ID XPC_HUMAN Reviewed; 940 AA. AC Q01831; B4DIP3; E9PB96; E9PH69; Q53GT7; Q96AX0; DT 01-JUL-1993, integrated into UniProtKB/Swiss-Prot. DT 18-MAY-2010, sequence version 4. DT 27-MAR-2024, entry version 222. DE RecName: Full=DNA repair protein complementing XP-C cells; DE AltName: Full=Xeroderma pigmentosum group C-complementing protein; DE AltName: Full=p125; GN Name=XPC; Synonyms=XPCC; 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] (ISOFORM 1), PROTEIN SEQUENCE OF 2-55, AND RP VARIANTS VAL-499 AND LYS-939. RX PubMed=8168482; DOI=10.1002/j.1460-2075.1994.tb06452.x; RA Masutani C., Sugasawa K., Yanagisawa J., Sonoyama T., Ui M., Enomoto T., RA Takio K., Tanaka K., van der Spek P.J., Bootsma D., Hoeijmakers J.H.J., RA Hanaoka F.; RT "Purification and cloning of a nucleotide excision repair complex involving RT the Xeroderma pigmentosum group C protein and a human homologue of yeast RT RAD23."; RL EMBO J. 13:1831-1843(1994). RN [2] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS VAL-499 AND LYS-939, AND RP ALTERNATIVE SPLICING. RX PubMed=12177305; DOI=10.1093/nar/gkf469; RA Khan S.G., Muniz-Medina V., Shahlavi T., Baker C.C., Inui H., Ueda T., RA Emmert S., Schneider T.D., Kraemer K.H.; RT "The human XPC DNA repair gene: arrangement, splice site information RT content and influence of a single nucleotide polymorphism in a splice RT acceptor site on alternative splicing and function."; RL Nucleic Acids Res. 30:3624-3631(2002). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3). RC TISSUE=Fetal brain; RX PubMed=24722188; DOI=10.1038/ncomms4650; RA Corominas R., Yang X., Lin G.N., Kang S., Shen Y., Ghamsari L., Broly M., RA Rodriguez M., Tam S., Wanamaker S.A., Fan C., Yi S., Tasan M., Lemmens I., RA Kuang X., Zhao N., Malhotra D., Michaelson J.J., Vacic V., Calderwood M.A., RA Roth F.P., Tavernier J., Horvath S., Salehi-Ashtiani K., Korkin D., RA Sebat J., Hill D.E., Hao T., Vidal M., Iakoucheva L.M.; RT "Protein interaction network of alternatively spliced isoforms from brain RT links genetic risk factors for autism."; RL Nat. Commun. 5:3650-3650(2014). RN [4] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS VAL-16; PHE-48; ARG-86; RP GLN-314; HIS-492; VAL-499; ILE-513; GLU-632; HIS-671; MET-689; GLN-928 AND RP LYS-939. RG NIEHS SNPs program; RL Submitted (JUL-2002) to the EMBL/GenBank/DDBJ databases. RN [5] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2). RC TISSUE=Hippocampus; 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 [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] (ISOFORM 1). RC TISSUE=Testis; 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 NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] OF 69-940 (ISOFORM 1). RC TISSUE=Liver; RA Suzuki Y., Sugano S., Totoki Y., Toyoda A., Takeda T., Sakaki Y., RA Tanaka A., Yokoyama S.; RL Submitted (APR-2005) to the EMBL/GenBank/DDBJ databases. RN [9] RP NUCLEOTIDE SEQUENCE [MRNA] OF 119-940 (ISOFORM 1). RX PubMed=1522891; DOI=10.1038/359070a0; RA Legerski R.J., Peterson C.A.; RT "Expression cloning of a human DNA repair gene involved in Xeroderma RT pigmentosum group C."; RL Nature 359:70-73(1992). RN [10] RP ERRATUM OF PUBMED:1522891. RX PubMed=1461286; DOI=10.1038/360610b0; RA Legerski R.J., Peterson C.A.; RL Nature 360:610-610(1992). RN [11] RP SUBCELLULAR LOCATION. RX PubMed=8692695; DOI=10.1093/nar/24.13.2551; RA van der Spek P.J., Eker A., Rademakers S., Visser C., Sugasawa K., RA Masutani C., Hanaoka F., Bootsma D., Hoeijmakers J.H.; RT "XPC and human homologs of RAD23: intracellular localization and RT relationship to other nucleotide excision repair complexes."; RL Nucleic Acids Res. 24:2551-2559(1996). RN [12] RP INTERACTION WITH RAD23A. RX PubMed=9372924; DOI=10.1128/mcb.17.12.6924; 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., Aboussekhra A., RA Wood R.D., Hanaoka F., Bootsma D., Hoeijmakers J.H.; RT "Two human homologs of Rad23 are functionally interchangeable in complex RT formation and stimulation of XPC repair activity."; RL Mol. Cell. Biol. 17:6924-6931(1997). RN [13] RP FUNCTION OF THE XPC COMPLEX. RX PubMed=9734359; DOI=10.1016/s1097-2765(00)80132-x; RA Sugasawa K., Ng J.M., Masutani C., Iwai S., van der Spek P.J., Eker A.P., RA Hanaoka F., Bootsma D., Hoeijmakers J.H.; RT "Xeroderma pigmentosum group C protein complex is the initiator of global RT genome nucleotide excision repair."; RL Mol. Cell 2:223-232(1998). RN [14] RP FUNCTION, SUBUNIT, AND INTERACTION WITH CCNH; GTF2H1 AND ERCC3. RX PubMed=10734143; DOI=10.1074/jbc.275.13.9870; RA Yokoi M., Masutani C., Maekawa T., Sugasawa K., Ohkuma Y., Hanaoka F.; RT "The xeroderma pigmentosum group C protein complex XPC-HR23B plays an RT important role in the recruitment of transcription factor IIH to damaged RT DNA."; RL J. Biol. Chem. 275:9870-9875(2000). RN [15] RP FUNCTION OF THE XPC COMPLEX. RX PubMed=10873465; DOI=10.1006/jmbi.2000.3857; RA Batty D., Rapic'-Otrin V., Levine A.S., Wood R.D.; RT "Stable binding of human XPC complex to irradiated DNA confers strong RT discrimination for damaged sites."; RL J. Mol. Biol. 300:275-290(2000). RN [16] RP INTERACTION WITH CETN2 AND RAD23B, SUBCELLULAR LOCATION, AND RP CHARACTERIZATION OF THE XPC COMPLEX. RX PubMed=11279143; DOI=10.1074/jbc.m100855200; RA Araki M., Masutani C., Takemura M., Uchida A., Sugasawa K., Kondoh J., RA Ohkuma Y., Hanaoka F.; RT "Centrosome