ERCC5_HUMAN
ID ERCC5_HUMAN Reviewed; 1186 AA.
AC P28715; A6NGT4; Q5JUS4; Q5JUS5; Q7Z2V3; Q8IZL6; Q8N1B7; Q9HD59; Q9HD60;
DT 01-APR-1993, integrated into UniProtKB/Swiss-Prot.
DT 02-SEP-2008, sequence version 3.
DT 03-AUG-2022, entry version 232.
DE RecName: Full=DNA excision repair protein ERCC-5 {ECO:0000305};
DE EC=3.1.-.- {ECO:0000269|PubMed:32522879, ECO:0000269|PubMed:32821917, ECO:0000269|PubMed:7651464, ECO:0000269|PubMed:8078765, ECO:0000269|PubMed:8090225, ECO:0000269|PubMed:8206890};
DE AltName: Full=DNA repair protein complementing XP-G cells;
DE AltName: Full=Xeroderma pigmentosum group G-complementing protein;
GN Name=ERCC5; Synonyms=ERCM2, XPG, XPGC;
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), AND VARIANTS ARG-1053; ARG-1080 AND
RP HIS-1104.
RX PubMed=8483504; DOI=10.1038/363182a0;
RA Scherly D., Nouspikel T., Corlet J., Ucla C., Bairoch A., Clarkson S.G.;
RT "Complementation of the DNA repair defect in Xeroderma pigmentosum group G
RT cells by a human cDNA related to yeast RAD2.";
RL Nature 363:182-185(1993).
RN [2]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-254; ARG-1053 AND
RP ARG-1080.
RX PubMed=7510366; DOI=10.1016/0921-8777(94)90080-9;
RA Shiomi T., Harada Y.-N., Saito T., Shiomi N., Okuno Y., Yamaizumi M.;
RT "An ERCC5 gene with homology to yeast RAD2 is involved in group G Xeroderma
RT pigmentosum.";
RL Mutat. Res. 314:167-175(1994).
RN [3]
RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), AND VARIANTS VAL-254; ARG-1053 AND
RP ARG-1080.
RX PubMed=8413238; DOI=10.1128/mcb.13.10.6393-6402.1993;
RA Macinnes M.A., Dickson J.A., Hernandez R.R., Learmonth D., Lin G.Y.,
RA Mudgett J.S., Park M.S., Schauer S., Reynolds R.J., Strniste G.F., Yu J.Y.;
RT "Human ERCC5 cDNA-cosmid complementation for excision repair and bipartite
RT amino acid domains conserved with RAD proteins of Saccharomyces cerevisiae
RT and Schizosaccharomyces pombe.";
RL Mol. Cell. Biol. 13:6393-6402(1993).
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND ALTERNATIVE SPLICING (ISOFORMS 1 AND
RP 3).
RX PubMed=11266544; DOI=10.1093/nar/29.7.1443;
RA Emmert S., Schneider T.D., Khan S.G., Kraemer K.H.;
RT "The human XPG gene: gene architecture, alternative splicing and single
RT nucleotide polymorphisms.";
RL Nucleic Acids Res. 29:1443-1452(2001).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS VAL-254;
RP ARG-1053 AND ARG-1080.
RC TISSUE=Bone marrow;
RA Zan Q., Guo J.H., Yu L.;
RL Submitted (DEC-2001) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-181; VAL-254; ARG-256;
RP CYS-311; LYS-399; SER-529; ILE-590; LEU-597; SER-879; HIS-1009 AND
RP ARG-1053; ARG-1080 AND GLN-1080.
