Full text data of RAD23A
RAD23A
[Confidence: low (only semi-automatic identification from reviews)]
UV excision repair protein RAD23 homolog A; HR23A; hHR23A
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UV excision repair protein RAD23 homolog A; HR23A; hHR23A
Note: presumably soluble (membrane word is not in UniProt keywords or features)
UniProt
P54725
ID RD23A_HUMAN Reviewed; 363 AA.
AC P54725; K7ESE3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 1.
DT 22-JAN-2014, entry version 142.
DE RecName: Full=UV excision repair protein RAD23 homolog A;
DE Short=HR23A;
DE Short=hHR23A;
GN Name=RAD23A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8168482;
RA Masutani C., Sugasawa K., Yanagisawa J., Sonoyama T., Ui M.,
RA Enomoto T., Takio K., Tanaka K., van der Spek P.J., Bootsma D.,
RA Hoeijmakers J.H.J., Hanaoka F.;
RT "Purification and cloning of a nucleotide excision repair complex
RT involving the Xeroderma pigmentosum group C protein and a human
RT homologue of yeast RAD23.";
RL EMBO J. 13:1831-1843(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-131 AND MET-200.
RG NIEHS SNPs program;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal liver;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH HIV-1 VPR.
RX PubMed=9371639;
RA Withers-Ward E.S., Jowett J.B., Stewart S.A., Xie Y.M., Garfinkel A.,
RA Shibagaki Y., Chow S.A., Shah N., Hanaoka F., Sawitz D.G.,
RA Armstrong R.W., Souza L.M., Chen I.S.;
RT "Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a
RT cellular protein implicated in nucleotide excision DNA repair.";
RL J. Virol. 71:9732-9742(1997).
RN [7]
RP FUNCTION IN DNA REPAIR.
RX PubMed=9372924;
RA Sugasawa K., Ng J.M., Masutani C., Maekawa T., Uchida A.,
RA van der Spek P.J., Eker A.P., Rademakers S., Visser C.,
RA Aboussekhra A., Wood R.D., Hanaoka F., Bootsma D., Hoeijmakers J.H.;
RT "Two human homologs of Rad23 are functionally interchangeable in
RT complex formation and stimulation of XPC repair activity.";
RL Mol. Cell. Biol. 17:6924-6931(1997).
RN [8]
RP INTERACTION WITH PSMD4.
RX PubMed=10488153; DOI=10.1074/jbc.274.39.28019;
RA Hiyama H., Yokoi M., Masutani C., Sugasawa K., Maekawa T., Tanaka K.,
RA Hoeijmakers J.H., Hanaoka F.;
RT "Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23
RT mediates interaction with S5a subunit of 26 S proteasome.";
RL J. Biol. Chem. 274:28019-28025(1999).
RN [9]
RP INTERACTION WITH ATXN3.
RX PubMed=10915768; DOI=10.1093/hmg/9.12.1795;
RA Wang G., Sawai N., Kotliarova S., Kanazawa I., Nukina N.;
RT "Ataxin-3, the MJD1 gene product, interacts with the two human
RT homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B.";
RL Hum. Mol. Genet. 9:1795-1803(2000).
RN [10]
RP FUNCTION, AND POLYUBIQUITIN-BINDING.
RX PubMed=14621999; DOI=10.1021/bi035391j;
RA Wang Q., Goh A.M., Howley P.M., Walters K.J.;
RT "Ubiquitin recognition by the DNA repair protein hHR23a.";
RL Biochemistry 42:13529-13535(2003).
RN [11]
RP FUNCTION IN PROTEASOMAL DEGRADATION, AND POLYUBIQUITIN-BINDING.
RX PubMed=12643283; DOI=10.1074/jbc.M212841200;
RA Raasi S., Pickart C.M.;
RT "Rad23 ubiquitin-associated domains (UBA) inhibit 26 S proteasome-
RT catalyzed proteolysis by sequestering lysine 48-linked polyubiquitin
RT chains.";
RL J. Biol. Chem. 278:8951-8959(2003).
RN [12]
RP FUNCTION IN POLYUBIQUITIN-BINDING.
RX PubMed=15321727; DOI=10.1016/j.jmb.2004.06.057;
RA Raasi S., Orlov I., Fleming K.G., Pickart C.M.;
RT "Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains
RT of HHR23A.";
RL J. Mol. Biol. 341:1367-1379(2004).
RN [13]
RP INTERACTION WITH PSMD1; PSMC1 AND EEF1A1, AND MUTAGENESIS OF LYS-8 AND
RP THR-79.
RX PubMed=16712842; DOI=10.1016/j.febslet.2006.05.012;
RA Chen L., Madura K.;
RT "Evidence for distinct functions for human DNA repair factors hHR23A
RT and hHR23B.";
RL FEBS Lett. 580:3401-3408(2006).
RN [14]
RP INTERACTION WITH UBQLN2.
RX PubMed=17098253; DOI=10.1016/j.jmb.2006.10.056;
RA Kang Y., Zhang N., Koepp D.M., Walters K.J.;
RT "Ubiquitin receptor proteins hHR23a and hPLIC2 interact.";
RL J. Mol. Biol. 365:1093-1101(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-357, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [16]
RP MUTAGENESIS OF LEU-10; LYS-47 AND THR-77.
RX PubMed=18234089; DOI=10.1186/1471-2091-9-4;
RA Goh A.M., Walters K.J., Elsasser S., Verma R., Deshaies R.J.,
RA Finley D., Howley P.M.;
RT "Components of the ubiquitin-proteasome pathway compete for surfaces
RT on Rad23 family proteins.";
RL BMC Biochem. 9:4-4(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123; SER-133; SER-205
RP AND SER-295, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-357, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP FUNCTION IN VIRAL REPLICATION.
RX PubMed=20614012; DOI=10.1371/journal.pone.0011371;
RA Li G., Elder R.T., Dubrovsky L., Liang D., Pushkarsky T., Chiu K.,
RA Fan T., Sire J., Bukrinsky M., Zhao R.Y.;
RT "HIV-1 replication through hHR23A-mediated interaction of Vpr with 26S
RT proteasome.";
RL PLoS ONE 5:E11371-E11371(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-357, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP STRUCTURE BY NMR OF 319-363.
RX PubMed=9846873; DOI=10.1038/4220;
RA Dieckmann T., Withers-Ward E.S., Jarosinski M.A., Liu C.F.,
RA Chen I.S.Y., Feigon J.;
RT "Structure of a human DNA repair protein UBA domain that interacts
RT with HIV-1 Vpr.";
RL Nat. Struct. Biol. 5:1042-1047(1998).
RN [24]
RP STRUCTURE BY NMR OF 319-363, INTERACTION WITH HIV-1 VPR, AND
RP MUTAGENESIS OF PRO-333.
RX PubMed=11087358; DOI=10.1021/bi0017071;
RA Withers-Ward E.S., Mueller T.D., Chen I.S.Y., Feigon J.;
RT "Biochemical and structural analysis of the interaction between the
RT UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr.";
RL Biochemistry 39:14103-14112(2000).
RN [25]
RP STRUCTURE BY NMR OF 156-204.
