELWVVMEYM 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVRENRGRLG-SQ-----------------------D------LLN-----------WCMQIAKVPIK----- 835
Cdd:cd06614     79 DGGSLTDIITQNPVRMNeSQiayvcrevlqgleylhsqnvihrDiksdniLLSkdgsvkladfgFAAQLTKEKSKrnsvv 158

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|
gi 1844139561  836 ----WMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPY 871
Cdd:cd06614    159 gtpyWMAPEVIKRKDYGPKVDIWSLGIMCIE-MAEGEPPY 197
GF_recep_IV pfam14843
Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine ...
 194-270 2.40e-05

Growth factor receptor domain IV; This is the fourth extracellular domain of receptor tyrosine protein kinases. Interaction between this domain and the furin-like domain (pfam00757) regulates the binding of ligands to the receptor L domains (pfam01030).


Pssm-ID: 464344 [Multi-domain]  Cd Length: 132  Bit Score: 45.06  E-value: 2.40e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  194 PCSPMCKGSRCWGESSEDCQS----LTRTVCAGGCARCKGP-----LPTDC--CHEQCA-----AGCTGPKHSDCLACLH 257
Cdd:pfam14843    1 VCDPLCSSEGCWGPGPDQCLScrnfSRGGTCVESCNILQGEpreyvVNSTCvpCHPECLpqngtATCSGPGADNCTKCAH 80

                           90
                   ....*....|...
gi 1844139561  258 FNHSGICELHCPA 270
Cdd:pfam14843   81 FRDGPHCVSSCPS 93
STKc_STK25 cd06642
Catalytic domain of Serine/Threonine Kinase 25 (also called Yeast Sps1/Ste20-related kinase 1); ...
 717-921 3.19e-05

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: 47.36  E-value: 3.19e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  717 ETELRKVKVLGSGAFGTVYKGIwipdGENVKIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST-VQ 795
Cdd:cd06642      3 EELFTKLERIGKGSFGEVYKGI----DNRTKEVVAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYITRYYGSYLKGTkLW 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  796 LVTQLMPYGCLLDHVREN-----------RGRLGSQDLLNW----------------------------CMQIAKVPIK- 835
Cdd:cd06642     79 IIMEYLGGGSALDLLKPGpleetyiatilREILKGLDYLHSerkihrdikaanvllseqgdvkladfgvAGQLTDTQIKr 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 --------WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGerlpQPPIC----TIDVYMIM 903
Cdd:cd06642    159 ntfvgtpfWMAPEVIKQSAYDFKADIWSLGITAIELAK-GEPPNSDLHPMRVLFLIPKN----SPPTLegqhSKPFKEFV 233

                          250
                   ....*....|....*...
gi 1844139561  904 VKCWMIDSECRPRFRELV 921
Cdd:cd06642    234 EACLNKDPRFRPTAKELL 251
STKc_MST3_like cd06609
Catalytic domain of Mammalian Ste20-like protein kinase 3-like Serine/Threonine Kinases; STKs ...
 719-882 3.58e-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: 46.85  E-value: 3.58e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  719 ELRKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL-TSTVQLV 797
Cdd:cd06609      2 LFTLLERIGKGSFGEVYKGIDKRTNQ----VVAIKVIDLEEAEDEIEDIQQEIQFLSQCDSPYITKYYGSFLkGSKLWII 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  798 TQLMPYGCLLDHVRenRGRLGSQDL----------LNWCMQIAKV--PIK------------------------------ 835
Cdd:cd06609     78 MEYCGGGSVLDLLK--PGPLDETYIafilrevllgLEYLHSEGKIhrDIKaanillseegdvkladfgvsgqltstmskr 155

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....
gi 1844139561  836 --------WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDG---------IPAREIPDL 882
Cdd:cd06609    156 ntfvgtpfWMAPEVIKQSGYDEKADIWSLGITAIELAK-GEPPLSDlhpmrvlflIPKNNPPSL 218
FU smart00261
Furin-like repeats;
509-544 3.97e-05

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 42.11  E-value: 3.97e-05
                            10        20        30
                    ....*....|....*....|....*....|....*...
gi 1844139561   509 LACHQLCArgHCWGPGPTQCVNCSQ--FLRGQECVEEC 544
Cdd:smart00261    5 KPCHPECA--TCTGPGPDDCTSCKHgfFLDGGKCVSEC 40
FU cd00064
Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is ...
 510-544 4.35e-05

Furin-like repeats. Cysteine rich region. Exact function of the domain is not known. Furin is a serine-kinase dependent proprotein processor. Other members of this family include endoproteases and cell surface receptors.


