Conserved Protein Domain Family
SH3_SKAP2

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cd12045: SH3_SKAP2 
Src Homology 3 domain of Src Kinase-Associated Phosphoprotein 2
SKAP2, also called SKAP55-Related (SKAP55R) or SKAP55 homolog (SKAP-HOM or SKAP55-HOM), is an immune cell-specific adaptor protein that plays an important role in adhesion and migration of B-cells and macrophages. Binding partners include ADAP (adhesion and degranulation-promoting adaptor protein), YopH, SHPS1, and HPK1. SKAP2 has also been identified as a substrate for lymphoid-specific tyrosine phosphatase (Lyp), which has been implicated in a wide variety of autoimmune diseases. It contains a pleckstrin homology (PH) domain, a C-terminal SH3 domain, and several tyrosine phosphorylation sites. Like SKAP1, SKAP2 is expected to bind primarily to a proline-rich region of ADAP through its SH3 domain; its degradation may be regulated by ADAP. 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: 212978
Aligned: 4 rows
Threshold Bit Score: 120.776
Created: 6-Mar-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          # #  #   #                   ##            # ## 
Q5U597    272 FYRGLWDCTGDHPDELSFKHGDTIYIISKEYNTYGWWVGEMKGTIGLVPKAYI 324 African clawed frog
Q6PG29    283 YFQGLWDCIGDQPDELSFKRGDTIYILSKEYDMFGWWVGEMKGVIGIVPKEYL 335 zebrafish
Q5RDS2    301 FYQGLWDCTGAFSDELSFKRGDVIYILSKEYNRYGWWVGEMKGAIGLVPKAYI 353 Sumatran orangutan
XP_418727 281 FYQGLWDCTGDVPDELTFKRGDVIYILSKEYNRFGWWVGEMKGTIGLVPKAYI 333 chicken

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