RG NIEHS SNPs program;
RL Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15057823; DOI=10.1038/nature02379;
RA Dunham A., Matthews L.H., Burton J., Ashurst J.L., Howe K.L.,
RA Ashcroft K.J., Beare D.M., Burford D.C., Hunt S.E., Griffiths-Jones S.,
RA Jones M.C., Keenan S.J., Oliver K., Scott C.E., Ainscough R., Almeida J.P.,
RA Ambrose K.D., Andrews D.T., Ashwell R.I.S., Babbage A.K., Bagguley C.L.,
RA Bailey J., Bannerjee R., Barlow K.F., Bates K., Beasley H., Bird C.P.,
RA Bray-Allen S., Brown A.J., Brown J.Y., Burrill W., Carder C., Carter N.P.,
RA Chapman J.C., Clamp M.E., Clark S.Y., Clarke G., Clee C.M., Clegg S.C.,
RA Cobley V., Collins J.E., Corby N., Coville G.J., Deloukas P., Dhami P.,
RA Dunham I., Dunn M., Earthrowl M.E., Ellington A.G., Faulkner L.,
RA Frankish A.G., Frankland J., French L., Garner P., Garnett J.,
RA Gilbert J.G.R., Gilson C.J., Ghori J., Grafham D.V., Gribble S.M.,
RA Griffiths C., Hall R.E., Hammond S., Harley J.L., Hart E.A., Heath P.D.,
RA Howden P.J., Huckle E.J., Hunt P.J., Hunt A.R., Johnson C., Johnson D.,
RA Kay M., Kimberley A.M., King A., Laird G.K., Langford C.J., Lawlor S.,
RA Leongamornlert D.A., Lloyd D.M., Lloyd C., Loveland J.E., Lovell J.,
RA Martin S., Mashreghi-Mohammadi M., McLaren S.J., McMurray A., Milne S.,
RA Moore M.J.F., Nickerson T., Palmer S.A., Pearce A.V., Peck A.I., Pelan S.,
RA Phillimore B., Porter K.M., Rice C.M., Searle S., Sehra H.K., Shownkeen R.,
RA Skuce C.D., Smith M., Steward C.A., Sycamore N., Tester J., Thomas D.W.,
RA Tracey A., Tromans A., Tubby B., Wall M., Wallis J.M., West A.P.,
RA Whitehead S.L., Willey D.L., Wilming L., Wray P.W., Wright M.W., Young L.,
RA Coulson A., Durbin R.M., Hubbard T., Sulston J.E., Beck S., Bentley D.R.,
RA Rogers J., Ross M.T.;
RT "The DNA sequence and analysis of human chromosome 13.";
RL Nature 428:522-528(2004).
RN [8]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANTS ARG-1053
RP AND ARG-1080.
RC TISSUE=Eye;
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 [9]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-88.
RX PubMed=8088806; DOI=10.1006/geno.1994.1261;
RA Samec S., Jones T.A., Corlet J., Scherly D., Sheer D., Wood R.D.,
RA Clarkson S.G.;
RT "The human gene for Xeroderma pigmentosum complementation group G (XPG)
RT maps to 13q33 by fluorescence in situ hybridization.";
RL Genomics 21:283-285(1994).
RN [10]
RP FUNCTION, CATALYTIC ACTIVITY, COFACTOR, AND BIOPHYSICOCHEMICAL PROPERTIES.
RX PubMed=8206890; DOI=10.1016/s0021-9258(17)33956-x;
RA O'Donovan A., Scherly D., Clarkson S.G., Wood R.D.;
RT "Isolation of active recombinant XPG protein, a human DNA repair
RT endonuclease.";
RL J. Biol. Chem. 269:15965-15968(1994).
RN [11]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8090225; DOI=10.1038/371432a0;
RA O'Donovan A., Davies A.A., Moggs J.G., West S.C., Wood R.D.;
RT "XPG endonuclease makes the 3' incision in human DNA nucleotide excision
RT repair.";
RL Nature 371:432-435(1994).
RN [12]
RP FUNCTION, AND CATALYTIC ACTIVITY.
RX PubMed=8078765; DOI=10.1093/nar/22.16.3312;
RA Habraken Y., Sung P., Prakash L., Prakash S.;
RT "Human Xeroderma pigmentosum group G gene encodes a DNA endonuclease.";
RL Nucleic Acids Res. 22:3312-3316(1994).
RN [13]
RP FUNCTION, CATALYTIC ACTIVITY, AND SUBCELLULAR LOCATION.
RX PubMed=7651464; DOI=10.1016/0165-7992(95)90070-5;
RA Cloud K.G., Shen B., Strniste G.F., Park M.S.;
RT "XPG protein has a structure-specific endonuclease activity.";
RL Mutat. Res. 347:55-60(1995).
RN [14]
RP INTERACTION WITH PCNA.
RX PubMed=9305916; DOI=10.1074/jbc.272.39.24522;
RA Gary R., Ludwig D.L., Cornelius H.L., MacInnes M.A., Park M.S.;
RT "The DNA repair endonuclease XPG binds to proliferating cell nuclear
RT antigen (PCNA) and shares sequence elements with the PCNA-binding regions
RT of FEN-1 and cyclin-dependent kinase inhibitor p21.";
RL J. Biol. Chem. 272:24522-24529(1997).
RN [15]
RP FUNCTION, AND INTERACTION WITH NTHL1.
RX PubMed=9927729; DOI=10.1093/nar/27.4.979;
RA Bessho T.;
RT "Nucleotide excision repair 3' endonuclease XPG stimulates the activity of
RT base excision repair enzyme thymine glycol DNA glycosylase.";
RL Nucleic Acids Res. 27:979-983(1999).
