UBE2A

UBE2A
Identifiers
Aliases	UBE2A , HHR6A, MRXS30, MRXSN, RAD6A, UBC2, ubiquitin conjugating enzyme E2 A
External IDs	OMIM: 312180 MGI: 102959 HomoloGene: 68308 GeneCards: UBE2A
Gene location (Human) Chr. X chromosome (human) [1] Band Xq24 Start 119,474,802 bp [1] End 119,591,083 bp [1]
Gene location (Mouse) Chr. X chromosome (mouse) [2] Band X|X A3.3 Start 36,137,553 bp [2] End 36,147,875 bp [2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in endothelial cell placenta rectum gastrocnemius muscle right ventricle optic nerve left ventricle monocyte palpebral conjunctiva smooth muscle tissue Top expressed in endocardial cushion atrium atrioventricular valve medial ganglionic eminence parotid gland dermis triceps brachii muscle epithelium of stomach abdominal wall left lung lobe More reference expression data BioGPS More reference expression data
Gene ontology Molecular function transferase activity nucleotide binding ubiquitin protein ligase activity ubiquitin-protein transferase activity protein binding ATP binding ubiquitin binding ubiquitin protein ligase binding ubiquitin conjugating enzyme activity Cellular component cytoplasm cytosol HULC complex nucleoplasm chromatin XY body Biological process histone H2A ubiquitination postreplication repair ubiquitin-dependent protein catabolic process protein polyubiquitination cellular response to DNA damage stimulus protein K11-linked ubiquitination protein K48-linked ubiquitination positive regulation of cell population proliferation response to UV DNA repair proteasome-mediated ubiquitin-dependent protein catabolic process protein autoubiquitination protein ubiquitination in utero embryonic development maternal process involved in female pregnancy chromatin organization blastocyst hatching Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 7319 22209 Ensembl ENSG00000077721 ENSMUSG00000016308 UniProt P49459 Q9Z255 RefSeq (mRNA) NM_181777 NM_001282161 NM_003336 NM_181762 NM_019668 NM_001313696 RefSeq (protein) NP_001269090 NP_003327 NP_861427 NP_001300625 NP_062642 Location (UCSC) Chr X: 119.47 – 119.59 Mb Chr X: 36.14 – 36.15 Mb PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse

Ubiquitin-conjugating enzyme E2 A is a protein that in humans is encoded by the UBE2A gene. ^{[5] [6]}

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. ^[6]

Interactions

UBE2A has been shown to interact with RAD18, ^{[7] [8]} UBR4 ^[9] and P53. ^[10]

Clinical

Mutations in this gene have been associated with X-linked intellectual disability type Nascimento, ^[11] also known as Nascimento syndrome. ^[12] This syndrome is characterized by moderate to severe intellectual disability, dysmorphic facial features, seizures, speech impairment, motor delay, micropenis, and skin abnormalities. ^[11]

References

1. GRCh38: Ensembl release 89: ENSG00000077721 - Ensembl, May 2017
2. GRCm38: Ensembl release 89: ENSMUSG00000016308 - 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. Koken MH, Smit EM, Jaspers-Dekker I, Oostra BA, Hagemeijer A, Bootsma D, Hoeijmakers JH (March 1992). "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. doi:10.1016/0888-7543(92)90433-S. hdl: 1765/3036 . PMID   1559696.
6. "Entrez Gene: UBE2A ubiquitin-conjugating enzyme E2A (RAD6 homolog)".
7. Xin H, Lin W, Sumanasekera W, Zhang Y, Wu X, Wang Z (July 2000). "The human RAD18 gene product interacts with HHR6A and HHR6B". Nucleic Acids Research. 28 (14): 2847–2854. doi:10.1093/nar/28.14.2847. PMC   102657 . PMID   10908344.
8. Tateishi S, Sakuraba Y, Masuyama S, Inoue H, Yamaizumi M (July 2000). "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. Bibcode:2000PNAS...97.7927T. doi: 10.1073/pnas.97.14.7927 . PMC   16647 . PMID   10884424.
9. 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/
10. Lyakhovich A, Shekhar MP (April 2003). "Supramolecular complex formation between Rad6 and proteins of the p53 pathway during DNA damage-induced response". Molecular and Cellular Biology. 23 (7): 2463–2475. doi:10.1128/MCB.23.7.2463-2475.2003. PMC   150718 . PMID   12640129.
11. Czeschik JC, Bauer P, Buiting K, Dufke C, Guillén-Navarro E, Johnson DS, et al. (September 2013). "X-linked intellectual disability type Nascimento is a clinically distinct, probably underdiagnosed entity". Orphanet Journal of Rare Diseases. 8: 146. doi: 10.1186/1750-1172-8-146 . PMC   4015352 . PMID   24053514.
12. "Gene linked to severe learning disabilities governs cell stress response". ScienceDaily. 27 May 2022. Retrieved 9 September 2022.

