RAD18_HUMAN
ID RAD18_HUMAN Reviewed; 495 AA.
AC Q9NS91; Q58F55; Q9NRT6;
DT 06-JUN-2002, integrated into UniProtKB/Swiss-Prot.
DT 30-NOV-2010, sequence version 2.
DT 03-AUG-2022, entry version 189.
DE RecName: Full=E3 ubiquitin-protein ligase RAD18;
DE EC=2.3.2.27;
DE AltName: Full=Postreplication repair protein RAD18;
DE Short=hHR18;
DE Short=hRAD18;
DE AltName: Full=RING finger protein 73;
DE AltName: Full=RING-type E3 ubiquitin transferase RAD18 {ECO:0000305};
GN Name=RAD18; Synonyms=RNF73;
OS Homo sapiens (Human).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC Homo.
OX NCBI_TaxID=9606;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-302.
RC TISSUE=Placenta;
RX PubMed=10884424; DOI=10.1073/pnas.97.14.7927;
RA Tateishi S., Sakuraba Y., Masuyama S., Inoue H., Yamaizumi M.;
RT "Dysfunction of human Rad18 results in defective postreplication repair and
RT hypersensitivity to multiple mutagens.";
RL Proc. Natl. Acad. Sci. U.S.A. 97:7927-7932(2000).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-302.
RX PubMed=10908344; DOI=10.1093/nar/28.14.2847;
RA Xin H., Lin W., Sumanasekera W., Zhang Y., Wu X., Wang Z.;
RT "The human RAD18 gene product interacts with HHR6A and HHR6B.";
RL Nucleic Acids Res. 28:2847-2854(2000).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA], AND VARIANT GLN-302.
RA Jang Y., Chae S.;
RT "Identification of human RAD18 (hHR18), a homolog of yeast RAD18.";
RL Submitted (JUL-2000) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-302.
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ALA-6; GLN-302 AND VAL-307.
RG NIEHS SNPs program;
RL Submitted (MAR-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16641997; DOI=10.1038/nature04728;
RA Muzny D.M., Scherer S.E., Kaul R., Wang J., Yu J., Sudbrak R., Buhay C.J.,
RA Chen R., Cree A., Ding Y., Dugan-Rocha S., Gill R., Gunaratne P.,
RA Harris R.A., Hawes A.C., Hernandez J., Hodgson A.V., Hume J., Jackson A.,
RA Khan Z.M., Kovar-Smith C., Lewis L.R., Lozado R.J., Metzker M.L.,
RA Milosavljevic A., Miner G.R., Morgan M.B., Nazareth L.V., Scott G.,
RA Sodergren E., Song X.-Z., Steffen D., Wei S., Wheeler D.A., Wright M.W.,
RA Worley K.C., Yuan Y., Zhang Z., Adams C.Q., Ansari-Lari M.A., Ayele M.,
RA Brown M.J., Chen G., Chen Z., Clendenning J., Clerc-Blankenburg K.P.,
RA Chen R., Chen Z., Davis C., Delgado O., Dinh H.H., Dong W., Draper H.,
RA Ernst S., Fu G., Gonzalez-Garay M.L., Garcia D.K., Gillett W., Gu J.,
RA Hao B., Haugen E., Havlak P., He X., Hennig S., Hu S., Huang W.,
RA Jackson L.R., Jacob L.S., Kelly S.H., Kube M., Levy R., Li Z., Liu B.,
RA Liu J., Liu W., Lu J., Maheshwari M., Nguyen B.-V., Okwuonu G.O.,
RA Palmeiri A., Pasternak S., Perez L.M., Phelps K.A., Plopper F.J., Qiang B.,
RA Raymond C., Rodriguez R., Saenphimmachak C., Santibanez J., Shen H.,
RA Shen Y., Subramanian S., Tabor P.E., Verduzco D., Waldron L., Wang J.,
RA Wang J., Wang Q., Williams G.A., Wong G.K.-S., Yao Z., Zhang J., Zhang X.,
RA Zhao G., Zhou J., Zhou Y., Nelson D., Lehrach H., Reinhardt R.,
RA Naylor S.L., Yang H., Olson M., Weinstock G., Gibbs R.A.;
RT "The DNA sequence, annotation and analysis of human chromosome 3.";
RL Nature 440:1194-1198(2006).
