ID   RAD18_MOUSE             Reviewed;         509 AA.
AC   Q9QXK2; Q9CZB8;
DT   06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT   06-JUN-2002, sequence version 2.
DT   27-MAR-2024, entry version 168.
DE   RecName: Full=E3 ubiquitin-protein ligase RAD18;
DE            EC=2.3.2.27;
DE   AltName: Full=Postreplication repair protein RAD18;
DE            Short=mRAD18Sc;
DE   AltName: Full=RING-type E3 ubiquitin transferase RAD18 {ECO:0000305};
GN   Name=Rad18; Synonyms=Rad18sc;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], AND CHARACTERIZATION.
RX   PubMed=11013078; DOI=10.1006/geno.2000.6220;
RA   van der Laan R., Roest H.P., Hoogerbrugge J.W., Smit E.M.E., Slater R.,
RA   Baarends W.M., Hoeijmakers J.H.J., Grootegoed J.A.;
RT   "Characterization of mRAD18Sc, a mouse homolog of the yeast postreplication
RT   repair gene RAD18.";
RL   Genomics 69:86-94(2000).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Embryo;
RX   PubMed=16141072; DOI=10.1126/science.1112014;
RA   Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA   Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA   Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA   Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA   Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA   Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA   Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA   Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA   Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA   Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA   Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA   Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA   Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA   Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA   Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA   Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA   Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA   Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA   Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA   Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA   Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA   Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA   Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA   Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA   Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA   van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA   Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA   Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA   Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA   Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA   Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA   Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA   Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA   Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT   "The transcriptional landscape of the mammalian genome.";
RL   Science 309:1559-1563(2005).
RN   [3]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99 AND SER-103, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Testis;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: E3 ubiquitin-protein ligase involved in postreplication
CC       repair of UV-damaged DNA. Postreplication repair functions in gap-
CC       filling of a daughter strand on replication of damaged DNA. Associates
CC       to the E2 ubiquitin conjugating enzyme UBE2B to form the UBE2B-RAD18
CC       ubiquitin ligase complex involved in mono-ubiquitination of DNA-
CC       associated PCNA on 'Lys-164'. Has ssDNA binding activity.
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 UBE2A and UBE2B, one homodimer
CC       binding one molecule of UBE2B. Interacts with HLTF. Interacts with
CC       SHPRH. Interacts with SPRTN; leading to enhance chromatin association
CC       of RAD18 and RAD18-mediated PCNA ubiquitination and translesion DNA
CC       synthesis. Interacts (via C-terminus and phosphorylated form) with SLF1
CC       (via BRCT domains); this interaction is required for efficient repair
CC       of UV-induced DNA damage. Interacts with SLF2. Interacts with SMC5;
CC       this interaction is increased in a SLF1 or SLF2-dependent manner.
CC       {ECO:0000250|UniProtKB:Q9NS91}.
CC   -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250|UniProtKB:Q9NS91}.
CC       Cytoplasm, cytoskeleton, microtubule organizing center, centrosome
CC       {ECO:0000250|UniProtKB:Q9NS91}. Note=Associates with chromatin.
CC       Colocalizes with SLF1 in the nucleus and to centrosomes. Relocalizes
CC       with SLF1 to nuclear foci in response to DNA damage. Accumulates with
CC       the SLF1-SLF2 and SMC5-SMC6 complexes at replication-coupled DNA
CC       interstrand repair and DNA double-strand breaks (DSBs) sites on
CC       chromatin in a ubiquitin-dependent manner.
CC       {ECO:0000250|UniProtKB:Q9NS91}.
CC   -!- TISSUE SPECIFICITY: Expressed in thymus, spleen, brain, and ovary.
CC   -!- SIMILARITY: Belongs to the RAD18 family. {ECO:0000305}.
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DR   EMBL; AF205278; AAF19193.1; -; mRNA.
DR   EMBL; AK012795; BAB28475.1; -; mRNA.
DR   CCDS; CCDS39589.1; -.
DR   RefSeq; NP_067360.2; NM_021385.2.
