Conserved Protein Domain Family
PTK_Jak1_rpt1

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cd05077: PTK_Jak1_rpt1 (this model, PSSM-Id:173643 is obsolete and has been replaced by 270662)
Pseudokinase (repeat 1) domain of the Protein Tyrosine Kinase, Janus kinase 1
Protein Tyrosine Kinase (PTK) family; Janus kinase 1 (Jak1); 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. Jak1 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). 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.
Statistics
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PSSM-Id: 173643
View PSSM: cd05077
Aligned: 4 rows
Threshold Bit Score: 551.085
Threshold Setting Gi: 21263757
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 21263757   584 EHLGRGTRTNIYAGILkpksddeddlggysqeVKVVLKVLGSGHRDiSLAFFETASMMRQISHKHTALLYGVCVrhqENI 663
gi 45382379   580 EHLGRGTRTQIYSGILnykddene-gyqnekeIKVLLKVLDPSHRDiSLAFFEAASMMRQVSHKHIVFLHGVCVrdlENI 658
gi 50415493   572 EHLGRGTRTQIYAGKLnykddndsesystekeIKVILKVLHPSHRDiSLAFFETASMMRQVSHKHIVLLHGVCVrdvENI 651
gi 215274013  587 EHLGRGTRTHIYSGTLmdykdde--gtseekkIKVILKVLDPSHRDiSLAFFEAASMMRQVSHKHIVYLYGVCVrdvENI 664
                          90       100       110       120       130       140       150       160
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21263757   664 MVEEFVQYGPLDLFMRRQttpLSTAWKFQVAKQLASALSYLEDKKMVHGYVCSKNILVARDGLdgegGPFIKLSDPGIPI 743
gi 45382379   659 MVEEFVEFGPLDLFMHRKselLTTPWKFNVAKQLASALSYLEDKDLVHGNVCTKNILLAREGIdteyGPFIKLSDPGIPI 738
gi 50415493   652 MVEEFVDFGPLDLFMHRKsdvLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNILLAREGIdndcGPFIKLSDPGIPI 731
gi 215274013  665 MVEEFVEGGPLDLFMHRKsdvLTTPWKFKVAKQLASALSYLEDKDLVHGNVCTKNLLLAREGIdsecGPFIKLSDPGIPI 744
                         170       180       190       200       210       220       230       240
                  ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21263757   744 TVlsreECVDRIPWIAPECVKDtaNLTIAADKWSFGTTLWEICYNGEIPLKDKKLSEKERFYAAQCQLATPDCDELAKLM 823
gi 45382379   739 TVlsrqECVERIPWIAPECVEDskNLSIAADKWSFGTTLWEICYNGETPLKDKTLAEKERFYEGHFMLITPSCKELADLM 818
gi 50415493   732 TVltrqERVERIPWIAPECVEDsrVLSVAADKWSFGTTLWEICFNGEVPLKDRTLAEKERFYGGCFMLVAPSCKELADLI 811
gi 215274013  745 TVlsrqECIERIPWIAPECVEDskNLSVAADKWSFGTTLWEICYNGEIPLKDKTLIEKERFYESRCRPVTPSCKELADLM 824
                         250       260
                  ....*....|....*....|..
gi 21263757   824 THCMTYdPRQRLFFRAIVRDIV 845
gi 45382379   819 KQCMNYdPHQRPFFRAIMRDIN 840
gi 50415493   812 NHCMNYdPNRRPFFRAIMREIN 833
gi 215274013  825 TRCMNYdPNQRPFFRAIMRDIN 846
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