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA], AND VARIANT GLN-302.
RC TISSUE=Placenta;
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH SLF1, AND SUBCELLULAR LOCATION.
RX PubMed=15632077; DOI=10.1128/mcb.25.2.779-788.2005;
RA Adams D.J., van der Weyden L., Gergely F.V., Arends M.J., Ng B.L.,
RA Tannahill D., Kanaar R., Markus A., Morris B.J., Bradley A.;
RT "BRCTx is a novel, highly conserved RAD18-interacting protein.";
RL Mol. Cell. Biol. 25:779-788(2005).
RN [9]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [10]
RP INTERACTION WITH SHPRH.
RX PubMed=17130289; DOI=10.1083/jcb.200606145;
RA Motegi A., Sood R., Moinova H., Markowitz S.D., Liu P.P., Myung K.;
RT "Human SHPRH suppresses genomic instability through proliferating cell
RT nuclear antigen polyubiquitination.";
RL J. Cell Biol. 175:703-708(2006).
RN [11]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-471, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [12]
RP FUNCTION, AND INTERACTION WITH SHPRH.
RX PubMed=17108083; DOI=10.1073/pnas.0608595103;
RA Unk I., Hajdu I., Fatyol K., Szakal B., Blastyak A., Bermudez V.,
RA Hurwitz J., Prakash L., Prakash S., Haracska L.;
RT "Human SHPRH is a ubiquitin ligase for Mms2-Ubc13-dependent
RT polyubiquitylation of proliferating cell nuclear antigen.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:18107-18112(2006).
RN [13]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18220336; DOI=10.1021/pr0705441;
RA Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III;
RT "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient
RT phosphoproteomic analysis.";
RL J. Proteome Res. 7:1346-1351(2008).
RN [14]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99; SER-103; THR-118 AND
RP SER-164, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 [15]
RP INTERACTION WITH HLTF.
RX PubMed=18316726; DOI=10.1073/pnas.0800563105;
RA Unk I., Hajdu I., Fatyol K., Hurwitz J., Yoon J.-H., Prakash L.,
RA Prakash S., Haracska L.;
RT "Human HLTF functions as a ubiquitin ligase for proliferating cell nuclear
RT antigen polyubiquitination.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:3768-3773(2008).
RN [16]
RP INTERACTION WITH HLTF.
RX PubMed=18719106; DOI=10.1073/pnas.0805685105;
RA Motegi A., Liaw H.-J., Lee K.-Y., Roest H.P., Maas A., Wu X., Moinova H.,
RA Markowitz S.D., Ding H., Hoeijmakers J.H.J., Myung K.;
RT "Polyubiquitination of proliferating cell nuclear antigen by HLTF and SHPRH
RT prevents genomic instability from stalled replication forks.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:12411-12416(2008).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19413330; DOI=10.1021/ac9004309;
RA Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT refined SCX-based approach.";
RL Anal. Chem. 81:4493-4501(2009).
RN [18]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99 AND SER-103, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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 PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99 AND SER-471, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
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., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [20]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99 AND SER-471, AND
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., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [21]
RP FUNCTION, AND IDENTIFICATION BY MASS SPECTROMETRY.
RX PubMed=21659603; DOI=10.1126/science.1203430;
RA Cotta-Ramusino C., McDonald E.R. III, Hurov K., Sowa M.E., Harper J.W.,
RA Elledge S.J.;
RT "A DNA damage response screen identifies RHINO, a 9-1-1 and TopBP1
RT interacting protein required for ATR signaling.";
RL Science 332:1313-1317(2011).