Pssm-ID: 238021 [Multi-domain]  Cd Length: 49  Bit Score: 42.12  E-value: 4.35e-05
                           10        20        30
                   ....*....|....*....|....*....|....*..
gi 1844139561  510 ACHQLCArgHCWGPGPTQCVNCSQF--LRGQECVEEC 544
Cdd:cd00064      1 PCHPSCA--TCTGPGPDQCTSCRHGfyLDGGTCVSEC 35
STKc_MST3 cd06641
Catalytic domain of the Serine/Threonine Kinase, Mammalian Ste20-like protein kinase 3; STKs ...
 717-894 4.94e-05

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: 46.60  E-value: 4.94e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  717 ETELRKVKVLGSGAFGTVYKGIwipDGENVKIpVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTST--- 793
Cdd:cd06641      3 EELFTKLEKIGKGSFGEVFKGI---DNRTQKV-VAIKIIDLEEAEDEIEDIQQEITVLSQCDSPYVTKYYGSYLKDTklw 78

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  794 ----------------------VQLVTQLMPYGCLLDHVRENR-------------GRLGSQDLLNWCM--QIAKVPIK- 835
Cdd:cd06641     79 iimeylgggsaldllepgpldeTQIATILREILKGLDYLHSEKkihrdikaanvllSEHGEVKLADFGVagQLTDTQIKr 158

                          170       180       190       200       210       220
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*..
gi 1844139561  836 --------WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGerlpQPPI 894
Cdd:cd06641    159 n*fvgtpfWMAPEVIKQSAYDSKADIWSLGITAIELAR-GEPPHSELHPMKVLFLIPKN----NPPT 220
STKc_LRRK cd14000
Catalytic domain of the Serine/Threonine kinase, Leucine-Rich Repeat Kinase; STKs catalyze the ...
 725-925 7.21e-05

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: 46.07  E-value: 7.21e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  725 VLGSGAFGTVYKGIW------------IPDGENVKIP--VAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL 790
Cdd:cd14000      1 LLGDGGFGSVYRASYkgepvavkifnkHTSSNFANVPadTMLRHLRATDAMKNFRLLRQELTVLSHLHHPSIVYLLGIGI 80

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  791 tSTVQLVTQLMPYGCLlDHV-RENR------GR--------------------------LGSQDLLNWCM---------- 827
Cdd:cd14000     81 -HPLMLVLELAPLGSL-DHLlQQDSrsfaslGRtlqqrialqvadglrylhsamiiyrdLKSHNVLVWTLypnsaiiiki 158

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  828 -------QIAKVPIK-------WMALEsILRRR--FTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEK-----G 886
Cdd:cd14000    159 adygisrQCCRMGAKgsegtpgFRAPE-IARGNviYNEKVDVFSFGMLLYEILSGGAPMVGHLKFPNEFDIHGGlrpplK 237

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  887 ERLPQPPICTIDvymIMVKCWMIDSECRPRFRELVSEFS 925
Cdd:cd14000    238 QYECAPWPEVEV---LMKKCWKENPQQRPTAVTVVSILN 273
STKc_TTBK cd14017
Catalytic domain of the Serine/Threonine protein kinase, Tau-Tubulin Kinase; STKs catalyze the ...
 723-849 7.69e-05

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: 45.71  E-value: 7.69e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  723 VKVLGSGAFGTVYKGIWIPDGENvkipVAIKVLRENtspkANKEILD-EAYVMAGV-GSPYVSRLLGICLTSTVQ-LVTQ 799
Cdd:cd14017      5 VKKIGGGGFGEIYKVRDVVDGEE----VAMKVESKS----QPKQVLKmEVAVLKKLqGKPHFCRLIGCGRTERYNyIVMT 76

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|..
gi 1844139561  800 LmpYGCLLDHVREN--RGRLGSQDLLNWCMQIAKvpikwmALESILRRRFTH 849
Cdd:cd14017     77 L--LGPNLAELRRSqpRGKFSVSTTLRLGIQILK------AIEDIHEVGFLH 120
PKc_Byr1_like cd06620
Catalytic domain of fungal Byr1-like dual-specificity Mitogen-activated protein Kinase Kinases; ...
 715-921 8.05e-05

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: 45.89  E-value: 8.05e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  715 LKETELRKVKVLGSGAFGTVYKGIWIPDGenvkIPVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICL--TS 792
Cdd:cd06620      2 LKNQDLETLKDLGAGNGGSVSKVLHIPTG----TIMAKKVIHIDAKSSVRKQILRELQILHECHSPYIVSFYGAFLneNN 77

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  793 TVQLVTQLMPYGCL-------------------------LDHV--------RE---------NRGRLG------SQDLLN 824
Cdd:cd06620     78 NIIICMEYMDCGSLdkilkkkgpfpeevlgkiavavlegLTYLynvhriihRDikpsnilvnSKGQIKlcdfgvSGELIN 157