RN [16]
RP REVIEW.
RX PubMed=14726017; DOI=10.1016/j.biochi.2003.10.014;
RA Clarkson S.G.;
RT "The XPG story.";
RL Biochimie 85:1113-1121(2003).
RN [17]
RP REVIEW ON VARIANTS XP-G.
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 [18]
RP FUNCTION, INTERACTION WITH ERCC6 AND RNA POLYMERASE II, SUBCELLULAR
RP LOCATION, AND DOMAIN.
RX PubMed=16246722; DOI=10.1016/j.molcel.2005.09.022;
RA Sarker A.H., Tsutakawa S.E., Kostek S., Ng C., Shin D.S., Peris M.,
RA Campeau E., Tainer J.A., Nogales E., Cooper P.K.;
RT "Recognition of RNA polymerase II and transcription bubbles by XPG, CSB,
RT and TFIIH: insights for transcription-coupled repair and Cockayne
RT Syndrome.";
RL Mol. Cell 20:187-198(2005).
RN [19]
RP ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-8, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=19608861; DOI=10.1126/science.1175371;
RA Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA Olsen J.V., Mann M.;
RT "Lysine acetylation targets protein complexes and co-regulates major
RT cellular functions.";
RL Science 325:834-840(2009).
RN [20]
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 [21]
RP FUNCTION, IDENTIFICATION IN THE HR COMPLEX, INTERACTION WITH BRCA1; BRCA2
RP AND PALB2, SUBCELLULAR LOCATION, AND INDUCTION.
RX PubMed=26833090; DOI=10.1016/j.molcel.2015.12.026;
RA Trego K.S., Groesser T., Davalos A.R., Parplys A.C., Zhao W., Nelson M.R.,
RA Hlaing A., Shih B., Rydberg B., Pluth J.M., Tsai M.S., Hoeijmakers J.H.J.,
RA Sung P., Wiese C., Campisi J., Cooper P.K.;
RT "Non-catalytic Roles for XPG with BRCA1 and BRCA2 in Homologous
RT Recombination and Genome Stability.";
RL Mol. Cell 61:535-546(2016).
RN [22] {ECO:0007744|PDB:5EKF, ECO:0007744|PDB:5EKG}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 1054-1077 AND OF 1168-1186 IN
RP COMPLEX WITH MOUSE KPNA2, AND NUCLEAR LOCALIZATION SIGNAL.
RX PubMed=26812207; DOI=10.1016/j.jmb.2016.01.019;
RA Barros A.C., Takeda A.A., Dreyer T.R., Velazquez-Campoy A., Kobe B.,
RA Fontes M.R.;
RT "Structural and Calorimetric Studies Demonstrate that Xeroderma Pigmentosum
RT Type G (XPG) Can Be Imported to the Nucleus by a Classical Nuclear Import
RT Pathway via a Monopartite NLS Sequence.";
RL J. Mol. Biol. 428:2120-2131(2016).
RN [23] {ECO:0007744|PDB:6TUR, ECO:0007744|PDB:6TUS, ECO:0007744|PDB:6TUW, ECO:0007744|PDB:6TUX}
RP X-RAY CRYSTALLOGRAPHY (2.50 ANGSTROMS) OF 1-747 AND 750-990; OF MUTANT
RP ALA-812; OF APO FORM AND IN COMPLEX WITH DNA, FUNCTION, CATALYTIC ACTIVITY,
RP DOMAIN, AND DNA BINDING.
RX PubMed=32821917; DOI=10.1093/nar/gkaa688;
RA Gonzalez-Corrochano R., Ruiz F.M., Taylor N.M.I., Huecas S., Drakulic S.,
RA Spinola-Amilibia M., Fernandez-Tornero C.;
RT "The crystal structure of human XPG, the xeroderma pigmentosum group G
RT endonuclease, provides insight into nucleotide excision DNA repair.";
RL Nucleic Acids Res. 48:9943-9958(2020).
RN [24] {ECO:0007744|PDB:6VBH}
RP X-RAY CRYSTALLOGRAPHY (2.00 ANGSTROMS) OF 766-987, FUNCTION, CATALYTIC
RP ACTIVITY, SUBUNIT, DOMAIN, AND MUTAGENESIS OF 67-PHE--PHE-68;
RP 955-LEU-ASP-956; PHE-978 AND LEU-981.