protein centrin 2/caltractin 1 is part of the xeroderma RT pigmentosum group C complex that initiates global genome nucleotide RT excision repair."; RL J. Biol. Chem. 276:18665-18672(2001). RN [17] RP FUNCTION OF THE XPC COMPLEX. RX PubMed=12509299; DOI=10.1016/s1568-7864(01)00008-8; RA Sugasawa K., Shimizu Y., Iwai S., Hanaoka F.; RT "A molecular mechanism for DNA damage recognition by the xeroderma RT pigmentosum group C protein complex."; RL DNA Repair 1:95-107(2002). RN [18] RP DNA-BINDING, AND INTERACTION WITH RAD23B; ERCC2 AND GTF2H1. RX PubMed=12509233; DOI=10.1016/s1568-7864(02)00031-9; RA Uchida A., Sugasawa K., Masutani C., Dohmae N., Araki M., Yokoi M., RA Ohkuma Y., Hanaoka F.; RT "The carboxy-terminal domain of the XPC protein plays a crucial role in RT nucleotide excision repair through interactions with transcription factor RT IIH."; RL DNA Repair 1:449-461(2002). RN [19] RP FUNCTION OF THE XPC COMPLEX. RX PubMed=12547395; DOI=10.1016/s1568-7864(02)00222-7; RA Janicijevic A., Sugasawa K., Shimizu Y., Hanaoka F., Wijgers N., RA Djurica M., Hoeijmakers J.H., Wyman C.; RT "DNA bending by the human damage recognition complex XPC-HR23B."; RL DNA Repair 2:325-336(2003). RN [20] RP INTERACTION WITH TDG. RX PubMed=12505994; DOI=10.1093/emboj/cdg016; RA Shimizu Y., Iwai S., Hanaoka F., Sugasawa K.; RT "Xeroderma pigmentosum group C protein interacts physically and RT functionally with thymine DNA glycosylase."; RL EMBO J. 22:164-173(2003). RN [21] RP UBIQUITINATION, AND INTERACTION WITH DDB2. RX PubMed=15882621; DOI=10.1016/j.cell.2005.02.035; RA Sugasawa K., Okuda Y., Saijo M., Nishi R., Matsuda N., Chu G., Mori T., RA Iwai S., Tanaka K., Tanaka K., Hanaoka F.; RT "UV-induced ubiquitylation of XPC protein mediated by UV-DDB-ubiquitin RT ligase complex."; RL Cell 121:387-400(2005). RN [22] RP INTERACTION WITH CETN2 AND RAD23B, AND MUTAGENESIS OF TRP-848; LEU-851 AND RP LEU-855. RX PubMed=15964821; DOI=10.1128/mcb.25.13.5664-5674.2005; RA Nishi R., Okuda Y., Watanabe E., Mori T., Iwai S., Masutani C., RA Sugasawa K., Hanaoka F.; RT "Centrin 2 stimulates nucleotide excision repair by interacting with RT xeroderma pigmentosum group C protein."; RL Mol. Cell. Biol. 25:5664-5674(2005). RN [23] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94 AND SER-129, AND RP IDENTIFICATION BY 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 [24] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Prostate cancer; RX PubMed=17487921; DOI=10.1002/elps.200600782; RA Giorgianni F., Zhao Y., Desiderio D.M., Beranova-Giorgianni S.; RT "Toward a global characterization of the phosphoproteome in prostate cancer RT cells: identification of phosphoproteins in the LNCaP cell line."; RL Electrophoresis 28:2027-2034(2007). RN [25] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Embryonic kidney; RX PubMed=17525332; DOI=10.1126/science.1140321; RA Matsuoka S., Ballif B.A., Smogorzewska A., McDonald E.R. III, Hurov K.E., RA Luo J., Bakalarski C.E., Zhao Z., Solimini N., Lerenthal Y., Shiloh Y., RA 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 [26] RP IDENTIFICATION BY 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 [27] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94; THR-169; SER-883; SER-884 RP AND SER-891, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE RP 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 [28] RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=18318008; DOI=10.1002/pmic.200700884; RA Han G., Ye M., Zhou H., Jiang X., Feng S., Jiang X., Tian R., Wan D., RA Zou H., Gu J.; RT "Large-scale phosphoproteome analysis of human liver tissue by enrichment RT and fractionation of phosphopeptides with strong anion exchange RT chromatography."; RL Proteomics 8:1346-1361(2008). RN [29] 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 [30] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94; SER-129; SER-883 AND RP SER-884, AND 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 [31] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94; THR-876; SER-883 AND RP SER-884, AND 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 [32] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-883 AND SER-884, AND RP 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 [33] RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-94; SER-140; SER-397; RP SER-398; SER-399; SER-453; SER-460; SER-883; SER-884 AND SER-903, AND RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS]. RC TISSUE=Liver; RX PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014; RA Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L., RA Ye M., Zou H.; RT "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver RT phosphoproteome."; RL J. Proteomics 96:253-262(2014). RN [34] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-81, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033; RA Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V., RA Vertegaal A.C.; RT "SUMO-2 orchestrates chromatin modifiers in response to DNA damage."; RL Cell Rep. 10:1778-1791(2015). RN [35] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-81, AND IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS]. RX PubMed=25755297; DOI=10.1074/mcp.o114.044792; RA Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V., RA Vertegaal A.C.; RT "System-wide analysis of SUMOylation dynamics in response