ERCC2_HUMAN
ID ERCC2_HUMAN Reviewed; 760 AA.
AC P18074; Q2TB78; Q2YDY2; Q7KZU6; Q8N721;
DT 01-NOV-1990, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1990, sequence version 1.
DT 03-AUG-2022, entry version 244.
DE RecName: Full=General transcription and DNA repair factor IIH helicase subunit XPD;
DE Short=TFIIH subunit XPD;
DE EC=3.6.4.12;
DE AltName: Full=Basic transcription factor 2 80 kDa subunit;
DE Short=BTF2 p80;
DE AltName: Full=CXPD;
DE AltName: Full=DNA excision repair protein ERCC-2;
DE AltName: Full=DNA repair protein complementing XP-D cells;
DE AltName: Full=TFIIH basal transcription factor complex 80 kDa subunit;
DE Short=TFIIH 80 kDa subunit;
DE Short=TFIIH p80;
DE AltName: Full=Xeroderma pigmentosum group D-complementing protein;
GN Name=ERCC2; Synonyms=XPD, XPDC;
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).
RC TISSUE=Fibroblast;
RX PubMed=2184031; DOI=10.1002/j.1460-2075.1990.tb08260.x;
RA Weber C.A., Salazar E.P., Stewart S.A., Thompson L.H.;
RT "ERCC2: cDNA cloning and molecular characterization of a human nucleotide
RT excision repair gene with high homology to yeast RAD3.";
RL EMBO J. 9:1437-1447(1990).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Fibroblast;
RX PubMed=8786141; DOI=10.1006/geno.1996.0303;
RA Lamerdin J.E., Stilwagen S.A., Ramirez M.H., Stubbs L., Carrano A.V.;
RT "Sequence analysis of the ERCC2 gene regions in human, mouse, and hamster
RT reveals three linked genes.";
RL Genomics 34:399-409(1996).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASN-312 AND GLN-751.
RG NIEHS SNPs program;
RL Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], AND VARIANT GLN-751.
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT GLN-751.
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 [7]
RP CHARACTERIZATION.
RX PubMed=1729695; DOI=10.1073/pnas.89.1.261;
RA Fletjer W.L., McDaniel L.D., Johns D., Friedberg E.C., Schultz R.A.;
RT "Correction of Xeroderma pigmentosum complementation group D mutant cell
RT phenotypes by chromosome and gene transfer: involvement of the human ERCC2
RT DNA repair gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 89:261-265(1992).
RN [8]
RP FUNCTION.
RX PubMed=8413672; DOI=10.1038/365852a0;
RA Sung P., Bailly V., Weber C.A., Thompson L.H., Prakash L., Prakash S.;
RT "Human Xeroderma pigmentosum group D gene encodes a DNA helicase.";
RL Nature 365:852-855(1993).
RN [9]
RP INTERACTION WITH EBV EBNA2.
RX PubMed=7724549; DOI=10.1073/pnas.92.8.3259;
RA Tong X., Drapkin R., Reinberg D., Kieff E.;
RT "The 62- and 80-kDa subunits of transcription factor IIH mediate the
RT interaction with Epstein-Barr virus nuclear protein 2.";
RL Proc. Natl. Acad. Sci. U.S.A. 92:3259-3263(1995).
RN [10]
RP IDENTIFICATION IN THE TFIIH BASAL TRANSCRIPTION FACTOR.
RX PubMed=9852112; DOI=10.1074/jbc.273.51.34444;
RA Kershnar E., Wu S.-Y., Chiang C.-M.;
RT "Immunoaffinity purification and functional characterization of human
RT transcription factor IIH and RNA polymerase II from clonal cell lines that
RT conditionally express epitope-tagged subunits of the multiprotein
RT complexes.";
RL J. Biol. Chem. 273:34444-34453(1998).
RN [11]
RP INTERACTION WITH GTF2H2.
RX PubMed=9771713; DOI=10.1038/2491;
RA Coin F., Marinoni J.-C., Rodolfo C., Fribourg S., Pedrini A.M., Egly J.-M.;
RT "Mutations in the XPD helicase gene result in XP and TTD phenotypes,
RT preventing interaction between XPD and the p44 subunit of TFIIH.";
RL Nat. Genet. 20:184-188(1998).
RN [12]
RP MUTAGENESIS OF LYS-48, AND FUNCTION.
RX PubMed=10024882; DOI=10.1016/s1097-2765(00)80177-x;
RA Tirode F., Busso D., Coin F., Egly J.-M.;
RT "Reconstitution of the transcription factor TFIIH: assignment of functions
RT for the three enzymatic subunits, XPB, XPD, and cdk7.";
RL Mol. Cell 3:87-95(1999).
RN [13]
RP FUNCTION, AND POSSIBLE PATHOLOGICAL MECHANISM OF VARIANT XP-D TRP-683.
RX PubMed=15494306; DOI=10.1016/j.molcel.2004.10.007;
RA Drane P., Compe E., Catez P., Chymkowitch P., Egly J.-M.;
RT "Selective regulation of vitamin D receptor-responsive genes by TFIIH.";
RL Mol. Cell 16:187-197(2004).
RN [14]
RP ISGYLATION.
RX PubMed=16884686; DOI=10.1016/j.bbrc.2006.07.076;
RA Takeuchi T., Inoue S., Yokosawa H.;
RT "Identification and Herc5-mediated ISGylation of novel target proteins.";
RL Biochem. Biophys. Res. Commun. 348:473-477(2006).
RN [15]
RP INTERACTION WITH ATF7IP.
RX PubMed=19106100; DOI=10.1074/jbc.m807098200;
RA Liu L., Ishihara K., Ichimura T., Fujita N., Hino S., Tomita S.,
RA Watanabe S., Saitoh N., Ito T., Nakao M.;
RT "MCAF1/AM is involved in Sp1-mediated maintenance of cancer-associated
RT telomerase activity.";
RL J. Biol. Chem. 284:5165-5174(2009).
RN [16]
RP FUNCTION, IDENTIFICATION IN MMXD COMPLEX, INTERACTION WITH CIAO2B, AND
RP SUBCELLULAR LOCATION.