DR   AlphaFoldDB; Q9QXK2; -.
DR   SMR; Q9QXK2; -.
DR   BioGRID; 208379; 3.
DR   IntAct; Q9QXK2; 2.
DR   STRING; 10090.ENSMUSP00000070619; -.
DR   iPTMnet; Q9QXK2; -.
DR   PhosphoSitePlus; Q9QXK2; -.
DR   EPD; Q9QXK2; -.
DR   MaxQB; Q9QXK2; -.
DR   PaxDb; 10090-ENSMUSP00000070619; -.
DR   ProteomicsDB; 300345; -.
DR   Pumba; Q9QXK2; -.
DR   Antibodypedia; 10148; 453 antibodies from 40 providers.
DR   DNASU; 58186; -.
DR   Ensembl; ENSMUST00000077088.11; ENSMUSP00000076341.5; ENSMUSG00000030254.17.
DR   GeneID; 58186; -.
DR   KEGG; mmu:58186; -.
DR   UCSC; uc009dec.2; mouse.
DR   AGR; MGI:1890476; -.
DR   MGI; MGI:1890476; Rad18.
DR   VEuPathDB; HostDB:ENSMUSG00000030254; -.
DR   eggNOG; KOG0287; Eukaryota.
DR   GeneTree; ENSGT00390000011230; -.
DR   InParanoid; Q9QXK2; -.
DR   OMA; IPNTGPR; -.
DR   OrthoDB; 6177at2759; -.
DR   PhylomeDB; Q9QXK2; -.
DR   Reactome; R-MMU-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR   Reactome; R-MMU-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR   UniPathway; UPA00143; -.
DR   BioGRID-ORCS; 58186; 5 hits in 114 CRISPR screens.
DR   ChiTaRS; Rad18; mouse.
DR   PRO; PR:Q9QXK2; -.
DR   Proteomes; UP000000589; Chromosome 6.
DR   RNAct; Q9QXK2; Protein.
DR   Bgee; ENSMUSG00000030254; Expressed in embryonic post-anal tail and 181 other cell types or tissues.
DR   ExpressionAtlas; Q9QXK2; baseline and differential.
DR   GO; GO:0005813; C:centrosome; ISS:UniProtKB.
DR   GO; GO:0000785; C:chromatin; IDA:MGI.
DR   GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR   GO; GO:0001673; C:male germ cell nucleus; IDA:MGI.
DR   GO; GO:0016604; C:nuclear body; ISO:MGI.
DR   GO; GO:0042405; C:nuclear inclusion body; ISS:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR   GO; GO:0005634; C:nucleus; IDA:MGI.
DR   GO; GO:0097505; C:Rad6-Rad18 complex; IBA:GO_Central.
DR   GO; GO:0005657; C:replication fork; ISO:MGI.
DR   GO; GO:0035861; C:site of double-strand break; ISS:UniProtKB.
DR   GO; GO:0001741; C:XY body; IDA:MGI.
DR   GO; GO:0042802; F:identical protein binding; ISO:MGI.
DR   GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0140678; F:molecular function inhibitor activity; ISO:MGI.
DR   GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; ISS:UniProtKB.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0003697; F:single-stranded DNA binding; IEA:InterPro.
DR   GO; GO:0061630; F:ubiquitin protein ligase activity; IEA:InterPro.
DR   GO; GO:0031625; F:ubiquitin protein ligase binding; ISO:MGI.
DR   GO; GO:0000403; F:Y-form DNA binding; ISO:MGI.
DR   GO; GO:0006974; P:DNA damage response; IMP:MGI.
DR   GO; GO:0045910; P:negative regulation of DNA recombination; IMP:MGI.
DR   GO; GO:0051984; P:positive regulation of chromosome segregation; ISS:UniProtKB.
DR   GO; GO:0006301; P:postreplication repair; IBA:GO_Central.
DR   GO; GO:0051865; P:protein autoubiquitination; ISO:MGI.
DR   GO; GO:0006513; P:protein monoubiquitination; IBA:GO_Central.
