1GRI,1R1P,3N84,3N8M


Conserved Protein Domain Family
SH2_Grb2_like

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cd09941: SH2_Grb2_like 
Click on image for an interactive view with Cn3D
Src homology 2 domain found in Growth factor receptor-bound protein 2 (Grb2) and similar proteins
The adaptor proteins here include homologs Grb2 in humans, Sex muscle abnormal protein 5 (Sem-5) in Caenorhabditis elegans, and Downstream of receptor kinase (drk) in Drosophila melanogaster. They are composed of one SH2 and two SH3 domains. Grb2/Sem-5/drk regulates the Ras pathway by linking the tyrosine kinases to the Ras guanine nucleotide releasing protein Sos, which converts Ras to the active GTP-bound state. The SH2 domain of Grb2/Sem-5/drk binds class II phosphotyrosyl peptides while its SH3 domain binds to Sos and Sos-derived, proline-rich peptides. Besides it function in Ras signaling, Grb2 is also thought to play a role in apoptosis. Unlike most SH2 structures in which the peptide binds in an extended conformation (such that the +3 peptide residue occupies a hydrophobic pocket in the protein, conferring a modest degree of selectivity), Grb2 forms several hydrogen bonds via main chain atoms with the side chain of +2 Asn. 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: 199828
Aligned: 24 rows
Threshold Bit Score: 122.764
Created: 25-Feb-2011
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
phosphotyrosine
Conserved site includes 6 residues -Click on image for an interactive view with Cn3D
Feature 1:phosphotyrosine binding pocket [polypeptide binding site]
Evidence:
  • Structure:3N8M: Human Grb2 SH2 domain binds phosphopeptide PyVNVP, contacts at 4A
  • Structure:1R1P: Mouse Gads-SH2 binds a LAT phosphopeptide, contacts at 4A
  • Comment:conserved Arg forms critical H-bonds with phosphate oxygens of pTyr side chain
  • Citation:PMID 9817027
  • Citation:PMID 8181064
  • Citation:PMID 8604142
  • Citation:PMID 7521735

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1                   #                          # #              #            # #         
1GRI_A        56 KPHPWFFGKIPRAKAEEMLSKq--------RHDGAFLIRESEs-------APGDFSLSVKFgn--dVQHFKVLRDgAGKY 118 human
1R1P_A         7 EFPEWFHEGLSRHQAENLLMG---------KDIGFFIIRASQs-------SPGDFSISVRHed--dVQHFKVMRDtKGNY 68  house mouse
3N8M_A         4 KPHPWFFGKIPRAKAEEMLSKq--------RHDGAFLIRESEs-------APGDFSLSVKFgn--dVQHFKVLRDgAGKY 66  human
NP_004801     54 QFPKWFHEGLSRHQAENLLMG---------KEVGFFIIRASQs-------SPGDFSISVRHed--dVQHFKVMRDnKGNY 115 human
AAP06014      56 RPHPWYIRHCSRMEAEERLQEvdqetaqhlQPDGAFILRQSEa-------DGKGFSLSVKQgc--eVLHFKVLQDeAGKY 126 Schistosoma jap...
NP_956972     54 TFPSWYKENTSRQSAQDELMC---------QPIGAFIIRGSQs-------SPGDFSISVRHen--dVQHFKVMRDrQGRY 115 zebrafish
AAW26772      56 CPHPWYIPKCSRREAEARLLEtdpnthrdvQPDGAFVLRQSEn-------DPGHFSISVKEgs--sVLHFRIFFDpSGKY 126 Schistosoma jap...
NP_001017756  54 QIPSWFKESASRGSAEETLMS---------REVGAFLIRGSQs-------SPGDFSISVRHdy--dVQHFKVMKDkSGHY 115 zebrafish
ADO28067     104 RPHTWFAGRISRHVSEGRLRQ---------RECGAFLVRESEs-------APGEFSMSVSYge--hVQHFKVLKDrEGQY 165 blue catfish
CBY20940      55 RQVPWFLGHIERPEAEDILRN---------VPHGAFLVRNHQqkdpnvreKESPFSLSVKNvslqiVQHYKINKSkEGHF 125 Oikopleura dioica
Feature 1                                         
1GRI_A       119 FLW-VVKFNSLNELVDYHRSTSVSRNQQIFLRD 150 human
1R1P_A        69 FLW-TEKFPSLNKLVDYYRTTSISKQKQVFLRD 100 house mouse
3N8M_A        67 FLW-VVKFNSLNELVDYHRSTSVSRNQQIFLRD 98  human
NP_004801    116 FLW-TEKFPSLNKLVDYYRTNSISRQKQIFLRD 147 human
AAP06014     127 FFW-ISRFDSVNQLIDHHRKTSISRNRLLTLVD 158 Schistosoma japonicum
NP_956972    116 YLW-SEMFTSLNKLVDYYTHNSISKQSRVFLLT 147 zebrafish
AAW26772     127 YIW-TNKFSSINALIDYHRHQTIYGIKALLLRD 158 Schistosoma japonicum
NP_001017756 116 YLW-TEKFTSLNKLVDFYKTTSISKQKEIFLRD 147 zebrafish
ADO28067     166 FIW-DEVFSSLNQLVDFYKSNSIAKERTVFLHE 197 blue catfish
CBY20940     126 WLYpQYEFASLNKLIAWYTAPHEDSDPHLVPVD 158 Oikopleura dioica

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