RX PubMed=20797633; DOI=10.1016/j.molcel.2010.07.029;
RA Ito S., Tan L.J., Andoh D., Narita T., Seki M., Hirano Y., Narita K.,
RA Kuraoka I., Hiraoka Y., Tanaka K.;
RT "MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome
RT segregation.";
RL Mol. Cell 39:632-640(2010).
RN [17]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA Bennett K.L., Superti-Furga G., Colinge J.;
RT "Initial characterization of the human central proteome.";
RL BMC Syst. Biol. 5:17-17(2011).
RN [18]
RP IRON-SULFUR-BINDING, COFACTOR, AND MUTAGENESIS OF CYS-190.
RX PubMed=22678361; DOI=10.1126/science.1219664;
RA Gari K., Leon Ortiz A.M., Borel V., Flynn H., Skehel J.M., Boulton S.J.;
RT "MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism.";
RL Science 337:243-245(2012).
RN [19]
RP INTERACTION WITH CIAO1 AND CIAO2B.
RX PubMed=23891004; DOI=10.1016/j.cmet.2013.06.015;
RA Stehling O., Mascarenhas J., Vashisht A.A., Sheftel A.D., Niggemeyer B.,
RA Roesser R., Pierik A.J., Wohlschlegel J.A., Lill R.;
RT "Human CIA2A-FAM96A and CIA2B-FAM96B integrate iron homeostasis and
RT maturation of different subsets of cytosolic-nuclear iron-sulfur
RT proteins.";
RL Cell Metab. 18:187-198(2013).
RN [20]
RP ERRATUM OF PUBMED:23891004.
RX PubMed=29320706; DOI=10.1016/j.cmet.2017.12.009;
RA Stehling O., Mascarenhas J., Vashisht A.A., Sheftel A.D., Niggemeyer B.,
RA Roesser R., Pierik A.J., Wohlschlegel J.A., Lill R.;
RT "Human CIA2A-FAM96A and CIA2B-FAM96B Integrate Iron Homeostasis and
RT Maturation of Different Subsets of Cytosolic-Nuclear Iron-Sulfur
RT Proteins.";
RL Cell Metab. 27:263-263(2018).
RN [21]
RP SUBCELLULAR LOCATION, AND INTERACTION WITH MMS19.
RX PubMed=23585563; DOI=10.1074/jbc.m112.416602;
RA Seki M., Takeda Y., Iwai K., Tanaka K.;
RT "IOP1 protein is an external component of the human cytosolic iron-sulfur
RT cluster assembly (CIA) machinery and functions in the MMS19 protein-
RT dependent CIA pathway.";
RL J. Biol. Chem. 288:16680-16689(2013).
RN [22]
RP VARIANT XP-D VAL-461.
RX PubMed=7849702; DOI=10.1093/hmg/3.10.1783;
RA Frederick G.D., Amirkhan R.H., Schultz R.A., Friedberg E.C.;
RT "Structural and mutational analysis of the xeroderma pigmentosum group D
RT (XPD) gene.";
RL Hum. Mol. Genet. 3:1783-1788(1994).
RN [23]
RP VARIANTS TTD1 HIS-112; PRO-616; TRP-722 AND 488-VAL--MET-493 DEL.
RX PubMed=7920640; DOI=10.1038/ng0694-189;
RA Broughton B.C., Steingrimsdottir H., Weber C.A., Lehmann A.R.;
RT "Mutations in the xeroderma pigmentosum group D DNA repair/transcription
RT gene in patients with trichothiodystrophy.";
RL Nat. Genet. 7:189-194(1994).
RN [24]
RP VARIANT XP-D ARG-675.
RX PubMed=7825573;
RA Broughton B.C., Thompson A.F., Harcourt S.A., Vermeulen W.,
RA Hoeijmakers J.H.J., Botta E., Stefanini M., King M.D., Weber C.A., Cole J.,
RA Arlett C.F., Lehmann A.R.;
RT "Molecular and cellular analysis of the DNA repair defect in a patient in
RT xeroderma pigmentosum complementation group D who has the clinical features
RT of xeroderma pigmentosum and Cockayne syndrome.";
RL Am. J. Hum. Genet. 56:167-174(1995).
RN [25]
RP VARIANTS XP-D.
RX PubMed=7585650;
RA Takayama K., Salazar E.P., Lehmann A.R., Stefanini M., Thompson L.H.,
RA Weber C.A.;
RT "Defects in the DNA repair and transcription gene ERCC2 in the cancer-prone
RT disorder xeroderma pigmentosum group D.";
RL Cancer Res. 55:5656-5663(1995).
RN [26]
RP VARIANTS TTD1 CYS-658 AND ARG-713.
RX PubMed=8571952;
RA Takayama K., Salazar E.P., Broughton B.C., Lehmann A.R., Sarasin A.,
RA Thompson L.H., Weber C.A.;
RT "Defects in the DNA repair and transcription gene ERCC2(XPD) in
RT trichothiodystrophy.";
RL Am. J. Hum. Genet. 58:263-270(1996).
RN [27]
RP VARIANT XP-D ARG-541.
RX PubMed=9101292;
RX DOI=10.1002/(sici)1098-1004(1997)9:4<322::aid-humu4>3.0.co;2-7;
RA Kobayashi T., Kuraoka I., Saijo M., Nakatsu Y., Tanaka A., Someda Y.,
RA Fukuro S., Tanaka K.;
RT "Mutations in the XPD gene leading to Xeroderma pigmentosum symptoms.";
RL Hum. Mutat. 9:322-331(1997).
RN [28]
RP VARIANTS TTD1 VAL-461; 716-VAL--ARG-730 DEL AND PRO-725.
RX PubMed=9195225;
RX DOI=10.1002/(sici)1098-1004(1997)9:6<519::aid-humu4>3.0.co;2-x;
RA Takayama K., Danks D.M., Salazar E.P., Cleaver J.E., Weber C.A.;
RT "DNA repair characteristics and mutations in the ERCC2 DNA repair and
RT transcription gene in a trichothiodystrophy patient.";
RL Hum. Mutat. 9:519-525(1997).
RN [29]
RP VARIANTS TTD1/XP.
RX PubMed=9238033; DOI=10.1073/pnas.94.16.8658;
RA Taylor E.M., Broughton B.C., Botta E., Stefanini M., Sarasin A.,
RA Jaspers N.G.J., Fawcett H., Harcourt S.A., Arlett C.F., Lehmann A.R.;
RT "Xeroderma pigmentosum and trichothiodystrophy are associated with
RT different mutations in the XPD (ERCC2) repair/transcription gene.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:8658-8663(1997).
