2K6D


Conserved Protein Domain Family
SH3_CIN85_3

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cd12057: SH3_CIN85_3 
Click on image for an interactive view with Cn3D
Third Src Homology 3 domain (SH3C) of Cbl-interacting protein of 85 kDa
CIN85, also called SH3 domain-containing kinase-binding protein 1 (SH3KBP1) or CD2-binding protein 3 (CD2BP3) or Ruk, is an adaptor protein that is involved in the downregulation of receptor tyrosine kinases by facilitating endocytosis through interaction with endophilin-associated ubiquitin ligase Cbl proteins. It is also important in many other cellular processes including vesicle-mediated transport, cytoskeletal remodelling, apoptosis, cell adhesion and migration, and viral infection, among others. CIN85 exists as multiple variants from alternative splicing; the main variant contains three SH3 domains, a proline-rich region, and a C-terminal coiled-coil domain. All of these domains enable CIN85 to bind various protein partners and assemble complexes that have been implicated in many different functions. This alignment model represents the third SH3 domain (SH3C) of CIN85. SH3C has been shown to bind ubiquitin. 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: 212990
Aligned: 4 rows
Threshold Bit Score: 119.233
Created: 3-Jun-2011
Updated: 2-Oct-2020
Structure
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Program:
Drawing:
Aligned Rows:
 
ubiquitinputative
Conserved site includes 22 residues -Click on image for an interactive view with Cn3D
Feature 1:ubiquitin interaction site [polypeptide binding site]
Evidence:
  • Comment:Ubiquitin competes with ligands for binding despite the lack of proline residues in ubiquitin at its SH3-binding interface.
  • Structure:2K6D: Human CIN85 SH3C domain in complex with ubiquitin; contacts at 4A.
  • Comment:Ubiquitin binding is important in regulating EGF-dependent ubiquitination of CIN85.

Sequence Alignment
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Format: Row Display: Color Bits: Type Selection:
Feature 1            ######## ##   ##            ####         ## # ## #  
2K6D_A         5 YCKVIFPYEAQNDDELTIKEGDIVTLINKDCIDVGWWEGELNGRRGVFPDNFVKLL 60  human
NP_001025976 346 YCKVIFPYEAQNDDELTIREGDVVTLISKDCIDVGWWEGELNGRRGVFPDNFVKLL 401 chicken
AAI66366     169 YCKVLFPYEAMNEDELTIRDGDIVTVLSKECVDAGWWEGELNGKKGVFPDNFVKLL 224 western clawed frog
CBN82173     288 QCKVLFPYEAQNEDELSVKEGDIVNIITKDCADAGWWMGEIGGRQGVFPDNFVKLL 343 European seabass

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