UBE2D1

UBE2D1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2C4P, 2YHO, 3OJ4, 3PTF, 4AP4, 4QPL, 5FER
Identifiers
Aliases	UBE2D1 , E2(17)KB1, SFT, UBC4/5, UBCH5, UBCH5A, ubiquitin conjugating enzyme E2 D1
External IDs	OMIM: 602961 MGI: 2384911 HomoloGene: 20714 GeneCards: UBE2D1
EC number	2.3.2.24
Gene location (Human) Chr. Chromosome 10 (human) [1] Band 10q21.1 Start 58,334,979 bp [1] End 58,370,751 bp [1]
Gene location (Mouse) Chr. Chromosome 10 (mouse) [2] Band 10|10 B5.3 Start 71,090,810 bp [2] End 71,121,092 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in biceps brachii vastus lateralis muscle right ventricle monocyte gastrocnemius muscle body of tongue thoracic diaphragm triceps brachii muscle amniotic fluid deltoid muscle Top expressed in interventricular septum triceps brachii muscle sternocleidomastoid muscle quadriceps femoris muscle temporal muscle skeletal muscle tissue ankle digastric muscle vastus lateralis muscle ganglionic eminence More reference expression data BioGPS More reference expression data
Gene ontology Molecular function nucleotide binding ubiquitin conjugating enzyme activity ATP binding protein binding ubiquitin-protein transferase activity ubiquitin protein ligase binding Cellular component cytoplasm nucleoplasm cytosol ubiquitin ligase complex protein-containing complex Biological process protein K48-linked ubiquitination BMP signaling pathway protein polyubiquitination negative regulation of transcription by RNA polymerase II anaphase-promoting complex-dependent catabolic process positive regulation of protein ubiquitination ubiquitin-dependent protein catabolic process protein ubiquitination protein deubiquitination positive regulation of protein polyubiquitination protein targeting to peroxisome regulation of mitotic cell cycle phase transition MyD88-independent toll-like receptor signaling pathway TRIF-dependent toll-like receptor signaling pathway Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7321 216080 Ensembl ENSG00000072401 ENSMUSG00000019927 UniProt P51668 P61080 RefSeq (mRNA) NM_003338 NM_001204880 NM_145420 RefSeq (protein) NP_001191809 NP_003329 NP_663395 Location (UCSC) Chr 10: 58.33 – 58.37 Mb Chr 10: 71.09 – 71.12 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ubiquitin-conjugating enzyme E2 D1 is a protein that in humans is encoded by the UBE2D1 gene. ^{[5] [6] [7]}

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. ^[7]

Interactions

UBE2D1 has been shown to interact with:

• BARD1, ^{[8] [9] [10] [11] [12] [13] [14] [15]}
• BRCA1, ^{[8] [9] [10] [11] [12] [13] [14] [15] [16] [17]} and
• UBE3A. ^{[18] [19]}

