Conserved Protein Domain Family
SH3_EFS

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cd12003: SH3_EFS 
Src homology 3 domain of CAS (Crk-Associated Substrate) scaffolding protein family member, Embryonal Fyn-associated Substrate
EFS is also called HEFS, CASS3 (Cas scaffolding protein family member 3) or SIN (Src-interacting protein). It was identified based on interactions with the Src kinases, Fyn and Yes. It plays a role in thymocyte development and acts as a negative regulator of T cell proliferation. CAS proteins function as molecular scaffolds to regulate protein complexes that are involved in many cellular processes. They share a common domain structure that includes an N-terminal SH3 domain, an unstructured substrate domain that contains many YxxP motifs, a serine-rich four-helix bundle, and a FAT-like C-terminal domain. The SH3 domain of CAS proteins binds to diverse partners including FAK, FRNK, Pyk2, PTP-PEST, DOCK180, among others. SH3 domains are protein interaction domains that bind to proline-rich ligands with moderate affinity and selectivity, preferentially to PxxP motifs. They play versatile and diverse roles in the cell including the regulation of enzymes, changing the subcellular localization of signaling pathway components, and mediating the formation of multiprotein complex assemblies.
Statistics
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PSSM-Id: 212936
Aligned: 3 rows
Threshold Bit Score: 116.913
Created: 6-Jan-2012
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
peptide ligand
Feature 1:peptide ligand binding site [polypeptide binding site]
Evidence:
  • Comment:based on the binding of peptide ligands to the SH3 domains of other superfamily members
  • Comment:SH3 domains typically bind proline-rich ligands, preferentially to PxxP motifs.
  • Citation:PMID 7664083
  • Citation:PMID 7735837
  • Comment:flanking hinge and loops (RT and n-Src) confer sequence specificity for ligand residues outside the core binding motif

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1               # #  #   #                     ##            # ##        
8134421         8 QLARALYDNTAESPQELSFRRGDVLRVLQREgagGLDGWCLCSLHGQQGIVPANRVKLLPAGP 70   human
NP_001088375    3 QLAQALYDNAAESPEELSFRRGDVMLVLERDd-pSLGGWWRCSLRGQQGIAPGNRLQLIPETP 64   African clawed frog
CAG05751        6 VLAKALFDNAAESPEELGFRKGDILMVLKREh--SGPGWWLCSLHGRQGIAPANRLRLLQTAP 66   spotted green pufferfish

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