RX PubMed=12079361; DOI=10.1016/S0022-2836(02)00302-9;
RA Mueller T.D., Feigon J.;
RT "Solution structures of UBA domains reveal a conserved hydrophobic
RT surface for protein-protein interactions.";
RL J. Mol. Biol. 319:1243-1255(2002).
RN [26]
RP STRUCTURE BY NMR OF 1-78, INTERACTION WITH PSMD4, AND MUTAGENESIS OF
RP ILE-49; ILE-54; PHE-71 AND THR-77.
RX PubMed=12970176; DOI=10.1093/emboj/cdg467;
RA Mueller T.D., Feigon J.;
RT "Structural determinants for the binding of ubiquitin-like domains to
RT the proteasome.";
RL EMBO J. 22:4634-4645(2003).
RN [27]
RP STRUCTURE BY NMR OF 2-363, INTERACTION WITH PSMD4, AND MUTAGENESIS OF
RP THR-9 AND ILE-49.
RX PubMed=14557549; DOI=10.1073/pnas.1634989100;
RA Walters K.J., Lech P.J., Goh A.M., Wang Q., Howley P.M.;
RT "DNA-repair protein hHR23a alters its protein structure upon binding
RT proteasomal subunit S5a.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12694-12699(2003).
RN [28]
RP STRUCTURE BY NMR OF 223-317.
RX PubMed=15322280; DOI=10.1110/ps.04824304;
RA Kamionka M., Feigon J.;
RT "Structure of the XPC binding domain of hHR23A reveals hydrophobic
RT patches for protein interaction.";
RL Protein Sci. 13:2370-2377(2004).
RN [29]
RP 3D-STRUCTURE MODELING OF 315-363.
RX PubMed=15949443; DOI=10.1016/j.molcel.2005.05.013;
RA Varadan R., Assfalg M., Raasi S., Pickart C., Fushman D.;
RT "Structural determinants for selective recognition of a Lys48-linked
RT polyubiquitin chain by a UBA domain.";
RL Mol. Cell 18:687-698(2005).
CC -!- FUNCTION: Multiubiquitin chain receptor involved in modulation of
CC proteasomal degradation. Binds to 'Lys-48'-linked polyubiquitin
CC chains in a length-dependent manner and with a lower affinity to
CC 'Lys-63'-linked polyubiquitin chains. Proposed to be capable to
CC bind simultaneously to the 26S proteasome and to polyubiquitinated
CC substrates and to deliver ubiquitinated proteins to the
CC proteasome.
CC -!- FUNCTION: Involved in nucleotide excision repair and is thought to
CC be functional equivalent for RAD23B in global genome nucleotide
CC excision repair (GG-NER) by association with XPC. In vitro, the
CC XPC:RAD23A dimer has NER activity. Can stabilize XPC.
CC -!- FUNCTION: Involved in vpr-dependent replication of HIV-1 in non-
CC proliferating cells and primary macrophages. Required for the
CC association of HIV-1 vpr with the host proteasome.
CC -!- SUBUNIT: Interacts with XPC; the interaction is suggesting the
CC existence of a functional equivalent variant XPC complex.
CC Interacts with PSMD4 and PSMC5. Interacts with ATXN3. Interacts
CC with HIV-1 vpr. Interacts with UBQLN2.
CC -!- INTERACTION:
CC P68104:EEF1A1; NbExp=2; IntAct=EBI-746453, EBI-352162;
CC Q9JI78:Ngly1 (xeno); NbExp=2; IntAct=EBI-746453, EBI-3648128;
CC P55036:PSMD4; NbExp=3; IntAct=EBI-746453, EBI-359318;
CC Q13501:SQSTM1; NbExp=2; IntAct=EBI-746453, EBI-307104;
CC Q9UHD9:UBQLN2; NbExp=3; IntAct=EBI-746453, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P54725-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54725-2; Sequence=VSP_047565;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The ubiquitin-like domain mediates interaction with ATXN3.
CC -!- DOMAIN: The ubiquitin-like (UBL) and the UBA (ubiquitin-
CC associated) domains interact intramolecularly in a highly dynamic
CC manner, as each UBA domain competes for an overlapping UBL domain
CC surface. Binding of ubiquitin or proteasome subunit PSMD4 disrupt
CC the UBL-UBA domain interactions and drive RAD23A in to an open
CC conformation.
CC -!- SIMILARITY: Belongs to the RAD23 family.
CC -!- SIMILARITY: Contains 2 UBA domains.
CC -!- SIMILARITY: Contains 1 ubiquitin-like domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BX448989; Type=Frameshift; Positions=159, 333, 339, 347;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/rad23a/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D21235; BAA04767.1; -; mRNA.
DR EMBL; AF549209; AAN39383.1; -; Genomic_DNA.
DR EMBL; BX448989; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC092069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AD000092; AAB51177.1; -; Genomic_DNA.
DR EMBL; BC014026; AAH14026.1; -; mRNA.
DR PIR; S44443; S44443.
DR RefSeq; NP_001257291.1; NM_001270362.1.
DR RefSeq; NP_001257292.1; NM_001270363.1.
DR RefSeq; NP_005044.1; NM_005053.3.
DR UniGene; Hs.643267; -.
DR PDB; 1DV0; NMR; -; A=319-363.
DR PDB; 1F4I; NMR; -; A=319-363.
DR PDB; 1IFY; NMR; -; A=156-204.
DR PDB; 1OQY; NMR; -; A=2-363.
DR PDB; 1P98; NMR; -; A=1-78.
DR PDB; 1P9D; NMR; -; U=1-78.
DR PDB; 1QZE; NMR; -; A=2-363.
DR PDB; 1TP4; NMR; -; A=223-317.
DR PDB; 1ZO6; Model; -; A=315-363.
DR PDB; 2WYQ; X-ray; 1.65 A; A=1-82.
DR PDBsum; 1DV0; -.
DR PDBsum; 1F4I; -.
DR PDBsum; 1IFY; -.
DR PDBsum; 1OQY; -.
DR PDBsum; 1P98; -.
DR PDBsum; 1P9D; -.
DR PDBsum; 1QZE; -.
DR PDBsum; 1TP4; -.
DR PDBsum; 1ZO6; -.
DR PDBsum; 2WYQ; -.
DR DisProt; DP00156; -.
DR ProteinModelPortal; P54725; -.
DR SMR; P54725; 2-363.
DR DIP; DIP-34442N; -.
DR IntAct; P54725; 35.
DR MINT; MINT-105454; -.
DR STRING; 9606.ENSP00000321365; -.
DR PhosphoSite; P54725; -.
DR DMDM; 1709983; -.
DR PaxDb; P54725; -.
DR PeptideAtlas; P54725; -.
DR PRIDE; P54725; -.
DR DNASU; 5886; -.
DR Ensembl; ENST00000586534; ENSP00000467024; ENSG00000179262.
DR Ensembl; ENST00000592268; ENSP00000468674; ENSG00000179262.
DR GeneID; 5886; -.
DR KEGG; hsa:5886; -.
DR UCSC; uc002mvw.2; human.
DR CTD; 5886; -.
DR GeneCards; GC19P013056; -.
