ID RAD18_YEAST Reviewed; 487 AA.
AC P10862; D6VR69; Q58AT6;
DT 01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT 01-JUL-1989, sequence version 1.
DT 27-MAR-2024, entry version 220.
DE RecName: Full=Postreplication repair E3 ubiquitin-protein ligase RAD18;
DE EC=2.3.2.27;
DE AltName: Full=RING-type E3 ubiquitin transferase RAD18 {ECO:0000305};
DE AltName: Full=Radiation sensitivity protein 18;
GN Name=RAD18; OrderedLocusNames=YCR066W; ORFNames=YCR66W;
OS Saccharomyces cerevisiae (strain ATCC 204508 / S288c) (Baker's yeast).
OC Eukaryota; Fungi; Dikarya; Ascomycota; Saccharomycotina; Saccharomycetes;
OC Saccharomycetales; Saccharomycetaceae; Saccharomyces.
OX NCBI_TaxID=559292;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=3073108; DOI=10.1016/0378-1119(88)90187-4;
RA Chanet R., Magana-Schwencke N., Fabre F.;
RT "Potential DNA-binding domains in the RAD18 gene product of Saccharomyces
RT cerevisiae.";
RL Gene 74:543-547(1988).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=2970061; DOI=10.1093/nar/16.14.7119;
RA Jones J.S., Weber S., Prakash L.;
RT "The Saccharomyces cerevisiae RAD18 gene encodes a protein that contains
RT potential zinc finger domains for nucleic acid binding and a putative
RT nucleotide binding sequence.";
RL Nucleic Acids Res. 16:7119-7131(1988).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1561837; DOI=10.1002/yea.320080209;
RA Benit P., Chanet R., Fabre F., Faye G., Fukuhara H., Sor F.;
RT "Sequence of the sup61-RAD18 region on chromosome III of Saccharomyces
RT cerevisiae.";
RL Yeast 8:147-153(1992).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=1574125; DOI=10.1038/357038a0;
RA Oliver S.G., van der Aart Q.J.M., Agostoni-Carbone M.L., Aigle M.,
RA Alberghina L., Alexandraki D., Antoine G., Anwar R., Ballesta J.P.G.,
RA Benit P., Berben G., Bergantino E., Biteau N., Bolle P.-A.,
RA Bolotin-Fukuhara M., Brown A., Brown A.J.P., Buhler J.-M., Carcano C.,
RA Carignani G., Cederberg H., Chanet R., Contreras R., Crouzet M.,
RA Daignan-Fornier B., Defoor E., Delgado M.D., Demolder J., Doira C.,
RA Dubois E., Dujon B., Duesterhoeft A., Erdmann D., Esteban M., Fabre F.,
RA Fairhead C., Faye G., Feldmann H., Fiers W., Francingues-Gaillard M.-C.,
RA Franco L., Frontali L., Fukuhara H., Fuller L.J., Galland P., Gent M.E.,
RA Gigot D., Gilliquet V., Glansdorff N., Goffeau A., Grenson M., Grisanti P.,
RA Grivell L.A., de Haan M., Haasemann M., Hatat D., Hoenicka J.,
RA Hegemann J.H., Herbert C.J., Hilger F., Hohmann S., Hollenberg C.P.,
RA Huse K., Iborra F., Indge K.J., Isono K., Jacq C., Jacquet M., James C.M.,
RA Jauniaux J.-C., Jia Y., Jimenez A., Kelly A., Kleinhans U., Kreisl P.,
RA Lanfranchi G., Lewis C., van der Linden C.G., Lucchini G.,
RA Lutzenkirchen K., Maat M.J., Mallet L., Mannhaupt G., Martegani E.,
RA Mathieu A., Maurer C.T.C., McConnell D., McKee R.A., Messenguy F.,
RA Mewes H.-W., Molemans F., Montague M.A., Muzi Falconi M., Navas L.,
RA Newlon C.S., Noone D., Pallier C., Panzeri L., Pearson B.M., Perea J.,
RA Philippsen P., Pierard A., Planta R.J., Plevani P., Poetsch B., Pohl F.M.,
RA Purnelle B., Ramezani Rad M., Rasmussen S.W., Raynal A., Remacha M.A.,
RA Richterich P., Roberts A.B., Rodriguez F., Sanz E.,
RA Schaaff-Gerstenschlaeger I., Scherens B., Schweitzer B., Shu Y., Skala J.,
RA Slonimski P.P., Sor F., Soustelle C., Spiegelberg R., Stateva L.I.,
RA Steensma H.Y., Steiner S., Thierry A., Thireos G., Tzermia M.,
RA Urrestarazu L.A., Valle G., Vetter I., van Vliet-Reedijk J.C., Voet M.,
RA Volckaert G., Vreken P., Wang H., Warmington J.R., von Wettstein D.,
RA Wicksteed B.L., Wilson C., Wurst H., Xu G., Yoshikawa A., Zimmermann F.K.,
RA Sgouros J.G.;
RT "The complete DNA sequence of yeast chromosome III.";
RL Nature 357:38-46(1992).