RN [30]
RP VARIANTS TTD1 HIS-112; TYR-259; VAL-461; THR-482 DEL; GLY-673 AND TRP-722.
RX PubMed=9758621; DOI=10.1086/302063;
RA Botta E., Nardo T., Broughton B.C., Marinoni S., Lehmann A.R.,
RA Stefanini M.;
RT "Analysis of mutations in the XPD gene in Italian patients with
RT trichothiodystrophy: site of mutation correlates with repair deficiency,
RT but gene dosage appears to determine clinical severity.";
RL Am. J. Hum. Genet. 63:1036-1048(1998).
RN [31]
RP REVIEW ON VARIANTS XP-D.
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 [32]
RP VARIANTS COFS2 TRP-616 AND ASN-681.
RX PubMed=11443545; DOI=10.1086/321295;
RA Graham J.M. Jr., Anyane-Yeboa K., Raams A., Appeldoorn E., Kleijer W.J.,
RA Garritsen V.H., Busch D., Edersheim T.G., Jaspers N.G.J.;
RT "Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair
RT defect and a mutated XPD gene, with prenatal diagnosis in a triplet
RT pregnancy.";
RL Am. J. Hum. Genet. 69:291-300(2001).
RN [33]
RP VARIANT CYS-616.
RX PubMed=11319176;
RA Caggana M., Kilgallen J., Conroy J.M., Wiencke J.K., Kelsey K.T., Miike R.,
RA Chen P., Wrensch M.R.;
RT "Associations between ercc2 polymorphisms and gliomas.";
RL Cancer Epidemiol. Biomarkers Prev. 10:355-360(2001).
RN [34]
RP VARIANTS ASN-312 AND GLN-751.
RX PubMed=11245433;
RA Spitz M.R., Wu X., Wang Y., Wang L.E., Shete S., Amos C.I., Guo Z., Lei L.,
RA Mohrenweiser H., Wei Q.;
RT "Modulation of nucleotide excision repair capacity by XPD polymorphisms in
RT lung cancer patients.";
RL Cancer Res. 61:1354-1357(2001).
RN [35]
RP VARIANTS ASN-312 AND GLN-751.
RX PubMed=11470747; DOI=10.1093/carcin/22.8.1185;
RA Hemminki K., Xu G., Angelini S., Snellman E., Jansen C.T., Lambert B.,
RA Hou S.M.;
RT "XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ.";
RL Carcinogenesis 22:1185-1188(2001).
RN [36]
RP REVIEW ON VARIANTS.
RX PubMed=11156600; DOI=10.1101/gad.859501;
RA Lehmann A.R.;
RT "The xeroderma pigmentosum group D (XPD) gene: one gene, two functions,
RT three diseases.";
RL Genes Dev. 15:15-23(2001).
RN [37]
RP VARIANTS XP-D HIS-112; PRO-485 AND 582-GLU-LYS-583 DELINS VAL-SER-GLU, AND
RP VARIANTS ASN-312 AND GLN-751.
RX PubMed=11709541; DOI=10.1093/hmg/10.22.2539;
RA Broughton B.C., Berneburg M., Fawcett H., Taylor E.M., Arlett C.F.,
RA Nardo T., Stefanini M., Menefee E., Price V.H., Queille S., Sarasin A.,
RA Bohnert E., Krutmann J., Davidson R., Kraemer K.H., Lehmann A.R.;
RT "Two individuals with features of both xeroderma pigmentosum and
RT trichothiodystrophy highlight the complexity of the clinical outcomes of
RT mutations in the XPD gene.";
RL Hum. Mol. Genet. 10:2539-2547(2001).
RN [38]
RP VARIANTS TTD1 CYS-658 AND ARG-713.
RX PubMed=11242112; DOI=10.1038/85864;
RA Vermeulen W., Rademakers S., Jaspers N.G.J., Appeldoorn E., Raams A.,
RA Klein B., Kleijer W.J., Hansen L.K., Hoeijmakers J.H.J.;
RT "A temperature-sensitive disorder in basal transcription and DNA repair in
RT humans.";
RL Nat. Genet. 27:299-303(2001).
CC -!- FUNCTION: ATP-dependent 5'-3' DNA helicase, component of the general
CC transcription and DNA repair factor IIH (TFIIH) core complex, which is
CC involved in general and transcription-coupled nucleotide excision
CC repair (NER) of damaged DNA and, when complexed to CAK, in RNA
CC transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA
CC around the lesion to allow the excision of the damaged oligonucleotide
CC and its replacement by a new DNA fragment. The ATP-dependent helicase
CC activity of XPD/ERCC2 is required for DNA opening. In transcription,
CC TFIIH has an essential role in transcription initiation. When the pre-
CC initiation complex (PIC) has been established, TFIIH is required for
CC promoter opening and promoter escape. Phosphorylation of the C-terminal
CC tail (CTD) of the largest subunit of RNA polymerase II by the kinase
CC module CAK controls the initiation of transcription. XPD/ERCC2 acts by
CC forming a bridge between CAK and the core-TFIIH complex. Involved in
CC the regulation of vitamin-D receptor activity. As part of the mitotic
CC spindle-associated MMXD complex it plays a role in chromosome
CC segregation. Might have a role in aging process and could play a
CC causative role in the generation of skin cancers.
CC {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:15494306,
CC ECO:0000269|PubMed:20797633, ECO:0000269|PubMed:8413672}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:22678361};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883;
CC Evidence={ECO:0000269|PubMed:22678361};
CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000269|PubMed:22678361};
CC -!- SUBUNIT: Component of the 7-subunit TFIIH core complex composed of
CC XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which
CC is active in NER. The core complex associates with the 3-subunit CDK-
CC activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and
CC MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in
CC transcription. The interaction with GTF2H2 results in the stimulation
CC of the 5'-->3' helicase activity (PubMed:9771713, PubMed:9852112).
