Conserved Protein Domain Family
PTK_Tyk2_rpt1

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cd05076: PTK_Tyk2_rpt1 (this model, PSSM-Id:133207 is obsolete and has been replaced by 270661)
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Tyrosine kinase 2
Protein Tyrosine Kinase (PTK) family; Tyrosine kinase 2 (Tyk2); pseudokinase domain (repeat 1). The PTKc (catalytic domain) family to which this subfamily belongs, 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. Tyk2 is a member of the Janus kinase (Jak) subfamily of proteins, which are cytoplasmic (or nonreceptor) tyr kinases 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 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). 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.
Statistics
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PSSM-Id: 133207
View PSSM: cd05076
Aligned: 4 rows
Threshold Bit Score: 552.591
Threshold Setting Gi: 148230434
Created: 19-Jun-2007
Updated: 17-Jan-2013
Structure
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Aligned Rows:
PubMed ReferencesClick to see Conserved Features Help

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
                          10        20        30        40        50        60        70        80
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56405328   593 SHLGQGTRTNVYEGRLRVegsgdpeegkmddedplvpgrdrgqELRVVLKVLDPSHHdiALAFYETASLMSQVSHTHLAF 672
gi 126322899  602 AHLGQGTRTNIYEGLLHVgggmeaedeeee--nipsepnnnhrELRVVLKVLDPSHRdiALAFFETASLMSQVSHIHLAF 679
gi 118113201  197 AHLGQGTRTNIYDGVLNVrgaagpdadeaeyfsteqnnnsdgrEMRVVLKVLDPTHRdiALAFFETASLMSQVSHVHLAF 276
gi 148230434  592 AHLGQGTRTNIYDGMLLVsegseqesdf-----esgelnnnshDLRVVLKVLDPSHRdiALAFFETASLMSQVSHIHLVF 666
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56405328   673 VHGVCVRgpENIMVTEYVEHGPLDVWLRRErghVPMAWKMVVAQQLASALSYLENKNLVHGNVCGRNILLARlglaegts 752
gi 126322899  680 VHGVCVRgsENIMVAEYVEHGPLDVCLRREkghVPVAWKITVAQQLASALSYLEDKNLVHGNVCAKNILLARrglgdgtq 759
gi 118113201  277 VHGVCVRgsENIMVEEFVEHGPLDVLLRKEkgrVPVGWKITVAKQLASALSYLEDKSLVHGNVCAKNVLLARtglcdgtl 356
gi 148230434  667 VHGVCVResENIMVEEFIEHGPLDVCLRKDklrIKTEWKFTVARQLASALSYLEDKNLVHGNVCAKNILLARkgleenss 746
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 56405328   753 PFIKLSDPGVGLGAlsreERVERIPWLAPECLPGganSLSTAMDKWGFGATLLEICFDGEAPLQSRSPSEKEHFYQRQHR 832
gi 126322899  760 PFIKLSDPGVSVTAlsreERVERIPWIAPECVPSg-tGLSTAADKWSFGTTLLEICFDGEAPLQGRTPSEKERFYEKKHR 838
gi 118113201  357 PFIKLSDPGVSFTAlsreERVDRIPWIAPECIQDv-gNLHPAADKWSFGTTLLEICFDADVPLKERTPAEKERFYEKKHR 435
gi 148230434  747 PFIKLSDPGVTFTVlsreERVERIPWIAPECVRNi-sSLSTAADKWSFGTTLLEICFNGEVPLKERTPPEKERFYEKELG 825
                         250       260       270
                  ....*....|....*....|....*....|....*
gi 56405328   833 LPEPSCPQLATLTSQCLTYePTQRPSFRTILRDLT 867
gi 126322899  839 LQEPSCKELATLISQCLTYeANQRPSFRTILRDLT 873
gi 118113201  436 LPEPSCQDLAALIQQCLSYtPAERPSFRTILRDLT 470
gi 148230434  826 LPEPSCKELADLIGQCHNYnAEGRPSFRTILRELT 860
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