DR HGNC; HGNC:9812; RAD23A.
DR MIM; 600061; gene.
DR neXtProt; NX_P54725; -.
DR PharmGKB; PA34172; -.
DR eggNOG; COG5272; -.
DR HOVERGEN; HBG055042; -.
DR InParanoid; P54725; -.
DR KO; K10839; -.
DR OMA; PTAREDK; -.
DR PhylomeDB; P54725; -.
DR ChiTaRS; RAD23A; human.
DR EvolutionaryTrace; P54725; -.
DR GeneWiki; RAD23A; -.
DR GenomeRNAi; 5886; -.
DR NextBio; 22888; -.
DR PMAP-CutDB; P54725; -.
DR PRO; PR:P54725; -.
DR ArrayExpress; P54725; -.
DR Bgee; P54725; -.
DR CleanEx; HS_RAD23A; -.
DR Genevestigator; P54725; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0003684; F:damaged DNA binding; IEA:InterPro.
DR GO; GO:0031593; F:polyubiquitin binding; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; TAS:ProtInc.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0006289; P:nucleotide-excision repair; IDA:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 1.10.10.540; -; 1.
DR InterPro; IPR004806; Rad23.
DR InterPro; IPR006636; STI1_HS-bd.
DR InterPro; IPR009060; UBA-like.
DR InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk.
DR InterPro; IPR000449; UBA/Ts_N.
DR InterPro; IPR000626; Ubiquitin_dom.
DR InterPro; IPR015360; XPC-bd.
DR Pfam; PF00627; UBA; 2.
DR Pfam; PF00240; ubiquitin; 1.
DR Pfam; PF09280; XPC-binding; 1.
DR PRINTS; PR01839; RAD23PROTEIN.
DR SMART; SM00727; STI1; 1.
DR SMART; SM00165; UBA; 2.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF101238; SSF101238; 1.
DR SUPFAM; SSF46934; SSF46934; 2.
DR TIGRFAMs; TIGR00601; rad23; 1.
DR PROSITE; PS50030; UBA; 2.
DR PROSITE; PS00299; UBIQUITIN_1; FALSE_NEG.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; DNA damage;
KW DNA repair; Host-virus interaction; Isopeptide bond; Nucleus;
KW Phosphoprotein; Polymorphism; Proteasome; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1 363 UV excision repair protein RAD23 homolog
FT A.
FT /FTId=PRO_0000114904.
FT DOMAIN 1 81 Ubiquitin-like.
FT DOMAIN 161 201 UBA 1.
FT DOMAIN 318 358 UBA 2.
FT REGION 319 363 HIV-1 vpr binding.
FT MOD_RES 123 123 Phosphoserine.
FT MOD_RES 133 133 Phosphoserine.
FT MOD_RES 205 205 Phosphoserine.
FT MOD_RES 295 295 Phosphoserine.
FT MOD_RES 357 357 Phosphoserine.
FT CROSSLNK 122 122 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VAR_SEQ 272 326 Missing (in isoform 2).
FT /FTId=VSP_047565.
FT VARIANT 131 131 T -> A (in dbSNP:rs11558955).
FT /FTId=VAR_016251.
FT VARIANT 179 179 R -> Q (in dbSNP:rs4987203).
FT /FTId=VAR_020377.
FT VARIANT 200 200 T -> M (in dbSNP:rs4987202).
FT /FTId=VAR_016252.
FT MUTAGEN 8 8 K->A: No effect on interaction with
FT EEF1A1.
FT MUTAGEN 9 9 T->A: Abolishes interaction with PSMD4;
FT when associated with T-49.
FT MUTAGEN 10 10 L->E: Impairs UBL-UBA domain interaction
FT and enhances ubiquitin-binding; when
FT associated with Glu-47.
FT MUTAGEN 47 47 K->A: No effect on UBL-UBA domain
FT interaction.
FT MUTAGEN 47 47 K->E: Impairs UBL-UBA domain interaction
FT and enhances ubiquitin-binding; when
FT associated with Glu-10.
FT MUTAGEN 47 47 K->E: Impairs UBL-UBA domain interaction
FT and enhances ubiquitin-binding; when
FT associated with Glu-77.
FT MUTAGEN 49 49 I->A: Impairs interaction with PSMD4.
FT MUTAGEN 49 49 I->T: Abolishes interaction with PSMD4;
FT when associated with A-9.
FT MUTAGEN 54 54 I->A: Impairs interaction with PSMD4.
FT MUTAGEN 71 71 F->A: Impairs interaction with PSMD4.
FT MUTAGEN 77 77 T->E: Impairs UBL-UBA domain interaction
FT and enhances ubiquitin-binding; when
FT associated with Glu-47.
FT MUTAGEN 77 77 T->S: No effect on interaction with
FT PSMD4.
FT MUTAGEN 79 79 T->P: Increases interaction with PSMD1
FT and PSMC1.
FT MUTAGEN 333 333 P->E: Abolishes interaction with HIV-1
FT vpr.
FT STRAND 3 9
FT TURN 10 12
FT STRAND 14 19
FT STRAND 21 23
FT HELIX 25 36
FT TURN 38 40
FT HELIX 43 45
FT STRAND 46 50
FT STRAND 53 55
FT STRAND 57 60
FT HELIX 61 64
FT STRAND 70 76
FT STRAND 81 83
FT STRAND 96 98
FT STRAND 106 108
FT STRAND 116 119
FT HELIX 161 172
FT HELIX 177 185
FT TURN 186 188
FT HELIX 192 200
FT HELIX 233 237
FT HELIX 239 246
FT TURN 248 250
FT HELIX 254 259
FT TURN 260 265
FT HELIX 267 285
FT STRAND 298 301
FT TURN 318 320
FT HELIX 321 324
FT TURN 325 331
FT HELIX 334 341
FT TURN 342 345
FT HELIX 348 354
SQ SEQUENCE 363 AA; 39609 MW; C4E47E9313BB47B5 CRC64;
MAVTITLKTL QQQTFKIRME PDETVKVLKE KIEAEKGRDA FPVAGQKLIY AGKILSDDVP
IRDYRIDEKN FVVVMVTKTK AGQGTSAPPE ASPTAAPESS TSFPPAPTSG MSHPPPAARE
DKSPSEESAP TTSPESVSGS VPSSGSSGRE EDAASTLVTG SEYETMLTEI MSMGYERERV
VAALRASYNN PHRAVEYLLT GIPGSPEPEH GSVQESQVSE QPATEAAGEN PLEFLRDQPQ
FQNMRQVIQQ NPALLPALLQ QLGQENPQLL QQISRHQEQF IQMLNEPPGE LADISDVEGE
VGAIGEEAPQ MNYIQVTPQE KEAIERLKAL GFPESLVIQA YFACEKNENL AANFLLSQNF
DDE
//
ID RD23A_HUMAN Reviewed; 363 AA.
AC P54725; K7ESE3;
DT 01-OCT-1996, integrated into UniProtKB/Swiss-Prot.
read moreDT 01-OCT-1996, sequence version 1.
DT 22-JAN-2014, entry version 142.
