1UJY,1ZSG,2DF6,2AK5


Conserved Protein Domain Family
SH3_PIX
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cd11877: SH3_PIX 
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Src Homology 3 domain of Pak Interactive eXchange factors
PIX proteins are Rho guanine nucleotide exchange factors (GEFs), which activate small GTPases by exchanging bound GDP for free GTP. They act as GEFs for both Cdc42 and Rac 1, and have been implicated in cell motility, adhesion, neurite outgrowth, and cell polarity. Vertebrates contain two proteins from the PIX subfamily, alpha-PIX and beta-PIX. Alpha-PIX, also called ARHGEF6, is localized in dendritic spines where it regulates spine morphogenesis. Mutations in the ARHGEF6 gene cause X-linked intellectual disability in humans. Beta-PIX play roles in regulating neuroendocrine exocytosis, focal adhesion maturation, cell migration, synaptic vesicle localization, and insulin secretion. PIX proteins contain an N-terminal SH3 domain followed by RhoGEF (also called Dbl-homologous or DH) and Pleckstrin Homology (PH) domains, and a C-terminal leucine-zipper domain for dimerization. The SH3 domain of PIX binds to an atypical PxxxPR motif in p21-activated kinases (PAKs) with high affinity. The binding of PAKs to PIX facilitate the localization of PAKs to focal complexes and also localizes PAKs to PIX targets Cdc43 and Rac, leading to the activation of PAKs. 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.
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Statistics
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PSSM-Id: 212810
Aligned: 18 rows
Threshold Bit Score: 99.3109
Created: 6-Jun-2011
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
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peptide ligand
Conserved site includes 13 residues -Click on image for an interactive view with Cn3D
Feature 1:peptide ligand binding site [polypeptide binding site]
Evidence:
  • Structure:1ZSG: Human beta-PIX SH3 domain binds with high affinity an atypical peptide from alpha-PAK; contacts at 4A.
  • Structure:2AK5: Rattus norvegicus beta-PIX SH3 domain binds Cbl-b peptide; contacts at 4A.
  • Structure:2DF6: Rattus norvegicus beta-PIX SH3 domain binds high affinity PAK2 peptide; contacts at 4A.
  • Comment:SH3 domains bind proline-rich ligands, preferentially to PxxP motifs.
  • Comment:flanking hinge and loops (RT and n-Src) confer sequence specificity for ligand residues outside the core binding motif
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Sequence Alignment
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Format: Row Display: Color Bits: Type Selection: 
Feature 1             # #  #  ##              # ###          # # ##   
1UJY_A        12 IVKARFNFKQTneDELSVCKGDIIYVTRVEeGGWWEGTLNgRTGWFPSNYVRE 64  human
1ZSG_A        10 VVRAKFNFQQTneDELSFSKGDVIHVTRVEeGGWWEGTLNgRTGWFPSNYVRE 62  human
XP_002128792   8 KVKAKYAYQRQneDELTFGKGSIIQLTSKTeGGWWEGKYNgKIGWFPSNYVKE 60  Ciona intestinalis
XP_784106     18 QYRARHNFEGSkdDELNFQKGDIITVTLQVpGGWWEGMLSgRSGWFPSNFVRE 70  purple urchin
XP_002434014   9 LVRAIHNFKGKnnDELCFKKGDILTVTQALeGGWWEGTLDgNTGWFPSNYVKE 61  black-legged tick
AAW24510       7 LVCALYDYNRRhtDELSFKKGDVLQVSKQLeGGWWEGSLDgFVGWFPSNYVTY 59  Schistosoma japonicum
EFW46429      45 KVKVAHSYEAEteDELTLAEGDIINVTQEVeGGWWEGDLNgRVGWFPSNFVEP 97  Capsaspora owczarzaki ATCC 30864
CBX53330      10 SARAKFQFEGSnnDELSFDKDDIITITQQQeGGWWEGTHEgVTGWFPCAYVTL 62  nematode
EFW43506      71 TALALYSFVATktDELSFDEGDIIVLTKVIdGGWWEGTVKnSTGWFPSNYCEI 123 Capsaspora owczarzaki ATCC 30864
EFX86493      10 QVQAVYSFKGKnnDELNFKKGDIITITQKEeGGWWEGTFEgKTGWFPSNYVKD 62  common water flea

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