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  825 wcmQIAKVPI---KWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDGIPARE--------IPDLL-----EKGER 888
Cdd:cd06620    158 ---SIADTFVgtsTYMSPERIQGGKYSVKSDVWSLGLSIIELAL-GEFPFAGSNDDDdgyngpmgILDLLqrivnEPPPR 233

                          250       260       270
                   ....*....|....*....|....*....|....*....
gi 1844139561  889 LPQ----PPICT--IDvymimvKCWMIDSECRPRFRELV 921
Cdd:cd06620    234 LPKdrifPKDLRdfVD------RCLLKDPRERPSPQLLL 266
FU smart00261
Furin-like repeats;
235-270 9.71e-05

Furin-like repeats;


Pssm-ID: 214589 [Multi-domain]  Cd Length: 45  Bit Score: 40.96  E-value: 9.71e-05
                            10        20        30
                    ....*....|....*....|....*....|....*...
gi 1844139561   235 CCHEQCAaGCTGPKHSDCLACLHFNH--SGICELHCPA 270
Cdd:smart00261    6 PCHPECA-TCTGPGPDDCTSCKHGFFldGGKCVSECPP 42
PKc_LIMK_like cd14065
Catalytic domain of the LIM domain kinase-like protein kinases; PKs catalyze the transfer of ...
 726-923 9.95e-05

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: 45.56  E-value: 9.95e-05
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIPDGEnvkipvaIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT-STVQLVTQLMPYG 804
Cdd:cd14065      1 LGKGFFGEVYKVTHRETGK-------VMVMKELKRFDEQRSFLKEVKLMRRLSHPNILRFIGVCVKdNKLNFITEYVNGG 73

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  805 CL--------------------LDHVR------------------------ENRGRLGSQDLLNWCMQIAKVPIK----- 835
Cdd:cd14065     74 TLeellksmdeqlpwsqrvslaKDIASgmaylhskniihrdlnsknclvreANRGRNAVVADFGLAREMPDEKTKkpdrk 153

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 ----------WMALESILRRRFTHQSDVWSYGVTVWELMT-FGAKPyDGIPAREIPDLLEKGERLPQPPICTIDVYMIMV 904
Cdd:cd14065    154 krltvvgspyWMAPEMLRGESYDEKVDVFSFGIVLCEIIGrVPADP-DYLPRTMDFGLDVRAFRTLYVPDCPPSFLPLAI 232

                          250
                   ....*....|....*....
gi 1844139561  905 KCWMIDSECRPRFRELVSE 923
Cdd:cd14065    233 RCCQLDPEKRPSFVELEHH 251
STKc_WNK cd13983
Catalytic domain of the Serine/Threonine kinase, With No Lysine (WNK) kinase; STKs catalyze ...
 725-871 1.03e-04

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


Pssm-ID: 270885 [Multi-domain]  Cd Length: 258  Bit Score: 45.29  E-value: 1.03e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  725 VLGSGAFGTVYKGIWIPDGenvkIPVAIKVLRENTSPKANKE-ILDEAYVMAGVGSPYVSRLLGI---CLTSTVQLVTQL 800
Cdd:cd13983      8 VLGRGSFKTVYRAFDTEEG----IEVAWNEIKLRKLPKAERQrFKQEIEILKSLKHPNIIKFYDSwesKSKKEVIFITEL 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  801 MPYGCLLDHVRENrGRLGSQDLLNWCMQIAK------------------------------VPIKWMALESILRRRFTH- 849
Cdd:cd13983     84 MTSGTLKQYLKRF-KRLKLKVIKSWCRQILEglnylhtrdppiihrdlkcdnifingntgeVKIGDLGLATLLRQSFAKs 162

                          170       180       190       200
                   ....*....|....*....|....*....|....*....|.
gi 1844139561  850 -------------------QSDVWSYGVTVWELMTfGAKPY 871
Cdd:cd13983    163 vigtpefmapemyeehydeKVDIYAFGMCLLEMAT-GEYPY 202
STKc_FA2-like cd08529
Catalytic domain of the Serine/Threonine Kinases, Chlamydomonas reinhardtii FA2 and similar ...
 726-920 1.07e-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: 45.48  E-value: 1.07e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  726 LGSGAFGTVYKGIWIPDGeNVKIPVAIKVLRENTSPKanKEILDEAYVMAGVGSPYVSRLLGiCLTSTVQL--VTQLMPY 803
Cdd:cd08529      8 LGKGSFGVVYKVVRKVDG-RVYALKQIDISRMSRKMR--EEAIDEARVLSKLNSPYVIKYYD-SFVDKGKLniVMEYAEN 83