RN [5]
RP GENOME REANNOTATION.
RC STRAIN=ATCC 204508 / S288c;
RX PubMed=24374639; DOI=10.1534/g3.113.008995;
RA Engel S.R., Dietrich F.S., Fisk D.G., Binkley G., Balakrishnan R.,
RA Costanzo M.C., Dwight S.S., Hitz B.C., Karra K., Nash R.S., Weng S.,
RA Wong E.D., Lloyd P., Skrzypek M.S., Miyasato S.R., Simison M., Cherry J.M.;
RT "The reference genome sequence of Saccharomyces cerevisiae: Then and now.";
RL G3 (Bethesda) 4:389-398(2014).
RN [6]
RP FUNCTION, SINGLE STRAND DNA-BINDING, AND INTERACTION WITH UBC2.
RX PubMed=7926769; DOI=10.1101/gad.8.7.811;
RA Bailly V., Lamb J., Sung P., Prakash S., Prakash L.;
RT "Specific complex formation between yeast RAD6 and RAD18 proteins: a
RT potential mechanism for targeting RAD6 ubiquitin-conjugating activity to
RT DNA damage sites.";
RL Genes Dev. 8:811-820(1994).
RN [7]
RP FUNCTION, AND INTERACTION WITH UBC2.
RX PubMed=9287349; DOI=10.1074/jbc.272.37.23360;
RA Bailly V., Lauder S., Prakash S., Prakash L.;
RT "Yeast DNA repair proteins Rad6 and Rad18 form a heterodimer that has
RT ubiquitin conjugating, DNA binding, and ATP hydrolytic activities.";
RL J. Biol. Chem. 272:23360-23365(1997).
RN [8]
RP FUNCTION, SUBCELLULAR LOCATION, SUBUNIT, AND INTERACTION WITH RAD5 AND
RP UBC13.
RX PubMed=10880451; DOI=10.1093/emboj/19.13.3388;
RA Ulrich H.D., Jentsch S.;
RT "Two RING finger proteins mediate cooperation between ubiquitin-conjugating
RT enzymes in DNA repair.";
RL EMBO J. 19:3388-3397(2000).
RN [9]
RP FUNCTION OF THE UBC13-MMS2 COMPLEX.
RX PubMed=10924462; DOI=10.1093/genetics/155.4.1633;
RA Xiao W., Chow B.L., Broomfield S., Hanna M.;
RT "The Saccharomyces cerevisiae RAD6 group is composed of an error-prone and
RT two error-free postreplication repair pathways.";
RL Genetics 155:1633-1641(2000).
RN [10]
RP FUNCTION, AND INTERACTION WITH POL30 AND UBC9.
RX PubMed=12226657; DOI=10.1038/nature00991;
RA Hoege C., Pfander B., Moldovan G.-L., Pyrowolakis G., Jentsch S.;
RT "RAD6-dependent DNA repair is linked to modification of PCNA by ubiquitin
RT and SUMO.";
RL Nature 419:135-141(2002).