RN [22]
RP INTERACTION WITH SLF1, SUBCELLULAR LOCATION, AND MUTAGENESIS OF SER-442 AND
RP SER-444.
RX PubMed=22036607; DOI=10.1016/j.dnarep.2011.10.012;
RA Liu T., Chen H., Kim H., Huen M.S., Chen J., Huang J.;
RT "RAD18-BRCTx interaction is required for efficient repair of UV-induced DNA
RT damage.";
RL DNA Repair 11:131-138(2012).
RN [23]
RP UBIQUITIN-BINDING, AND LR MOTIF.
RX PubMed=22742833; DOI=10.1016/j.molcel.2012.05.045;
RA Panier S., Ichijima Y., Fradet-Turcotte A., Leung C.C., Kaustov L.,
RA Arrowsmith C.H., Durocher D.;
RT "Tandem protein interaction modules organize the ubiquitin-dependent
RT response to DNA double-strand breaks.";
RL Mol. Cell 47:383-395(2012).
RN [24]
RP INTERACTION WITH SPRTN.
RX PubMed=22681887; DOI=10.1016/j.molcel.2012.05.020;
RA Centore R.C., Yazinski S.A., Tse A., Zou L.;
RT "Spartan/C1orf124, a reader of PCNA ubiquitylation and a regulator of UV-
RT induced DNA damage response.";
RL Mol. Cell 46:625-635(2012).
RN [25]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT MET-1, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=22814378; DOI=10.1073/pnas.1210303109;
RA Van Damme P., Lasa M., Polevoda B., Gazquez C., Elosegui-Artola A.,
RA Kim D.S., De Juan-Pardo E., Demeyer K., Hole K., Larrea E., Timmerman E.,
RA Prieto J., Arnesen T., Sherman F., Gevaert K., Aldabe R.;
RT "N-terminal acetylome analyses and functional insights of the N-terminal
RT acetyltransferase NatB.";
RL Proc. Natl. Acad. Sci. U.S.A. 109:12449-12454(2012).
RN [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-99; SER-103; THR-118;
RP SER-122; SER-125; SER-142; SER-158; SER-164; SER-322; SER-471 AND SER-483,
RP AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [27]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-376, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=25218447; DOI=10.1038/nsmb.2890;
RA Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA Vertegaal A.C.;
RT "Uncovering global SUMOylation signaling networks in a site-specific
RT manner.";
RL Nat. Struct. Mol. Biol. 21:927-936(2014).
RN [28]
RP INTERACTION WITH SLF1; SLF2 AND SMC5, SUBCELLULAR LOCATION, IDENTIFICATION
RP BY MASS SPECTROMETRY, AND MUTAGENESIS OF SER-442 AND SER-444.
RX PubMed=25931565; DOI=10.1126/science.1253671;
RA Raeschle M., Smeenk G., Hansen R.K., Temu T., Oka Y., Hein M.Y.,
RA Nagaraj N., Long D.T., Walter J.C., Hofmann K., Storchova Z., Cox J.,
RA Bekker-Jensen S., Mailand N., Mann M.;
RT "DNA repair. Proteomics reveals dynamic assembly of repair complexes during
RT bypass of DNA cross-links.";
RL Science 348:1253671-1253671(2015).
RN [29]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-376, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [30]
RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 1-99, SUBUNIT, AND MUTAGENESIS OF
RP ILE-27.
RX PubMed=21549715; DOI=10.1016/j.jmb.2011.04.051;
RA Huang A., Hibbert R.G., de Jong R.N., Das D., Sixma T.K., Boelens R.;
RT "Symmetry and asymmetry of the RING-RING dimer of Rad18.";
RL J. Mol. Biol. 410:424-435(2011).
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 {ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:21659603}.