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  804 GCLLDHVRENRGR------------------------------------------------LGSQDLLNWCMQIAKVPIK 835
Cdd:cd08529     84 GDLHSLIKSQRGRplpedqiwkffiqtllglshlhskkilhrdiksmnifldkgdnvkigdLGVAKILSDTTNFAQTIVG 163

                          170       180       190       200       210       220       230       240
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 ---WMALESILRRRFTHQSDVWSYGVTVWELMTFgAKPYD----GIPAREIPdlleKGERLPQPPICTIDVYMIMVKCWM 908
Cdd:cd08529    164 tpyYLSPELCEDKPYNEKSDVWALGCVLYELCTG-KHPFEaqnqGALILKIV----RGKYPPISASYSQDLSQLIDSCLT 238

                          250
                   ....*....|..
gi 1844139561  909 IDSECRPRFREL 920
Cdd:cd08529    239 KDYRQRPDTTEL 250
PTKc_Aatyk2 cd05086
Catalytic domain of the Protein Tyrosine Kinase, Apoptosis-associated tyrosine kinase 2; PTKs ...
 832-920 1.50e-04

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


Pssm-ID: 270669 [Multi-domain]  Cd Length: 271  Bit Score: 44.86  E-value: 1.50e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  832 VPIKWMALE-------SILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPD--LLEKGERLPQPPI---CTIDV 899
Cdd:cd05086    166 APLRWTAPElvtsfqdGLLAAEQTKYSNIWSLGVTLWELFENAAQPYSDLSDREVLNhvIKERQVKLFKPHLeqpYSDRW 245

                           90       100
                   ....*....|....*....|.
gi 1844139561  900 YMIMVKCWMiDSECRPRFREL 920
Cdd:cd05086    246 YEVLQFCWL-SPEKRPTAEEV 265
STKc_Nek cd08215
Catalytic domain of the Serine/Threonine Kinase, Never In Mitosis gene A (NIMA)-related kinase; ...
 721-894 2.00e-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: 44.38  E-value: 2.00e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  721 RKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLTSTVQLVtq 799
Cdd:cd08215      3 EKIRVIGKGSFGSAYLVRRKSDGK----LYVLKEIDlSNMSEKEREEALNEVKLLSKLKHPNIVKYYESFEENGKLCI-- 76

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  800 LMPY---GCLLDHVRENR--GRLGSQD-LLNWCMQ-------------------------------------IAKV---- 832
Cdd:cd08215     77 VMEYadgGDLAQKIKKQKkkGQPFPEEqILDWFVQiclalkylhsrkilhrdlktqnifltkdgvvklgdfgISKVlest 156

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139561  833 ----------PIkWMALESILRRRFTHQSDVWSYGVTVWELMTFgAKPYDgipAREIPDLLEKGERLPQPPI 894
Cdd:cd08215    157 tdlaktvvgtPY-YLSPELCENKPYNYKSDIWALGCVLYELCTL-KHPFE---ANNLPALVYKIVKGQYPPI 223
PTK_Jak2_rpt1 cd05078
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 2; Jak2 is widely ...
 834-925 2.97e-04

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


Pssm-ID: 270663 [Multi-domain]  Cd Length: 262  Bit Score: 44.17  E-value: 2.97e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  834 IKWMALESILR-RRFTHQSDVWSYGVTVWELMTFGAKPYDGIPAREIPDLLEKGERLPQPPicTIDVYMIMVKCWMIDSE 912
Cdd:cd05078    172 IPWVPPECIENpKNLSLATDKWSFGTTLWEICSGGDKPLSALDSQRKLQFYEDRHQLPAPK--WTELANLINNCMDYEPD 249

                           90
                   ....*....|...
gi 1844139561  913 CRPRFRELVSEFS 925
Cdd:cd05078    250 HRPSFRAIIRDLN 262
STKc_RCK1-like cd14096
Catalytic domain of RCK1-like Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 718-810 3.02e-04

Catalytic domain of RCK1-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 fungal STKs including Saccharomyces cerevisiae RCK1 and RCK2, Schizosaccharomyces pombe Sty1-regulated kinase 1 (Srk1), and similar proteins. RCK1, RCK2 (or Rck2p), and Srk1 are MAPK-activated protein kinases. RCK1 and RCK2 are involved in oxidative and metal stress resistance in budding yeast. RCK2 also regulates rapamycin sensitivity in both S. cerevisiae and Candida albicans. Srk1 is activated by Sty1/Spc1 and is involved in negatively regulating cell cycle progression by inhibiting Cdc25. The RCK1-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: 270998 [Multi-domain]  Cd Length: 295  Bit Score: 44.35  E-value: 3.02e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  718 TELRKVKVLGSGAFGTVYKGIWIPdgeNVKIPVAIKVLR------ENTSPKANKEILDEAYVMAGVGSPYVSRLLGICLT 791
Cdd:cd14096      1 ENYRLINKIGEGAFSNVYKAVPLR---NTGKPVAIKVVRkadlssDNLKGSSRANILKEVQIMKRLSHPNIVKLLDFQES 77