References

1. GRCh38: Ensembl release 89: ENSG00000072401 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000019927 - Ensembl, May 2017
3. "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
4. "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
5. Robinson PA, Leek JP, Ardley HC, Thompson J, Rose SA, Markham AF (March 1999). "Assignment of UBE2D1 to human chromosome bands 10q11.2→q21 by in situ hybridization". Cytogenet Cell Genet. 83 (3–4): 247–8. doi:10.1159/000015195. PMID   10072594. S2CID   3059748.
6. Jensen JP, Bates PW, Yang M, Vierstra RD, Weissman AM (January 1996). "Identification of a family of closely related human ubiquitin conjugating enzymes". J Biol Chem. 270 (51): 30408–14. doi:10.1074/jbc.270.51.30408. PMID   8530467.
7. "Entrez Gene: UBE2D1 ubiquitin-conjugating enzyme E2D 1 (UBC4/5 homolog, yeast)".
8. Mallery DL, Vandenberg CJ, Hiom K (Dec 2002). "Activation of the E3 ligase function of the BRCA1/BARD1 complex by polyubiquitin chains". EMBO J. 21 (24): 6755–62. doi:10.1093/emboj/cdf691. PMC   139111 . PMID   12485996.
9. Kentsis A, Gordon RE, Borden KL (November 2002). "Control of biochemical reactions through supramolecular RING domain self-assembly". Proc. Natl. Acad. Sci. U.S.A. 99 (24): 15404–9. Bibcode:2002PNAS...9915404K. doi: 10.1073/pnas.202608799 . PMC   137729 . PMID   12438698.
10. Chen A, Kleiman FE, Manley JL, Ouchi T, Pan ZQ (June 2002). "Autoubiquitination of the BRCA1*BARD1 RING ubiquitin ligase". J. Biol. Chem. 277 (24): 22085–92. doi: 10.1074/jbc.M201252200 . PMID   11927591.
11. Dong Y, Hakimi MA, Chen X, Kumaraswamy E, Cooch NS, Godwin AK, Shiekhattar R (November 2003). "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. doi: 10.1016/s1097-2765(03)00424-6 . PMID   14636569.
12. Sato K, Hayami R, Wu W, Nishikawa T, Nishikawa H, Okuda Y, Ogata H, Fukuda M, Ohta T (July 2004). "Nucleophosmin/B23 is a candidate substrate for the BRCA1-BARD1 ubiquitin ligase". J. Biol. Chem. 279 (30): 30919–22. doi: 10.1074/jbc.C400169200 . PMID   15184379.
13. Wu-Baer F, Lagrazon K, Yuan W, Baer R (September 2003). "The BRCA1/BARD1 heterodimer assembles polyubiquitin chains through an unconventional linkage involving lysine residue K6 of ubiquitin". J. Biol. Chem. 278 (37): 34743–6. doi: 10.1074/jbc.C300249200 . PMID   12890688.
14. Vandenberg CJ, Gergely F, Ong CY, Pace P, Mallery DL, Hiom K, Patel KJ (July 2003). "BRCA1-independent ubiquitination of FANCD2". Mol. Cell. 12 (1): 247–54. doi: 10.1016/s1097-2765(03)00281-8 . PMID   12887909.
15. Hashizume R, Fukuda M, Maeda I, Nishikawa H, Oyake D, Yabuki Y, Ogata H, Ohta T (May 2001). "The RING heterodimer BRCA1-BARD1 is a ubiquitin ligase inactivated by a breast cancer-derived mutation". J. Biol. Chem. 276 (18): 14537–40. doi: 10.1074/jbc.C000881200 . PMID   11278247.
16. Brzovic PS, Keeffe JR, Nishikawa H, Miyamoto K, Fox D, Fukuda M, Ohta T, Klevit R (May 2003). "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. Bibcode:2003PNAS..100.5646B. doi: 10.1073/pnas.0836054100 . PMC   156255 . PMID   12732733.
17. Nishikawa H, Ooka S, Sato K, Arima K, Okamoto J, Klevit RE, Fukuda M, Ohta T (February 2004). "Mass spectrometric and mutational analyses reveal Lys-6-linked polyubiquitin chains catalyzed by BRCA1-BARD1 ubiquitin ligase". J. Biol. Chem. 279 (6): 3916–24. doi: 10.1074/jbc.M308540200 . PMID   14638690.
18. Nuber U, Schwarz S, Kaiser P, Schneider R, Scheffner M (February 1996). "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. doi:10.1074/jbc.271.5.2795. PMID   8576257.
19. Nuber U, Scheffner M (March 1999). "Identification of determinants in E2 ubiquitin-conjugating enzymes required for hect E3 ubiquitin-protein ligase interaction". J. Biol. Chem. 274 (11): 7576–82. doi: 10.1074/jbc.274.11.7576 . PMID   10066826.

Further reading

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