UBE2D1

The modification of proteins with ubiquitin is an important cellular mechanism for targeting abnormal or short-lived proteins for degradation. Ubiquitination involves at least three classes of enzymes: ubiquitin-activating enzymes, or E1s, ubiquitin-conjugating enzymes, or E2s, and ubiquitin-protein ligases, or E3s. This gene encodes a member of the E2 ubiquitin-conjugating enzyme family. This enzyme is closely related to a stimulator of iron transport (SFT), and is up-regulated in hereditary hemochromatosis. It also functions in the ubiquitination of the tumor-suppressor protein p53 and the hypoxia-inducible transcription factor HIF1alpha by interacting with the E1 ubiquitin-activating enzyme and the E3 ubiquitin-protein ligases.

UBE2D1 has been shown to interact with:

• BARD1,{{cite journal | vauthors = Mallery DL, Vandenberg CJ, Hiom K | title = Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains | journal = EMBO J. | volume = 21 | issue = 24 | pages = 6755–62 | date = Dec 2002 | pmid = 12485996 | pmc = 139111 | doi = 10.1093/emboj/cdf691}}{{cite journal | vauthors = Kentsis A, Gordon RE, Borden KL | title = Control of biochemical reactions through supramolecular RING domain self-assembly | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 24 | pages = 15404–9 | date = November 2002 | pmid = 12438698 | pmc = 137729 | doi = 10.1073/pnas.202608799 | bibcode = 2002PNAS...9915404K | doi-access = free }}{{cite journal | vauthors = Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ | title = Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase | journal = J. Biol. Chem. | volume = 277 | issue = 24 | pages = 22085–92 | date = June 2002 | pmid = 11927591 | doi = 10.1074/jbc.M201252200 | doi-access = free }}{{cite journal | vauthors = Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R | title = Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair | journal = Mol. Cell | volume = 12 | issue = 5 | pages = 1087–99 | date = November 2003 | pmid = 14636569 | doi = 10.1016/s1097-2765(03)00424-6| doi-access = free }}{{cite journal | vauthors = Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, Ogata H, Fukuda M, Ohta T | title = Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase | journal = J. Biol. Chem. | volume = 279 | issue = 30 | pages = 30919–22 | date = July 2004 | pmid = 15184379 | doi = 10.1074/jbc.C400169200 | doi-access = free }}{{cite journal | vauthors = Wu-Baer F, Lagrazon K, Yuan W, Baer R | title = The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin | journal = J. Biol. Chem. | volume = 278 | issue = 37 | pages = 34743–6 | date = September 2003 | pmid = 12890688 | doi = 10.1074/jbc.C300249200 | doi-access = free }}{{cite journal | vauthors = Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K, Patel KJ | title = BRCA1-independent ubiquitination of FANCD2 | journal = Mol. Cell | volume = 12 | issue = 1 | pages = 247–54 | date = July 2003 | pmid = 12887909 | doi = 10.1016/s1097-2765(03)00281-8| doi-access = free }}{{cite journal | vauthors = Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T | title = The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation | journal = J. Biol. Chem. | volume = 276 | issue = 18 | pages = 14537–40 | date = May 2001 | pmid = 11278247 | doi = 10.1074/jbc.C000881200 | doi-access = free }}
• BRCA1,{{cite journal | vauthors = Brzovic PS, Keeffe JR, Nishikawa H, Miyamoto K, Fox D, Fukuda M, Ohta T, Klevit R | title = Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 100 | issue = 10 | pages = 5646–51 | date = May 2003 | pmid = 12732733 | pmc = 156255 | doi = 10.1073/pnas.0836054100 | bibcode = 2003PNAS..100.5646B | doi-access = free }}{{cite journal | vauthors = Nishikawa H, Ooka S, Sato K, Arima K, Okamoto J, Klevit RE, Fukuda M, Ohta T | title = Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase | journal = J. Biol. Chem. | volume = 279 | issue = 6 | pages = 3916–24 | date = February 2004 | pmid = 14638690 | doi = 10.1074/jbc.M308540200 | doi-access = free }} and
• UBE3A.{{cite journal | vauthors = Nuber U, Schwarz S, Kaiser P, Schneider R, Scheffner M | title = Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5 | journal = J. Biol. Chem. | volume = 271 | issue = 5 | pages = 2795–800 | date = February 1996 | pmid = 8576257 | doi = 10.1074/jbc.271.5.2795| doi-access = free}}{{cite journal | vauthors = Nuber U, Scheffner M | title = Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction | journal = J. Biol. Chem. | volume = 274 | issue = 11 | pages = 7576–82 | date = March 1999 | pmid = 10066826 | doi = 10.1074/jbc.274.11.7576| doi-access = free }}