                           90       100
                   ....*....|....*....|
gi 1844139561  792 -STVQLVTQLMPYGCLLDHV 810
Cdd:cd14096     78 dEYYYIVLELADGGEIFHQI 97
Furin-like pfam00757
Furin-like cysteine rich region;
504-603 4.83e-04

Furin-like cysteine rich region;


Pssm-ID: 395614 [Multi-domain]  Cd Length: 143  Bit Score: 41.65  E-value: 4.83e-04
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  504 CVGEGLACHQLCArGHCWGPGPTQCVNCSQFLRGQECVEECRvlqglPREYVNARHCLPcHPECqPQNGSVTCFgpeadq 583
Cdd:pfam00757   42 CTKPGECCHEQCL-GGCTGPNDSDCLACRHFNDEGTCVDQCP-----PGTYQFGWRCVT-FKEC-PKSHLPGYN------ 107

                           90       100
                   ....*....|....*....|
gi 1844139561  584 cvacAHYKDPPFCVARCPSG 603
Cdd:pfam00757  108 ----PLVIHNGECVRECPSG 123
STKc_EIF2AK cd13996
Catalytic domain of the Serine/Threonine kinase, eukaryotic translation Initiation Factor ...
 723-849 1.17e-03

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: 42.28  E-value: 1.17e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  723 VKVLGSGAFGTVYKGIWIPDGENvkipVAIKVLRENTSPKANKEILDEAYVMAGVGSPYVSRLLGI-CLTSTVQLVTQLM 801
Cdd:cd13996     11 IELLGSGGFGSVYKVRNKVDGVT----YAIKKIRLTEKSSASEKVLREVKALAKLNHPNIVRYYTAwVEEPPLYIQMELC 86

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|
gi 1844139561  802 PYGCLLDHVRENRGRLGSQDLLNWCM--QIAKvpikwmALESILRRRFTH 849
Cdd:cd13996     87 EGGTLRDWIDRRNSSSKNDRKLALELfkQILK------GVSYIHSKGIVH 130
STKc_NAK1_like cd06917
Catalytic domain of Fungal Nak1-like Serine/Threonine Kinases; STKs catalyze the transfer of ...
 718-890 1.54e-03

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: 42.08  E-value: 1.54e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  718 TELRKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLRENTSPKANKEILDEAYVMAGV---GSPYVSRLLGiCLTSTV 794
Cdd:cd06917      1 SLYRRLELVGRGSYGAVYRGYHVKTGR----VVALKVLNLDTDDDDVSDIQKEVALLSQLklgQPKNIIKYYG-SYLKGP 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  795 QL-----------VTQLM-------PYGCLLdhVRE--------------------------NRGRL-----GSQDLLNW 825
Cdd:cd06917     76 SLwiimdyceggsIRTLMragpiaeRYIAVI--MREvlvalkfihkdgiihrdikaanilvtNTGNVklcdfGVAASLNQ 153

                          170       180       190       200       210       220       230
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|..
gi 1844139561  826 C----MQIAKVPIkWMALESILR-RRFTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLLEKGE--RLP 890
Cdd:cd06917    154 NsskrSTFVGTPY-WMAPEVITEgKYYDTKADIWSLGITTYEMAT-GNPPYSDVDALRAVMLIPKSKppRLE 223
STKc_GSK3 cd14137
The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze ...
 716-753 1.61e-03

The catalytic domain of the Serine/Threonine Kinase, Glycogen Synthase Kinase 3; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. GSK3 is a mutifunctional kinase involved in many cellular processes including cell division, proliferation, differentiation, adhesion, and apoptosis. In plants, GSK3 plays a role in the response to osmotic stress. In Caenorhabditis elegans, it plays a role in regulating normal oocyte-to-embryo transition and response to oxidative stress. In Chlamydomonas reinhardtii, GSK3 regulates flagellar length and assembly. In mammals, there are two isoforms, GSK3alpha and GSK3beta, which show both distinct and redundant functions. The two isoforms differ mainly in their N-termini. They are both involved in axon formation and in Wnt signaling.They play distinct roles in cardiogenesis, with GSKalpha being essential in cardiomyocyte survival, and GSKbeta regulating heart positioning and left-right symmetry. GSK3beta was first identified as a regulator of glycogen synthesis, but has since been determined to play other roles. It regulates the degradation of beta-catenin and IkB. Beta-catenin is the main effector of Wnt, which is involved in normal haematopoiesis and stem cell function. IkB is a central inhibitor of NF-kB, which is critical in maintaining leukemic cell growth. GSK3beta is enriched in the brain and is involved in regulating neuronal signaling pathways. It is implicated in the pathogenesis of many diseases including Type II diabetes, obesity, mood disorders, Alzheimer's disease, osteoporosis, and some types of cancer, among others. The GSK3 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: 271039 [Multi-domain]  Cd Length: 293  Bit Score: 42.10  E-value: 1.61e-03
                           10        20        30
                   ....*....|....*....|....*....|....*...
gi 1844139561  716 KETELRKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIK 753
Cdd:cd14137      2 VEISYTIEKVIGSGSFGVVYQAKLLETGE----VVAIK 35
STKc_CMGC cd05118
Catalytic domain of CMGC family Serine/Threonine Kinases; STKs catalyze the transfer of the ...
 721-872 1.61e-03

