Ubiquitin-conjugating enzyme E2 T

Definition:

Accepts ubiquitin from the E1 complex and catalyzes its covalent attachment to other proteins. Catalyzes monoubiquitination. Involved in mitomycin-C (MMC)-induced DNA repair. Acts as a specific E2 ubiquitin-conjugating enzyme for the Fanconi anemia complex by associating with E3 ubiquitin-protein ligase FANCL and catalyzing monoubiquitination of FANCD2, a key step in the DNA damage pathway. Also mediates monoubiquitination of FANCL and FANCI. May contribute to ubiquitination and degradation of BRCA1. In vitro able to promote polyubiquitination using all 7 ubiquitin Lys residues, but may prefer 'Lys-11'-, 'Lys-27'-, 'Lys-48'- and 'Lys-63'-linked polyubiquitination.

References:

[1]. Simonne Longerich, et al. FANCI binds branched DNA and is monoubiquitinated by UBE2T-FANCL. J Biol Chem. 2009 Aug 28;284(35):23182-6. [Content Brief]

[2]. Yuichi J Machida, et al. UBE2T is the E2 in the Fanconi anemia pathway and undergoes negative autoregulation. Mol Cell. 2006 Aug;23(4):589-96. [Content Brief]

[3]. Yael David, et al. The E2 ubiquitin-conjugating enzymes direct polyubiquitination to preferred lysines. J Biol Chem. 2010 Mar 19;285(12):8595-604. [Content Brief]

[4]. Arno F Alpi, et al. Mechanistic insight into site-restricted monoubiquitination of FANCD2 by Ube2t, FANCL, and FANCI. Mol Cell. 2008 Dec 26;32(6):767-77. [Content Brief]

[5]. Francesca E Morreale, et al. Allosteric Targeting of the Fanconi Anemia Ubiquitin-Conjugating Enzyme Ube2T by Fragment Screening. J Med Chem. 2017 May 11;60(9):4093-4098. [Content Brief]

[6]. Tomomi Ueki, et al. Ubiquitination and downregulation of BRCA1 by ubiquitin-conjugating enzyme E2T overexpression in human breast cancer cells. Cancer Res. 2009 Nov 15;69(22):8752-60. [Content Brief]

[7]. Arno Alpi, et al. UBE2T, the Fanconi anemia core complex, and FANCD2 are recruited independently to chromatin: a basis for the regulation of FANCD2 monoubiquitination. Mol Cell Biol. 2007 Dec;27(24):8421-30. [Content Brief]

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