Further reading

• Koken MH, Reynolds P, Jaspers-Dekker I, Prakash L, Prakash S, Bootsma D, Hoeijmakers JH (October 1991). "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. Bibcode:1991PNAS...88.8865K. doi: 10.1073/pnas.88.20.8865 . PMC   52611 . PMID   1717990.
• Kato S, Sekine S, Oh SW, Kim NS, Umezawa Y, Abe N, et al. (December 1994). "Construction of a human full-length cDNA bank". Gene. 150 (2): 243–250. doi:10.1016/0378-1119(94)90433-2. PMID   7821789.
• Maruyama K, Sugano S (January 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene. 138 (1–2): 171–174. doi:10.1016/0378-1119(94)90802-8. PMID   8125298.
• Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (October 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene. 200 (1–2): 149–156. doi:10.1016/S0378-1119(97)00411-3. PMID   9373149.
• Tateishi S, Sakuraba Y, Masuyama S, Inoue H, Yamaizumi M (July 2000). "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. Bibcode:2000PNAS...97.7927T. doi: 10.1073/pnas.97.14.7927 . PMC   16647 . PMID   10884424.
• Xin H, Lin W, Sumanasekera W, Zhang Y, Wu X, Wang Z (July 2000). "The human RAD18 gene product interacts with HHR6A and HHR6B". Nucleic Acids Research. 28 (14): 2847–2854. doi:10.1093/nar/28.14.2847. PMC   102657 . PMID   10908344.
• Miura T, Klaus W, Ross A, Güntert P, Senn H (January 2002). "The NMR structure of the class I human ubiquitin-conjugating enzyme 2b". Journal of Biomolecular NMR. 22 (1): 89–92. doi:10.1023/A:1013807519703. PMID   11885984. S2CID   27799378.
• Shekhar MP, Lyakhovich A, Visscher DW, Heng H, Kondrat N (April 2002). "Rad6 overexpression induces multinucleation, centrosome amplification, abnormal mitosis, aneuploidy, and transformation". Cancer Research. 62 (7): 2115–2124. PMID   11929833.
• Sarcevic B, Mawson A, Baker RT, Sutherland RL (April 2002). "Regulation of the ubiquitin-conjugating enzyme hHR6A by CDK-mediated phosphorylation". The EMBO Journal. 21 (8): 2009–2018. doi:10.1093/emboj/21.8.2009. PMC   125963 . PMID   11953320.
• Suzumori N, Burns KH, Yan W, Matzuk MM (January 2003). "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. Bibcode:2003PNAS..100..550S. doi: 10.1073/pnas.0234474100 . PMC   141033 . PMID   12525704.
• Lyakhovich A, Shekhar MP (April 2003). "Supramolecular complex formation between Rad6 and proteins of the p53 pathway during DNA damage-induced response". Molecular and Cellular Biology. 23 (7): 2463–2475. doi:10.1128/MCB.23.7.2463-2475.2003. PMC   150718 . PMID   12640129.
• Kunapuli P, Somerville R, Still IH, Cowell JK (May 2003). "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. doi:10.1038/sj.onc.1206408. PMID   12776193. S2CID   21536204.
• Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, et al. (October 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–1178. Bibcode:2005Natur.437.1173R. doi:10.1038/nature04209. PMID   16189514. S2CID   4427026.
• Nascimento RM, Otto PA, de Brouwer AP, Vianna-Morgante AM (September 2006). "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. doi:10.1086/507047. PMC   1559544 . PMID   16909393.