Conserved Protein Domain Family
SH3_MPP2

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cd12037: SH3_MPP2 
Src Homology 3 domain of Membrane Protein, Palmitoylated 2 (or MAGUK p55 subfamily member 2)
MPP2 is a scaffolding protein that interacts with the non-receptor tyrosine kinase c-Src in epithelial cells to negatively regulate its activity and morphological function. It is one of seven vertebrate homologs of the Drosophila Stardust protein, which is required in establishing cell polarity, and it contains two L27 domains followed by the core of three domains characteristic of MAGUK (membrane-associated guanylate kinase) proteins: PDZ, SH3, and guanylate kinase (GuK). In addition, it also contains the Hook (Protein 4.1 Binding) motif in between the SH3 and GuK domains. The GuK domain in MAGUK proteins is enzymatically inactive; instead, the domain mediates protein-protein interactions and associates intramolecularly with the SH3 domain. 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: 212970
Aligned: 4 rows
Threshold Bit Score: 136.235
Created: 2-Jun-2011
Updated: 2-Oct-2020
Structure
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Aligned Rows:
 
peptide ligandGuK domain
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             # #  #          #                 ##              # ##
Q14168       253 FVKCHFDYDPARDSLIPCKEAGLRFNAGDLLQIVNQDDANWWQACHVEGGSAGLIPSQL 311 human
NP_001002223 225 FVKCHFDYDPSHDNLIPCKEAGLKFSSGDILQIFNQEDPNWWQACHLEGGSAGLIPSQL 283 zebrafish
NP_001087762 236 FVKCHFSYDPSSDSLIPCKEAGLAFRAGDLLQIVNQEDPNWWQACLVKGGTAGLIPSQL 294 African clawed frog
XP_003222690 212 FVKAHFDYDPATDNLIPCKEAGLKFVAGDLLQIVNQDDPNWWQACHVEGGSAGLIPSQL 270 green anole

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