{{Reflist}}

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• {{cite journal | vauthors = Scheffner M, Huibregtse JM, Howley PM | title = Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53 | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 91 | issue = 19 | pages = 8797–801 | year = 1994 | pmid = 8090726 | pmc = 44693 | doi = 10.1073/pnas.91.19.8797 | bibcode = 1994PNAS...91.8797S | doi-access = free }}
• {{cite journal | vauthors = Bonaldo MF, Lennon G, Soares MB | title = Normalization and subtraction: two approaches to facilitate gene discovery | journal = Genome Res. | volume = 6 | issue = 9 | pages = 791–806 | year = 1997 | pmid = 8889548 | doi = 10.1101/gr.6.9.791 | doi-access = free }}
• {{cite journal | vauthors = Hatakeyama S, Jensen JP, Weissman AM | title = Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases | journal = J. Biol. Chem. | volume = 272 | issue = 24 | pages = 15085–92 | year = 1997 | pmid = 9182527 | doi = 10.1074/jbc.272.24.15085 | doi-access = free }}
• {{cite journal | vauthors = Gutierrez JA, Yu J, Rivera S, Wessling-Resnick M | title = Functional Expression Cloning and Characterization of SFT, a Stimulator of Fe Transport | journal = J. Cell Biol. | volume = 139 | issue = 4 | pages = 895–905 | year = 1997 | pmid = 9362508 | pmc = 2139974 | doi = 10.1083/jcb.139.4.895 }}
• {{cite journal | vauthors = Gutierrez JA, Yu J, Wessling-Resnick M | title = Characterization and chromosomal mapping of the human gene for SFT, a stimulator of Fe transport | journal = Biochem. Biophys. Res. Commun. | volume = 253 | issue = 3 | pages = 739–42 | year = 1999 | pmid = 9918797 | doi = 10.1006/bbrc.1998.9836 }}
• {{cite journal | vauthors = Nuber U, Scheffner M | title = Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction | journal = J. Biol. Chem. | volume = 274 | issue = 11 | pages = 7576–82 | year = 1999 | pmid = 10066826 | doi = 10.1074/jbc.274.11.7576 | doi-access = free }}
• {{cite journal | vauthors = Kamura T, Sato S, Iwai K, Czyzyk-Krzeska M, Conaway RC, Conaway JW | title = Activation of HIF1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 97 | issue = 19 | pages = 10430–5 | year = 2000 | pmid = 10973499 | pmc = 27041 | doi = 10.1073/pnas.190332597 | bibcode = 2000PNAS...9710430K | doi-access = free }}
• {{cite journal | vauthors = Pringa E, Martinez-Noel G, Muller U, Harbers K | title = Interaction of the ring finger-related U-box motif of a nuclear dot protein with ubiquitin-conjugating enzymes | journal = J. Biol. Chem. | volume = 276 | issue = 22 | pages = 19617–23 | year = 2001 | pmid = 11274149 | doi = 10.1074/jbc.M100192200 | doi-access = free }}
• {{cite journal | vauthors = Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T | title = The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation | journal = J. Biol. Chem. | volume = 276 | issue = 18 | pages = 14537–40 | year = 2001 | pmid = 11278247 | doi = 10.1074/jbc.C000881200 | doi-access = free }}
• {{cite journal | vauthors = Matsuzawa SI, Reed JC | title = Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses | journal = Mol. Cell | volume = 7 | issue = 5 | pages = 915–26 | year = 2001 | pmid = 11389839 | doi = 10.1016/S1097-2765(01)00242-8 | doi-access = free }}
• {{cite journal | vauthors = Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C | title = CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation | journal = J. Biol. Chem. | volume = 276 | issue = 46 | pages = 42938–44 | year = 2001 | pmid = 11557750 | doi = 10.1074/jbc.M101968200 | doi-access = free }}
• {{cite journal | vauthors = Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ | title = Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase | journal = J. Biol. Chem. | volume = 277 | issue = 24 | pages = 22085–92 | year = 2002 | pmid = 11927591 | doi = 10.1074/jbc.M201252200 | doi-access = free }}
• {{cite journal | vauthors = Badciong JC, Haas AL | title = MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination | journal = J. Biol. Chem. | volume = 277 | issue = 51 | pages = 49668–75 | year = 2003 | pmid = 12393902 | doi = 10.1074/jbc.M208593200 | doi-access = free }}
• {{cite journal | vauthors = Kentsis A, Gordon RE, Borden KL | title = Control of biochemical reactions through supramolecular RING domain self-assembly | journal = Proc. Natl. Acad. Sci. U.S.A. | volume = 99 | issue = 24 | pages = 15404–9 | year = 2003 | pmid = 12438698 | pmc = 137729 | doi = 10.1073/pnas.202608799 | bibcode = 2002PNAS...9915404K | doi-access = free }}
• {{cite journal | vauthors = Gehrke SG, Riedel HD, Herrmann T, Hadaschik B, Bents K, Veltkamp C, Stremmel W | title = UbcH5A, a member of human E2 ubiquitin-conjugating enzymes, is closely related to SFT, a stimulator of iron transport, and is up-regulated in hereditary hemochromatosis | journal = Blood | volume = 101 | issue = 8 | pages = 3288–93 | year = 2003 | pmid = 12480712 | doi = 10.1182/blood-2002-07-2192 | doi-access = free }}
• {{cite journal | vauthors = Mallery DL, Vandenberg CJ, Hiom K | title = Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains | journal = EMBO J. | volume = 21 | issue = 24 | pages = 6755–62 | year = 2004 | pmid = 12485996 | pmc = 139111 | doi = 10.1093/emboj/cdf691 }}
• {{cite journal | vauthors = Takeyama K, Aguiar RC, Gu L, He C, Freeman GJ, Kutok JL, Aster JC, Shipp MA | title = The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity | journal = J. Biol. Chem. | volume = 278 | issue = 24 | pages = 21930–7 | year = 2003 | pmid = 12670957 | doi = 10.1074/jbc.M301157200 | doi-access = free }}

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{{Ubiquitin-conjugating enzymes}}