CC Component of the MMXD complex, which includes CIAO1, ERCC2, CIAO2B,
CC MMS19 and SLC25A5 (PubMed:20797633). Interacts with CIAO1 and CIAO2B;
CC the interaction WITH CIAO2B is direct (PubMed:23891004). Interacts with
CC ATF7IP (PubMed:19106100). Interacts directly with MMS19
CC (PubMed:23585563). {ECO:0000269|PubMed:19106100,
CC ECO:0000269|PubMed:20797633, ECO:0000269|PubMed:23585563,
CC ECO:0000269|PubMed:23891004, ECO:0000269|PubMed:9771713,
CC ECO:0000269|PubMed:9852112}.
CC -!- SUBUNIT: (Microbial infection) Interacts with Epstein-Barr virus EBNA2.
CC {ECO:0000269|PubMed:7724549}.
CC -!- INTERACTION:
CC P18074; P19447: ERCC3; NbExp=5; IntAct=EBI-6380590, EBI-1183307;
CC P18074; Q13888: GTF2H2; NbExp=9; IntAct=EBI-6380590, EBI-1565170;
CC P18074; Q6P1K8: GTF2H2C_2; NbExp=3; IntAct=EBI-6380590, EBI-8469755;
CC P18074; Q96T76: MMS19; NbExp=7; IntAct=EBI-6380590, EBI-1044169;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:20797633,
CC ECO:0000269|PubMed:23585563}. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000269|PubMed:20797633}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=P18074-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P18074-2; Sequence=VSP_043132, VSP_043133, VSP_043134;
CC -!- PTM: ISGylated. {ECO:0000305|PubMed:16884686}.
CC -!- DISEASE: Xeroderma pigmentosum complementation group D (XP-D)
CC [MIM:278730]: 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. Some XP-D patients
CC present features of Cockayne syndrome, including cachectic dwarfism,
CC pigmentary retinopathy, ataxia, decreased nerve conduction velocities.
CC The phenotype combining xeroderma pigmentosum and Cockayne syndrome
CC traits is referred to as XP-CS complex. {ECO:0000269|PubMed:10447254,
CC ECO:0000269|PubMed:11709541, ECO:0000269|PubMed:15494306,
CC ECO:0000269|PubMed:7585650, ECO:0000269|PubMed:7825573,
CC ECO:0000269|PubMed:7849702, ECO:0000269|PubMed:9101292}. Note=The
CC disease is caused by variants affecting the gene represented in this
CC entry.
CC -!- DISEASE: Trichothiodystrophy 1, photosensitive (TTD1) [MIM:601675]: A
CC form of trichothiodystrophy, an autosomal recessive disease
CC characterized by sulfur-deficient brittle hair and multisystem variable
CC abnormalities. The spectrum of clinical features varies from mild
CC disease with only hair involvement to severe disease with cutaneous,
CC neurologic and profound developmental defects. Ichthyosis, intellectual
CC and developmental disabilities, decreased fertility, abnormal
CC characteristics at birth, ocular abnormalities, short stature, and
CC infections are common manifestations. There are both photosensitive and
CC non-photosensitive forms of the disorder. TTD1 patients manifest
CC cutaneous photosensitivity. {ECO:0000269|PubMed:11242112,
CC ECO:0000269|PubMed:7920640, ECO:0000269|PubMed:8571952,
CC ECO:0000269|PubMed:9195225, ECO:0000269|PubMed:9238033,
CC ECO:0000269|PubMed:9758621}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cerebro-oculo-facio-skeletal syndrome 2 (COFS2) [MIM:610756]:
CC A disorder of prenatal onset characterized by microcephaly, congenital
CC cataracts, facial dysmorphism, neurogenic arthrogryposis, growth
CC failure and severe psychomotor retardation. COFS is considered to be
CC part of the nucleotide-excision repair disorders spectrum that include
CC also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome.
CC {ECO:0000269|PubMed:11443545}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the helicase family. RAD3/XPD subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAM45142.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/XPDID297.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ercc2/";
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DR EMBL; X52221; CAA36463.1; -; mRNA.
DR EMBL; X52222; CAA36464.1; -; mRNA.
DR EMBL; L47234; AAL48323.1; -; Genomic_DNA.
DR EMBL; AY092780; AAM45142.1; ALT_SEQ; Genomic_DNA.
DR EMBL; BT006883; AAP35529.1; -; mRNA.
DR EMBL; CH471126; EAW57341.1; -; Genomic_DNA.
DR EMBL; BC108255; AAI08256.1; -; mRNA.
DR EMBL; BC110523; AAI10524.1; -; mRNA.
DR CCDS; CCDS33049.1; -. [P18074-1]
DR CCDS; CCDS46112.1; -. [P18074-2]
DR PIR; S10888; S10888.
DR RefSeq; NP_000391.1; NM_000400.3. [P18074-1]
DR RefSeq; NP_001124339.1; NM_001130867.1. [P18074-2]
DR PDB; 5IVW; EM; 10.00 A; W=1-760.
DR PDB; 5IY6; EM; 7.20 A; W=1-760.
DR PDB; 5IY7; EM; 8.60 A; W=1-760.
DR PDB; 5IY8; EM; 7.90 A; W=1-760.
DR PDB; 5IY9; EM; 6.30 A; W=1-760.
DR PDB; 5OF4; EM; 4.40 A; B=1-760.
DR PDB; 6NMI; EM; 3.70 A; B=1-760.
DR PDB; 6O9L; EM; 7.20 A; 0=1-760.
DR PDB; 6O9M; EM; 4.40 A; 0=1-760.
DR PDB; 6RO4; EM; 3.50 A; B=1-760.
DR PDB; 6TUN; X-ray; 2.07 A; A/B=245-439.
DR PDB; 7AD8; EM; 3.50 A; B=1-760.
DR PDB; 7EGB; EM; 3.30 A; 7=1-760.
DR PDB; 7EGC; EM; 3.90 A; 7=1-760.
DR PDB; 7ENA; EM; 4.07 A; 7=1-760.
DR PDB; 7ENC; EM; 4.13 A; 7=1-760.
DR PDB; 7LBM; EM; 4.80 A; X=1-760.
DR PDB; 7NVR; EM; 4.50 A; 0=1-760.
DR PDB; 7NVW; EM; 4.30 A; 0=1-760.
DR PDB; 7NVX; EM; 3.90 A; 0=1-760.
DR PDB; 7NVY; EM; 7.30 A; 0=1-760.
DR PDB; 7NVZ; EM; 7.20 A; 0=1-760.
