1A81,1M61


Conserved Protein Domain Family
SH2_N-SH2_Zap70_Syk_like

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cd09938: SH2_N-SH2_Zap70_Syk_like 
Click on image for an interactive view with Cn3D
N-terminal Src homology 2 (SH2) domain found in Zeta-chain-associated protein kinase 70 (ZAP-70) and Spleen tyrosine kinase (Syk) proteins
ZAP-70 and Syk comprise a family of hematopoietic cell specific protein tyrosine kinases (PTKs) that are required for antigen and antibody receptor function. ZAP-70 is expressed in T and natural killer (NK) cells and Syk is expressed in B cells, mast cells, polymorphonuclear leukocytes, platelets, macrophages, and immature T cells. They are required for the proper development of T and B cells, immune receptors, and activating NK cells. They consist of two N-terminal Src homology 2 (SH2) domains and a C-terminal kinase domain separated from the SH2 domains by a linker or hinge region. Phosphorylation of both tyrosine residues within the Immunoreceptor Tyrosine-based Activation Motifs (ITAM; consensus sequence Yxx[LI]x(7,8)Yxx[LI]) by the Src-family PTKs is required for efficient interaction of ZAP-70 and Syk with the receptor subunits and for receptor function. ZAP-70 forms two phosphotyrosine binding pockets, one of which is shared by both SH2 domains. In Syk the two SH2 domains do not form such a phosphotyrosine-binding site. The SH2 domains here are believed to function independently. In addition, the two SH2 domains of Syk display flexibility in their relative orientation, allowing Syk to accommodate a greater variety of spacing sequences between the ITAM phosphotyrosines and singly phosphorylated non-classical ITAM ligands. This model contains the N-terminus SH2 domains of both Syk and Zap70. In general SH2 domains are involved in signal transduction. They typically bind pTyr-containing ligands via two surface pockets, a pTyr and hydrophobic binding pocket, allowing proteins with SH2 domains to localize to tyrosine phosphorylated sites.
Statistics
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PSSM-Id: 198191
Aligned: 11 rows
Threshold Bit Score: 180.283
Created: 25-Feb-2011
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
phosphotyrosinehydrophobic
Conserved site includes 4 residues -Click on image for an interactive view with Cn3D
Feature 1:phosphotyrosine binding pocket [polypeptide binding site]
Evidence:

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                  #                    #                    # #                          
1A81_A          5 LPFFFGNITREEAEDYLVQGG-MSDGLYLLRQSRnyLGGFALSVAHGRKAHHYTIERELNGTYAIAGGRTHASPADLCHY 83   human
1M61_A         11 LPFFYGSISRAEAEEHLKLAG-MADGLFLLRQCLrsLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEF 89   human
1177044         8 LPFFYGSISRAEAEEHLKLAG-MADGLFLLRQCLrsLGGYVLSLVHDVRFHHFPIERQLNGTYAIAGGKAHCGPAELCEF 86   human
AAK49118        8 LPYFFGNITREESEVYLQQGG-SGDGLYLLRQSRsfLGGYALSLSYGRQFYHYTIERELNDTYAIAGGKSHRTPIDVINY 86   zebrafish
CAD13249       47 TNYFYGKITREQAEELLFTNG-ANEGLFLLRESV--NRNYAVSICHLGRVHHYNVERHTDCSYRIQTGHKFIGPVELVQH 123  Schistosoma m...
NP_001018425    8 LPFFYGSISRSEAEEHLKLAG-MGGGLFLLRQCLrsLGGYVLSMIWNLDFYHYSIEKQLNGTYCIAGGKPHCGPAELCEY 86   zebrafish
NP_001026601   12 LPYFFGNITREEAEEYLMQGG-MSDGLYLLRQSRnyLGGFALSLAYGRKVHHYTIERELSGTYAIAGGKSHASPAELINY 90   chicken
NP_001087005    8 LPFYYGSISRADAEEYLKLGG-MMDGLFLLRQCLrtLGGYVLSMVYNVHFHHYPVERQLNGTYAIAGGKAHCGPAELCEY 86   African clawe...
NP_001086665    8 LPYFFGNITREESEDYLRQAG-ASDGLYLLRQSRsyLGGYALSVAHGRHFYHYTIERELNGTYAISGGISHNSPAELCHY 86   African clawe...
XP_003213232    8 LPFYYGSIARSEAEEYLKLAG-MSDGLFLLRQCLrsLGGYVLSMVCNLQFYHYAIERQMNGTYAIAGGKAHCGPEELCEF 86   turkey
AAC28629        7 LRWFHGRITRDIAENCLQTTTsMDDGTYLLRESAseIGSYVLSVCKDKKVIHYAIQRQPSGMVGIADGPQFPGPVELVNH 86   Hydra vulgaris
Feature 1                                  
1A81_A         84 HSQESDGLVCLLKKPFNRPQGVQPK 108  human
1M61_A         90 YSRDPDGLPCNLRKPCNRPSGLEPQ 114  human
1177044        87 YSRDPDGLPCNLRKPCNRPSGLEPQ 111  human
AAK49118       87 HSQESDGLICLLKKPFHRPRGTEPK 111  zebrafish
CAD13249      124 HSTQLDGFLTLAQLPLNRPVGMSPI 148  Schistosoma mansoni
NP_001018425   87 YSKDPDGLVCTLRKPCLRSPETEIR 111  zebrafish
NP_001026601   91 HSEEADGLICLLRKSFNRPPGVEPK 115  chicken
NP_001087005   87 YSKDADGLSCTLRRPCNRPVGVECQ 111  African clawed frog
NP_001086665   87 HTLESSGLVCLLKKPCNLPPGVQPK 111  African clawed frog
XP_003213232   87 YSKDADGLCCTLRKPCNRPSGVEPQ 111  turkey
AAC28629       87 HKTSLGGLMTKLTYPCERPAGVKAT 111  Hydra vulgaris

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