RAD23A explained

UV excision repair protein RAD23 homolog A is a protein that in humans is encoded by the RAD23A gene.^[1]

Function

The protein encoded by this gene is one of two human homologs of Saccharomyces cerevisiae Rad23, a protein involved in nucleotide excision repair (NER). This protein was shown to interact with, and elevate the nucleotide excision activity of 3-methyladenine-DNA glycosylase (MPG), which suggested a role in DNA damage recognition in base excision repair. This protein contains an N-terminal ubiquitin-like domain, which was reported to interact with 26S proteasome, as well as with ubiquitin protein ligase E6AP, and thus suggests that this protein may be involved in the ubiquitin mediated proteolytic pathway in cells.^[2]

Interactions

RAD23A has been shown to interact with:

• Ataxin 3,^[3]
• PSMD4,^{[4] [5]} and
• Sequestosome 1.^[6]

Further reading

• Eichbaum QG, Beatty DW, Parker MI . Identification of cardiac autoantigens in human heart cDNA libraries using acute rheumatic fever sera . J. Autoimmun. . 7 . 2 . 243–261 . 1994 . 8037842 . 10.1006/jaut.1994.1019 .
• Masutani C, Sugasawa K, Yanagisawa J, Sonoyama T, Ui M, Enomoto T, Takio K, Tanaka K, van der Spek PJ, Bootsma D . Purification and cloning of a nucleotide excision repair complex involving the xeroderma pigmentosum group C protein and a human homologue of yeast RAD23 . EMBO J. . 13 . 8 . 1831–43 . 1994 . 8168482 . 395023 . 10.1002/j.1460-2075.1994.tb06452.x.
• van der Spek PJ, Eker A, Rademakers S, Visser C, Sugasawa K, Masutani C, Hanaoka F, Bootsma D, Hoeijmakers JH . XPC and human homologs of RAD23: intracellular localization and relationship to other nucleotide excision repair complexes . Nucleic Acids Res. . 24 . 13 . 2551–2559 . 1996 . 8692695 . 145966 . 10.1093/nar/24.13.2551 .
• van der Spek PJ, Visser CE, Hanaoka F, Smit B, Hagemeijer A, Bootsma D, Hoeijmakers JH . Cloning, comparative mapping, and RNA expression of the mouse homologues of the Saccharomyces cerevisiae nucleotide excision repair gene RAD23 . Genomics . 31 . 1 . 20–27 . 1996 . 8808275 . 10.1006/geno.1996.0004 . 1765/3097 . free .
• Li L, Lu X, Peterson C, Legerski R . XPC interacts with both HHR23B and HHR23A in vivo . Mutat. Res. . 383 . 3 . 197–203 . 1997 . 9164480 . 10.1016/s0921-8777(97)00002-5 .
• Withers-Ward ES, Jowett JB, Stewart SA, Xie YM, Garfinkel A, Shibagaki Y, Chow SA, Shah N, Hanaoka F, Sawitz DG, Armstrong RW, Souza LM, Chen IS . Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a cellular protein implicated in nucleotide excision DNA repair . J. Virol. . 71 . 12 . 9732–42 . 1997 . 9371639 . 230283 . 10.1128/JVI.71.12.9732-9742.1997.
• Schauber C, Chen L, Tongaonkar P, Vega I, Lambertson D, Potts W, Madura K . Rad23 links DNA repair to the ubiquitin/proteasome pathway . Nature . 391 . 6668 . 715–718 . 1998 . 9490418 . 10.1038/35661 . 1998Natur.391..715S . 4417020 .
• Gragerov A, Kino T, Ilyina-Gragerova G, Chrousos GP, Pavlakis GN . HHR23A, the human homologue of the yeast repair protein RAD23, interacts specifically with Vpr protein and prevents cell cycle arrest but not the transcriptional effects of Vpr . Virology . 245 . 2 . 323–330 . 1998 . 9636371 . 10.1006/viro.1998.9138 . free .
• Dieckmann T, Withers-Ward ES, Jarosinski MA, Liu CF, Chen IS, Feigon J . Structure of a human DNA repair protein UBA domain that interacts with HIV-1 Vpr . Nat. Struct. Biol. . 5 . 12 . 1042–1047 . 1998 . 9846873 . 10.1038/4220 . 30478711 .
• Kumar S, Talis AL, Howley PM . Identification of HHR23A as a substrate for E6-associated protein-mediated ubiquitination . J. Biol. Chem. . 274 . 26 . 18785–18792 . 1999 . 10373495 . 10.1074/jbc.274.26.18785 . free .
• Hiyama H, Yokoi M, Masutani C, Sugasawa K, Maekawa T, Tanaka K, Hoeijmakers JH, Hanaoka F . Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome . J. Biol. Chem. . 274 . 39 . 28019–28025 . 1999 . 10488153 . 10.1074/jbc.274.39.28019 . free . 1765/9166 . free .
• Miao F, Bouziane M, Dammann R, Masutani C, Hanaoka F, Pfeifer G, O'Connor TR . 3-Methyladenine-DNA glycosylase (MPG protein) interacts with human RAD23 proteins . J. Biol. Chem. . 275 . 37 . 28433–28438 . 2000 . 10854423 . 10.1074/jbc.M001064200 . free .
• Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N . Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B . Hum. Mol. Genet. . 9 . 12 . 1795–1803 . 2000 . 10915768 . 10.1093/hmg/9.12.1795 . free .
• Withers-Ward ES, Mueller TD, Chen IS, Feigon J . Biochemical and structural analysis of the interaction between the UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr . Biochemistry . 39 . 46 . 14103–14112 . 2001 . 11087358 . 10.1021/bi0017071 .
• Zhu Q, Wani G, Wani MA, Wani AA . Human homologue of yeast Rad23 protein A interacts with p300/cyclic AMP-responsive element binding (CREB)-binding protein to down-regulate transcriptional activity of p53 . Cancer Res. . 61 . 1 . 64–70 . 2001 . 11196199 .
• Mansky LM, Preveral S, Le Rouzic E, Bernard LC, Selig L, Depienne C, Benarous R, Benichou S . Interaction of human immunodeficiency virus type 1 Vpr with the HHR23A DNA repair protein does not correlate with multiple biological functions of Vpr . Virology . 282 . 1 . 176–185 . 2001 . 11259200 . 10.1006/viro.2000.0791 . free .
• Gaynor EM, Chen IS . Analysis of apoptosis induced by HIV-1 Vpr and examination of the possible role of the hHR23A protein . Exp. Cell Res. . 267 . 2 . 243–257 . 2001 . 11426943 . 10.1006/excr.2001.5247 .
• Chen L, Shinde U, Ortolan TG, Madura K . Ubiquitin-associated (UBA) domains in Rad23 bind ubiquitin and promote inhibition of multi-ubiquitin chain assembly . EMBO Rep. . 2 . 10 . 933–938 . 2002 . 11571271 . 1084081 . 10.1093/embo-reports/kve203 .
• Elder RT, Song XQ, Chen M, Hopkins KM, Lieberman HB, Zhao Y . Involvement of rhp23, a Schizosaccharomyces pombe homolog of the human HHR23A and Saccharomyces cerevisiae RAD23 nucleotide excision repair genes, in cell cycle control and protein ubiquitination . Nucleic Acids Res. . 30 . 2 . 581–591 . 2002 . 11788722 . 99819 . 10.1093/nar/30.2.581 .

