UBE2D1 explained
Ubiquitin-conjugating enzyme E2 D1 is a protein that in humans is encoded by the UBE2D1 gene.[1] [2] [3]
Function
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.[3]
Interactions
UBE2D1 has been shown to interact with:
Further reading
- Scheffner M, Huibregtse JM, Howley PM . Identification of a human ubiquitin-conjugating enzyme that mediates the E6-AP-dependent ubiquitination of p53 . Proc. Natl. Acad. Sci. U.S.A. . 91 . 19 . 8797–801 . 1994 . 8090726 . 44693 . 10.1073/pnas.91.19.8797 . 1994PNAS...91.8797S . free .
- Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Res. . 6 . 9 . 791–806 . 1997 . 8889548 . 10.1101/gr.6.9.791 . free .
- Hatakeyama S, Jensen JP, Weissman AM . Subcellular localization and ubiquitin-conjugating enzyme (E2) interactions of mammalian HECT family ubiquitin protein ligases . J. Biol. Chem. . 272 . 24 . 15085–92 . 1997 . 9182527 . 10.1074/jbc.272.24.15085 . free .
- Gutierrez JA, Yu J, Rivera S, Wessling-Resnick M . Functional Expression Cloning and Characterization of SFT, a Stimulator of Fe Transport . J. Cell Biol. . 139 . 4 . 895–905 . 1997 . 9362508 . 2139974 . 10.1083/jcb.139.4.895 .
- Gutierrez JA, Yu J, Wessling-Resnick M . Characterization and chromosomal mapping of the human gene for SFT, a stimulator of Fe transport . Biochem. Biophys. Res. Commun. . 253 . 3 . 739–42 . 1999 . 9918797 . 10.1006/bbrc.1998.9836 .
- Nuber U, Scheffner M . Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction . J. Biol. Chem. . 274 . 11 . 7576–82 . 1999 . 10066826 . 10.1074/jbc.274.11.7576 . free .
- Kamura T, Sato S, Iwai K, Czyzyk-Krzeska M, Conaway RC, Conaway JW . Activation of HIF1α ubiquitination by a reconstituted von Hippel-Lindau (VHL) tumor suppressor complex . Proc. Natl. Acad. Sci. U.S.A. . 97 . 19 . 10430–5 . 2000 . 10973499 . 27041 . 10.1073/pnas.190332597 . 2000PNAS...9710430K . free .
- Pringa E, Martinez-Noel G, Muller U, Harbers K . Interaction of the ring finger-related U-box motif of a nuclear dot protein with ubiquitin-conjugating enzymes . J. Biol. Chem. . 276 . 22 . 19617–23 . 2001 . 11274149 . 10.1074/jbc.M100192200 . free .
- Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T . The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation . J. Biol. Chem. . 276 . 18 . 14537–40 . 2001 . 11278247 . 10.1074/jbc.C000881200 . free .
- Matsuzawa SI, Reed JC . Siah-1, SIP, and Ebi collaborate in a novel pathway for beta-catenin degradation linked to p53 responses . Mol. Cell . 7 . 5 . 915–26 . 2001 . 11389839 . 10.1016/S1097-2765(01)00242-8 . free .
- Jiang J, Ballinger CA, Wu Y, Dai Q, Cyr DM, Höhfeld J, Patterson C . CHIP is a U-box-dependent E3 ubiquitin ligase: identification of Hsc70 as a target for ubiquitylation . J. Biol. Chem. . 276 . 46 . 42938–44 . 2001 . 11557750 . 10.1074/jbc.M101968200 . free .
- Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ . Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase . J. Biol. Chem. . 277 . 24 . 22085–92 . 2002 . 11927591 . 10.1074/jbc.M201252200 . free .
- Badciong JC, Haas AL . MdmX is a RING finger ubiquitin ligase capable of synergistically enhancing Mdm2 ubiquitination . J. Biol. Chem. . 277 . 51 . 49668–75 . 2003 . 12393902 . 10.1074/jbc.M208593200 . free .
- Kentsis A, Gordon RE, Borden KL . Control of biochemical reactions through supramolecular RING domain self-assembly . Proc. Natl. Acad. Sci. U.S.A. . 99 . 24 . 15404–9 . 2003 . 12438698 . 137729 . 10.1073/pnas.202608799 . 2002PNAS...9915404K . free .
- Gehrke SG, Riedel HD, Herrmann T, Hadaschik B, Bents K, Veltkamp C, Stremmel W . 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 . Blood . 101 . 8 . 3288–93 . 2003 . 12480712 . 10.1182/blood-2002-07-2192 . free .