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 (PubMed:21549715). Interacts with UBE2A and UBE2B,
CC one homodimer binding one molecule of UBE2B. Interacts with SHPRH
CC (PubMed:17130289, PubMed:17108083). Interacts with HLTF
CC (PubMed:18316726, PubMed:18719106). Interacts with SPRTN; leading to
CC enhance chromatin association of RAD18 and RAD18-mediated PCNA
CC ubiquitination and translesion DNA synthesis (PubMed:22681887).
CC Interacts (via C-terminus and phosphorylated form) with SLF1 (via BRCT
CC domains); this interaction is required for efficient repair of UV-
CC induced DNA damage (PubMed:15632077, PubMed:22036607, PubMed:25931565).
CC Interacts with SLF2 (PubMed:25931565). Interacts with SMC5; this
CC interaction is increased in a SLF1 or SLF2-dependent manner
CC (PubMed:25931565). {ECO:0000269|PubMed:15632077,
CC ECO:0000269|PubMed:17108083, ECO:0000269|PubMed:17130289,
CC ECO:0000269|PubMed:18316726, ECO:0000269|PubMed:18719106,
CC ECO:0000269|PubMed:21549715, ECO:0000269|PubMed:22036607,
CC ECO:0000269|PubMed:22681887, ECO:0000269|PubMed:25931565}.
CC -!- INTERACTION:
CC Q9NS91; Q96B67: ARRDC3; NbExp=3; IntAct=EBI-2339393, EBI-2875665;
CC Q9NS91; P54253: ATXN1; NbExp=6; IntAct=EBI-2339393, EBI-930964;
CC Q9NS91; Q15038: DAZAP2; NbExp=3; IntAct=EBI-2339393, EBI-724310;
CC Q9NS91; Q08379: GOLGA2; NbExp=3; IntAct=EBI-2339393, EBI-618309;
CC Q9NS91; Q14527: HLTF; NbExp=3; IntAct=EBI-2339393, EBI-1045161;
CC Q9NS91; P43358: MAGEA4; NbExp=4; IntAct=EBI-2339393, EBI-743122;
CC Q9NS91; Q13416: ORC2; NbExp=3; IntAct=EBI-2339393, EBI-374957;
CC Q9NS91; O14737: PDCD5; NbExp=3; IntAct=EBI-2339393, EBI-712290;
CC Q9NS91; Q13148: TARDBP; NbExp=3; IntAct=EBI-2339393, EBI-372899;
CC Q9NS91; Q86VP1: TAX1BP1; NbExp=6; IntAct=EBI-2339393, EBI-529518;
CC Q9NS91; P49459: UBE2A; NbExp=4; IntAct=EBI-2339393, EBI-2339348;
CC Q9NS91; P63146: UBE2B; NbExp=6; IntAct=EBI-2339393, EBI-712629;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:15632077,
CC ECO:0000269|PubMed:22036607, ECO:0000269|PubMed:25931565}. Cytoplasm,
CC cytoskeleton, microtubule organizing center, centrosome
CC {ECO:0000269|PubMed:15632077}. Note=Associates with chromatin
CC (PubMed:25931565). Colocalizes with SLF1 in the nucleus and to
CC centrosomes (PubMed:15632077). Relocalizes with SLF1 to nuclear foci in
CC response to DNA damage (PubMed:22036607). Accumulates with the SLF1-
CC SLF2 and SMC5-SMC6 complexes at replication-coupled DNA interstrand
CC repair and DNA double-strand breaks (DSBs) sites on chromatin in a
CC ubiquitin-dependent manner (PubMed:25931565).
CC {ECO:0000269|PubMed:15632077, ECO:0000269|PubMed:22036607,
CC ECO:0000269|PubMed:25931565}.
CC -!- SIMILARITY: Belongs to the RAD18 family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/rad18/";
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DR EMBL; AB035274; BAA99284.1; -; mRNA.