DR PDB; 7NW0; EM; 6.60 A; 0=1-760.
DR PDBsum; 5IVW; -.
DR PDBsum; 5IY6; -.
DR PDBsum; 5IY7; -.
DR PDBsum; 5IY8; -.
DR PDBsum; 5IY9; -.
DR PDBsum; 5OF4; -.
DR PDBsum; 6NMI; -.
DR PDBsum; 6O9L; -.
DR PDBsum; 6O9M; -.
DR PDBsum; 6RO4; -.
DR PDBsum; 6TUN; -.
DR PDBsum; 7AD8; -.
DR PDBsum; 7EGB; -.
DR PDBsum; 7EGC; -.
DR PDBsum; 7ENA; -.
DR PDBsum; 7ENC; -.
DR PDBsum; 7LBM; -.
DR PDBsum; 7NVR; -.
DR PDBsum; 7NVW; -.
DR PDBsum; 7NVX; -.
DR PDBsum; 7NVY; -.
DR PDBsum; 7NVZ; -.
DR PDBsum; 7NW0; -.
DR AlphaFoldDB; P18074; -.
DR SMR; P18074; -.
DR BioGRID; 108380; 82.
DR CORUM; P18074; -.
DR DIP; DIP-644N; -.
DR IntAct; P18074; 51.
DR MINT; P18074; -.
DR STRING; 9606.ENSP00000375809; -.
DR ChEMBL; CHEMBL4105743; -.
DR iPTMnet; P18074; -.
DR PhosphoSitePlus; P18074; -.
DR BioMuta; ERCC2; -.
DR DMDM; 119540; -.
DR EPD; P18074; -.
DR jPOST; P18074; -.
DR MassIVE; P18074; -.
DR MaxQB; P18074; -.
DR PaxDb; P18074; -.
DR PeptideAtlas; P18074; -.
DR PRIDE; P18074; -.
DR ProteomicsDB; 53542; -. [P18074-1]
DR ProteomicsDB; 53543; -. [P18074-2]
DR Antibodypedia; 17895; 288 antibodies from 37 providers.
DR CPTC; P18074; 1 antibody.
DR DNASU; 2068; -.
DR Ensembl; ENST00000391945.10; ENSP00000375809.4; ENSG00000104884.17. [P18074-1]
DR Ensembl; ENST00000485403.6; ENSP00000431229.2; ENSG00000104884.17. [P18074-2]
DR Ensembl; ENST00000682414.1; ENSP00000507019.1; ENSG00000104884.17. [P18074-1]
DR GeneID; 2068; -.
DR KEGG; hsa:2068; -.
DR MANE-Select; ENST00000391945.10; ENSP00000375809.4; NM_000400.4; NP_000391.1.
DR UCSC; uc002pbj.3; human. [P18074-1]
DR CTD; 2068; -.
DR DisGeNET; 2068; -.
DR GeneCards; ERCC2; -.
DR GeneReviews; ERCC2; -.
DR HGNC; HGNC:3434; ERCC2.
DR HPA; ENSG00000104884; Low tissue specificity.
DR MalaCards; ERCC2; -.
DR MIM; 126340; gene.
DR MIM; 278730; phenotype.
DR MIM; 601675; phenotype.
DR MIM; 610756; phenotype.
DR neXtProt; NX_P18074; -.
DR OpenTargets; ENSG00000104884; -.
DR Orphanet; 1466; COFS syndrome.
DR Orphanet; 33364; Trichothiodystrophy.
DR Orphanet; 910; Xeroderma pigmentosum.
DR Orphanet; 220295; Xeroderma pigmentosum-Cockayne syndrome complex.
DR PharmGKB; PA27848; -.
DR VEuPathDB; HostDB:ENSG00000104884; -.
DR eggNOG; KOG1131; Eukaryota.
DR GeneTree; ENSGT00950000182970; -.
DR HOGENOM; CLU_045429_0_0_1; -.
DR InParanoid; P18074; -.
DR OMA; IREQFFR; -.
DR OrthoDB; 186062at2759; -.
DR PhylomeDB; P18074; -.
DR TreeFam; TF101232; -.
DR BRENDA; 3.6.4.12; 2681.
DR PathwayCommons; P18074; -.
DR Reactome; R-HSA-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-HSA-113418; Formation of the Early Elongation Complex.
DR Reactome; R-HSA-167152; Formation of HIV elongation complex in the absence of HIV Tat.
DR Reactome; R-HSA-167158; Formation of the HIV-1 Early Elongation Complex.
DR Reactome; R-HSA-167160; RNA Pol II CTD phosphorylation and interaction with CE during HIV infection.
DR Reactome; R-HSA-167161; HIV Transcription Initiation.
DR Reactome; R-HSA-167162; RNA Polymerase II HIV Promoter Escape.
DR Reactome; R-HSA-167172; Transcription of the HIV genome.
DR Reactome; R-HSA-167200; Formation of HIV-1 elongation complex containing HIV-1 Tat.
DR Reactome; R-HSA-167246; Tat-mediated elongation of the HIV-1 transcript.
DR Reactome; R-HSA-2564830; Cytosolic iron-sulfur cluster assembly.
DR Reactome; R-HSA-427413; NoRC negatively regulates rRNA expression.
DR Reactome; R-HSA-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-HSA-5696400; Dual Incision in GG-NER.
DR Reactome; R-HSA-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-HSA-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-HSA-6781827; Transcription-Coupled Nucleotide Excision Repair (TC-NER).
DR Reactome; R-HSA-6782135; Dual incision in TC-NER.
DR Reactome; R-HSA-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-HSA-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-HSA-72086; mRNA Capping.
DR Reactome; R-HSA-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-HSA-73772; RNA Polymerase I Promoter Escape.
DR Reactome; R-HSA-73776; RNA Polymerase II Promoter Escape.
DR Reactome; R-HSA-73779; RNA Polymerase II Transcription Pre-Initiation And Promoter Opening.
DR Reactome; R-HSA-73863; RNA Polymerase I Transcription Termination.
DR Reactome; R-HSA-75953; RNA Polymerase II Transcription Initiation.
DR Reactome; R-HSA-75955; RNA Polymerase II Transcription Elongation.
DR Reactome; R-HSA-76042; RNA Polymerase II Transcription Initiation And Promoter Clearance.
