3EYG,3EYH


Conserved Protein Domain Family
PTKc_Jak1_rpt2

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cd05079: PTKc_Jak1_rpt2 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 173644
View PSSM: cd05079
Aligned: 5 rows
Threshold Bit Score: 604.615
Threshold Setting Gi: 21263757
Created: 19-Jun-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 19 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:3EYG; Human Jak1 binds the inhibitor CP-690550; contacts at 4A.
    View structure with Cn3D
  • Structure:3EYH; Human Jak1 binds the inhibitor CMP6; contacts at 4A.
    View structure with Cn3D

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                 ####  ###                # #                                         
3EYG_A       6 FEKRFLKRIRDLGEGHFGKVELCRYDPegdNTGEQVAVKSLKPESggnhIADLKKEIEILRNLYHENIVKYKGICTedgg 85   human
3EYH_A       6 FEKRFLKRIRDLGEGHFGKVELCRYDPegdNTGEQVAVKSLKPESggnhIADLKKEIEILRNLYHENIVKYKGICTedgg 85   human
O12990     867 FEKRFLKKIRDLGEGHFGKVELCRYDPrgdRTGELVAVKSLKPENreeqSNNLWREIHILRELYHENIVKYKGICNeegg 946  zebrafish
NP_990201  864 FEKRFLKRIRDLGEGHFGKVELCRYDPegdNTGEQVAVKSLKPESggnhIADLKKEIEILRNLYHENIVKYKGICTedgg 943  chicken
AAH77570   857 FEKRFLKRVRDLGEGHFGKVELCRYDPegdNTGELVAVKSLKPGTggshIADLKKEIEILRNLYHENIVKYKGICEdg-d 935  African clawed frog
Feature 1            ####   #                                           ## #         ##        
3EYG_A      86 nGIKLIMEFLPSGSLKEYLPKNknkINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESeHQVKIGDFGLTKAIE 165  human
3EYH_A      86 nGIKLIMEFLPSGSLKEYLPKNknkINLKQQLKYAVQICKGMDYLGSRQYVHRDLAARNVLVESeHQVKIGDFGLTKAIE 165  human
O12990     947 rSIKLIMEFLPAGSLKEYLPRNkahINLKTLHNYSVQICQGMDYLGSRNYIHRDLAARNVLVENeGTVKIGDFGLTKSIK 1026 zebrafish
NP_990201  944 nGIKLIMEFLPSGSLKEYLPRNknkINLKQLLRYAVQICKGMDYLGSRQYVHRDLAARNVLVESeNRVKIGDFGLTKAIE 1023 chicken
AAH77570   936 sGIKLIMEYLPSGSLKEYLPRNvnkINLKQQLKYATQICKGMDYLGSRQYVHRDLAARNVLVENeQIIKIGDFGLTKAIQ 1015 African clawed frog
Feature 1                                                                                      
3EYG_A     166 TDKEXXTVKDDRDSPVFWYAPECLMQsKFYIASDVWSFGVTLHELLTYCDSDSSPMALFLKMigpthgQMTVTRLVNTLK 245  human
3EYH_A     166 TDKEXXTVKDDRDSPVFWYAPECLMQsKFYIASDVWSFGVTLHELLTYCDSDSSPMALFLKMigpthgQMTVTRLVNTLK 245  human
O12990    1027 DNEGYYTVKDDLDSPVFWYAPECLIHcKFYRASDVWSFGVTMYELLTYCDASCSPMSVFLKLigpthgQMTVTRLVKVLE 1106 zebrafish
NP_990201 1024 TDKEYYTVKDDLDSPVFWYAPECLIQsKFYIASDVWSFGVTLYELLTYCDSESSPMTEFLKMigptqgQMTVARLVRVLQ 1103 chicken
AAH77570  1016 TDKEYYTVKDDLDSPVFWYAPECLLHcKFYIASDVWSFGVTLYELLTYCNSEYSPMTMFLKMigptqgQMTVTRLVRVLE 1095 African clawed frog
Feature 1                                                  
3EYG_A     246 EGKRLPCPPNCPDEVYQLMRKCWEFqPSNRTSFQNLIEGFEALL 289  human
3EYH_A     246 EGKRLPCPPNCPDEVYQLMRKCWEFqPSNRTSFQNLIEGFEALL 289  human
O12990    1107 EGKRLPRPDDCSEQLYNLMRRCWEAtPEKRIDFKSLIANFQQML 1150 zebrafish
NP_990201 1104 EEKRLPRPPNCPEEIDQLMRKCWIFkHDKRTTFHNLIQGFETIM 1147 chicken
AAH77570  1096 EGKRLPIPANCPKQVYQLMTKCWEQnPSDRTTFQDLIKGFEAII 1139 African clawed frog

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