1H3H,1UTI,2W10


Conserved Protein Domain Family
SH3_GRAP2_C

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cd11950: SH3_GRAP2_C 
Click on image for an interactive view with Cn3D
C-terminal Src homology 3 domain of GRB2-related adaptor protein 2
GRAP2 is also called GADS (GRB2-related adapter downstream of Shc), GrpL, GRB2L, Mona, or GRID (Grb2-related protein with insert domain). It is expressed specifically in the hematopoietic system. It plays an important role in T cell receptor (TCR) signaling by promoting the formation of the SLP-76:LAT complex, which couples the TCR to the Ras pathway. It also has roles in antigen-receptor and tyrosine kinase mediated signaling. GRAP2 is unique from other GRB2-like adaptor proteins in that it can be regulated by caspase cleavage. It contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain. The C-terminal SH3 domain of GRAP2 binds to different motifs found in substrate peptides including the typical PxxP motif in hematopoietic progenitor kinase 1 (HPK1), the RxxK motif in SLP-76 and HPK1, and the RxxxxK motif in phosphatase-like protein HD-PTP. SH3 domains are protein interaction domains that typically 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: 212883
Aligned: 6 rows
Threshold Bit Score: 100.67
Created: 31-May-2011
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
peptide ligand
Conserved site includes 15 residues -Click on image for an interactive view with Cn3D
Feature 1:peptide ligand binding site [polypeptide binding site]
Evidence:
  • Comment:SH3 domains typically bind proline-rich ligands, preferentially to PxxP motifs.
  • Comment:RxxK- and RxxxxK-motif peptides also bind to this site.
  • Structure:1H3H; Human GRAP2/GADS C-terminal SH3 domain binds RxxK-motif SLP-76 peptide (apsidrstkpa); contacts at 4A.
  • Structure:1UTI; Mus musculus GADS C-terminal SH3 domain binds HPK peptide with PxxP and RxxK motifs (gqpplvpprkekmrgk); contacts at 4A.
  • Structure:2W10; Mus musculus GADS C-terminal SH3 domain binds HP-PTP peptide with PxxP and RxxxxK motifs (ppprptapkp); contacts at 4A.
  • 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             # ## ## ##               # ## #        # # ##   
1H3H_A         5 WARALYDFEALEeDELGFRSGEVVEVLDSSNPSWWTGRLHnKLGLFPANYVAP 57  house mouse
1UTI_A         3 WARALYDFEALEeDELGFRSGEVVEVLDSSNPSWWTGRLHnKLGLFPANYVAP 55  house mouse
2W10_A         7 WARALYDFEALEeDELGFRSGEVVEVLDSSNPSWWTGRLHnKLGLFPANYVAP 59  house mouse
NP_001017756 231 QVRAIYDFTAEEdDELGFNSGDIIEVLDRSDASWWKGRLRgRSGLFPANYTEQ 283 zebrafish
XP_002933793 246 MVKALYDFQAMEpDELGFIYSDVIEVLDCSDASWWMGRLGeRVGLFPSNYVAN 298 western clawed frog
XP_003442553 167 QVMAVCDFPAIQdDELGFNAGDVIEVLDMSHPFWWKGKLKgIIGLFPVNATRP 219 Nile tilapia

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