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: 41.45  E-value: 1.61e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  721 RKVKVLGSGAFGTVYKGIwipDGENVKIpVAIKVLR--ENTSPKANKEI--LDEAYvmAGVGSPYVSRLLGICLTSTVQ- 795
Cdd:cd05118      2 EVLRKIGEGAFGTVWLAR---DKVTGEK-VAIKKIKndFRHPKAALREIklLKHLN--DVEGHPNIVKLLDVFEHRGGNh 75

                           90       100       110       120       130       140       150       160
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  796 --LVTQLMPYGcLLDHVRENRGRLGSQDLLNWCMQIAKVpIKWMALESILRR------------------------RFTH 849
Cdd:cd05118     76 lcLVFELMGMN-LYELIKDYPRGLPLDLIKSYLYQLLQA-LDFLHSNGIIHRdlkpenilinlelgqlkladfglaRSFT 153

                          170       180
                   ....*....|....*....|....*..
gi 1844139561  850 QSDVWSYGVTVW----ELMtFGAKPYD 872
Cdd:cd05118    154 SPPYTPYVATRWyrapEVL-LGAKPYG 179
STKc_MEKK4 cd06626
Catalytic domain of the Protein Serine/Threonine Kinase, Mitogen-Activated Protein (MAP) ...
 724-788 2.18e-03

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


Pssm-ID: 270796 [Multi-domain]  Cd Length: 265  Bit Score: 41.52  E-value: 2.18e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139561  724 KVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLR-ENTSPKANKEILDEAYVMAGVGSPYVSRLLGI 788
Cdd:cd06626      6 NKIGEGTFGKVYTAVNLDTGE----LMAMKEIRfQDNDPKTIKEIADEMKVLEGLDHPNLVRYYGV 67
CooF_like cd10563
CooF, iron-sulfur subunit of carbon monoxide dehydrogenase; This family includes CooF, the ...
 544-643 2.26e-03

CooF, iron-sulfur subunit of carbon monoxide dehydrogenase; This family includes CooF, the iron-sulfur subunit of carbon monoxide dehydrogenase (CODH), found in anaerobic bacteria and archaea. Carbon monoxide dehydrogenase is a key enzyme for carbon monoxide (CO) metabolism, where CooF is the proposed mediator of electron transfer between CODH and the CO-induced hydrogenase, catalyzing the reaction that uses CO as a single carbon and energy source, and producing only H2 and CO2. The ion-sulfur subunit contains four Fe4/S4 and/or Fe3/S4 clusters which transfer the electrons in the protein complex during reaction.


Pssm-ID: 319885 [Multi-domain]  Cd Length: 140  Bit Score: 39.55  E-value: 2.26e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  544 CRVLQGLPREY-VNARHCLpcHPEC-----------QPQNGSVTCfgpEADQCVACAhykdppFCVARCPSGV-KPDLSY 610
Cdd:cd10563     43 IRVEESGGRSFpLQCRHCD--EPPCvkacmsgamhkDPETGIVIH---DEEKCVGCW------MCVMVCPYGAiRPDKER 111

                           90       100       110
                   ....*....|....*....|....*....|...
gi 1844139561  611 MPIWKfpdeegaCQPCPINCTHSCVdlddKGCP 643
Cdd:cd10563    112 KVALK-------CDLCPDRETPACV----EACP 133
STKc_PAK6 cd06659
Catalytic domain of the Serine/Threonine Kinase, p21-activated kinase 6; STKs catalyze the ...
 815-871 2.36e-03

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: 41.51  E-value: 2.36e-03
                           10        20        30        40        50        60
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*.
gi 1844139561  815 GRLGSQDLlNWCMQIAK-VPIK--------WMALESILRRRFTHQSDVWSYGVTVWElMTFGAKPY 871
Cdd:cd06659    154 GRVKLSDF-GFCAQISKdVPKRkslvgtpyWMAPEVISRCPYGTEVDIWSLGIMVIE-MVDGEPPY 217
PTZ00267 PTZ00267
NIMA-related protein kinase; Provisional
 836-944 2.54e-03