DR Reactome; R-HSA-77075; RNA Pol II CTD phosphorylation and interaction with CE.
DR SignaLink; P18074; -.
DR SIGNOR; P18074; -.
DR BioGRID-ORCS; 2068; 730 hits in 1094 CRISPR screens.
DR ChiTaRS; ERCC2; human.
DR GeneWiki; ERCC2; -.
DR GenomeRNAi; 2068; -.
DR Pharos; P18074; Tchem.
DR PRO; PR:P18074; -.
DR Proteomes; UP000005640; Chromosome 19.
DR RNAct; P18074; protein.
DR Bgee; ENSG00000104884; Expressed in stromal cell of endometrium and 110 other tissues.
DR ExpressionAtlas; P18074; baseline and differential.
DR Genevisible; P18074; HS.
DR GO; GO:0070516; C:CAK-ERCC2 complex; IDA:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; IDA:UniProtKB.
DR GO; GO:0005829; C:cytosol; IDA:HPA.
DR GO; GO:0071817; C:MMXD complex; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0005819; C:spindle; IDA:UniProtKB.
DR GO; GO:0005669; C:transcription factor TFIID complex; IDA:UniProtKB.
DR GO; GO:0000439; C:transcription factor TFIIH core complex; IDA:UniProtKB.
DR GO; GO:0005675; C:transcription factor TFIIH holo complex; IDA:UniProtKB.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0043139; F:5'-3' DNA helicase activity; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003684; F:damaged DNA binding; IBA:GO_Central.
DR GO; GO:0003678; F:DNA helicase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; IPI:UniProtKB.
DR GO; GO:0007568; P:aging; IEA:Ensembl.
DR GO; GO:0006915; P:apoptotic process; IMP:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; IEA:Ensembl.
DR GO; GO:0032289; P:central nervous system myelin formation; IEA:Ensembl.
DR GO; GO:0007059; P:chromosome segregation; IMP:UniProtKB.
DR GO; GO:0040016; P:embryonic cleavage; IEA:Ensembl.
DR GO; GO:0043249; P:erythrocyte maturation; IEA:Ensembl.
DR GO; GO:0030198; P:extracellular matrix organization; IEA:Ensembl.
DR GO; GO:0035315; P:hair cell differentiation; IMP:UniProtKB.
DR GO; GO:0048820; P:hair follicle maturation; IEA:Ensembl.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IEA:Ensembl.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IEA:Ensembl.
DR GO; GO:0001701; P:in utero embryonic development; IEA:Ensembl.
DR GO; GO:0000462; P:maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:0006289; P:nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:0000717; P:nucleotide-excision repair, DNA duplex unwinding; IBA:GO_Central.
DR GO; GO:0033683; P:nucleotide-excision repair, DNA incision; IBA:GO_Central.
DR GO; GO:0043388; P:positive regulation of DNA binding; IEA:Ensembl.
DR GO; GO:0045951; P:positive regulation of mitotic recombination; IBA:GO_Central.
DR GO; GO:0009791; P:post-embryonic development; IEA:Ensembl.
DR GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; IMP:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IMP:UniProtKB.
DR GO; GO:0021510; P:spinal cord development; IEA:Ensembl.
DR GO; GO:0006366; P:transcription by RNA polymerase II; IDA:UniProtKB.
DR GO; GO:0006362; P:transcription elongation from RNA polymerase I promoter; IEA:Ensembl.
DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; IDA:UniProtKB.
DR GO; GO:0009650; P:UV protection; IGI:MGI.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR006555; ATP-dep_Helicase_C.
DR InterPro; IPR010614; DEAD_2.
DR InterPro; IPR045028; DinG/Rad3-like.
DR InterPro; IPR002464; DNA/RNA_helicase_DEAH_CS.
DR InterPro; IPR010643; HBB.
DR InterPro; IPR014013; Helic_SF1/SF2_ATP-bd_DinG/Rad3.
DR InterPro; IPR006554; Helicase-like_DEXD_c2.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR013020; Rad3/Chl1-like.
DR InterPro; IPR001945; RAD3/XPD.
DR PANTHER; PTHR11472; PTHR11472; 1.
DR PANTHER; PTHR11472:SF1; PTHR11472:SF1; 1.
DR Pfam; PF06733; DEAD_2; 1.
DR Pfam; PF06777; HBB; 1.
DR Pfam; PF13307; Helicase_C_2; 1.
DR PRINTS; PR00852; XRODRMPGMNTD.
DR SMART; SM00488; DEXDc2; 1.
DR SMART; SM00491; HELICc2; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00604; rad3; 1.
DR PROSITE; PS00690; DEAH_ATP_HELICASE; 1.
DR PROSITE; PS51193; HELICASE_ATP_BIND_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; 4Fe-4S; Alternative splicing; ATP-binding; Cataract;
KW Chromosome partition; Cockayne syndrome; Cytoplasm; Cytoskeleton; Deafness;
KW Disease variant; DNA damage; DNA repair; DNA-binding; Dwarfism; Helicase;
KW Host-virus interaction; Hydrolase; Ichthyosis; Iron; Iron-sulfur;
KW Magnesium; Metal-binding; Nucleotide-binding; Nucleus; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation;
KW Xeroderma pigmentosum.
