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 27-MAR-2024, entry version 198. 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 INTERACTION WITH DDUP AND H2AX. RX PubMed=35849344; DOI=10.1093/nar/gkac611; RA Yu R., Hu Y., Zhang S., Li X., Tang M., Yang M., Wu X., Li Z., Liao X., RA Xu Y., Li M., Chen S., Qian W., Gong L.Y., Song L., Li J.; RT "LncRNA CTBP1-DT-encoded microprotein DDUP sustains DNA damage response RT signalling to trigger dual DNA repair mechanisms."; RL Nucleic Acids Res. 50:8060-8079(2022). RN [31] 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). Interacts with DNA damage up-regulated protein DDUP CC (PubMed:35849344). Forms a complex with DDUP and H2AX following DDUP CC phosphorylation (PubMed:35849344). {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 ECO:0000269|PubMed:35849344}. 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/"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 464. DR DIP; DIP-29831N; -. DR IntAct; Q9NS91; 75. DR MINT; Q9NS91; -. DR STRING; 9606.ENSP00000264926; -. DR GlyGen; Q9NS91; 3 sites, 1 O-linked glycan (3 sites). 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; 9606-ENSP00000264926; -. DR PeptideAtlas; Q9NS91; -. DR ProteomicsDB; 82515; -. DR Pumba; Q9NS91; -. DR Antibodypedia; 10148; 453 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 AGR; HGNC:18278; -. 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; IPNTGPR; -. DR OrthoDB; 6177at2759; -. 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 1199 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 male germ line stem cell (sensu Vertebrata) in testis and 145 other cell types or tissues. DR ExpressionAtlas; Q9NS91; baseline and differential. 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:0140678; F:molecular function inhibitor activity; EXP:DisProt. 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:DNA damage response; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; NAS: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 CDD; cd16529; RING-HC_RAD18; 1. DR DisProt; DP01796; -. 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 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; 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; Q9NS91; HS. 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 //