to replication RT stress reveals novel small ubiquitin-like modified target proteins and RT acceptor lysines relevant for genome stability."; RL Mol. Cell. Proteomics 14:1419-1434(2015). RN [36] RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-41; LYS-81; LYS-89 AND LYS-161, RP AND IDENTIFICATION BY MASS 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 [37] RP CHARACTERIZATION OF VARIANT XP-C SER-690. RX PubMed=17682058; DOI=10.1128/mcb.02166-06; RA Yasuda G., Nishi R., Watanabe E., Mori T., Iwai S., Orioli D., RA Stefanini M., Hanaoka F., Sugasawa K.; RT "In vivo destabilization and functional defects of the xeroderma RT pigmentosum C protein caused by a pathogenic missense mutation."; RL Mol. Cell. Biol. 27:6606-6614(2007). RN [38] RP CHARACTERIZATION OF VARIANT XP-C SER-690, AND MUTAGENESIS OF PHE-733. RX PubMed=17355181; DOI=10.1371/journal.pbio.0050079; RA Maillard O., Solyom S., Naegeli H.; RT "An aromatic sensor with aversion to damaged strands confers versatility to RT DNA repair."; RL PLoS Biol. 5:E79-E79(2007). RN [39] RP SUBCELLULAR LOCATION. RX PubMed=18682493; DOI=10.1242/jcs.031708; RA Hoogstraten D., Bergink S., Ng J.M., Verbiest V.H., Luijsterburg M.S., RA Geverts B., Raams A., Dinant C., Hoeijmakers J.H., Vermeulen W., RA Houtsmuller A.B.; RT "Versatile DNA damage detection by the global genome nucleotide excision RT repair protein XPC."; RL J. Cell Sci. 121:2850-2859(2008). RN [40] RP ERRATUM OF PUBMED:18682493. RA Hoogstraten D., Bergink S., Ng J.M., Verbiest V.H., Luijsterburg M.S., RA Geverts B., Raams A., Dinant C., Hoeijmakers J.H., Vermeulen W., RA Houtsmuller A.B.; RL J. Cell Sci. 121:2972-2972(2008). RN [41] RP ERRATUM OF PUBMED:18682493. RA Hoogstraten D., Bergink S., Ng J.M., Verbiest V.H., Luijsterburg M.S., RA Geverts B., Raams A., Dinant C., Hoeijmakers J.H., Vermeulen W., RA Houtsmuller A.B.; RL J. Cell Sci. 121:3991-3991(2008). RN [42] RP FUNCTION, CHARACTERIZATION OF VARIANT OF VARIANT XP-C SER-690, AND RP MUTAGENESIS OF TRP-531; TRP-542; PHE-733 AND GLU-755. RX PubMed=19609301; DOI=10.1038/emboj.2009.187; RA Camenisch U., Trautlein D., Clement F.C., Fei J., Leitenstorfer A., RA Ferrando-May E., Naegeli H.; RT "Two-stage dynamic DNA quality check by xeroderma pigmentosum group C RT protein."; RL EMBO J. 28:2387-2399(2009). RN [43] RP FUNCTION OF THE XPC COMPLEX. RX PubMed=19941824; DOI=10.1016/j.molcel.2009.09.035; RA Sugasawa K., Akagi J., Nishi R., Iwai S., Hanaoka F.; RT "Two-step recognition of DNA damage for mammalian nucleotide excision RT repair: Directional binding of the XPC complex and DNA strand scanning."; RL Mol. Cell 36:642-653(2009). RN [44] RP FUNCTION, AND MUTAGENESIS OF ASN-754; PHE-756; PHE-797 AND PHE-799. RX PubMed=20649465; DOI=10.1089/ars.2010.3399; RA Clement F.C., Kaczmarek N., Mathieu N., Tomas M., Leitenstorfer A., RA Ferrando-May E., Naegeli H.; RT "Dissection of the xeroderma pigmentosum group C protein function by site- RT directed mutagenesis."; RL Antioxid. Redox Signal. 14:2479-2490(2011). RN [45] RP FUNCTION OF THE XPC COMPLEX. RX PubMed=20028083; DOI=10.1021/bi901575h; RA Neher T.M., Rechkunova N.I., Lavrik O.I., Turchi J.J.; RT "Photo-cross-linking of XPC-Rad23B to cisplatin-damaged DNA reveals RT contacts with both strands of the DNA duplex and spans the DNA adduct."; RL Biochemistry 49:669-678(2010). RN [46] RP FUNCTION OF THE XPC COMPLEX, AND INTERACTION WITH TDG AND SMUG1. RX PubMed=20798892; DOI=10.4061/2010/805698; RA Shimizu Y., Uchimura Y., Dohmae N., Saitoh H., Hanaoka F., Sugasawa K.; RT "Stimulation of DNA glycosylase activities by XPC Protein Complex: Roles of RT protein-protein interactions."; RL J. Nucleic Acids 2010:455-459(2010). RN [47] RP UBIQUITINATION, AND SUMOYLATION. RX PubMed=23751493; DOI=10.1083/jcb.201212075; RA Poulsen S.L., Hansen R.K., Wagner S.A., van Cuijk L., van Belle G.J., RA Streicher W., Wikstroem M., Choudhary C., Houtsmuller A.B., Marteijn J.A., RA Bekker-Jensen S., Mailand N.; RT "RNF111/Arkadia is a SUMO-targeted ubiquitin ligase that facilitates the RT DNA damage response."; RL J. Cell Biol. 201:797-807(2013). RN [48] RP FUNCTION, INTERACTION WITH E2F1 AND KAT2A, AND CHARACTERIZATION OF VARIANT RP XP-C HIS-334. RX PubMed=29973595; DOI=10.1038/s41467-018-05010-0; RA Bidon B., Iltis I., Semer M., Nagy Z., Larnicol A., Cribier A., RA Benkirane M., Coin F., Egly J.M., Le May N.; RT "XPC is an RNA polymerase II cofactor recruiting ATAC to promoters by RT interacting with E2F1."; RL Nat. Commun. 9:2610-2610(2018). RN [49] RP INTERACTION WITH KAT2A. RX PubMed=31527837; DOI=10.1038/s41589-019-0354-y; RA Semer M., Bidon B., Larnicol A., Caliskan G., Catez P., Egly J.M., Coin F., RA Le May N.; RT "DNA repair complex licenses acetylation of H2A.Z.1 by KAT2A during RT transcription."; RL Nat. Chem. Biol. 15:992-1000(2019). RN [50] RP STRUCTURE BY NMR OF 847-863 IN COMPLEX WITH CETN2. RX PubMed=16533048; DOI=10.1021/bi0524868; RA Yang A., Miron S., Mouawad L., Duchambon P., Blouquit Y., Craescu C.T.; RT "Flexibility and plasticity of human centrin 2 binding to the xeroderma RT pigmentosum group C protein (XPC) from nuclear excision repair."; RL Biochemistry 45:3653-3663(2006). RN [51] RP X-RAY CRYSTALLOGRAPHY (2.35 ANGSTROMS) OF 847-863 IN COMPLEX WITH CETN2. RX PubMed=16627479; DOI=10.1074/jbc.m513667200; RA Thompson J.R., Ryan Z.C., Salisbury J.L., Kumar R.; RT "The structure of the human centrin 2-xeroderma pigmentosum group C protein RT complex."; RL J. Biol. Chem. 281:18746-18752(2006). RN [52] RP X-RAY CRYSTALLOGRAPHY (1.8 ANGSTROMS) OF 847-863 IN COMPLEX WITH CETN2. RX PubMed=17897675; DOI=10.1016/j.jmb.2007.08.046; RA Charbonnier J.B., Renaud E., Miron S., Le Du M.H., Blouquit Y., RA Duchambon P., Christova P., Shosheva A., Rose T., Angulo J.F., RA Craescu C.T.; RT "Structural, thermodynamic, and cellular characterization of human centrin RT 2 interaction with xeroderma pigmentosum group C protein."; RL J. Mol. Biol. 373:1032-1046(2007). RN [53] RP REVIEW ON VARIANTS XP-C. RX PubMed=10447254; RX DOI=10.1002/(sici)1098-1004(1999)14:1<9::aid-humu2>3.0.co;2-6; RA Cleaver J.E., Thompson L.H., Richardson A.S., States J.C.; RT "A summary of mutations in the UV-sensitive disorders: xeroderma RT pigmentosum, Cockayne syndrome, and trichothiodystrophy."; RL Hum. Mutat. 14:9-22(1999). RN [54] RP VARIANTS XP-C HIS-334 AND VAL-697 INS. RX PubMed=8298653; DOI=10.1038/ng1293-413; RA Li L., Bales E.S., Peterson C.A., Legerski R.J.; RT "Characterization of molecular defects in Xeroderma pigmentosum group C."; RL Nat. Genet. 5:413-417(1993). RN [55] RP VARIANT XP-C SER-690. RX PubMed=10766188; RA Chavanne F., Broughton B.C., Pietra D., Nardo T., Browitt A., Lehmann A.R., RA Stefanini M.; RT "Mutations in the XPC gene in families with xeroderma pigmentosum and RT consequences at the cell, protein, and transcript levels."; RL Cancer Res. 60:1974-1982(2000). CC -!- FUNCTION: Involved in global genome nucleotide excision repair (GG-NER) CC by acting as damage sensing and DNA-binding factor component of the XPC CC complex (PubMed:10734143, PubMed:19609301, PubMed:20649465, CC PubMed:9734359, PubMed:10873465, PubMed:12509299, PubMed:12547395, CC PubMed:19941824, PubMed:20028083, PubMed:20798892). Has only a low DNA CC repair activity by itself which is stimulated by RAD23B and RAD23A. Has CC a preference to bind DNA containing a short single-stranded segment but CC not to damaged oligonucleotides (PubMed:10734143, PubMed:19609301, CC PubMed:20649465). This feature is proposed to be related to a dynamic CC sensor function: XPC can rapidly screen duplex DNA for non-hydrogen- CC bonded bases by forming a transient nucleoprotein intermediate complex CC which matures into a stable recognition complex through an intrinsic CC single-stranded DNA-binding activity (PubMed:10734143, PubMed:19609301, CC PubMed:20649465). The XPC complex is proposed to represent the first CC factor bound at the sites of DNA damage and together with other core CC recognition factors, XPA, RPA and the TFIIH complex, is part of the CC pre-incision (or initial recognition) complex (PubMed:9734359, CC PubMed:10873465, PubMed:12509299, PubMed:12547395, PubMed:19941824, CC PubMed:20028083, PubMed:20798892). The XPC complex recognizes a wide CC spectrum of damaged DNA characterized by distortions of the DNA helix CC such as single-stranded loops, mismatched bubbles or single-stranded CC overhangs (PubMed:9734359, PubMed:10873465, PubMed:12509299, CC PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892). CC The orientation of XPC complex binding appears to be crucial for CC inducing a productive NER (PubMed:9734359, PubMed:10873465, CC PubMed:12509299, PubMed:12547395, PubMed:19941824, PubMed:20028083, CC PubMed:20798892). XPC complex is proposed to recognize and to interact CC with unpaired bases on the undamaged DNA strand which is followed by CC recruitment of the TFIIH complex and subsequent scanning for lesions in CC the opposite strand in a 5'-to-3' direction by the NER machinery CC (PubMed:9734359, PubMed:10873465, PubMed:12509299, PubMed:12547395, CC PubMed:19941824, PubMed:20028083, PubMed:20798892). Cyclobutane CC pyrimidine dimers (CPDs) which are formed upon UV-induced DNA damage CC esacpe detection by the XPC complex due to a low degree of structural CC perurbation. Instead they are detected by the UV-DDB complex which in CC turn recruits and cooperates with the XPC complex in the respective DNA CC repair (PubMed:9734359, PubMed:10873465, PubMed:12509299, CC PubMed:12547395, PubMed:19941824, PubMed:20028083, PubMed:20798892). In CC vitro, the XPC:RAD23B dimer is sufficient to initiate NER; it CC preferentially binds to cisplatin and UV-damaged double-stranded DNA CC and also binds to a variety of chemically and structurally diverse DNA CC adducts (PubMed:20028083). XPC:RAD23B contacts DNA both 5' and 3' of a CC cisplatin lesion with a preference for the 5' side. XPC:RAD23B induces CC a bend in DNA upon binding. XPC:RAD23B stimulates the activity of DNA CC glycosylases TDG and SMUG1 (PubMed:20028083). CC {ECO:0000269|PubMed:10734143, ECO:0000269|PubMed:10873465, CC ECO:0000269|PubMed:12509299, ECO:0000269|PubMed:12547395, CC ECO:0000269|PubMed:19609301, ECO:0000269|PubMed:19941824, CC ECO:0000269|PubMed:20028083, ECO:0000269|PubMed:20649465, CC ECO:0000269|PubMed:20798892, ECO:0000269|PubMed:9734359}. CC -!- FUNCTION: In absence of DNA repair, the XPC complex also acts as a CC transcription coactivator: XPC interacts with the DNA-binding CC transcription factor E2F1 at a subset of promoters to recruit KAT2A and CC histone acetyltransferase complexes (HAT) (PubMed:29973595, CC PubMed:31527837). KAT2A recruitment specifically promotes acetylation CC of histone variant H2A.Z.1/H2A.Z, but not H2A.Z.2/H2A.V, thereby CC promoting expression of target genes (PubMed:31527837). CC {ECO:0000269|PubMed:29973595, ECO:0000269|PubMed:31527837}. CC -!- SUBUNIT: Component of the XPC complex composed of XPC, RAD23B and CETN2 CC (PubMed:11279143, PubMed:12509233, PubMed:15964821, PubMed:17897675, CC PubMed:16627479, PubMed:16533048). Interacts with RAD23A; the CC interaction is suggesting the existence of a functional equivalent CC variant XPC complex (PubMed:9372924). Interacts with TDG; the CC interaction is demonstrated using the XPC:RAD23B dimer CC (PubMed:12505994, PubMed:20798892). Interacts with SMUG1; the CC interaction is demonstrated using the XPC:RAD23B dimer CC (PubMed:20798892). Interacts with DDB2 (PubMed:15882621). Interacts CC with CCNH, GTF2H1 and ERCC3 (PubMed:10734143, PubMed:12509233). CC Interacts with E2F1 and KAT2A; leading to KAT2A recruitment to CC promoters and subsequent acetylation of histones (PubMed:29973595, CC PubMed:31527837). {ECO:0000269|PubMed:10734143, CC ECO:0000269|PubMed:11279143, ECO:0000269|PubMed:12505994, CC ECO:0000269|PubMed:12509233, ECO:0000269|PubMed:15882621, CC ECO:0000269|PubMed:15964821, ECO:0000269|PubMed:16533048, CC ECO:0000269|PubMed:16627479, ECO:0000269|PubMed:17897675, CC ECO:0000269|PubMed:20798892, ECO:0000269|PubMed:29973595, CC ECO:0000269|PubMed:31527837, ECO:0000269|PubMed:9372924}. CC -!- INTERACTION: CC Q01831; P41208: CETN2; NbExp=10; IntAct=EBI-372610, EBI-1789926; CC Q01831; P19447: ERCC3; NbExp=3; IntAct=EBI-372610, EBI-1183307; CC Q01831; P32780: GTF2H1; NbExp=3; IntAct=EBI-372610, EBI-715539; CC Q01831; P62195: PSMC5; NbExp=2; IntAct=EBI-372610, EBI-357745; CC Q01831; P54727: RAD23B; NbExp=12; IntAct=EBI-372610, EBI-954531; CC Q01831; P13288: BGLF4; Xeno; NbExp=9; IntAct=EBI-372610, EBI-1630636; CC Q01831-1; Q92466: DDB2; NbExp=4; IntAct=EBI-15950383, EBI-1176171; CC Q01831-1; P32780: GTF2H1; NbExp=3; IntAct=EBI-15950383, EBI-715539; CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:11279143, CC ECO:0000269|PubMed:18682493, ECO:0000269|PubMed:8692695}. Chromosome CC {ECO:0000269|PubMed:29973595}. Cytoplasm {ECO:0000269|PubMed:18682493}. CC Note=Omnipresent in the nucleus and consistently associates with and CC dissociates from DNA in the absence of DNA damage (PubMed:18682493). CC Continuously shuttles between the cytoplasm and the nucleus, which is CC impeded by the presence of NER lesions (PubMed:18682493). CC {ECO:0000269|PubMed:18682493}. CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=3; CC Name=1; CC IsoId=Q01831-1; Sequence=Displayed; CC Name=2; CC IsoId=Q01831-2; Sequence=VSP_046344; CC Name=3; Synonyms=B; CC IsoId=Q01831-3; Sequence=VSP_055890, VSP_055891; CC -!- PTM: Ubiquitinated upon UV irradiation; the ubiquitination requires the CC UV-DDB complex, appears to be reversible and does not serve as a signal CC for degradation (PubMed:15882621, PubMed:23751493). Ubiquitinated by CC RNF11 via 'Lys-63'-linked ubiquitination (PubMed:23751493). CC Ubiquitination by RNF111 is polysumoylation-dependent and promotes CC nucleotide excision repair (PubMed:23751493). CC {ECO:0000269|PubMed:15882621, ECO:0000269|PubMed:23751493}. CC -!- PTM: Sumoylated; sumoylation promotes ubiquitination by RNF111. CC {ECO:0000269|PubMed:23751493}. CC -!- DISEASE: Xeroderma pigmentosum complementation group C (XP-C) CC [MIM:278720]: An autosomal recessive pigmentary skin disorder CC characterized by solar hypersensitivity of the skin, high CC predisposition for developing cancers on areas exposed to sunlight and, CC in some cases, neurological abnormalities. The skin develops marked CC freckling and other pigmentation abnormalities. CC {ECO:0000269|PubMed:10447254, ECO:0000269|PubMed:10766188, CC ECO:0000269|PubMed:17355181, ECO:0000269|PubMed:17682058, CC ECO:0000269|PubMed:19609301, ECO:0000269|PubMed:29973595, CC ECO:0000269|PubMed:8298653}. Note=The disease is caused by variants CC affecting the gene represented in this entry. CC -!- SIMILARITY: Belongs to the XPC family. {ECO:0000305}. CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and CC Haematology; CC URL="https://atlasgeneticsoncology.org/gene/122/XPC"; CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/xpc/"; 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; D21089; BAA04651.1; -; mRNA. DR EMBL; AF261901; AAF87574.1; -; Genomic_DNA. DR EMBL; AF261892; AAF87574.1; JOINED; Genomic_DNA. DR EMBL; AF261893; AAF87574.1; JOINED; Genomic_DNA. DR EMBL; AF261894; AAF87574.1; JOINED; Genomic_DNA. DR EMBL; AF261895; AAF87574.1; JOINED; Genomic_DNA. DR EMBL; AF261896; AAF87574.1; JOINED; Genomic_DNA. DR EMBL; AF261897; AAF87574.1; JOINED; Genomic_DNA. DR EMBL; AF261898; AAF87574.1; JOINED; Genomic_DNA. DR EMBL; AF261899; AAF87574.1; JOINED; Genomic_DNA. DR EMBL; AF261900; AAF87574.1; JOINED; Genomic_DNA. DR EMBL; KJ535085; AHW56724.1; -; mRNA. DR EMBL; AY131066; AAM77801.1; -; Genomic_DNA. DR EMBL; AK295711; BAG58555.1; -; mRNA. DR EMBL; AC093495; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; FJ695191; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; FJ695192; -; NOT_ANNOTATED_CDS; Genomic_DNA. DR EMBL; BC016620; AAH16620.1; -; mRNA. DR EMBL; AK222844; BAD96564.1; -; mRNA. DR EMBL; X65024; CAA46158.1; -; mRNA. DR CCDS; CCDS46763.1; -. [Q01831-1] DR PIR; S44345; S44345. DR RefSeq; NP_004619.3; NM_004628.4. [Q01831-1] DR PDB; 2A4J; NMR; -; B=847-863. DR PDB; 2GGM; X-ray; 2.35 A; C/D=847-863. DR PDB; 2OBH; X-ray; 1.80 A; C/D=847-863. DR PDB; 2RVB; NMR; -; A=109-156. DR PDB; 8EBS; EM; 4.00 A; H=1-940. DR PDB; 8EBT; EM; 3.90 A; H=635-940. DR PDB; 8EBU; EM; 3.30 A; H=1-940. DR PDB; 8EBV; EM; 7.10 A; H=1-940. DR PDB; 8EBW; EM; 5.60 A; H=1-940. DR PDB; 8EBX; EM; 3.60 A; H=1-940. DR PDB; 8EBY; EM; 3.60 A; H=1-940. DR PDBsum; 2A4J; -. DR PDBsum; 2GGM; -. DR PDBsum; 2OBH; -. DR PDBsum; 2RVB; -. DR PDBsum; 8EBS; -. DR PDBsum; 8EBT; -. DR PDBsum; 8EBU; -. DR PDBsum; 8EBV; -. DR PDBsum; 8EBW; -. DR PDBsum; 8EBX; -. DR PDBsum; 8EBY; -. DR AlphaFoldDB; Q01831; -. DR BMRB; Q01831; -. DR EMDB; EMD-27997; -. DR EMDB; EMD-6495; -. DR EMDB; EMD-6497; -. DR EMDB; EMD-6498; -. DR SMR; Q01831; -. DR BioGRID; 113345; 178. DR ComplexPortal; CPX-2669; XPC complex, RAD23B variant. DR ComplexPortal; CPX-2672; XPC complex, RAD23A variant. DR DIP; DIP-31225N; -. DR IntAct; Q01831; 129. DR MINT; Q01831; -. DR STRING; 9606.ENSP00000285021; -. DR GlyGen; Q01831; 2 sites, 1 O-linked glycan (2 sites). DR iPTMnet; Q01831; -. DR PhosphoSitePlus; Q01831; -. DR SwissPalm; Q01831; -. DR BioMuta; XPC; -. DR DMDM; 296453081; -. DR EPD; Q01831; -. DR jPOST; Q01831; -. DR MassIVE; Q01831; -. DR MaxQB; Q01831; -. DR PaxDb; 9606-ENSP00000285021; -. DR PeptideAtlas; Q01831; -. DR ProteomicsDB; 19176; -. DR ProteomicsDB; 20470; -. DR ProteomicsDB; 58003; -. [Q01831-1] DR Pumba; Q01831; -. DR Antibodypedia; 4092; 369 antibodies from 31 providers. DR DNASU; 7508; -. DR Ensembl; ENST00000285021.12; ENSP00000285021.8; ENSG00000154767.15. [Q01831-1] DR Ensembl; ENST00000476581.6; ENSP00000424548.1; ENSG00000154767.15. [Q01831-3] DR GeneID; 7508; -. DR KEGG; hsa:7508; -. DR MANE-Select; ENST00000285021.12; ENSP00000285021.8; NM_004628.5; NP_004619.3. DR UCSC; uc062gzd.1; human. [Q01831-1] DR AGR; HGNC:12816; -. DR CTD; 7508; -. DR DisGeNET; 7508; -. DR GeneCards; XPC; -. DR GeneReviews; XPC; -. DR HGNC; HGNC:12816; XPC. DR HPA; ENSG00000154767; Low tissue specificity. DR MalaCards; XPC; -. DR MIM; 278720; phenotype. DR MIM; 613208; gene. DR neXtProt; NX_Q01831; -. DR OpenTargets; ENSG00000154767; -. DR Orphanet; 910; Xeroderma pigmentosum. DR PharmGKB; PA37413; -. DR VEuPathDB; HostDB:ENSG00000154767; -. DR eggNOG; KOG2179; Eukaryota. DR GeneTree; ENSGT00390000005194; -. DR HOGENOM; CLU_009925_1_1_1; -. DR InParanoid; Q01831; -. DR OMA; FQAKHLG; -. DR OrthoDB; 181129at2759; -. DR PhylomeDB; Q01831; -. DR TreeFam; TF101242; -. DR PathwayCommons; Q01831; -. DR Reactome; R-HSA-3108214; SUMOylation of DNA damage response and repair proteins. DR Reactome; R-HSA-5696394; DNA Damage Recognition in GG-NER. DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER. DR SignaLink; Q01831; -. DR SIGNOR; Q01831; -. DR BioGRID-ORCS; 7508; 14 hits in 1160 CRISPR screens. DR ChiTaRS; XPC; human. DR EvolutionaryTrace; Q01831; -. DR GeneWiki; XPC_(gene); -. DR GenomeRNAi; 7508; -. DR Pharos; Q01831; Tbio. DR PRO; PR:Q01831; -. DR Proteomes; UP000005640; Chromosome 3. DR RNAct; Q01831; Protein. DR Bgee; ENSG00000154767; Expressed in sural nerve and 204 other cell types or tissues. DR ExpressionAtlas; Q01831; baseline and differential. DR GO; GO:0000785; C:chromatin; ISS:UniProt. DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB. DR GO; GO:0005829; C:cytosol; IDA:HPA. DR GO; GO:0043231; C:intracellular membrane-bounded organelle; IDA:HPA. DR GO; GO:0005739; C:mitochondrion; IDA:HPA. DR GO; GO:0005730; C:nucleolus; IDA:HPA. DR GO; GO:0005654; C:nucleoplasm; IDA:HPA. DR GO; GO:0000109; C:nucleotide-excision repair complex; IDA:UniProtKB. DR GO; GO:0000111; C:nucleotide-excision repair factor 2 complex; IBA:GO_Central. DR GO; GO:0005634; C:nucleus; IDA:UniProtKB. DR GO; GO:0005886; C:plasma membrane; IDA:HPA. DR GO; GO:0090734; C:site of DNA damage; IEA:Ensembl. DR GO; GO:0071942; C:XPC complex; IDA:UniProtKB. DR GO; GO:0000405; F:bubble DNA binding; TAS:UniProtKB. DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB. DR GO; GO:0140612; F:DNA damage sensor activity; IDA:GO_Central. DR GO; GO:0000404; F:heteroduplex DNA loop binding; TAS:UniProtKB. DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB. DR GO; GO:0061629; F:RNA polymerase II-specific DNA-binding transcription factor binding; IEA:Ensembl. DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB. DR GO; GO:0003713; F:transcription coactivator activity; IDA:UniProtKB. DR GO; GO:0006281; P:DNA repair; TAS:ProtInc. DR GO; GO:0006298; P:mismatch repair; IBA:GO_Central. DR GO; GO:0031573; P:mitotic intra-S DNA damage checkpoint signaling; IEA:Ensembl. DR GO; GO:0006289; P:nucleotide-excision repair; IDA:UniProtKB. DR GO; GO:0045893; P:positive regulation of DNA-templated transcription; IDA:UniProtKB. DR GO; GO:0000720; P:pyrimidine dimer repair by nucleotide-excision repair; IEA:Ensembl. DR GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; IMP:UniProtKB. DR GO; GO:0010996; P:response to auditory stimulus; IEA:Ensembl. DR GO; GO:0010224; P:response to UV-B; IEA:Ensembl. DR GO; GO:0009410; P:response to xenobiotic stimulus; IEA:Ensembl. DR GO; GO:0070914; P:UV-damage excision repair; IDA:CACAO. DR DisProt; DP01626; -. DR Gene3D; 2.20.20.110; Rad4, beta-hairpin domain BHD1; 1. DR Gene3D; 3.30.70.2460; Rad4, beta-hairpin domain BHD3; 1. DR Gene3D; 3.90.260.10; Transglutaminase-like; 2. DR IDEAL; IID00164; -. DR InterPro; IPR018327; BHD_2. DR InterPro; IPR004583; DNA_repair_Rad4. DR InterPro; IPR018026; DNA_repair_Rad4-like. DR InterPro; IPR038765; Papain-like_cys_pep_sf. DR InterPro; IPR018325; Rad4/PNGase_transGLS-fold. DR InterPro; IPR018326; Rad4_beta-hairpin_dom1. DR InterPro; IPR018328; Rad4_beta-hairpin_dom3. DR InterPro; IPR042488; Rad4_BHD3_sf. DR InterPro; IPR036985; Transglutaminase-like_sf. DR NCBIfam; TIGR00605; rad4; 1. DR PANTHER; PTHR12135:SF0; DNA REPAIR PROTEIN COMPLEMENTING XP-C CELLS; 1. DR PANTHER; PTHR12135; DNA REPAIR PROTEIN XP-C / RAD4; 1. DR Pfam; PF10403; BHD_1; 1. DR Pfam; PF10404; BHD_2; 1. DR Pfam; PF10405; BHD_3; 1. DR Pfam; PF03835; Rad4; 1. DR SMART; SM01030; BHD_1; 1. DR SMART; SM01031; BHD_2; 1. DR SMART; SM01032; BHD_3; 1. DR SUPFAM; SSF54001; Cysteine proteinases; 1. DR Genevisible; Q01831; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Chromosome; Cytoplasm; KW Direct protein sequencing; Disease variant; DNA damage; DNA repair; KW DNA-binding; Isopeptide bond; Nucleus; Phosphoprotein; Reference proteome; KW Transcription; Transcription regulation; Ubl conjugation; KW Xeroderma pigmentosum. FT INIT_MET 1 FT /note="Removed" FT /evidence="ECO:0000269|PubMed:8168482" FT CHAIN 2..940 FT /note="DNA repair protein complementing XP-C cells" FT /id="PRO_0000218293" FT REGION 1..78 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 111..136 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 327..519 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT REGION 496..734 FT /note="Interaction with RAD23B" FT REGION 607..766 FT /note="Minimal sensor domain involved in damage FT recognition" FT REGION 607..741 FT /note="DNA-binding; preference for heteroduplex DNA" FT REGION 767..831 FT /note="DNA-binding; preference for single stranded DNA; FT required for formation of stable nucleoprotein complex" FT REGION 816..940 FT /note="Interaction with ERCC2 and GTF2H1" FT /evidence="ECO:0000269|PubMed:12509233" FT REGION 847..866 FT /note="Interaction with CETN2" FT REGION 866..940 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOTIF 390..395 FT /note="Nuclear localization signal" FT /evidence="ECO:0000255" FT COMPBIAS 1..46 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 121..136 FT /note="Acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 342..359 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 393..438 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 496..510 FT /note="Polar residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT COMPBIAS 905..919 FT /note="Basic and acidic residues" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT MOD_RES 94 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:18669648, ECO:0007744|PubMed:20068231, FT ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:24275569" FT MOD_RES 129 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:17081983, FT ECO:0007744|PubMed:20068231" FT MOD_RES 140 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 169 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 397 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 398 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 399 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 453 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 460 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT MOD_RES 876 FT /note="Phosphothreonine" FT /evidence="ECO:0007744|PubMed:21406692" FT MOD_RES 883 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 884 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648, FT ECO:0007744|PubMed:20068231, ECO:0007744|PubMed:21406692, FT ECO:0007744|PubMed:23186163, ECO:0007744|PubMed:24275569" FT MOD_RES 891 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:18669648" FT MOD_RES 903 FT /note="Phosphoserine" FT /evidence="ECO:0007744|PubMed:24275569" FT CROSSLNK 41 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 81 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:25755297, FT ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733" FT CROSSLNK 89 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT CROSSLNK 161 FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with FT G-Cter in SUMO2)" FT /evidence="ECO:0007744|PubMed:28112733" FT VAR_SEQ 136..172 FT /note="Missing (in isoform 2)" FT /evidence="ECO:0000303|PubMed:14702039" FT /id="VSP_046344" FT VAR_SEQ 138..140 FT /note="ELS -> VKR (in isoform 3)" FT /evidence="ECO:0000303|PubMed:24722188" FT /id="VSP_055890" FT VAR_SEQ 141..940 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:24722188" FT /id="VSP_055891" FT VARIANT 16 FT /note="L -> V (in dbSNP:rs1870134)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018894" FT VARIANT 48 FT /note="L -> F (in dbSNP:rs2229089)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018895" FT VARIANT 86 FT /note="K -> R (in dbSNP:rs3731063)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018896" FT VARIANT 287 FT /note="F -> C (in dbSNP:rs35629274)" FT /id="VAR_057475" FT VARIANT 314 FT /note="R -> Q (in dbSNP:rs3731126)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018897" FT VARIANT 334 FT /note="P -> H (in XP-C; severe; does not affect interaction FT with KAT2A and transcription coactivator activity in FT absence of DNA damage; dbSNP:rs74737358)" FT /evidence="ECO:0000269|PubMed:29973595, FT ECO:0000269|PubMed:8298653" FT /id="VAR_005846" FT VARIANT 492 FT /note="R -> H (in dbSNP:rs2227999)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018898" FT VARIANT 499 FT /note="A -> V (in dbSNP:rs2228000)" FT /evidence="ECO:0000269|PubMed:12177305, FT ECO:0000269|PubMed:8168482, ECO:0000269|Ref.4" FT /id="VAR_018899" FT VARIANT 511 FT /note="K -> Q (in dbSNP:rs6413541)" FT /id="VAR_059963" FT VARIANT 513 FT /note="M -> I (in dbSNP:rs3731130)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018900" FT VARIANT 514 FT /note="C -> S (in dbSNP:rs3731130)" FT /id="VAR_057476" FT VARIANT 632 FT /note="Q -> E (in dbSNP:rs3731139)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018901" FT VARIANT 671 FT /note="R -> H (in dbSNP:rs3731140)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018902" FT VARIANT 689 FT /note="T -> M (in dbSNP:rs3731152)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018903" FT VARIANT 690 FT /note="W -> S (in XP-C; diminishes repair activity and FT impairs DNA binding)" FT /evidence="ECO:0000269|PubMed:10766188, FT ECO:0000269|PubMed:17355181, ECO:0000269|PubMed:17682058, FT ECO:0000269|PubMed:19609301" FT /id="VAR_064039" FT VARIANT 697 FT /note="V -> VV (in XP-C; mild)" FT /evidence="ECO:0000269|PubMed:8298653" FT /id="VAR_005847" FT VARIANT 928 FT /note="K -> Q (in dbSNP:rs3731177)" FT /evidence="ECO:0000269|Ref.4" FT /id="VAR_018904" FT VARIANT 939 FT /note="Q -> K (in dbSNP:rs2228001)" FT /evidence="ECO:0000269|PubMed:12177305, FT ECO:0000269|PubMed:8168482, ECO:0000269|Ref.4" FT /id="VAR_005848" FT MUTAGEN 531 FT /note="W->A: Slightly diminishes repair activity and FT slightly impairs DNA binding." FT /evidence="ECO:0000269|PubMed:19609301" FT MUTAGEN 542 FT /note="W->A: Slightly diminishes repair activity and FT slightly impairs DNA binding." FT /evidence="ECO:0000269|PubMed:19609301" FT MUTAGEN 733 FT /note="F->A: Diminishes repair activity and impairs DNA FT binding." FT /evidence="ECO:0000269|PubMed:17355181, FT ECO:0000269|PubMed:19609301" FT MUTAGEN 754 FT /note="N->A: Reduces DNA repair activity; abolishes FT single-stranded DNA binding; reduces binding to homoduplex FT DNA; reduces localization at DNA damaged foci." FT /evidence="ECO:0000269|PubMed:20649465" FT MUTAGEN 755 FT /note="E->K: Reduces nuclear mobility and impairs repair FT activity." FT /evidence="ECO:0000269|PubMed:19609301" FT MUTAGEN 756 FT /note="F->A: Reduces DNA repair activity; abolishes FT single-stranded DNA binding; reduces binding to homoduplex FT DNA; reduces localization at DNA damaged foci." FT /evidence="ECO:0000269|PubMed:20649465" FT MUTAGEN 797 FT /note="F->A: Reduces DNA repair activity; abolishes FT single-stranded DNA binding; reduces binding to homoduplex FT DNA; reduces localization at DNA damaged foci; decreases FT recruitment of TFIIH complex to lesion sites." FT /evidence="ECO:0000269|PubMed:20649465" FT MUTAGEN 799 FT /note="F->A: Reduces DNA repair activity; abolishes FT single-stranded DNA binding; reduces binding to homoduplex FT DNA; greatly reduces localization at DNA damaged foci; FT decreases recruitment of TFIIH complex to lesion sites." FT /evidence="ECO:0000269|PubMed:20649465" FT MUTAGEN 848 FT /note="W->A: Reduces NER activity and abolishes interaction FT with CETN2; when associated with A-851 and A-855." FT /evidence="ECO:0000269|PubMed:15964821" FT MUTAGEN 851 FT /note="L->A: Reduces NER activity and abolishes interaction FT with CETN2; when associated with A-848 and A-855." FT /evidence="ECO:0000269|PubMed:15964821" FT MUTAGEN 855 FT /note="L->A: Reduces NER activity and abolishes interaction FT with CETN2; when associated with A-848 and A-851." FT /evidence="ECO:0000269|PubMed:15964821" FT CONFLICT 135 FT /note="E -> Q (in Ref. 5; BAG58555)" FT /evidence="ECO:0000305" FT CONFLICT 489 FT /note="G -> E (in Ref. 5; BAG58555)" FT /evidence="ECO:0000305" FT TURN 120..123 FT /evidence="ECO:0007829|PDB:2RVB" FT STRAND 124..126 FT /evidence="ECO:0007829|PDB:2RVB" FT STRAND 134..137 FT /evidence="ECO:0007829|PDB:2RVB" FT HELIX 150..153 FT /evidence="ECO:0007829|PDB:2RVB" FT HELIX 848..861 FT /evidence="ECO:0007829|PDB:2OBH" FT HELIX 890..901 FT /evidence="ECO:0007829|PDB:8EBU" FT TURN 905..908 FT /evidence="ECO:0007829|PDB:8EBU" FT HELIX 909..915 FT /evidence="ECO:0007829|PDB:8EBU" FT HELIX 936..938 FT /evidence="ECO:0007829|PDB:8EBU" SQ SEQUENCE 940 AA; 105953 MW; 2F8C80D43FAA1256 CRC64; MARKRAAGGE PRGRELRSQK SKAKSKARRE EEEEDAFEDE KPPKKSLLSK VSQGKRKRGC SHPGGSADGP AKKKVAKVTV KSENLKVIKD EALSDGDDLR DFPSDLKKAH HLKRGATMNE DSNEEEEESE NDWEEVEELS EPVLGDVRES TAFSRSLLPV KPVEIEIETP EQAKTRERSE KIKLEFETYL RRAMKRFNKG VHEDTHKVHL LCLLANGFYR NNICSQPDLH AIGLSIIPAR FTRVLPRDVD TYYLSNLVKW FIGTFTVNAE LSASEQDNLQ TTLERRFAIY SARDDEELVH IFLLILRALQ LLTRLVLSLQ PIPLKSATAK GKKPSKERLT ADPGGSSETS SQVLENHTKP KTSKGTKQEE TFAKGTCRPS AKGKRNKGGR KKRSKPSSSE EDEGPGDKQE KATQRRPHGR ERRVASRVSY KEESGSDEAG SGSDFELSSG EASDPSDEDS EPGPPKQRKA PAPQRTKAGS KSASRTHRGS HRKDPSLPAA SSSSSSSKRG KKMCSDGEKA EKRSIAGIDQ WLEVFCEQEE KWVCVDCVHG VVGQPLTCYK YATKPMTYVV GIDSDGWVRD VTQRYDPVWM TVTRKCRVDA EWWAETLRPY QSPFMDREKK EDLEFQAKHM DQPLPTAIGL YKNHPLYALK RHLLKYEAIY PETAAILGYC RGEAVYSRDC VHTLHSRDTW LKKARVVRLG EVPYKMVKGF SNRARKARLA EPQLREENDL GLFGYWQTEE YQPPVAVDGK VPRNEFGNVY LFLPSMMPIG CVQLNLPNLH RVARKLDIDC VQAITGFDFH GGYSHPVTDG YIVCEEFKDV LLTAWENEQA VIERKEKEKK EKRALGNWKL LAKGLLIRER LKRRYGPKSE AAAPHTDAGG GLSSDEEEGT SSQAEAARIL AASWPQNRED EEKQKLKGGP KKTKREKKAA ASHLFPFEQL //