DR EMBL; AF169796; AAF80856.1; -; mRNA.
DR EMBL; AY004333; AAF86618.1; -; mRNA.
DR EMBL; AK023075; BAB14392.1; -; mRNA.
DR EMBL; AY961989; AAX44049.1; -; Genomic_DNA.
DR EMBL; AC008151; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AC034186; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC001302; AAH01302.1; -; mRNA.
DR CCDS; CCDS2571.1; -.
DR RefSeq; NP_064550.3; NM_020165.3.
DR PDB; 2MRE; NMR; -; B=198-227.
DR PDB; 2MRF; NMR; -; A=198-227.
DR PDB; 2Y43; X-ray; 1.80 A; A/B=1-99.
DR PDB; 2YBF; X-ray; 2.00 A; B=340-366.
DR PDB; 5VF0; NMR; -; B=198-240.
DR PDBsum; 2MRE; -.
DR PDBsum; 2MRF; -.
DR PDBsum; 2Y43; -.
DR PDBsum; 2YBF; -.
DR PDBsum; 5VF0; -.
DR AlphaFoldDB; Q9NS91; -.
DR SMR; Q9NS91; -.
DR BioGRID; 121212; 455.
DR DIP; DIP-29831N; -.
DR IntAct; Q9NS91; 74.
DR MINT; Q9NS91; -.
DR STRING; 9606.ENSP00000264926; -.
DR GlyGen; Q9NS91; 1 site, 1 O-linked glycan (1 site).
DR iPTMnet; Q9NS91; -.
DR MetOSite; Q9NS91; -.
DR PhosphoSitePlus; Q9NS91; -.
DR SwissPalm; Q9NS91; -.
DR BioMuta; RAD18; -.
DR DMDM; 313104165; -.
DR CPTAC; CPTAC-3246; -.
DR CPTAC; CPTAC-3247; -.
DR CPTAC; CPTAC-3285; -.
DR CPTAC; CPTAC-939; -.
DR CPTAC; CPTAC-940; -.
DR EPD; Q9NS91; -.
DR jPOST; Q9NS91; -.
DR MassIVE; Q9NS91; -.
DR MaxQB; Q9NS91; -.
DR PaxDb; Q9NS91; -.
DR PeptideAtlas; Q9NS91; -.
DR PRIDE; Q9NS91; -.
DR ProteomicsDB; 82515; -.
DR Antibodypedia; 10148; 426 antibodies from 40 providers.
DR CPTC; Q9NS91; 5 antibodies.
DR DNASU; 56852; -.
DR Ensembl; ENST00000264926.7; ENSP00000264926.2; ENSG00000070950.10.
DR GeneID; 56852; -.
DR KEGG; hsa:56852; -.
DR MANE-Select; ENST00000264926.7; ENSP00000264926.2; NM_020165.4; NP_064550.3.
DR UCSC; uc003brd.4; human.
DR CTD; 56852; -.
DR DisGeNET; 56852; -.
DR GeneCards; RAD18; -.
DR HGNC; HGNC:18278; RAD18.
DR HPA; ENSG00000070950; Low tissue specificity.
DR MIM; 605256; gene.
DR neXtProt; NX_Q9NS91; -.
DR OpenTargets; ENSG00000070950; -.
DR PharmGKB; PA134912253; -.
DR VEuPathDB; HostDB:ENSG00000070950; -.
DR eggNOG; KOG0287; Eukaryota.
DR GeneTree; ENSGT00390000011230; -.
DR InParanoid; Q9NS91; -.
DR OMA; ERTQGGH; -.
DR OrthoDB; 1013108at2759; -.
DR PhylomeDB; Q9NS91; -.
DR TreeFam; TF101214; -.
DR PathwayCommons; Q9NS91; -.
DR Reactome; R-HSA-110314; Recognition of DNA damage by PCNA-containing replication complex.
