| Structural highlights
Function
[UB2V1_HUMAN] Has no ubiquitin ligase activity on its own. The UBE2V1-UBE2N heterodimer catalyzes the synthesis of non-canonical poly-ubiquitin chains that are linked through Lys-63. This type of poly-ubiquitination activates IKK and does not seem to involve protein degradation by the proteasome. Plays a role in the activation of NF-kappa-B mediated by IL1B, TNF, TRAF6 and TRAF2. Mediates transcriptional activation of target genes. Plays a role in the control of progress through the cell cycle and differentiation. Plays a role in the error-free DNA repair pathway and contributes to the survival of cells after DNA damage. Promotes TRIM5 capsid-specific restriction activity and the UBE2V1-UBE2N heterodimer acts in concert with TRIM5 to generate 'Lys-63'-linked polyubiquitin chains which activate the MAP3K7/TAK1 complex which in turn results in the induction and expression of NF-kappa-B and MAPK-responsive inflammatory genes.[1] [2] [3] [4] [5] [6] [7]
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
CHIP is a dimeric U box E3 ubiquitin ligase that binds Hsp90 and/or Hsp70 via its TPR-domain, facilitating ubiquitylation of chaperone bound client proteins. We have determined the crystal structure of CHIP bound to an Hsp90 C-terminal decapeptide. The structure explains how CHIP associates with either chaperone type and reveals an unusual asymmetric homodimer in which the protomers adopt radically different conformations. Additionally, we identified CHIP as a functional partner of Ubc13-Uev1a in formation of Lys63-linked polyubiquitin chains, extending CHIP's roles into ubiquitin regulation as well as targeted destruction. The structure of Ubc13-Uev1a bound to the CHIP U box domain defines the basis for selective cooperation of CHIP with specific ubiquitin-conjugating enzymes. Remarkably, the asymmetric arrangement of the TPR domains in the CHIP dimer occludes one Ubc binding site, so that CHIP operates with half-of-sites activity, providing an elegant means for coupling a dimeric chaperone to a single ubiquitylation system.
Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex.,Zhang M, Windheim M, Roe SM, Peggie M, Cohen P, Prodromou C, Pearl LH Mol Cell. 2005 Nov 23;20(4):525-38. PMID:16307917[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Rothofsky ML, Lin SL. CROC-1 encodes a protein which mediates transcriptional activation of the human FOS promoter. Gene. 1997 Aug 22;195(2):141-9. PMID:9305758
- ↑ Sancho E, Vila MR, Sanchez-Pulido L, Lozano JJ, Paciucci R, Nadal M, Fox M, Harvey C, Bercovich B, Loukili N, Ciechanover A, Lin SL, Sanz F, Estivill X, Valencia A, Thomson TM. Role of UEV-1, an inactive variant of the E2 ubiquitin-conjugating enzymes, in in vitro differentiation and cell cycle behavior of HT-29-M6 intestinal mucosecretory cells. Mol Cell Biol. 1998 Jan;18(1):576-89. PMID:9418904
- ↑ Deng L, Wang C, Spencer E, Yang L, Braun A, You J, Slaughter C, Pickart C, Chen ZJ. Activation of the IkappaB kinase complex by TRAF6 requires a dimeric ubiquitin-conjugating enzyme complex and a unique polyubiquitin chain. Cell. 2000 Oct 13;103(2):351-61. PMID:11057907
- ↑ Thomson TM, Khalid H, Lozano JJ, Sancho E, Arino J. Role of UEV-1A, a homologue of the tumor suppressor protein TSG101, in protection from DNA damage. FEBS Lett. 1998 Feb 13;423(1):49-52. PMID:9580084
- ↑ Xiao W, Lin SL, Broomfield S, Chow BL, Wei YF. The products of the yeast MMS2 and two human homologs (hMMS2 and CROC-1) define a structurally and functionally conserved Ubc-like protein family. Nucleic Acids Res. 1998 Sep 1;26(17):3908-14. PMID:9705497
- ↑ David Y, Ziv T, Admon A, Navon A. The E2 ubiquitin conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Jan 8. PMID:20061386 doi:M109.089003
- ↑ Pertel T, Hausmann S, Morger D, Zuger S, Guerra J, Lascano J, Reinhard C, Santoni FA, Uchil PD, Chatel L, Bisiaux A, Albert ML, Strambio-De-Castillia C, Mothes W, Pizzato M, Grutter MG, Luban J. TRIM5 is an innate immune sensor for the retrovirus capsid lattice. Nature. 2011 Apr 21;472(7343):361-5. doi: 10.1038/nature09976. PMID:21512573 doi:10.1038/nature09976
- ↑ Zhang M, Windheim M, Roe SM, Peggie M, Cohen P, Prodromou C, Pearl LH. Chaperoned ubiquitylation--crystal structures of the CHIP U box E3 ubiquitin ligase and a CHIP-Ubc13-Uev1a complex. Mol Cell. 2005 Nov 23;20(4):525-38. PMID:16307917 doi:10.1016/j.molcel.2005.09.023
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