FT CHAIN 1..760
FT /note="General transcription and DNA repair factor IIH
FT helicase subunit XPD"
FT /id="PRO_0000101980"
FT DOMAIN 7..283
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT REGION 438..637
FT /note="Mediates interaction with MMS19"
FT MOTIF 234..237
FT /note="DEAH box"
FT MOTIF 682..695
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT BINDING 42..49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 116
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 134
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 190
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000305"
FT VAR_SEQ 1..24
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_043132"
FT VAR_SEQ 414..429
FT /note="FTIIIEPFDDRTPTIA -> QAQHCGSSRNQKRSHP (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_043133"
FT VAR_SEQ 430..760
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|Ref.4"
FT /id="VSP_043134"
FT VARIANT 47
FT /note="G -> R (in XP-D; dbSNP:rs1360631927)"
FT /id="VAR_008187"
FT VARIANT 76
FT /note="T -> A (in XP-D)"
FT /id="VAR_017282"
FT VARIANT 112
FT /note="R -> H (in TTD1 and XP-D; dbSNP:rs121913020)"
FT /evidence="ECO:0000269|PubMed:11709541,
FT ECO:0000269|PubMed:7920640, ECO:0000269|PubMed:9758621"
FT /id="VAR_003622"
FT VARIANT 199
FT /note="I -> M (in dbSNP:rs1799791)"
FT /id="VAR_011412"
FT VARIANT 201
FT /note="H -> Y (in dbSNP:rs1799792)"
FT /id="VAR_011413"
FT VARIANT 234
FT /note="D -> N (in XP-D; dbSNP:rs1340806384)"
FT /id="VAR_008188"
FT VARIANT 259
FT /note="C -> Y (in TTD1; dbSNP:rs370454709)"
FT /evidence="ECO:0000269|PubMed:9758621"
FT /id="VAR_008189"
FT VARIANT 312
FT /note="D -> N (in dbSNP:rs1799793)"
FT /evidence="ECO:0000269|PubMed:11245433,
FT ECO:0000269|PubMed:11470747, ECO:0000269|PubMed:11709541,
FT ECO:0000269|Ref.3"
FT /id="VAR_011414"
FT VARIANT 461
FT /note="L -> V (in XP-D and TTD1; dbSNP:rs121913016)"
FT /evidence="ECO:0000269|PubMed:7849702,
FT ECO:0000269|PubMed:9195225, ECO:0000269|PubMed:9758621"
FT /id="VAR_003623"
FT VARIANT 482
FT /note="Missing (in TTD1)"
FT /evidence="ECO:0000269|PubMed:9758621"
FT /id="VAR_008190"
FT VARIANT 485
FT /note="L -> P (in XP-D; the corresponding mutation in
FT fission yeast causes complete loss of activity;
FT dbSNP:rs121913025)"
FT /evidence="ECO:0000269|PubMed:11709541"
FT /id="VAR_017283"
FT VARIANT 487
FT /note="R -> G (in TTD1)"
FT /id="VAR_017284"
FT VARIANT 488..493
FT /note="Missing (in TTD1; mild)"
FT /evidence="ECO:0000269|PubMed:7920640"
FT /id="VAR_003624"
FT VARIANT 511
FT /note="R -> Q (in XP-D; dbSNP:rs772572683)"
FT /id="VAR_017285"
FT VARIANT 541
FT /note="S -> R (in XP-D; mild; dbSNP:rs121913019)"
FT /evidence="ECO:0000269|PubMed:9101292"
FT /id="VAR_003625"
FT VARIANT 542
FT /note="Y -> C (in XP-D)"
FT /id="VAR_008191"
FT VARIANT 582..583
FT /note="EK -> VSE (in XP-D)"
FT /evidence="ECO:0000269|PubMed:11709541"
FT /id="VAR_017286"
FT VARIANT 592
FT /note="R -> P (in TTD1)"
FT /id="VAR_017287"
FT VARIANT 594
FT /note="A -> P (in TTD1)"
FT /id="VAR_017288"
FT VARIANT 601
FT /note="R -> L (in XP-D; dbSNP:rs140522180)"
FT /id="VAR_008192"
FT VARIANT 601
FT /note="R -> W (in XP-D; dbSNP:rs753641926)"
FT /id="VAR_017289"
FT VARIANT 602
FT /note="G -> D (in XP-D; combined with features of Cockayne
FT syndrome; dbSNP:rs771824813)"
FT /id="VAR_003627"
FT VARIANT 616
FT /note="R -> C"
FT /evidence="ECO:0000269|PubMed:11319176"
FT /id="VAR_011415"
FT VARIANT 616
FT /note="R -> P (in XP-D and TTD1; dbSNP:rs376556895)"
FT /evidence="ECO:0000269|PubMed:7920640"
FT /id="VAR_003626"
FT VARIANT 616
FT /note="R -> W (in XP-D and COFS2; dbSNP:rs121913024)"
FT /evidence="ECO:0000269|PubMed:11443545"
FT /id="VAR_008193"
FT VARIANT 658
FT /note="R -> C (in TTD1; dbSNP:rs121913021)"
FT /evidence="ECO:0000269|PubMed:11242112,
FT ECO:0000269|PubMed:8571952"
FT /id="VAR_008194"
FT VARIANT 658
FT /note="R -> G (in TTD1)"
FT /id="VAR_017290"
FT VARIANT 658
FT /note="R -> H (in TTD1; dbSNP:rs762141272)"
FT /id="VAR_008195"
FT VARIANT 663
FT /note="C -> R (in TTD1; dbSNP:rs770367713)"
FT /id="VAR_017291"
FT VARIANT 666
FT /note="R -> W (in XP-D; dbSNP:rs752510317)"
FT /id="VAR_017292"
FT VARIANT 673
FT /note="D -> G (in TTD1)"
FT /evidence="ECO:0000269|PubMed:9758621"
FT /id="VAR_008196"
FT VARIANT 675
FT /note="G -> R (in XP-D/CS; severe form)"
FT /evidence="ECO:0000269|PubMed:7825573"
FT /id="VAR_003628"
FT VARIANT 681
FT /note="D -> N (in XP-D and COFS2; dbSNP:rs121913023)"
FT /evidence="ECO:0000269|PubMed:11443545"
FT /id="VAR_017293"
FT VARIANT 683
FT /note="R -> Q (in XP-D; dbSNP:rs758439420)"
FT /id="VAR_008197"
FT VARIANT 683
FT /note="R -> W (in XP-D; vitamin D-mediated activation of
FT CYP24A1 is impaired in patient fibroblasts due to altered
FT TFIIH-dependent phosphorylation of ETS1, subsequent
FT impaired cooperation of ETS1 with VDR and altered VDR
FT recruitment to CYP24A1 promoter; dbSNP:rs41556519)"
FT /evidence="ECO:0000269|PubMed:15494306"
FT /id="VAR_008198"
FT VARIANT 713
FT /note="G -> R (in TTD1; dbSNP:rs121913022)"
FT /evidence="ECO:0000269|PubMed:11242112,
FT ECO:0000269|PubMed:8571952"
FT /id="VAR_008199"
FT VARIANT 716..730
FT /note="Missing (in XP-D and TTD1)"
FT /evidence="ECO:0000269|PubMed:9195225"
FT /id="VAR_003629"
FT VARIANT 722
FT /note="R -> W (in TTD1; dbSNP:rs121913026)"
FT /evidence="ECO:0000269|PubMed:7920640,
FT ECO:0000269|PubMed:9758621"
FT /id="VAR_003630"
FT VARIANT 725
FT /note="A -> P (in TTD1; dbSNP:rs121913018)"
FT /evidence="ECO:0000269|PubMed:9195225"
FT /id="VAR_003631"
FT VARIANT 751
FT /note="K -> Q (may be associated with increased
FT susceptibility to DNA damage; dbSNP:rs13181)"
FT /evidence="ECO:0000269|PubMed:11245433,
FT ECO:0000269|PubMed:11470747, ECO:0000269|PubMed:11709541,
FT ECO:0000269|PubMed:15489334, ECO:0000269|Ref.3,
FT ECO:0000269|Ref.5"
FT /id="VAR_011416"
FT MUTAGEN 48
FT /note="K->R: Decreased transcriptional activity of the
FT reconstituted TFIIH complex."