DR Reactome; R-HSA-8866654; E3 ubiquitin ligases ubiquitinate target proteins.
DR SignaLink; Q9NS91; -.
DR SIGNOR; Q9NS91; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 56852; 52 hits in 1121 CRISPR screens.
DR ChiTaRS; RAD18; human.
DR GeneWiki; RAD18; -.
DR GenomeRNAi; 56852; -.
DR Pharos; Q9NS91; Tbio.
DR PRO; PR:Q9NS91; -.
DR Proteomes; UP000005640; Chromosome 3.
DR RNAct; Q9NS91; protein.
DR Bgee; ENSG00000070950; Expressed in calcaneal tendon and 144 other tissues.
DR ExpressionAtlas; Q9NS91; baseline and differential.
DR Genevisible; Q9NS91; HS.
DR GO; GO:0005813; C:centrosome; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IEA:UniProtKB-KW.
DR GO; GO:0016604; C:nuclear body; IDA:HPA.
DR GO; GO:0042405; C:nuclear inclusion body; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0097505; C:Rad6-Rad18 complex; IBA:GO_Central.
DR GO; GO:0005657; C:replication fork; IDA:UniProtKB.
DR GO; GO:0035861; C:site of double-strand break; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; NAS:UniProtKB.
DR GO; GO:0042802; F:identical protein binding; IDA:MGI.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0031593; F:polyubiquitin modification-dependent protein binding; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IPI:UniProtKB.
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; IPI:UniProtKB.
DR GO; GO:0000403; F:Y-form DNA binding; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0006281; P:DNA repair; NAS:UniProtKB.
DR GO; GO:0060548; P:negative regulation of cell death; IDA:UniProtKB.
DR GO; GO:0051984; P:positive regulation of chromosome segregation; IMP:UniProtKB.
DR GO; GO:0006301; P:postreplication repair; IBA:GO_Central.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:MGI.
DR GO; GO:0006513; P:protein monoubiquitination; IBA:GO_Central.
DR DisProt; DP01796; -.
DR Gene3D; 1.10.720.30; -; 1.
DR Gene3D; 3.30.40.10; -; 1.
DR IDEAL; IID00588; -.
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; PTHR14134; 1.
DR Pfam; PF02037; SAP; 1.
DR SMART; SM00184; RING; 1.
DR SMART; SM00513; SAP; 1.
DR SMART; SM00734; ZnF_Rad18; 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 3D-structure; Acetylation; Cytoplasm; Cytoskeleton; DNA damage; DNA repair;
KW DNA-binding; Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Transferase; Ubl conjugation; Ubl conjugation pathway;
KW Zinc; Zinc-finger.
FT CHAIN 1..495
FT /note="E3 ubiquitin-protein ligase RAD18"
FT /id="PRO_0000056149"
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 152..197
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 400..423
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 456..495
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 232..240
FT /note="LR motif"
FT COMPBIAS 166..184
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:0007744|PubMed:22814378"
FT MOD_RES 99
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:17081983,
FT ECO:0007744|PubMed:18220336, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT MOD_RES 103
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:19690332, ECO:0007744|PubMed:23186163"
FT MOD_RES 118
FT /note="Phosphothreonine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 122
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 125
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 142
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 158
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 164
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 322
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT MOD_RES 471
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:16964243,
FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 483
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:23186163"
FT CROSSLNK 376
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:25218447,
FT ECO:0007744|PubMed:28112733"
FT VARIANT 6
FT /note="E -> A (in dbSNP:rs45520133)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_023423"
FT VARIANT 302
FT /note="R -> Q (in dbSNP:rs373572)"
FT /evidence="ECO:0000269|PubMed:10884424,
FT ECO:0000269|PubMed:10908344, ECO:0000269|PubMed:14702039,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.5"
FT /id="VAR_023424"
FT VARIANT 307
FT /note="I -> V (in dbSNP:rs45569933)"
FT /evidence="ECO:0000269|Ref.5"
FT /id="VAR_023425"
FT MUTAGEN 27
FT /note="I->A: Lower activity toward PCNA
FT monoubiquitination."
