1XBC,3EMG


Conserved Protein Domain Family
PTKc_Syk

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cd05116: PTKc_Syk 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 133247
View PSSM: cd05116
Aligned: 5 rows
Threshold Bit Score: 532.231
Threshold Setting Gi: 56554456
Created: 15-Jun-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 21 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:1XBC; Human Syk tyr kinase binds the inhibitor, staurosporine; defined at 4A contacts.
    View structure with Cn3D
  • Structure:3EMG; Human Syk tyr kinase binds phenylaminopyrimidine inhibitor; contacts at 4A.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1          ###  #  #              # #                 #            #              ##### #
1XBC_A        23 KELGSGNFGTVKKGYYQMKkvVKTVAVKILKNEAndpalKDELLAEANVMQQLDNPYIVRMIGICEaeSWMLVMEMAELG 102 human
NP_001026601 353 GELGSGNFGTVKKGFYKMKkgAKPVAVKILKNESndpaiKDELLRGANVMQQLDNPYIVRMIGICEaeAWMLVMEMAELG 432 chicken
NP_001083616 349 TELGSGNFGNVKKGMLKTLksEKTVAVKILKNDNndeslKDELLKEAKVMQLLNNPYIVRMLGICEgeSWMLVMELAGLG 428 African clawed ...
NP_998008    326 GELGSGNFGTVLRGVYQMKktQKVVAVKILKNDDdnaavKDEMLREANVMQQLDNPYIVRMIGICEaeNLMLVMELAELG 405 zebrafish
3EMG_A        31 KELGSGNFGTVKKGYYQMKkvVKTVAVKILKNEAndpalKDELLAEANVMQQLDNPYIVRMIGICEaeSWMLVMEMAELG 110 human
Feature 1        #                                          ## #         ##                      
1XBC_A       103 PLNKYLQQNrhVKDKNIIELVHQVSMGMKYLEESNFVHRDLAARNVLLVTqHYAKISDFGLSKALRADENYYKAQTHGKW 182 human
NP_001026601 433 PLNKFLQKNrhVTEKNITELVHQVSMGMKYLEENNFVHRDLAARNVLLVTqHYAKISDFGLSKALSADENYYKAQSHGKW 512 chicken
NP_001083616 429 PLNKFLAKNknVTEHNVTELVHQVSMGMKYLEETNFVHRDLAARNVLLVTqHYAKISDFGLSKALGSDENYYQAKTTGKW 508 African clawed ...
NP_998008    406 PLHKFLQKNkhITVKNLTELVHQVSMGMKYLEEHNFVHRDLAARNVLLVTqHYAKISDFGLSKALTEDENYYKAKGHGKW 485 zebrafish
3EMG_A       111 PLNKYLQQNrhVKDKNIIELVHQVSMGMKYLEESNFVHRDLAARNVLLVTqHYAKISDFGLSKALRADENYYKAQTHGKW 190 human
Feature 1                                                                                        
1XBC_A       183 PVKWYAPECINYyKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPAGCPREMYDLMNLCWTYDVE 262 human
NP_001026601 513 PVKWYAPECMNFyKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGGEVAQMIERGERMECPEACPVEVYDLMKLCWTYNVD 592 chicken
NP_001083616 509 PMKWYAPECLNYhKFSSKSDVWSFGVLMWEAYSYGLKPYLRMKGNDVTVFIESGKRLESPQRCSPEMYNLMKLCWTYGMD 588 African clawed ...
NP_998008    486 PLKWYAPECMNYlKFSSKSDVWSFGVLMWEAFSYGQKPYKGMKGNEVIQMIENGQRMSAPPDCPPEMYDLMKKCWTYKPD 565 zebrafish
3EMG_A       191 PVKWYAPECINYyKFSSKSDVWSFGVLMWEAFSYGQKPYRGMKGSEVTAMLEKGERMGCPAGCPREMYDLMNLCWTYDVE 270 human
Feature 1                         
1XBC_A       263 NRPGFAAVELRLRNYYY 279 human
NP_001026601 593 DRPGFVAVELRLRNYYY 609 chicken
NP_001083616 589 ERPSFAVVELKLRSYYY 605 African clawed frog
NP_998008    566 ERPGFSVVEPRLRHYYY 582 zebrafish
3EMG_A       271 NRPGFAAVELRLRNYYY 287 human

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