1ZSG,2DF6,2AK5,2ESW


Conserved Protein Domain Family
SH3_betaPIX

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cd12061: SH3_betaPIX 
Click on image for an interactive view with Cn3D
Src Homology 3 domain of beta-Pak Interactive eXchange factor
Beta-PIX, also called Rho guanine nucleotide exchange factor 7 (ARHGEF7) or Cool (Cloned out of Library)-1, activates small GTPases by exchanging bound GDP for free GTP. It acts as a GEF for both Cdc42 and Rac 1, and plays important 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.
Statistics
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PSSM-Id: 212994
Aligned: 5 rows
Threshold Bit Score: 105.923
Created: 3-Jun-2011
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
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.
    View structure with Cn3D
  • Structure:2AK5: Rattus norvegicus beta-PIX SH3 domain binds Cbl-b peptide; contacts at 4A.
    View structure with Cn3D
  • Structure:2DF6: Rattus norvegicus beta-PIX SH3 domain binds high affinity PAK2 peptide; contacts at 4A.
    View structure with Cn3D
  • 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

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1             # #  #  ##              # ###          # # ##    
1ZSG_A        10 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTLNGRTGWFPSNYVREV 63  human
NP_001085995 166 VVRAKFNFQQTNEDELSFNKGDIIHVTRQEDGGWWEGTHSGKTGWFPSNYVREV 219 African clawed frog
2DF6_A         6 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVREI 59  Norway rat
2AK5_B         8 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVREI 61  Norway rat
2ESW_A         8 VVRAKFNFQQTNEDELSFSKGDVIHVTRVEEGGWWEGTHNGRTGWFPSNYVREI 61  house mouse

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