NIMA-related protein kinase; Provisional


Pssm-ID: 140293 [Multi-domain]  Cd Length: 478  Bit Score: 41.93  E-value: 2.54e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALESILRRRFTHQSDVWSYGVTVWELMTFgAKPYDGIPAREIPDLLEKGERLPQPpiCTIDVYM--IMVKCWMIDSEC 913
Cdd:PTZ00267   237 YLAPELWERKRYSKKADMWSLGVILYELLTL-HRPFKGPSQREIMQQVLYGKYDPFP--CPVSSGMkaLLDPLLSKNPAL 313

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1844139561  914 RPRFRELV-SEFSRMARDPQRFVVIQNEDLGP 944
Cdd:PTZ00267   314 RPTTQQLLhTEFLKYVANLFQDIVRHSETISP 345
STKc_RSK_N cd05582
N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; ...
 834-873 2.57e-03

N-terminal catalytic domain of the Serine/Threonine Kinase, 90 kDa ribosomal protein S6 kinase; STKs catalyze the transfer of the gamma-phosphoryl group from ATP to serine/threonine residues on protein substrates. 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. Mammals possess four RSK isoforms (RSK1-4) from distinct genes. RSK proteins are also referred to as MAP kinase-activated protein kinases (MAPKAPKs), p90-RSKs, or p90S6Ks. The RSK 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: 270734 [Multi-domain]  Cd Length: 317  Bit Score: 41.23  E-value: 2.57e-03
                           10        20        30        40
                   ....*....|....*....|....*....|....*....|
gi 1844139561  834 IKWMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPYDG 873
Cdd:cd05582    161 VEYMAPEVVNRRGHTQSADWWSFGVLMFEMLT-GSLPFQG 199
PHA02988 PHA02988
hypothetical protein; Provisional
 847-925 2.67e-03

hypothetical protein; Provisional


Pssm-ID: 165291 [Multi-domain]  Cd Length: 283  Bit Score: 41.27  E-value: 2.67e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  847 FTHQSDVWSYGVTVWELMTfGAKPYDGIPAREIPDLL-EKGERLPQPPICTIDVYMIMVKCWMIDSECRPRFRELVSEFS 925
Cdd:PHA02988   199 YTIKDDIYSLGVVLWEIFT-GKIPFENLTTKEIYDLIiNKNNSLKLPLDCPLEIKCIVEACTSHDSIKRPNIKEILYNLS 277
PK_GC-2D cd14043
Pseudokinase domain of the membrane Guanylate Cyclase receptor, GC-2D; The pseudokinase domain ...
 836-929 3.65e-03

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: 40.85  E-value: 3.65e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALEsILR-----RRFTHQSDVWSYGVTVWELMTFGAkPYD--GIPAREIPDLLEKgerlpQPPICTIDVYM------- 901
Cdd:cd14043    164 WTAPE-LLRdprleRRGTFPGDVFSFAIIMQEVIVRGA-PYCmlGLSPEEIIEKVRS-----PPPLCRPSVSMdqaplec 236

                           90       100       110
                   ....*....|....*....|....*....|
gi 1844139561  902 --IMVKCWMIDSECRPRFRELVSEFSRMAR 929
Cdd:cd14043    237 iqLMKQCWSEAPERRPTFDQIFDQFKSINK 266
PK_GC cd13992
Pseudokinase domain of membrane Guanylate Cyclase receptors; The pseudokinase domain shows ...
 836-927 5.29e-03

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: 40.07  E-value: 5.29e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALE----SILRRRFTHQSDVWSYGVTVWELMtFGAKPYDGIPAREIPDLLEKGERLPQPPI-------CTIDVYMIMV 904
Cdd:cd13992    167 WTAPEllrgSLLEVRGTQKGDVYSFAIILYEIL-FRSDPFALEREVAIVEKVISGGNKPFRPElavlldeFPPRLVLLVK 245

                           90       100
                   ....*....|....*....|...
gi 1844139561  905 KCWMIDSECRPRFRELVSEFSRM 927
Cdd:cd13992    246 QCWAENPEKRPSFKQIKKTLTEN 268
PK_GC-A_B cd14042
Pseudokinase domain of the membrane Guanylate Cyclase receptors, GC-A and GC-B; The ...
 836-930 5.41e-03

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


Pssm-ID: 270944 [Multi-domain]  Cd Length: 279  Bit Score: 40.27  E-value: 5.41e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALEsILRR-----RFTHQSDVWSYGVTVWELMT----FGAKPYDGIPaREIpdLLEKGERLPQPP--------ICTID 898
Cdd:cd14042    172 WTAPE-LLRDpnpppPGTQKGDVYSFGIILQEIATrqgpFYEEGPDLSP-KEI--IKKKVRNGEKPPfrpsldelECPDE 247

