UBE2A explained

Ubiquitin-conjugating enzyme E2 A is a protein that in humans is encoded by the UBE2A gene.^{[1] [2]}

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 required for post-replicative DNA damage repair. Multiple alternatively spliced transcript variants have been found for this gene and they encode distinct isoforms.^[2]

Interactions

UBE2A has been shown to interact with RAD18,^{[3] [4]} UBR4^[5] and P53.^[6]

Clinical

Mutations in this gene have been associated with X-linked intellectual disability type Nascimento,^[7] also known as Nascimento syndrome.^[8] This syndrome is characterized by moderate to severe intellectual disability, dysmorphic facial features, seizures, speech impairment, motor delay, micropenis, and skin abnormalities.

Further reading

• Koken MH, Reynolds P, Jaspers-Dekker I, Prakash L, Prakash S, Bootsma D, Hoeijmakers JH . Structural and functional conservation of two human homologs of the yeast DNA repair gene RAD6 . Proceedings of the National Academy of Sciences of the United States of America . 88 . 20 . 8865–8869 . October 1991 . 1717990 . 52611 . 10.1073/pnas.88.20.8865 . free . 1991PNAS...88.8865K .
• Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, Yokoyama-Kobayashi M, Aoki T . 6 . Construction of a human full-length cDNA bank . Gene . 150 . 2 . 243–250 . December 1994 . 7821789 . 10.1016/0378-1119(94)90433-2 .
• Maruyama K, Sugano S . Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides . Gene . 138 . 1–2 . 171–174 . January 1994 . 8125298 . 10.1016/0378-1119(94)90802-8 .
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S . Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library . Gene . 200 . 1–2 . 149–156 . October 1997 . 9373149 . 10.1016/S0378-1119(97)00411-3 .
• Tateishi S, Sakuraba Y, Masuyama S, Inoue H, Yamaizumi M . Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens . Proceedings of the National Academy of Sciences of the United States of America . 97 . 14 . 7927–7932 . July 2000 . 10884424 . 16647 . 10.1073/pnas.97.14.7927 . free . 2000PNAS...97.7927T .
• Xin H, Lin W, Sumanasekera W, Zhang Y, Wu X, Wang Z . The human RAD18 gene product interacts with HHR6A and HHR6B . Nucleic Acids Research . 28 . 14 . 2847–2854 . July 2000 . 10908344 . 102657 . 10.1093/nar/28.14.2847 .
• Miura T, Klaus W, Ross A, Güntert P, Senn H . The NMR structure of the class I human ubiquitin-conjugating enzyme 2b . Journal of Biomolecular NMR . 22 . 1 . 89–92 . January 2002 . 11885984 . 10.1023/A:1013807519703 . 27799378 .
• Shekhar MP, Lyakhovich A, Visscher DW, Heng H, Kondrat N . Rad6 overexpression induces multinucleation, centrosome amplification, abnormal mitosis, aneuploidy, and transformation . Cancer Research . 62 . 7 . 2115–2124 . April 2002 . 11929833 .
• Sarcevic B, Mawson A, Baker RT, Sutherland RL . Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated phosphorylation . The EMBO Journal . 21 . 8 . 2009–2018 . April 2002 . 11953320 . 125963 . 10.1093/emboj/21.8.2009 .
• Suzumori N, Burns KH, Yan W, Matzuk MM . RFPL4 interacts with oocyte proteins of the ubiquitin-proteasome degradation pathway . Proceedings of the National Academy of Sciences of the United States of America . 100 . 2 . 550–555 . January 2003 . 12525704 . 141033 . 10.1073/pnas.0234474100 . free . 2003PNAS..100..550S .
• Lyakhovich A, Shekhar MP . Supramolecular complex formation between Rad6 and proteins of the p53 pathway during DNA damage-induced response . Molecular and Cellular Biology . 23 . 7 . 2463–2475 . April 2003 . 12640129 . 150718 . 10.1128/MCB.23.7.2463-2475.2003 .
• Kunapuli P, Somerville R, Still IH, Cowell JK . ZNF198 protein, involved in rearrangement in myeloproliferative disease, forms complexes with the DNA repair-associated HHR6A/6B and RAD18 proteins . Oncogene . 22 . 22 . 3417–3423 . May 2003 . 12776193 . 10.1038/sj.onc.1206408 . 21536204 .
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . 6 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–1178 . October 2005 . 16189514 . 10.1038/nature04209 . 4427026 . 2005Natur.437.1173R .
• Nascimento RM, Otto PA, de Brouwer AP, Vianna-Morgante AM . UBE2A, which encodes a ubiquitin-conjugating enzyme, is mutated in a novel X-linked mental retardation syndrome . American Journal of Human Genetics . 79 . 3 . 549–555 . September 2006 . 16909393 . 1559544 . 10.1086/507047 .

Notes and References

1. Koken MH, Smit EM, Jaspers-Dekker I, Oostra BA, Hagemeijer A, Bootsma D, Hoeijmakers JH . Localization of two human homologs, HHR6A and HHR6B, of the yeast DNA repair gene RAD6 to chromosomes Xq24-q25 and 5q23-q31 . Genomics . 12 . 3 . 447–453 . March 1992 . 1559696 . 10.1016/0888-7543(92)90433-S . free . 1765/3036 .
2. Web site: Entrez Gene: UBE2A ubiquitin-conjugating enzyme E2A (RAD6 homolog).
3. Xin H, Lin W, Sumanasekera W, Zhang Y, Wu X, Wang Z . The human RAD18 gene product interacts with HHR6A and HHR6B . Nucleic Acids Research . 28 . 14 . 2847–2854 . July 2000 . 10908344 . 102657 . 10.1093/nar/28.14.2847 .
4. Tateishi S, Sakuraba Y, Masuyama S, Inoue H, Yamaizumi M . Dysfunction of human Rad18 results in defective postreplication repair and hypersensitivity to multiple mutagens . Proceedings of the National Academy of Sciences of the United States of America . 97 . 14 . 7927–7932 . July 2000 . 10884424 . 16647 . 10.1073/pnas.97.14.7927 . 2000PNAS...97.7927T . free .
5. Barnsby-Greer L, Mabbitt PD, Dery MA, Squair DR, Wood NT, Lamoliatte F, Lange SM, Virdee S. UBE2A and UBE2B are recruited by an atypical E3 ligase module in UBR4. Nat Struct Mol Biol| doi: 10.1038/s41594-023-01192-4/
6. Lyakhovich A, Shekhar MP . Supramolecular complex formation between Rad6 and proteins of the p53 pathway during DNA damage-induced response . Molecular and Cellular Biology . 23 . 7 . 2463–2475 . April 2003 . 12640129 . 150718 . 10.1128/MCB.23.7.2463-2475.2003 .
7. Czeschik JC, Bauer P, Buiting K, Dufke C, Guillén-Navarro E, Johnson DS, Koehler U, López-González V, Lüdecke HJ, Male A, Morrogh D, Rieß A, Tzschach A, Wieczorek D, Kuechler A . 6 . X-linked intellectual disability type Nascimento is a clinically distinct, probably underdiagnosed entity . Orphanet Journal of Rare Diseases . 8 . 146 . September 2013 . 24053514 . 4015352 . 10.1186/1750-1172-8-146 . free .
8. Web site: Gene linked to severe learning disabilities governs cell stress response. ScienceDaily. 27 May 2022. 9 September 2022.