DE RecName: Full=UV excision repair protein RAD23 homolog A;
DE Short=HR23A;
DE Short=hHR23A;
GN Name=RAD23A;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC Catarrhini; Hominidae; Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RX PubMed=8168482;
RA Masutani C., Sugasawa K., Yanagisawa J., Sonoyama T., Ui M.,
RA Enomoto T., Takio K., Tanaka K., van der Spek P.J., Bootsma D.,
RA Hoeijmakers J.H.J., Hanaoka F.;
RT "Purification and cloning of a nucleotide excision repair complex
RT involving the Xeroderma pigmentosum group C protein and a human
RT homologue of yeast RAD23.";
RL EMBO J. 13:1831-1843(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-131 AND MET-200.
RG NIEHS SNPs program;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Fetal liver;
RA Li W.B., Gruber C., Jessee J., Polayes D.;
RT "Full-length cDNA libraries and normalization.";
RL Submitted (APR-2003) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057824; DOI=10.1038/nature02399;
RA Grimwood J., Gordon L.A., Olsen A.S., Terry A., Schmutz J.,
RA Lamerdin J.E., Hellsten U., Goodstein D., Couronne O., Tran-Gyamfi M.,
RA Aerts A., Altherr M., Ashworth L., Bajorek E., Black S., Branscomb E.,
RA Caenepeel S., Carrano A.V., Caoile C., Chan Y.M., Christensen M.,
RA Cleland C.A., Copeland A., Dalin E., Dehal P., Denys M., Detter J.C.,
RA Escobar J., Flowers D., Fotopulos D., Garcia C., Georgescu A.M.,
RA Glavina T., Gomez M., Gonzales E., Groza M., Hammon N., Hawkins T.,
RA Haydu L., Ho I., Huang W., Israni S., Jett J., Kadner K., Kimball H.,
RA Kobayashi A., Larionov V., Leem S.-H., Lopez F., Lou Y., Lowry S.,
RA Malfatti S., Martinez D., McCready P.M., Medina C., Morgan J.,
RA Nelson K., Nolan M., Ovcharenko I., Pitluck S., Pollard M.,
RA Popkie A.P., Predki P., Quan G., Ramirez L., Rash S., Retterer J.,
RA Rodriguez A., Rogers S., Salamov A., Salazar A., She X., Smith D.,
RA Slezak T., Solovyev V., Thayer N., Tice H., Tsai M., Ustaszewska A.,
RA Vo N., Wagner M., Wheeler J., Wu K., Xie G., Yang J., Dubchak I.,
RA Furey T.S., DeJong P., Dickson M., Gordon D., Eichler E.E.,
RA Pennacchio L.A., Richardson P., Stubbs L., Rokhsar D.S., Myers R.M.,
RA Rubin E.M., Lucas S.M.;
RT "The DNA sequence and biology of human chromosome 19.";
RL Nature 428:529-535(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Pancreas;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA
RT project: the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [6]
RP INTERACTION WITH HIV-1 VPR.
RX PubMed=9371639;
RA Withers-Ward E.S., Jowett J.B., Stewart S.A., Xie Y.M., Garfinkel A.,
RA Shibagaki Y., Chow S.A., Shah N., Hanaoka F., Sawitz D.G.,
RA Armstrong R.W., Souza L.M., Chen I.S.;
RT "Human immunodeficiency virus type 1 Vpr interacts with HHR23A, a
RT cellular protein implicated in nucleotide excision DNA repair.";
RL J. Virol. 71:9732-9742(1997).
RN [7]
RP FUNCTION IN DNA REPAIR.
RX PubMed=9372924;
RA Sugasawa K., Ng J.M., Masutani C., Maekawa T., Uchida A.,
RA van der Spek P.J., Eker A.P., Rademakers S., Visser C.,
RA Aboussekhra A., Wood R.D., Hanaoka F., Bootsma D., Hoeijmakers J.H.;
RT "Two human homologs of Rad23 are functionally interchangeable in
RT complex formation and stimulation of XPC repair activity.";
RL Mol. Cell. Biol. 17:6924-6931(1997).
RN [8]
RP INTERACTION WITH PSMD4.
RX PubMed=10488153; DOI=10.1074/jbc.274.39.28019;
RA Hiyama H., Yokoi M., Masutani C., Sugasawa K., Maekawa T., Tanaka K.,
RA Hoeijmakers J.H., Hanaoka F.;
RT "Interaction of hHR23 with S5a. The ubiquitin-like domain of hHR23
RT mediates interaction with S5a subunit of 26 S proteasome.";
RL J. Biol. Chem. 274:28019-28025(1999).
RN [9]
RP INTERACTION WITH ATXN3.
RX PubMed=10915768; DOI=10.1093/hmg/9.12.1795;
RA Wang G., Sawai N., Kotliarova S., Kanazawa I., Nukina N.;
RT "Ataxin-3, the MJD1 gene product, interacts with the two human
RT homologs of yeast DNA repair protein RAD23, HHR23A and HHR23B.";
RL Hum. Mol. Genet. 9:1795-1803(2000).
RN [10]
RP FUNCTION, AND POLYUBIQUITIN-BINDING.
RX PubMed=14621999; DOI=10.1021/bi035391j;
RA Wang Q., Goh A.M., Howley P.M., Walters K.J.;
RT "Ubiquitin recognition by the DNA repair protein hHR23a.";
RL Biochemistry 42:13529-13535(2003).
RN [11]
RP FUNCTION IN PROTEASOMAL DEGRADATION, AND POLYUBIQUITIN-BINDING.
RX PubMed=12643283; DOI=10.1074/jbc.M212841200;
RA Raasi S., Pickart C.M.;
RT "Rad23 ubiquitin-associated domains (UBA) inhibit 26 S proteasome-
RT catalyzed proteolysis by sequestering lysine 48-linked polyubiquitin
RT chains.";
RL J. Biol. Chem. 278:8951-8959(2003).
RN [12]
RP FUNCTION IN POLYUBIQUITIN-BINDING.
RX PubMed=15321727; DOI=10.1016/j.jmb.2004.06.057;
RA Raasi S., Orlov I., Fleming K.G., Pickart C.M.;
RT "Binding of polyubiquitin chains to ubiquitin-associated (UBA) domains
RT of HHR23A.";
RL J. Mol. Biol. 341:1367-1379(2004).
RN [13]
RP INTERACTION WITH PSMD1; PSMC1 AND EEF1A1, AND MUTAGENESIS OF LYS-8 AND
RP THR-79.
RX PubMed=16712842; DOI=10.1016/j.febslet.2006.05.012;
RA Chen L., Madura K.;
RT "Evidence for distinct functions for human DNA repair factors hHR23A
RT and hHR23B.";
RL FEBS Lett. 580:3401-3408(2006).
RN [14]
RP INTERACTION WITH UBQLN2.
RX PubMed=17098253; DOI=10.1016/j.jmb.2006.10.056;
RA Kang Y., Zhang N., Koepp D.M., Walters K.J.;
RT "Ubiquitin receptor proteins hHR23a and hPLIC2 interact.";
RL J. Mol. Biol. 365:1093-1101(2007).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-357, AND MASS
RP SPECTROMETRY.