FT /evidence="ECO:0000269|PubMed:10024882"
FT MUTAGEN 190
FT /note="C->S: Reduced iron-sulfur-binding. Iron-sulfur-
FT binding is further decreased in absence of MMS19."
FT /evidence="ECO:0000269|PubMed:22678361"
FT STRAND 2..4
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 9..11
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 13..15
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 19..34
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 38..41
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 48..62
FT /evidence="ECO:0007829|PDB:6RO4"
FT TURN 64..66
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 69..73
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 77..98
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 106..108
FT /evidence="ECO:0007829|PDB:6RO4"
FT TURN 112..114
FT /evidence="ECO:0007829|PDB:6RO4"
FT TURN 119..123
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 127..138
FT /evidence="ECO:0007829|PDB:6RO4"
FT TURN 140..144
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 145..147
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 151..153
FT /evidence="ECO:0007829|PDB:7AD8"
FT HELIX 156..159
FT /evidence="ECO:0007829|PDB:6RO4"
FT TURN 160..167
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 177..187
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 191..197
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 203..207
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 209..211
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 215..221
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 222..225
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 227..234
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 240..245
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 249..252
FT /evidence="ECO:0007829|PDB:6TUN"
FT HELIX 253..276
FT /evidence="ECO:0007829|PDB:6TUN"
FT HELIX 278..290
FT /evidence="ECO:0007829|PDB:6TUN"
FT STRAND 323..325
FT /evidence="ECO:0007829|PDB:6TUN"
FT HELIX 326..343
FT /evidence="ECO:0007829|PDB:6TUN"
FT STRAND 350..352
FT /evidence="ECO:0007829|PDB:6TUN"
FT HELIX 354..365
FT /evidence="ECO:0007829|PDB:6TUN"
FT HELIX 369..373
FT /evidence="ECO:0007829|PDB:6TUN"
FT HELIX 375..385
FT /evidence="ECO:0007829|PDB:6TUN"
FT HELIX 392..394
FT /evidence="ECO:0007829|PDB:6TUN"
FT HELIX 395..409
FT /evidence="ECO:0007829|PDB:6TUN"
FT TURN 410..412
FT /evidence="ECO:0007829|PDB:6TUN"
FT STRAND 414..421
FT /evidence="ECO:0007829|PDB:6TUN"
FT STRAND 432..437
FT /evidence="ECO:0007829|PDB:6TUN"
FT TURN 440..446
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 447..450
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 451..459
FT /evidence="ECO:0007829|PDB:6RO4"
FT TURN 464..466
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 467..470
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 490..493
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 508..513
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 514..527
FT /evidence="ECO:0007829|PDB:6RO4"
FT TURN 528..530
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 535..540
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 543..552
FT /evidence="ECO:0007829|PDB:6RO4"
FT TURN 553..556
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 558..564
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 566..569
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 574..587
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 590..592
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 594..599
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 603..606
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 616..620
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 633..642
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 648..656
FT /evidence="ECO:0007829|PDB:6RO4"
FT TURN 657..664
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 665..667
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 670..672
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 675..679
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 682..685
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 687..690
FT /evidence="ECO:0007829|PDB:6RO4"
FT HELIX 695..698
FT /evidence="ECO:0007829|PDB:6RO4"
FT STRAND 706..708
FT /evidence="ECO:0007829|PDB:7AD8"
FT HELIX 710..724
FT /evidence="ECO:0007829|PDB:6RO4"
SQ SEQUENCE 760 AA; 86909 MW; 746C0888CDF2E331 CRC64;
MKLNVDGLLV YFPYDYIYPE QFSYMRELKR TLDAKGHGVL EMPSGTGKTV SLLALIMAYQ
RAYPLEVTKL IYCSRTVPEI EKVIEELRKL LNFYEKQEGE KLPFLGLALS SRKNLCIHPE
VTPLRFGKDV DGKCHSLTAS YVRAQYQHDT SLPHCRFYEE FDAHGREVPL PAGIYNLDDL
KALGRRQGWC PYFLARYSIL HANVVVYSYH YLLDPKIADL VSKELARKAV VVFDEAHNID
NVCIDSMSVN LTRRTLDRCQ GNLETLQKTV LRIKETDEQR LRDEYRRLVE GLREASAARE
TDAHLANPVL PDEVLQEAVP GSIRTAEHFL GFLRRLLEYV KWRLRVQHVV QESPPAFLSG
LAQRVCIQRK PLRFCAERLR SLLHTLEITD LADFSPLTLL ANFATLVSTY AKGFTIIIEP
FDDRTPTIAN PILHFSCMDA SLAIKPVFER FQSVIITSGT LSPLDIYPKI LDFHPVTMAT
FTMTLARVCL CPMIIGRGND QVAISSKFET REDIAVIRNY GNLLLEMSAV VPDGIVAFFT
SYQYMESTVA SWYEQGILEN IQRNKLLFIE TQDGAETSVA LEKYQEACEN GRGAILLSVA
RGKVSEGIDF VHHYGRAVIM FGVPYVYTQS RILKARLEYL RDQFQIREND FLTFDAMRHA
AQCVGRAIRG KTDYGLMVFA DKRFARGDKR GKLPRWIQEH LTDANLNLTV DEGVQVAKYF
LRQMAQPFHR EDQLGLSLLS LEQLESEETL KRIEQIAQQL