DR   GO; GO:0009411; P:response to UV; IMP:MGI.
DR   GO; GO:0007283; P:spermatogenesis; IMP:MGI.
DR   CDD; cd16529; RING-HC_RAD18; 1.
DR   Gene3D; 3.30.160.60; Classic Zinc Finger; 1.
DR   Gene3D; 1.10.720.30; SAP domain; 1.
DR   Gene3D; 3.30.40.10; Zinc/RING finger domain, C3HC4 (zinc finger); 1.
DR   InterPro; IPR039577; Rad18.
DR   InterPro; IPR006642; Rad18_UBZ4.
DR   InterPro; IPR003034; SAP_dom.
DR   InterPro; IPR036361; SAP_dom_sf.
DR   InterPro; IPR001841; Znf_RING.
DR   InterPro; IPR013083; Znf_RING/FYVE/PHD.
DR   InterPro; IPR017907; Znf_RING_CS.
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.
DR   Genevisible; Q9QXK2; MM.
PE   1: Evidence at protein level;
KW   Acetylation; Cytoplasm; Cytoskeleton; DNA damage; DNA repair; DNA-binding;
KW   Metal-binding; Nucleus; Phosphoprotein; Reference proteome; Transferase;
KW   Ubl conjugation pathway; Zinc; Zinc-finger.
FT   CHAIN           1..509
FT                   /note="E3 ubiquitin-protein ligase RAD18"
FT                   /id="PRO_0000056150"
FT   DOMAIN          248..282
FT                   /note="SAP"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00186"
FT   ZN_FING         25..64
FT                   /note="RING-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00175"
FT   ZN_FING         201..228
FT                   /note="UBZ4-type"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT   REGION          365..401
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   REGION          435..509
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   MOTIF           232..240
FT                   /note="LR motif"
FT   COMPBIAS        462..493
FT                   /note="Polar residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        494..509
FT                   /note="Basic and acidic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         204
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT   BINDING         207
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT   BINDING         219
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT   BINDING         223
FT                   /ligand="Zn(2+)"
FT                   /ligand_id="ChEBI:CHEBI:29105"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01256"
FT   MOD_RES         1
FT                   /note="N-acetylmethionine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NS91"
FT   MOD_RES         99
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         103
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:21183079"
FT   MOD_RES         158
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NS91"
FT   MOD_RES         164
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NS91"
FT   MOD_RES         485
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q9NS91"
FT   CONFLICT        9
FT                   /note="W -> C (in Ref. 1; AAF19193)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        268
FT                   /note="Q -> P (in Ref. 1; AAF19193)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   509 AA;  57412 MW;  BF7717D1A69738F9 CRC64;
     MEVLAEPRWP PGLAVMKTID DLLRCGICFE YFNIAVIIPQ CSHNYCSLCI RKFLSYKTQC
     PTCCVAVTEP DLRNNRLLDE LVKSMNFART HLLQFALESP PISPVSSTSK KVVVKVHNAD
     AAQHPVKQAN RLMDKFLIRE TGDCVFELLG KENERKFSPQ KELSTSAEIK ETSLLGKPVL
     GLSDANGPVT PSTSTMKLDT KVSCPVCGVS IPENHINKHL DSCLSREEKK ESLRSSAHKR
     KPLPKTVYNL LSDRDLKKKL KQYGLSVQGN KQQLIKRHQE FVHMYNAQCD ALHPKSAAEI
     VQEIESMEKT RMRLEASKLN ENVMVFTKNQ TEKEIEEVHS EYRKKHQNAF QLLVDQAKKG
     YKKTGRVSQA AAMRTDEPAE TLPSMRTDEP AETLPSMRTD EPAETLPLMR ADEPAETLPS
     ECIAQEDNVS FSDTVSVTNH FPQPQLDSPG PSEPERPDDS SSCTDILFSS DSDSCNRNDQ
     NREVSPQQTR RTRASECVEI EPRNKRNKN
//