RC TISSUE=Embryonic kidney;
RX PubMed=17525332; DOI=10.1126/science.1140321;
RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III,
RA Hurov K.E., Luo J., Bakalarski C.E., Zhao Z., Solimini N.,
RA Lerenthal Y., Shiloh Y., Gygi S.P., Elledge S.J.;
RT "ATM and ATR substrate analysis reveals extensive protein networks
RT responsive to DNA damage.";
RL Science 316:1160-1166(2007).
RN [16]
RP MUTAGENESIS OF LEU-10; LYS-47 AND THR-77.
RX PubMed=18234089; DOI=10.1186/1471-2091-9-4;
RA Goh A.M., Walters K.J., Elsasser S., Verma R., Deshaies R.J.,
RA Finley D., Howley P.M.;
RT "Components of the ubiquitin-proteasome pathway compete for surfaces
RT on Rad23 family proteins.";
RL BMC Biochem. 9:4-4(2008).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-123; SER-133; SER-205
RP AND SER-295, AND MASS SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-357, AND MASS
RP SPECTROMETRY.
RC TISSUE=Leukemic T-cell;
RX PubMed=19690332; DOI=10.1126/scisignal.2000007;
RA Mayya V., Lundgren D.H., Hwang S.-I., Rezaul K., Wu L., Eng J.K.,
RA Rodionov V., Han D.K.;
RT "Quantitative phosphoproteomic analysis of T cell receptor signaling
RT reveals system-wide modulation of protein-protein interactions.";
RL Sci. Signal. 2:RA46-RA46(2009).
RN [19]
RP FUNCTION IN VIRAL REPLICATION.
RX PubMed=20614012; DOI=10.1371/journal.pone.0011371;
RA Li G., Elder R.T., Dubrovsky L., Liang D., Pushkarsky T., Chiu K.,
RA Fan T., Sire J., Bukrinsky M., Zhao R.Y.;
RT "HIV-1 replication through hHR23A-mediated interaction of Vpr with 26S
RT proteasome.";
RL PLoS ONE 5:E11371-E11371(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-357, AND MASS
RP SPECTROMETRY.
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S.,
RA Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full
RT phosphorylation site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [21]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P.,
RA Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [22]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J.,
RA Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V.,
RA Blagoev B.;
RT "System-wide temporal characterization of the proteome and
RT phosphoproteome of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [23]
RP STRUCTURE BY NMR OF 319-363.
RX PubMed=9846873; DOI=10.1038/4220;
RA Dieckmann T., Withers-Ward E.S., Jarosinski M.A., Liu C.F.,
RA Chen I.S.Y., Feigon J.;
RT "Structure of a human DNA repair protein UBA domain that interacts
RT with HIV-1 Vpr.";
RL Nat. Struct. Biol. 5:1042-1047(1998).
RN [24]
RP STRUCTURE BY NMR OF 319-363, INTERACTION WITH HIV-1 VPR, AND
RP MUTAGENESIS OF PRO-333.
RX PubMed=11087358; DOI=10.1021/bi0017071;
RA Withers-Ward E.S., Mueller T.D., Chen I.S.Y., Feigon J.;
RT "Biochemical and structural analysis of the interaction between the
RT UBA(2) domain of the DNA repair protein HHR23A and HIV-1 Vpr.";
RL Biochemistry 39:14103-14112(2000).
RN [25]
RP STRUCTURE BY NMR OF 156-204.
RX PubMed=12079361; DOI=10.1016/S0022-2836(02)00302-9;
RA Mueller T.D., Feigon J.;
RT "Solution structures of UBA domains reveal a conserved hydrophobic
RT surface for protein-protein interactions.";
RL J. Mol. Biol. 319:1243-1255(2002).
RN [26]
RP STRUCTURE BY NMR OF 1-78, INTERACTION WITH PSMD4, AND MUTAGENESIS OF
RP ILE-49; ILE-54; PHE-71 AND THR-77.
RX PubMed=12970176; DOI=10.1093/emboj/cdg467;
RA Mueller T.D., Feigon J.;
RT "Structural determinants for the binding of ubiquitin-like domains to
RT the proteasome.";
RL EMBO J. 22:4634-4645(2003).
RN [27]
RP STRUCTURE BY NMR OF 2-363, INTERACTION WITH PSMD4, AND MUTAGENESIS OF
RP THR-9 AND ILE-49.
RX PubMed=14557549; DOI=10.1073/pnas.1634989100;
RA Walters K.J., Lech P.J., Goh A.M., Wang Q., Howley P.M.;
RT "DNA-repair protein hHR23a alters its protein structure upon binding
RT proteasomal subunit S5a.";
RL Proc. Natl. Acad. Sci. U.S.A. 100:12694-12699(2003).
RN [28]
RP STRUCTURE BY NMR OF 223-317.
RX PubMed=15322280; DOI=10.1110/ps.04824304;
RA Kamionka M., Feigon J.;
RT "Structure of the XPC binding domain of hHR23A reveals hydrophobic
RT patches for protein interaction.";
RL Protein Sci. 13:2370-2377(2004).
RN [29]
RP 3D-STRUCTURE MODELING OF 315-363.
RX PubMed=15949443; DOI=10.1016/j.molcel.2005.05.013;
RA Varadan R., Assfalg M., Raasi S., Pickart C., Fushman D.;
RT "Structural determinants for selective recognition of a Lys48-linked
RT polyubiquitin chain by a UBA domain.";
RL Mol. Cell 18:687-698(2005).
CC -!- FUNCTION: Multiubiquitin chain receptor involved in modulation of
CC proteasomal degradation. Binds to 'Lys-48'-linked polyubiquitin
CC chains in a length-dependent manner and with a lower affinity to
CC 'Lys-63'-linked polyubiquitin chains. Proposed to be capable to
CC bind simultaneously to the 26S proteasome and to polyubiquitinated
CC substrates and to deliver ubiquitinated proteins to the
CC proteasome.
CC -!- FUNCTION: Involved in nucleotide excision repair and is thought to
CC be functional equivalent for RAD23B in global genome nucleotide
CC excision repair (GG-NER) by association with XPC. In vitro, the
CC XPC:RAD23A dimer has NER activity. Can stabilize XPC.
CC -!- FUNCTION: Involved in vpr-dependent replication of HIV-1 in non-
CC proliferating cells and primary macrophages. Required for the
CC association of HIV-1 vpr with the host proteasome.
CC -!- SUBUNIT: Interacts with XPC; the interaction is suggesting the
CC existence of a functional equivalent variant XPC complex.
CC Interacts with PSMD4 and PSMC5. Interacts with ATXN3. Interacts
CC with HIV-1 vpr. Interacts with UBQLN2.
CC -!- INTERACTION:
CC P68104:EEF1A1; NbExp=2; IntAct=EBI-746453, EBI-352162;
CC Q9JI78:Ngly1 (xeno); NbExp=2; IntAct=EBI-746453, EBI-3648128;
CC P55036:PSMD4; NbExp=3; IntAct=EBI-746453, EBI-359318;
CC Q13501:SQSTM1; NbExp=2; IntAct=EBI-746453, EBI-307104;
CC Q9UHD9:UBQLN2; NbExp=3; IntAct=EBI-746453, EBI-947187;
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P54725-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P54725-2; Sequence=VSP_047565;
CC Note=No experimental confirmation available;
CC -!- DOMAIN: The ubiquitin-like domain mediates interaction with ATXN3.