- Mallery DL, Vandenberg CJ, Hiom K . Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains . EMBO J. . 21 . 24 . 6755–62 . 2004 . 12485996 . 139111 . 10.1093/emboj/cdf691 .
- Takeyama K, Aguiar RC, Gu L, He C, Freeman GJ, Kutok JL, Aster JC, Shipp MA . The BAL-binding protein BBAP and related Deltex family members exhibit ubiquitin-protein isopeptide ligase activity . J. Biol. Chem. . 278 . 24 . 21930–7 . 2003 . 12670957 . 10.1074/jbc.M301157200 . free .
Notes and References
- Robinson PA, Leek JP, Ardley HC, Thompson J, Rose SA, Markham AF . Assignment of UBE2D1 to human chromosome bands 10q11.2→q21 by in situ hybridization . Cytogenet Cell Genet . 83 . 3–4 . 247–8 . March 1999 . 10072594 . 10.1159/000015195 . 3059748 .
- Jensen JP, Bates PW, Yang M, Vierstra RD, Weissman AM . Identification of a family of closely related human ubiquitin conjugating enzymes . J Biol Chem . 270 . 51 . 30408–14 . January 1996 . 8530467 . 10.1074/jbc.270.51.30408 . free .
- Web site: Entrez Gene: UBE2D1 ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast).
- Mallery DL, Vandenberg CJ, Hiom K . Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains . EMBO J. . 21 . 24 . 6755–62 . Dec 2002 . 12485996 . 139111 . 10.1093/emboj/cdf691.
- Kentsis A, Gordon RE, Borden KL . Control of biochemical reactions through supramolecular RING domain self-assembly . Proc. Natl. Acad. Sci. U.S.A. . 99 . 24 . 15404–9 . November 2002 . 12438698 . 137729 . 10.1073/pnas.202608799 . 2002PNAS...9915404K . free .
- Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ . Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase . J. Biol. Chem. . 277 . 24 . 22085–92 . June 2002 . 11927591 . 10.1074/jbc.M201252200 . free .
- Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R . Regulation of BRCC, a holoenzyme complex containing BRCA1 and BRCA2, by a signalosome-like subunit and its role in DNA repair . Mol. Cell . 12 . 5 . 1087–99 . November 2003 . 14636569 . 10.1016/s1097-2765(03)00424-6. free .
- Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, Ogata H, Fukuda M, Ohta T . Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase . J. Biol. Chem. . 279 . 30 . 30919–22 . July 2004 . 15184379 . 10.1074/jbc.C400169200 . free .
- Wu-Baer F, Lagrazon K, Yuan W, Baer R . The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin . J. Biol. Chem. . 278 . 37 . 34743–6 . September 2003 . 12890688 . 10.1074/jbc.C300249200 . free .
- Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K, Patel KJ . BRCA1-independent ubiquitination of FANCD2 . Mol. Cell . 12 . 1 . 247–54 . July 2003 . 12887909 . 10.1016/s1097-2765(03)00281-8. free .
- Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T . The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation . J. Biol. Chem. . 276 . 18 . 14537–40 . May 2001 . 11278247 . 10.1074/jbc.C000881200 . free .
- Brzovic PS, Keeffe JR, Nishikawa H, Miyamoto K, Fox D, Fukuda M, Ohta T, Klevit R . Binding and recognition in the assembly of an active BRCA1/BARD1 ubiquitin-ligase complex . Proc. Natl. Acad. Sci. U.S.A. . 100 . 10 . 5646–51 . May 2003 . 12732733 . 156255 . 10.1073/pnas.0836054100 . 2003PNAS..100.5646B . free .
- Nishikawa H, Ooka S, Sato K, Arima K, Okamoto J, Klevit RE, Fukuda M, Ohta T . Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase . J. Biol. Chem. . 279 . 6 . 3916–24 . February 2004 . 14638690 . 10.1074/jbc.M308540200 . free .
- Nuber U, Schwarz S, Kaiser P, Schneider R, Scheffner M . Cloning of human ubiquitin-conjugating enzymes UbcH6 and UbcH7 (E2-F1) and characterization of their interaction with E6-AP and RSP5 . J. Biol. Chem. . 271 . 5 . 2795–800 . February 1996 . 8576257 . 10.1074/jbc.271.5.2795. free.
- Nuber U, Scheffner M . Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction . J. Biol. Chem. . 274 . 11 . 7576–82 . March 1999 . 10066826 . 10.1074/jbc.274.11.7576. free .