RN [11]
RP LEVEL OF PROTEIN EXPRESSION [LARGE SCALE ANALYSIS].
RX PubMed=14562106; DOI=10.1038/nature02046;
RA Ghaemmaghami S., Huh W.-K., Bower K., Howson R.W., Belle A., Dephoure N.,
RA O'Shea E.K., Weissman J.S.;
RT "Global analysis of protein expression in yeast.";
RL Nature 425:737-741(2003).
RN [12]
RP FUNCTION.
RX PubMed=15507115; DOI=10.1111/j.1365-2443.2004.00787.x;
RA Branzei D., Seki M., Enomoto T.;
RT "Rad18/Rad5/Mms2-mediated polyubiquitination of PCNA is implicated in
RT replication completion during replication stress.";
RL Genes Cells 9:1031-1042(2004).
RN [13]
RP FUNCTION.
RX PubMed=15388802; DOI=10.1093/nar/gkh831;
RA de Padula M., Slezak G., Auffret van Der Kemp P., Boiteux S.;
RT "The post-replication repair RAD18 and RAD6 genes are involved in the
RT prevention of spontaneous mutations caused by 7,8-dihydro-8-oxoguanine in
RT Saccharomyces cerevisiae.";
RL Nucleic Acids Res. 32:5003-5010(2004).
RN [14]
RP FUNCTION.
RX PubMed=16247017; DOI=10.1073/pnas.0504586102;
RA Zhang H., Lawrence C.W.;
RT "The error-free component of the RAD6/RAD18 DNA damage tolerance pathway of
RT budding yeast employs sister-strand recombination.";
RL Proc. Natl. Acad. Sci. U.S.A. 102:15954-15959(2005).
RN [15]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT THR-155 AND SER-174, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=17287358; DOI=10.1073/pnas.0607084104;
RA Chi A., Huttenhower C., Geer L.Y., Coon J.J., Syka J.E.P., Bai D.L.,
RA Shabanowitz J., Burke D.J., Troyanskaya O.G., Hunt D.F.;
RT "Analysis of phosphorylation sites on proteins from Saccharomyces
RT cerevisiae by electron transfer dissociation (ETD) mass spectrometry.";
RL Proc. Natl. Acad. Sci. U.S.A. 104:2193-2198(2007).
RN [16]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=18407956; DOI=10.1074/mcp.m700468-mcp200;
RA Albuquerque C.P., Smolka M.B., Payne S.H., Bafna V., Eng J., Zhou H.;
RT "A multidimensional chromatography technology for in-depth phosphoproteome
RT analysis.";
RL Mol. Cell. Proteomics 7:1389-1396(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19779198; DOI=10.1126/science.1172867;
RA Holt L.J., Tuch B.B., Villen J., Johnson A.D., Gygi S.P., Morgan D.O.;
RT "Global analysis of Cdk1 substrate phosphorylation sites provides insights
RT into evolution.";
RL Science 325:1682-1686(2009).
RN [18]
RP UBIQUITINATION [LARGE SCALE ANALYSIS] AT LYS-204, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22106047; DOI=10.1002/pmic.201100166;
RA Starita L.M., Lo R.S., Eng J.K., von Haller P.D., Fields S.;
RT "Sites of ubiquitin attachment in Saccharomyces cerevisiae.";
RL Proteomics 12:236-240(2012).