CC -!- DOMAIN: The ubiquitin-like (UBL) and the UBA (ubiquitin-
CC associated) domains interact intramolecularly in a highly dynamic
CC manner, as each UBA domain competes for an overlapping UBL domain
CC surface. Binding of ubiquitin or proteasome subunit PSMD4 disrupt
CC the UBL-UBA domain interactions and drive RAD23A in to an open
CC conformation.
CC -!- SIMILARITY: Belongs to the RAD23 family.
CC -!- SIMILARITY: Contains 2 UBA domains.
CC -!- SIMILARITY: Contains 1 ubiquitin-like domain.
CC -!- SEQUENCE CAUTION:
CC Sequence=BX448989; Type=Frameshift; Positions=159, 333, 339, 347;
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/rad23a/";
CC -----------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution-NoDerivs License
CC -----------------------------------------------------------------------
DR EMBL; D21235; BAA04767.1; -; mRNA.
DR EMBL; AF549209; AAN39383.1; -; Genomic_DNA.
DR EMBL; BX448989; -; NOT_ANNOTATED_CDS; mRNA.
DR EMBL; AC092069; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AD000092; AAB51177.1; -; Genomic_DNA.
DR EMBL; BC014026; AAH14026.1; -; mRNA.
DR PIR; S44443; S44443.
DR RefSeq; NP_001257291.1; NM_001270362.1.
DR RefSeq; NP_001257292.1; NM_001270363.1.
DR RefSeq; NP_005044.1; NM_005053.3.
DR UniGene; Hs.643267; -.
DR PDB; 1DV0; NMR; -; A=319-363.
DR PDB; 1F4I; NMR; -; A=319-363.
DR PDB; 1IFY; NMR; -; A=156-204.
DR PDB; 1OQY; NMR; -; A=2-363.
DR PDB; 1P98; NMR; -; A=1-78.
DR PDB; 1P9D; NMR; -; U=1-78.
DR PDB; 1QZE; NMR; -; A=2-363.
DR PDB; 1TP4; NMR; -; A=223-317.
DR PDB; 1ZO6; Model; -; A=315-363.
DR PDB; 2WYQ; X-ray; 1.65 A; A=1-82.
DR PDBsum; 1DV0; -.
DR PDBsum; 1F4I; -.
DR PDBsum; 1IFY; -.
DR PDBsum; 1OQY; -.
DR PDBsum; 1P98; -.
DR PDBsum; 1P9D; -.
DR PDBsum; 1QZE; -.
DR PDBsum; 1TP4; -.
DR PDBsum; 1ZO6; -.
DR PDBsum; 2WYQ; -.
DR DisProt; DP00156; -.
DR ProteinModelPortal; P54725; -.
DR SMR; P54725; 2-363.
DR DIP; DIP-34442N; -.
DR IntAct; P54725; 35.
DR MINT; MINT-105454; -.
DR STRING; 9606.ENSP00000321365; -.
DR PhosphoSite; P54725; -.
DR DMDM; 1709983; -.
DR PaxDb; P54725; -.
DR PeptideAtlas; P54725; -.
DR PRIDE; P54725; -.
DR DNASU; 5886; -.
DR Ensembl; ENST00000586534; ENSP00000467024; ENSG00000179262.
DR Ensembl; ENST00000592268; ENSP00000468674; ENSG00000179262.
DR GeneID; 5886; -.
DR KEGG; hsa:5886; -.
DR UCSC; uc002mvw.2; human.
DR CTD; 5886; -.
DR GeneCards; GC19P013056; -.
DR HGNC; HGNC:9812; RAD23A.
DR MIM; 600061; gene.
DR neXtProt; NX_P54725; -.
DR PharmGKB; PA34172; -.
DR eggNOG; COG5272; -.
DR HOVERGEN; HBG055042; -.
DR InParanoid; P54725; -.
DR KO; K10839; -.
DR OMA; PTAREDK; -.
DR PhylomeDB; P54725; -.
DR ChiTaRS; RAD23A; human.
DR EvolutionaryTrace; P54725; -.
DR GeneWiki; RAD23A; -.
DR GenomeRNAi; 5886; -.
DR NextBio; 22888; -.
DR PMAP-CutDB; P54725; -.
DR PRO; PR:P54725; -.
DR ArrayExpress; P54725; -.
DR Bgee; P54725; -.
DR CleanEx; HS_RAD23A; -.
DR Genevestigator; P54725; -.
DR GO; GO:0005634; C:nucleus; IEA:UniProtKB-SubCell.
DR GO; GO:0000502; C:proteasome complex; IEA:UniProtKB-KW.
DR GO; GO:0003684; F:damaged DNA binding; IEA:InterPro.
DR GO; GO:0031593; F:polyubiquitin binding; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; TAS:ProtInc.
DR GO; GO:0019048; P:modulation by virus of host morphology or physiology; IEA:UniProtKB-KW.
DR GO; GO:0006289; P:nucleotide-excision repair; IDA:UniProtKB.
DR GO; GO:0045070; P:positive regulation of viral genome replication; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IEA:InterPro.
DR GO; GO:0032434; P:regulation of proteasomal ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR Gene3D; 1.10.10.540; -; 1.
DR InterPro; IPR004806; Rad23.
DR InterPro; IPR006636; STI1_HS-bd.
DR InterPro; IPR009060; UBA-like.
DR InterPro; IPR015940; UBA/transl_elong_EF1B_N_euk.
DR InterPro; IPR000449; UBA/Ts_N.
DR InterPro; IPR000626; Ubiquitin_dom.
DR InterPro; IPR015360; XPC-bd.
DR Pfam; PF00627; UBA; 2.
DR Pfam; PF00240; ubiquitin; 1.
DR Pfam; PF09280; XPC-binding; 1.
DR PRINTS; PR01839; RAD23PROTEIN.
DR SMART; SM00727; STI1; 1.
DR SMART; SM00165; UBA; 2.
DR SMART; SM00213; UBQ; 1.
DR SUPFAM; SSF101238; SSF101238; 1.
DR SUPFAM; SSF46934; SSF46934; 2.
DR TIGRFAMs; TIGR00601; rad23; 1.
DR PROSITE; PS50030; UBA; 2.
DR PROSITE; PS00299; UBIQUITIN_1; FALSE_NEG.
DR PROSITE; PS50053; UBIQUITIN_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Complete proteome; DNA damage;
KW DNA repair; Host-virus interaction; Isopeptide bond; Nucleus;
KW Phosphoprotein; Polymorphism; Proteasome; Reference proteome; Repeat;
KW Ubl conjugation.
FT CHAIN 1 363 UV excision repair protein RAD23 homolog
FT A.
FT /FTId=PRO_0000114904.
FT DOMAIN 1 81 Ubiquitin-like.
FT DOMAIN 161 201 UBA 1.
FT DOMAIN 318 358 UBA 2.
FT REGION 319 363 HIV-1 vpr binding.
