3NYX,3LXN


Conserved Protein Domain Family
PTKc_Tyk2_rpt2

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cd05080: PTKc_Tyk2_rpt2 
Click on image for an interactive view with Cn3D
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.
Statistics
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PSSM-Id: 270664
Aligned: 4 rows
Threshold Bit Score: 557.206
Created: 19-Jun-2007
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
Conserved site includes 18 residues -Click on image for an interactive view with Cn3D
Feature 1:ATP binding site [chemical binding site]
Evidence:
  • Structure:3NYX; Human Tyk2 catalytic kinase domain binds Quinoline-Thiadiazole-Thiophene inhibitor; contacts at 4A.
  • Structure:3LXN; Human Tyk2 catalytic kinase domain binds Cp-690550 inhibitor; contacts at 4A.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                 ## #    #                # #                             #           
3NYX_A      11 FHKRYLKKIRDLGEGHFGKVSLYCYDPtndGTGEMVAVKALKADCgpqhRSGWKQEIDILRTLYHEHIIKYKGCCEdqge 90   human
AAH73112   884 FQKRYLKKIRELGEGHFGKVSLYCYDPnndGTGEMVAVKSLKSGCsqqlESSWKGEIKILKTLYHENIVKYKGCCSeqgd 963  African clawed frog
AAD50351   839 FHKRFLKMQQVLGEGNFGKVILYRYDPandDTGELVAVKTLKRENg--nTEGWIKEINVLKSLDHRNIVKYKGCCSeggg 916  Tetraodon fluvia...
3LXN_A      28 FHKRYLKKIRDLGEGHFGKVSLYCYDPtndGTGEMVAVKALKADAgpqhRSGWKQEIDILRTLYHEHIIKYKGCCEdaga 107  human
Feature 1            ##### #                                          ## #         ##          
3NYX_A      91 kSLQLVMEYVPLGSLRDYLPRHsIGLAQLLLFAQQICEGMAYLHSQHYIHRNLAARNVLLDNdRLVKIGDFGLAKAVPEG 170  human
AAH73112   964 kIVQLIMEYVPLGSLRDYLPKHnVSLAQILLFAQQICEGMAYLHSQHYIHRDLAARNVLVENeNVVKIGDFGLAKAVPEG 1043 African clawed frog
AAD50351   917 qGLLLIMEFLPLGSLLKYLPKNkLNLSQLMIFAQQICEGMEYLHSKRYIHRDLATRNVLLDRdRLVKIGDFGLTKHIPTG 996  Tetraodon fluvia...
3LXN_A     108 aSLQLVMEYVPLGSLRDYLPRHsIGLAQLLLFAQQICEGMAYLHAQHYIHRDLAARNVLLDNdRLVKIGDFGLAKAVPEG 187  human
Feature 1                                                                                      
3NYX_A     171 HEYYRVREDGDSPVFWYAPECLKEyKFYYASDVWSFGVTLYELLTHCDSSQSPPTKFLELIgiaqgqmtVLRLTELLERG 250  human
AAH73112  1044 HEYYRVREDGDSPVFWYATECLKEcKFFYASDVWSFGVTFYELLTRCDSYLSPPAKFIEMIgvtqgqmtVVRLIDLLERG 1123 African clawed frog
AAD50351   997 ELYYRVSENGENPVFWFAVECLKEnKFSFASDVWSFGVTLYEILTHCDPKQSPRKKFEEMLepks-linQVPLIELLEKK 1075 Tetraodon fluvia...
3LXN_A     188 HEXYRVREDGDSPVFWYAPECLKEyKFYYASDVWSFGVTLYELLTHCDSSQSPPTKFLELIgiaqgqmtVLRLTELLERG 267  human
Feature 1                                                 
3NYX_A     251 ERLPRPDKCPCEVYHLMKNCWETeASFRPTFENLIPILKTVHE 293  human
AAH73112  1124 QRLPCPNDCPLEIYKLMKNCWETeANFRPTFNHLIPILKSYHN 1166 African clawed frog
AAD50351  1076 MRLPCPKNCPQEVRIIMEQCWAAePKQRPSFRSLIEKFQEMCH 1118 Tetraodon fluviatilis
3LXN_A     268 ERLPRPDKCPAEVYHLMKNCWETeASFRPTFENLIPILKTVHE 310  human

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