                           90       100       110
                   ....*....|....*....|....*....|..
gi 1844139561  899 VYMIMVKCWMIDSECRPRFRELVSEFSRMARD 930
Cdd:cd14042    248 VLSLMQRCWAEDPEERPDFSTLRNKLKKLNKG 279
PLN00034 PLN00034
mitogen-activated protein kinase kinase; Provisional
 699-784 5.68e-03

mitogen-activated protein kinase kinase; Provisional


Pssm-ID: 215036 [Multi-domain]  Cd Length: 353  Bit Score: 40.58  E-value: 5.68e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  699 PLTPSGAMP-------NQAQMRILKETELRKVKVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVLRENTSPKANKEILDEA 771
Cdd:PLN00034    48 PPPSSSSSSsssssasGSAPSAAKSLSELERVNRIGSGAGGTVYKVIHRPTGR----LYALKVIYGNHEDTVRRQICREI 123

                           90
                   ....*....|...
gi 1844139561  772 YVMAGVGSPYVSR 784
Cdd:PLN00034   124 EILRDVNHPNVVK 136
STKc_PDK1 cd05581
Catalytic domain of the Serine/Threonine Kinase, Phosphoinositide-dependent kinase 1; STKs ...
 724-849 6.41e-03

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: 39.89  E-value: 6.41e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  724 KVLGSGAFGTVYKGIWIPDGEnvkiPVAIKVL------RENTSPKANKEILdeayVMAGVGSPYVSRLLGicltsTVQ-- 795
Cdd:cd05581      7 KPLGEGSYSTVVLAKEKETGK----EYAIKVLdkrhiiKEKKVKYVTIEKE----VLSRLAHPGIVKLYY-----TFQde 73

                           90       100       110       120       130
                   ....*....|....*....|....*....|....*....|....*....|....*...
gi 1844139561  796 ----LVTQLMPYGCLLDHVRENrGRLGSQDLLNWCMQIAkvpikwMALESILRRRFTH 849
Cdd:cd05581     74 sklyFVLEYAPNGDLLEYIRKY-GSLDEKCTRFYTAEIV------LALEYLHSKGIIH 124
STKc_Byr2_like cd06628
Catalytic domain of the Serine/Threonine Kinases, fungal Byr2-like Mitogen-Activated Protein ...
 836-922 6.62e-03

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: 39.82  E-value: 6.62e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALESILRRRFTHQSDVWSYGVTVWELMTfGAKPY-DGIPAREIPDLLEKGERLPqPPICTIDVYMIMVKCWMIDSECR 914
Cdd:cd06628    178 WMAPEVVKQTSYTRKADIWSLGCLVVEMLT-GTHPFpDCTQMQAIFKIGENASPTI-PSNISSEARDFLEKTFEIDHNKR 255


                   ....*...
gi 1844139561  915 PRFRELVS 922
Cdd:cd06628    256 PTADELLK 263
PK_ILK cd14057
Pseudokinase domain of Integrin Linked Kinase; The pseudokinase domain shows similarity to ...
 836-927 7.49e-03

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: 39.78  E-value: 7.49e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALESILRR---RFTHQSDVWSYGVTVWELMTFGAkPYDGIPAREIP-DLLEKGERLPQPPICTIDVYMIMVKCWMIDS 911
Cdd:cd14057    157 WMAPEALQKKpedINRRSADMWSFAILLWELVTREV-PFADLSNMEIGmKIALEGLRVTIPPGISPHMCKLMKICMNEDP 235

                           90
                   ....*....|....*.
gi 1844139561  912 ECRPRFRELVSEFSRM 927
Cdd:cd14057    236 GKRPKFDMIVPILEKM 251
STKc_LIMK1 cd14221
Catalytic domain of the Serine/Threonine Kinase, LIM domain kinase 1; STKs catalyze the ...
 836-920 8.13e-03

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: 39.55  E-value: 8.13e-03
                           10        20        30        40        50        60        70        80
                   ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 1844139561  836 WMALESILRRRFTHQSDVWSYGVTVWELMTFGAKPYDGIPaREIPDLLEKGERLPQ--PPICTIDVYMIMVKCWMIDSEC 913
Cdd:cd14221    171 WMAPEMINGRSYDEKVDVFSFGIVLCEIIGRVNADPDYLP-RTMDFGLNVRGFLDRycPPNCPPSFFPIAVLCCDLDPEK 249


                   ....*..
gi 1844139561  914 RPRFREL 920
Cdd:cd14221    250 RPSFSKL 256
 
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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