Notes and References

1. van der Spek PJ, Smit EM, Beverloo HB, Sugasawa K, Masutani C, Hanaoka F, Hoeijmakers JH, Hagemeijer A . Chromosomal localization of three repair genes: the xeroderma pigmentosum group C gene and two human homologs of yeast RAD23 . Genomics . 23 . 3 . 651–658 . March 1995 . 7851894 . 10.1006/geno.1994.1554 . 1765/3069 . free .
2. Web site: Entrez Gene: RAD23A RAD23 homolog A (S. cerevisiae).
3. Wang G, Sawai N, Kotliarova S, Kanazawa I, Nukina N . Ataxin-3, the MJD1 gene product, interacts with the two human homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B . Hum. Mol. Genet. . 9 . 12 . 1795–803 . July 2000 . 10915768 . 10.1093/hmg/9.12.1795. free .
4. Hiyama H, Yokoi M, Masutani C, Sugasawa K, Maekawa T, Tanaka K, Hoeijmakers JH, Hanaoka F . Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23 mediates interaction with S5a subunit of 26 S proteasome . J. Biol. Chem. . 274 . 39 . 28019–25 . September 1999 . 10488153 . 10.1074/jbc.274.39.28019. free . 1765/9166 . free .
5. Mueller TD, Feigon J . Structural determinants for the binding of ubiquitin-like domains to the proteasome . EMBO J. . 22 . 18 . 4634–45 . September 2003 . 12970176 . 212733 . 10.1093/emboj/cdg467 .
6. 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 . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . October 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .