XPC_HUMAN
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 03-AUG-2022, entry version 213.
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=5; IntAct=EBI-372610, EBI-1789926;
CC Q01831; P19447: ERCC3; NbExp=2; IntAct=EBI-372610, EBI-1183307;
CC Q01831; P32780: GTF2H1; NbExp=2; IntAct=EBI-372610, EBI-715539;
CC Q01831; P62195: PSMC5; NbExp=2; IntAct=EBI-372610, EBI-357745;
CC Q01831; P54727: RAD23B; NbExp=6; 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="http://atlasgeneticsoncology.org/Genes/XPCID122.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/xpc/";
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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 PDBsum; 2A4J; -.
DR PDBsum; 2GGM; -.
DR PDBsum; 2OBH; -.
DR PDBsum; 2RVB; -.
DR AlphaFoldDB; Q01831; -.
DR BMRB; Q01831; -.
DR SMR; Q01831; -.
DR BioGRID; 113345; 146.
DR DIP; DIP-31225N; -.
DR IntAct; Q01831; 67.
DR MINT; Q01831; -.
DR STRING; 9606.ENSP00000285021; -.
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; Q01831; -.
DR PeptideAtlas; Q01831; -.
DR PRIDE; Q01831; -.
DR ProteomicsDB; 19176; -.
DR ProteomicsDB; 20470; -.
DR ProteomicsDB; 58003; -. [Q01831-1]
DR Antibodypedia; 4092; 332 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 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; PLTCYKY; -.
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 1082 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 202 other tissues.
DR ExpressionAtlas; Q01831; baseline and differential.
DR Genevisible; Q01831; HS.
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: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 transcription, DNA-templated; 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; 3.30.70.2460; -; 1.
DR Gene3D; 3.90.260.10; -; 2.
DR IDEAL; IID00164; -.
DR InterPro; IPR018327; BHD_2.
DR InterPro; IPR004583; DNA_repair_Rad4.
DR InterPro; IPR018026; DNA_repair_Rad4_subgr.
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 PANTHER; PTHR12135; PTHR12135; 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; SSF54001; 1.
DR TIGRFAMs; TIGR00605; rad4; 1.
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 single-
FT stranded DNA binding; reduces binding to homoduplex DNA;
FT 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 single-
FT stranded DNA binding; reduces binding to homoduplex DNA;
FT reduces localization at DNA damaged foci."
FT /evidence="ECO:0000269|PubMed:20649465"
FT MUTAGEN 797
FT /note="F->A: Reduces DNA repair activity; abolishes single-
FT stranded DNA binding; reduces binding to homoduplex DNA;
FT 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 single-
FT stranded DNA binding; reduces binding to homoduplex DNA;
FT greatly reduces localization at DNA damaged foci; decreases
FT 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"
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