CC -!- FUNCTION: E3 RING-finger protein, member of the UBC2/RAD6 epistasis
CC group. Associates to the E2 ubiquitin conjugating enzyme UBC2/RAD6 to
CC form the UBC2-RAD18 ubiquitin ligase complex involved in
CC postreplicative repair (PRR) of damaged DNA. The UBC2-RAD18 complex
CC cooperates with RAD5 and the UBC13-MMS2 dimer to attach mono-ubiquitin
CC chains on 'Lys-164' of POL30, which is necessary for PRR. The UBC2-
CC RAD18 complex is also involved in prevention of spontaneous mutations
CC caused by 7,8-dihydro-8-oxoguanine. {ECO:0000269|PubMed:10880451,
CC ECO:0000269|PubMed:10924462, ECO:0000269|PubMed:12226657,
CC ECO:0000269|PubMed:15388802, ECO:0000269|PubMed:15507115,
CC ECO:0000269|PubMed:16247017, ECO:0000269|PubMed:7926769,
CC ECO:0000269|PubMed:9287349}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=S-ubiquitinyl-[E2 ubiquitin-conjugating enzyme]-L-cysteine +
CC [acceptor protein]-L-lysine = [E2 ubiquitin-conjugating enzyme]-L-
CC cysteine + N(6)-ubiquitinyl-[acceptor protein]-L-lysine.;
CC EC=2.3.2.27;
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Homodimer. Interacts with E2 UBC2, forming a complex with
CC ubiquitin ligase activity. The UBC2-RAD18 complex interacts itself with
CC the UBC13-MMS2 ubiquitin ligase complex through direct interactions of
CC both RAD18 and UBC13 with RAD5. Interacts also with UBC9. Binds single
CC strand DNA. {ECO:0000269|PubMed:10880451, ECO:0000269|PubMed:12226657,
CC ECO:0000269|PubMed:7926769, ECO:0000269|PubMed:9287349}.
CC -!- INTERACTION:
CC P10862; P06104: RAD6; NbExp=4; IntAct=EBI-14659, EBI-19722;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:10880451}.
CC -!- MISCELLANEOUS: Present with 206 molecules/cell in log phase SD medium.
CC {ECO:0000269|PubMed:14562106}.
CC -!- SIMILARITY: Belongs to the RAD18 family. {ECO:0000305}.
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DR EMBL; X12542; CAA31059.1; -; Genomic_DNA.
DR EMBL; M36405; AAA34932.1; -; Genomic_DNA.
DR EMBL; X12588; CAA31101.1; -; Genomic_DNA.
DR EMBL; X59720; CAA42281.1; -; Genomic_DNA.
DR EMBL; BK006937; DAA07538.1; -; Genomic_DNA.
DR PIR; S05802; DDBY18.
DR RefSeq; NP_009992.1; NM_001178777.1.
DR AlphaFoldDB; P10862; -.
DR SMR; P10862; -.
DR BioGRID; 31042; 243.
DR ComplexPortal; CPX-2902; RAD6-RAD18 ubiquitin ligase complex.
DR DIP; DIP-1172N; -.
DR IntAct; P10862; 12.
DR MINT; P10862; -.
DR STRING; 4932.YCR066W; -.
DR iPTMnet; P10862; -.
DR MaxQB; P10862; -.
DR PaxDb; 4932-YCR066W; -.
DR PeptideAtlas; P10862; -.
DR EnsemblFungi; YCR066W_mRNA; YCR066W; YCR066W.
DR GeneID; 850430; -.
DR KEGG; sce:YCR066W; -.
DR AGR; SGD:S000000662; -.
DR SGD; S000000662; RAD18.
DR VEuPathDB; FungiDB:YCR066W; -.
DR eggNOG; KOG0287; Eukaryota.
DR GeneTree; ENSGT00390000011230; -.
DR HOGENOM; CLU_028491_2_0_1; -.
DR InParanoid; P10862; -.
DR OMA; IPNTGPR; -.
DR OrthoDB; 6177at2759; -.
DR BioCyc; YEAST:G3O-29369-MONOMER; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 850430; 0 hits in 10 CRISPR screens.
DR PRO; PR:P10862; -.
DR Proteomes; UP000002311; Chromosome III.
DR RNAct; P10862; Protein.
DR GO; GO:0000785; C:chromatin; IDA:SGD.
DR GO; GO:0005634; C:nucleus; IDA:SGD.
DR GO; GO:0097505; C:Rad6-Rad18 complex; IDA:SGD.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:SGD.
DR GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR GO; GO:0032508; P:DNA duplex unwinding; IEA:GOC.