FT MOD_RES 123 123 Phosphoserine.
FT MOD_RES 133 133 Phosphoserine.
FT MOD_RES 205 205 Phosphoserine.
FT MOD_RES 295 295 Phosphoserine.
FT MOD_RES 357 357 Phosphoserine.
FT CROSSLNK 122 122 Glycyl lysine isopeptide (Lys-Gly)
FT (interchain with G-Cter in ubiquitin).
FT VAR_SEQ 272 326 Missing (in isoform 2).
FT /FTId=VSP_047565.
FT VARIANT 131 131 T -> A (in dbSNP:rs11558955).
FT /FTId=VAR_016251.
FT VARIANT 179 179 R -> Q (in dbSNP:rs4987203).
FT /FTId=VAR_020377.
FT VARIANT 200 200 T -> M (in dbSNP:rs4987202).
FT /FTId=VAR_016252.
FT MUTAGEN 8 8 K->A: No effect on interaction with
FT EEF1A1.
FT MUTAGEN 9 9 T->A: Abolishes interaction with PSMD4;
FT when associated with T-49.
FT MUTAGEN 10 10 L->E: Impairs UBL-UBA domain interaction
FT and enhances ubiquitin-binding; when
FT associated with Glu-47.
FT MUTAGEN 47 47 K->A: No effect on UBL-UBA domain
FT interaction.
FT MUTAGEN 47 47 K->E: Impairs UBL-UBA domain interaction
FT and enhances ubiquitin-binding; when
FT associated with Glu-10.
FT MUTAGEN 47 47 K->E: Impairs UBL-UBA domain interaction
FT and enhances ubiquitin-binding; when
FT associated with Glu-77.
FT MUTAGEN 49 49 I->A: Impairs interaction with PSMD4.
FT MUTAGEN 49 49 I->T: Abolishes interaction with PSMD4;
FT when associated with A-9.
FT MUTAGEN 54 54 I->A: Impairs interaction with PSMD4.
FT MUTAGEN 71 71 F->A: Impairs interaction with PSMD4.
FT MUTAGEN 77 77 T->E: Impairs UBL-UBA domain interaction
FT and enhances ubiquitin-binding; when
FT associated with Glu-47.
FT MUTAGEN 77 77 T->S: No effect on interaction with
FT PSMD4.
FT MUTAGEN 79 79 T->P: Increases interaction with PSMD1
FT and PSMC1.
FT MUTAGEN 333 333 P->E: Abolishes interaction with HIV-1
FT vpr.
FT STRAND 3 9
FT TURN 10 12
FT STRAND 14 19
FT STRAND 21 23
FT HELIX 25 36
FT TURN 38 40
FT HELIX 43 45
FT STRAND 46 50
FT STRAND 53 55
FT STRAND 57 60
FT HELIX 61 64
FT STRAND 70 76
FT STRAND 81 83
FT STRAND 96 98
FT STRAND 106 108
FT STRAND 116 119
FT HELIX 161 172
FT HELIX 177 185
FT TURN 186 188
FT HELIX 192 200
FT HELIX 233 237
FT HELIX 239 246
FT TURN 248 250
FT HELIX 254 259
FT TURN 260 265
FT HELIX 267 285
FT STRAND 298 301
FT TURN 318 320
FT HELIX 321 324
FT TURN 325 331
FT HELIX 334 341
FT TURN 342 345
FT HELIX 348 354
SQ SEQUENCE 363 AA; 39609 MW; C4E47E9313BB47B5 CRC64;
MAVTITLKTL QQQTFKIRME PDETVKVLKE KIEAEKGRDA FPVAGQKLIY AGKILSDDVP
IRDYRIDEKN FVVVMVTKTK AGQGTSAPPE ASPTAAPESS TSFPPAPTSG MSHPPPAARE
DKSPSEESAP TTSPESVSGS VPSSGSSGRE EDAASTLVTG SEYETMLTEI MSMGYERERV
VAALRASYNN PHRAVEYLLT GIPGSPEPEH GSVQESQVSE QPATEAAGEN PLEFLRDQPQ
FQNMRQVIQQ NPALLPALLQ QLGQENPQLL QQISRHQEQF IQMLNEPPGE LADISDVEGE
VGAIGEEAPQ MNYIQVTPQE KEAIERLKAL GFPESLVIQA YFACEKNENL AANFLLSQNF
DDE
//
MIM
600061
*RECORD*
*FIELD* NO
600061
*FIELD* TI
*600061 RAD23, YEAST, HOMOLOG OF, A; RAD23A
;;HHR23A
*FIELD* TX
CLONING
Masutani et al. (1994) reported the purification to homogeneity and
read moresubsequent cDNA cloning from HeLa cells of a repair complex by in vitro
complementation of the xeroderma pigmentosum group C (278720) defect in
a cell-free repair system containing UV-damaged SV40 minichromosomes.
The complex had a high affinity for ssDNA and consisted of 2 tightly
associated proteins of 125 and 58 kD. The 125-kD subunit represented the
previously reported XPC gene (613208) product, which represents the
human homolog of the nucleotide excision repair (NER) gene RAD4 of
Saccharomyces cerevisiae. The 58-kD species turned out to be a human
homolog of yeast RAD23. Unexpectedly, a second human counterpart of
RAD23 was identified. The 2 genes, which Masutani et al. (1994) referred
to as HHR23A (RAD23A) and HHR23B (RAD23B; 600062), were expressed in the
same cells. In the XPC purification scheme, however, only the RAD23B
protein was found in a complex with p125/XPC.
In the mouse, van der Spek et al. (1996) cloned the homologs of both
RAD23A and RAD23B. Detailed sequence comparisons permitted deductions
concerning the structure of all RAD23 homologs. Northern blot analysis
revealed constitutive expression of both RAD23 genes in all tissues
examined. Elevated RNA expression of both genes was observed in testis.
MAPPING
Using fluorescence in situ hybridization (FISH), van der Spek et al.
(1994) demonstrated that the RAD23A gene is located on 19p13.2.
By FISH, van der Spek et al. (1996) assigned the Rad23a gene to mouse
chromosome 8C3 and the Rad23b gene to mouse chromosome 4B3.
GENE FUNCTION
Masutani et al. (1994) commented that no human mutant defective in
RAD23A had been identified. They suggested that the nature of the defect
in xeroderma pigmentosum group C implies that the XPC-RAD23B complex
exerts a unique function in the genome-overall repair pathway that is
important for prevention of skin cancer.
Van der Spek et al. (1996) found that although the RAD23 equivalents are
well conserved during evolution, the mammalian genes do not express the
UV-inducible phenotype of their yeast counterpart. The authors stated
that this discovery may point to a fundamental difference between the UV
responses of yeast and human.
Machado-Joseph disease (MJD; 109150) is an autosomal dominant
neurodegenerative disorder caused by an expansion of the polyglutamine
tract near the C terminus of the MJD1 gene product, ataxin-3. The mutant
ataxin-3 forms intranuclear inclusions in cultured cells as well as in
diseased human brain and also causes cell death in transfected cells.
