Conserved Protein Domain Family
SH3_SH3RF_2
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cd11787: SH3_SH3RF_2 
Second Src Homology 3 domain of SH3 domain containing ring finger proteins
This model represents the second SH3 domain of SH3RF1 (or POSH), SH3RF2 (or POSHER), SH3RF3 (POSH2), and similar domains. Members of this family are scaffold proteins that function as E3 ubiquitin-protein ligases. They all contain an N-terminal RING finger domain and multiple SH3 domains; SH3RF1 and SH3RF3 have four SH3 domains while SH3RF2 has three. SH3RF1 plays a role in calcium homeostasis through the control of the ubiquitin domain protein Herp. It may also have a role in regulating death receptor mediated and JNK mediated apoptosis. SH3RF3 interacts with p21-activated kinase 2 (PAK2) and GTP-loaded Rac1. It may play a role in regulating JNK mediated apoptosis in certain conditions. SH3RF2 acts as an anti-apoptotic regulator of the JNK pathway by binding to and promoting the degradation of SH3RF1. 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.
Links
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Statistics
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PSSM-Id: 212721
Aligned: 12 rows
Threshold Bit Score: 86.2338
Created: 31-May-2011
Updated: 2-Oct-2020
Structure
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Aligned Rows:
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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
Scroll to Sequence Alignment Display
Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1              # #  #         #                 ##            # ##
Q7Z6J0        200 QCKALYDFEVKDkea--dkdCLPFAKDDVLTVIRRvDENWAEGMLAdKIGIFPISY 253  human
ABC25188      215 QGKALYDFEMKDkdq--dkdCLTFTKDEILTVLRRvDENWAEGMLGdKIGIFPLLY 268  human
Q8TEC5        191 LCRALYNFDLRGkdksenqdCLTFLKDDIITVISRvDENWAEGKLGdKVGIFPILF 246  human
XP_002416605  211 QCKALYDFRMADsde---kdCLAFLKGDVITVIRRvDENWAEGKLGeRIGIFPISF 263  black-legged tick
XP_002123694  218 YCFALYDFESSDaek--drdCLTFSKNEKILVIRRvDENWVEGMLRdKIGIFPLSF 271  Ciona intestinalis
XP_002611581  196 TGKAKYKFDVTDnee--dkdCLTFEKDEIVTVIRRvDENWAEGMIGdKIGIFPISF 249  Florida lancelet
XP_002157228  174 FAKALYSYESKDes-----eIISFREGDIIGVIKKvDDKWLEGILAgQYGIFPLNF 224  green hydra
XP_793907      70 QCKALYDFDVNEqee---kdCLTFNKDEVLMVIRRvDDNWIEGQRGdKIGIFPISF 122  purple urchin
XP_001636467  161 VAKALYDFDGGEeq-----dILPFKQGDVISVIRKvDENWCEGKLNnKCGIFPINF 211  starlet sea anemone
EFX81681      205 QCVALYDFKMSAede---kdCLTFNKGAVVTVIRRvDENWAEGRLTeRIGIFPISF 257  common water flea
AAF37265      199 QCIAMYDFKMGPnde---egCLEFKKSTVIQVMRRvDHNWAEGRIGqTIGIFPIAF 251  fruit fly
CAF99076      210 LCKALFHFNPAEinledshsFLSFHKGDVLTVIRRlDEHWIEARLGdKVGVCPLQF 265  spotted green pufferfish

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