DR GO; GO:0042275; P:error-free postreplication DNA repair; IGI:SGD.
DR GO; GO:0070987; P:error-free translesion synthesis; IGI:SGD.
DR GO; GO:0042276; P:error-prone translesion synthesis; IGI:SGD.
DR GO; GO:0006301; P:postreplication repair; IBA:GO_Central.
DR GO; GO:0006513; P:protein monoubiquitination; IMP:SGD.
DR CDD; cd23148; RING-HC_ScRAD18-like; 1.
DR Gene3D; 3.30.160.60; Classic Zinc Finger; 1.
DR Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR InterPro; IPR039577; Rad18.
DR InterPro; IPR004580; Rad18_fungi.
DR InterPro; IPR006642; Rad18_UBZ4.
DR InterPro; IPR003034; SAP_dom.
DR InterPro; IPR001841; Znf_RING.
DR InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR InterPro; IPR017907; Znf_RING_CS.
DR NCBIfam; TIGR00599; rad18; 1.
DR PANTHER; PTHR14134; E3 UBIQUITIN-PROTEIN LIGASE RAD18; 1.
DR PANTHER; PTHR14134:SF2; E3 UBIQUITIN-PROTEIN LIGASE RAD18; 1.
DR Pfam; PF02037; SAP; 1.
DR Pfam; PF13923; zf-C3HC4_2; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00513; SAP; 1.
DR SMART; SM00734; ZnF_Rad18; 1.
DR SUPFAM; SSF57850; RING/U-box; 1.
DR PROSITE; PS50800; SAP; 1.
DR PROSITE; PS00518; ZF_RING_1; 1.
DR PROSITE; PS50089; ZF_RING_2; 1.
DR PROSITE; PS51908; ZF_UBZ4; 1.
PE 1: Evidence at protein level;
KW DNA damage; DNA repair; DNA-binding; Isopeptide bond; Metal-binding;
KW Nucleus; Phosphoprotein; Reference proteome; Transferase; Ubl conjugation;
KW Ubl conjugation pathway; Zinc; Zinc-finger.
FT CHAIN 1..487
FT /note="Postreplication repair E3 ubiquitin-protein ligase
FT RAD18"
FT /id="PRO_0000056161"
FT DOMAIN 278..312
FT /note="SAP"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00186"
FT ZN_FING 28..66
FT /note="RING-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT ZN_FING 187..215
FT /note="UBZ4-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT REGION 222..254
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 407..487
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 222..238
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 239..254
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 425..478
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 190
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 193
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 206
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT BINDING 210
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT MOD_RES 155
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:17287358"
FT MOD_RES 174
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17287358"
FT CROSSLNK 204
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in ubiquitin)"
FT /evidence="ECO:0007744|PubMed:22106047"
SQ SEQUENCE 487 AA; 55230 MW; 70F5F12A3FA99532 CRC64;
MDHQITTASD FTTTSIPSLY QLDTLLRCHI CKDFLKVPVL TPCGHTFCSL CIRTHLNNQP
NCPLCLFEFR ESLLRSEFLV SEIIQSYTSL RSSLLDALRI PKPTPVPENE EVPGPENSSW
IELISESESD SVNAADDDLQ IVATSERKLA KRSMTDILPL SSKPSKRNFA MFRSERIKKK
SKPNEQMAQC PICQQFYPLK ALEKTHLDEC LTLQSLGKKP KISTTFPTES NPHNKSSSRF
KVRTPEVDKS SCGETSHVDK YLNSMMSAEH QRLPKINFTS MTQSQIKQKL SSLGLSTNGT
RQNMIKRYNH YEMLWNSNFC DSLEPVDEAE LKRQLLSWDV SHNKTPQNSS NKGGISKLMI
MKSNGKSSSY RKLLENFKND KFNRKGWMVM FRKDFARLIR EAKMKIKTGS SDSSGSVGHS
NDGDGVEKVQ SDQGTEDQQM EKDQDTVINE DRVAGERNLP NEDSTDADLS RELMDLNEYS
KDPPGNN
//