Using a 2-hybrid system, Wang et al. (2000) found that ataxin-3
interacts with 2 human homologs of the yeast DNA repair protein RAD23,
RAD23A and RAD23B. Both normal and mutant ataxin-3 proteins interact
with the ubiquitin-like domain at the N terminus of the RAD23 proteins,
which is a motif important for nucleotide excision repair. However, in
human embryonic kidney cells RAD23 is recruited to intranuclear
inclusions formed by the mutant ataxin-3 through its interaction with
ataxin-3. The authors suggested that this interaction may be associated
with the normal function of ataxin-3, and that some functional
abnormality of the RAD23 proteins may exist in MJD.
*FIELD* RF
1. Masutani, C.; Sugasawa, K.; Yanagisawa, J.; Sonoyama, T.; Ui, M.;
Enomoto, T.; Takio, K.; Tanaka, K.; van der Spek, P. J.; Bootsma,
D.; Hoeijmakers, J. H. J.; Hanaoka, F.: 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:
1831-1843, 1994.
2. van der Spek, P. J.; Smit, E. M. E.; Beverloo, H. B.; Sugasawa,
K.; Masutani, C.; Hanaoka, F.; Hoeijmakers, J. H. J.; Hagemeijer,
A.: Chromosomal localization of three repair genes: the xeroderma
pigmentosum group C gene and two human homologs of yeast RAD23. Genomics 23:
651-658, 1994.
3. van der Spek, P. J.; Visser, C. E.; Hanaoka, F.; Smit, B.; Hagemeijer,
A.; Bootsma, D.; Hoeijmakers, J. H. J.: Cloning, comparative mapping,
and RNA expression of the mouse homologues of the Saccharomyces cerevisiae
nucleotide excision repair gene RAD23. Genomics 31: 20-27, 1996.
4. 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. Molec.
Genet. 9: 1795-1803, 2000.
*FIELD* CN
George E. Tiller - updated: 9/21/2000
*FIELD* CD
Victor A. McKusick: 7/28/1994
*FIELD* ED
carol: 01/12/2010
carol: 4/15/2002
alopez: 9/21/2000
dkim: 10/16/1998
mark: 2/7/1996
terry: 2/1/1996
terry: 12/14/1994
mimadm: 7/30/1994
jason: 7/28/1994
*RECORD*
*FIELD* NO
600061
*FIELD* TI
*600061 RAD23, YEAST, HOMOLOG OF, A; RAD23A
;;HHR23A
*FIELD* TX
CLONING
Masutani et al. (1994) reported the purification to homogeneity and
read moresubsequent cDNA cloning from HeLa cells of a repair complex by in vitro
complementation of the xeroderma pigmentosum group C (278720) defect in
a cell-free repair system containing UV-damaged SV40 minichromosomes.
The complex had a high affinity for ssDNA and consisted of 2 tightly
associated proteins of 125 and 58 kD. The 125-kD subunit represented the
previously reported XPC gene (613208) product, which represents the
human homolog of the nucleotide excision repair (NER) gene RAD4 of
Saccharomyces cerevisiae. The 58-kD species turned out to be a human
homolog of yeast RAD23. Unexpectedly, a second human counterpart of
RAD23 was identified. The 2 genes, which Masutani et al. (1994) referred
to as HHR23A (RAD23A) and HHR23B (RAD23B; 600062), were expressed in the
same cells. In the XPC purification scheme, however, only the RAD23B
protein was found in a complex with p125/XPC.
In the mouse, van der Spek et al. (1996) cloned the homologs of both
RAD23A and RAD23B. Detailed sequence comparisons permitted deductions
concerning the structure of all RAD23 homologs. Northern blot analysis
revealed constitutive expression of both RAD23 genes in all tissues
examined. Elevated RNA expression of both genes was observed in testis.
MAPPING
Using fluorescence in situ hybridization (FISH), van der Spek et al.
(1994) demonstrated that the RAD23A gene is located on 19p13.2.
By FISH, van der Spek et al. (1996) assigned the Rad23a gene to mouse
chromosome 8C3 and the Rad23b gene to mouse chromosome 4B3.
GENE FUNCTION
Masutani et al. (1994) commented that no human mutant defective in
RAD23A had been identified. They suggested that the nature of the defect
in xeroderma pigmentosum group C implies that the XPC-RAD23B complex
exerts a unique function in the genome-overall repair pathway that is
important for prevention of skin cancer.
Van der Spek et al. (1996) found that although the RAD23 equivalents are
well conserved during evolution, the mammalian genes do not express the
UV-inducible phenotype of their yeast counterpart. The authors stated
that this discovery may point to a fundamental difference between the UV
responses of yeast and human.
Machado-Joseph disease (MJD; 109150) is an autosomal dominant
neurodegenerative disorder caused by an expansion of the polyglutamine
tract near the C terminus of the MJD1 gene product, ataxin-3. The mutant
ataxin-3 forms intranuclear inclusions in cultured cells as well as in
diseased human brain and also causes cell death in transfected cells.
Using a 2-hybrid system, Wang et al. (2000) found that ataxin-3
interacts with 2 human homologs of the yeast DNA repair protein RAD23,
RAD23A and RAD23B. Both normal and mutant ataxin-3 proteins interact
with the ubiquitin-like domain at the N terminus of the RAD23 proteins,
which is a motif important for nucleotide excision repair. However, in
human embryonic kidney cells RAD23 is recruited to intranuclear
inclusions formed by the mutant ataxin-3 through its interaction with
ataxin-3. The authors suggested that this interaction may be associated
with the normal function of ataxin-3, and that some functional
abnormality of the RAD23 proteins may exist in MJD.
*FIELD* RF
1. Masutani, C.; Sugasawa, K.; Yanagisawa, J.; Sonoyama, T.; Ui, M.;
Enomoto, T.; Takio, K.; Tanaka, K.; van der Spek, P. J.; Bootsma,
D.; Hoeijmakers, J. H. J.; Hanaoka, F.: 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:
1831-1843, 1994.
2. van der Spek, P. J.; Smit, E. M. E.; Beverloo, H. B.; Sugasawa,
K.; Masutani, C.; Hanaoka, F.; Hoeijmakers, J. H. J.; Hagemeijer,
A.: Chromosomal localization of three repair genes: the xeroderma
pigmentosum group C gene and two human homologs of yeast RAD23. Genomics 23:
651-658, 1994.
3. van der Spek, P. J.; Visser, C. E.; Hanaoka, F.; Smit, B.; Hagemeijer,
A.; Bootsma, D.; Hoeijmakers, J. H. J.: Cloning, comparative mapping,
and RNA expression of the mouse homologues of the Saccharomyces cerevisiae
nucleotide excision repair gene RAD23. Genomics 31: 20-27, 1996.
4. 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. Molec.
Genet. 9: 1795-1803, 2000.
*FIELD* CN
George E. Tiller - updated: 9/21/2000
*FIELD* CD
Victor A. McKusick: 7/28/1994
*FIELD* ED
carol: 01/12/2010
carol: 4/15/2002
alopez: 9/21/2000
dkim: 10/16/1998
mark: 2/7/1996
terry: 2/1/1996
terry: 12/14/1994
mimadm: 7/30/1994
jason: 7/28/1994