FT /evidence="ECO:0000269|PubMed:21549715"
FT MUTAGEN 442
FT /note="S->A: Does not interact with SLF1 and is defective
FT in restoring cell survival after DNA damage; when
FT associated with A-444."
FT /evidence="ECO:0000269|PubMed:22036607,
FT ECO:0000269|PubMed:25931565"
FT MUTAGEN 444
FT /note="S->A: Does not interact with SLF1 and is defective
FT in restoring cell survival after DNA damage; when
FT associated with A-442."
FT /evidence="ECO:0000269|PubMed:22036607,
FT ECO:0000269|PubMed:25931565"
FT CONFLICT 191
FT /note="P -> L (in Ref. 2; AAF80856)"
FT /evidence="ECO:0000305"
FT CONFLICT 482..484
FT /note="ESA -> GKC (in Ref. 2; AAF80856)"
FT /evidence="ECO:0000305"
FT HELIX 11..16
FT /evidence="ECO:0007829|PDB:2Y43"
FT HELIX 17..22
FT /evidence="ECO:0007829|PDB:2Y43"
FT TURN 26..28
FT /evidence="ECO:0007829|PDB:2Y43"
FT STRAND 33..37
FT /evidence="ECO:0007829|PDB:2Y43"
FT TURN 39..41
FT /evidence="ECO:0007829|PDB:2Y43"
FT STRAND 44..46
FT /evidence="ECO:0007829|PDB:2Y43"
FT HELIX 47..54
FT /evidence="ECO:0007829|PDB:2Y43"
FT TURN 61..63
FT /evidence="ECO:0007829|PDB:2Y43"
FT HELIX 69..71
FT /evidence="ECO:0007829|PDB:2Y43"
FT HELIX 76..90
FT /evidence="ECO:0007829|PDB:2Y43"
FT STRAND 201..204
FT /evidence="ECO:0007829|PDB:2MRE"
FT TURN 205..208
FT /evidence="ECO:0007829|PDB:2MRE"
FT STRAND 209..212
FT /evidence="ECO:0007829|PDB:2MRE"
FT HELIX 213..223
FT /evidence="ECO:0007829|PDB:2MRE"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:5VF0"
FT HELIX 342..345
FT /evidence="ECO:0007829|PDB:2YBF"
FT HELIX 347..358
FT /evidence="ECO:0007829|PDB:2YBF"
SQ SEQUENCE 495 AA; 56223 MW; 744A053A50C65DD7 CRC64;
MDSLAESRWP PGLAVMKTID DLLRCGICFE YFNIAMIIPQ CSHNYCSLCI RKFLSYKTQC
PTCCVTVTEP DLKNNRILDE LVKSLNFARN HLLQFALESP AKSPASSSSK NLAVKVYTPV
ASRQSLKQGS RLMDNFLIRE MSGSTSELLI KENKSKFSPQ KEASPAAKTK ETRSVEEIAP
DPSEAKRPEP PSTSTLKQVT KVDCPVCGVN IPESHINKHL DSCLSREEKK ESLRSSVHKR
KPLPKTVYNL LSDRDLKKKL KEHGLSIQGN KQQLIKRHQE FVHMYNAQCD ALHPKSAAEI
VREIENIEKT RMRLEASKLN ESVMVFTKDQ TEKEIDEIHS KYRKKHKSEF QLLVDQARKG
YKKIAGMSQK TVTITKEDES TEKLSSVCMG QEDNMTSVTN HFSQSKLDSP EELEPDREED
SSSCIDIQEV LSSSESDSCN SSSSDIIRDL LEEEEAWEAS HKNDLQDTEI SPRQNRRTRA
AESAEIEPRN KRNRN
