| Structural highlights
2k6d is a 2 chain structure with sequence from Homo sapiens. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance.
| Gene: | SH3KBP1, CIN85 (Homo sapiens), RPS27A, UBA80, UBCEP1, UBA52, UBCEP2, UBB, UBC (Homo sapiens) |
Resources: | FirstGlance, OCA, RCSB, PDBsum |
Evolutionary Conservation
Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.
Publication Abstract from PubMed
CIN85 is an adaptor protein linking the ubiquitin ligase Cbl and clathrin-binding proteins in clathrin-mediated receptor endocytosis. The SH3 domains of CIN85 bind to a proline-rich region of Cbl. Here we show that all three SH3 domains of CIN85 bind to ubiquitin. We also present a data-based structural model of the CIN85 SH3-C domain in complex with ubiquitin. In this complex, ubiquitin binds to the canonical interaction surface of the SH3 domain for proline-rich ligands and mimics the PPII helix, and we provide evidence that ubiquitin competes with these ligands for binding. We demonstrate that disruption of ubiquitin binding results in constitutive ubiquitination of CIN85 and an increased level of ubiquitination of EGFR in the absence of EGF stimulation. These results suggest that competition between Cbl and ubiquitin binding to CIN85 regulates Cbl function and EGFR endocytosis.
Interactions between the Three CIN85 SH3 Domains and Ubiquitin: Implications for CIN85 Ubiquitination.,Bezsonova I, Bruce MC, Wiesner S, Lin H, Rotin D, Forman-Kay JD Biochemistry. 2008 Aug 5. PMID:18680311[1]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Bezsonova I, Bruce MC, Wiesner S, Lin H, Rotin D, Forman-Kay JD. Interactions between the Three CIN85 SH3 Domains and Ubiquitin: Implications for CIN85 Ubiquitination. Biochemistry. 2008 Aug 5. PMID:18680311 doi:10.1021/bi800439t
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