RX PubMed=32522879; DOI=10.1073/pnas.1921311117;
RA Tsutakawa S.E., Sarker A.H., Ng C., Arvai A.S., Shin D.S., Shih B.,
RA Jiang S., Thwin A.C., Tsai M.S., Willcox A., Her M.Z., Trego K.S.,
RA Raetz A.G., Rosenberg D., Bacolla A., Hammel M., Griffith J.D.,
RA Cooper P.K., Tainer J.A.;
RT "Human XPG nuclease structure, assembly, and activities with insights for
RT neurodegeneration and cancer from pathogenic mutations.";
RL Proc. Natl. Acad. Sci. U.S.A. 117:14127-14138(2020).
RN [25]
RP INVOLVEMENT IN COFS3.
RX PubMed=24700531; DOI=10.1002/ajmg.a.36506;
RA Drury S., Boustred C., Tekman M., Stanescu H., Kleta R., Lench N.,
RA Chitty L.S., Scott R.H.;
RT "A novel homozygous ERCC5 truncating mutation in a family with prenatal
RT arthrogryposis--further evidence of genotype-phenotype correlation.";
RL Am. J. Med. Genet. A 164A:1777-1783(2014).
RN [26]
RP VARIANT XP-G VAL-792.
RX PubMed=7951246; DOI=10.1093/hmg/3.6.963;
RA Nouspikel T., Clarkson S.G.;
RT "Mutations that disable the DNA repair gene XPG in a Xeroderma pigmentosum
RT group G patient.";
RL Hum. Mol. Genet. 3:963-967(1994).
RN [27]
RP RETRACTED PAPER.
RX PubMed=9096355; DOI=10.1073/pnas.94.7.3116;
RA Nouspikel T., Lalle P., Leadon S.A., Cooper P.K., Clarkson S.G.;
RT "A common mutational pattern in Cockayne syndrome patients from Xeroderma
RT pigmentosum group G: implications for a second XPG function.";
RL Proc. Natl. Acad. Sci. U.S.A. 94:3116-3121(1997).
RN [28]
RP RETRACTION NOTICE OF PUBMED:9096355.
RX PubMed=17179216; DOI=10.1073/pnas.0609759103;
RA Nouspikel T., Lalle P., Leadon S.A., Cooper P.K., Clarkson S.G.;
RL Proc. Natl. Acad. Sci. U.S.A. 103:19606-19606(2006).
RN [29]
RP VARIANT XP-G HIS-72.
RX PubMed=11228268; DOI=10.1203/00006450-200103000-00016;
RA Zafeiriou D.I., Thorel F., Andreou A., Kleijer W.J., Raams A.,
RA Garritsen V.H., Gombakis N., Jaspers N.G.J., Clarkson S.G.;
RT "Xeroderma pigmentosum group G with severe neurological involvement and
RT features of Cockayne syndrome in infancy.";
RL Pediatr. Res. 49:407-412(2001).
RN [30]
RP VARIANT XP-G PRO-858.
RX PubMed=11841555; DOI=10.1046/j.0022-202x.2001.01673.x;
RA Lalle P., Nouspikel T., Constantinou A., Thorel F., Clarkson S.G.;
RT "The founding members of xeroderma pigmentosum group G produce XPG protein
RT with severely impaired endonuclease activity.";
RL J. Invest. Dermatol. 118:344-351(2002).
RN [31]
RP VARIANT XP-G THR-874.
RX PubMed=12060391; DOI=10.1046/j.1523-1747.2002.01782.x;
RA Emmert S., Slor H., Busch D.B., Batko S., Albert R.B., Coleman D.,
RA Khan S.G., Abu-Libdeh B., DiGiovanna J.J., Cunningham B.B., Lee M.M.,
RA Crollick J., Inui H., Ueda T., Hedayati M., Grossman L., Shahlavi T.,
RA Cleaver J.E., Kraemer K.H.;
RT "Relationship of neurologic degeneration to genotype in three xeroderma
RT pigmentosum group G patients.";
RL J. Invest. Dermatol. 118:972-982(2002).
RN [32]
RP VARIANTS XP-G ASP-28 AND CYS-968, AND CHARACTERIZATION OF VARIANTS XP-G
RP ASP-28 AND CYS-968.
RX PubMed=23255472; DOI=10.1002/humu.22259;
RA Soltys D.T., Rocha C.R., Lerner L.K., de Souza T.A., Munford V., Cabral F.,
RA Nardo T., Stefanini M., Sarasin A., Cabral-Neto J.B., Menck C.F.;
RT "Novel XPG (ERCC5) mutations affect DNA repair and cell survival after
RT ultraviolet but not oxidative stress.";
RL Hum. Mutat. 34:481-489(2013).
RN [33]
RP VARIANT ALA-1078.
RX PubMed=30533531; DOI=10.1212/nxg.0000000000000285;
RA Reinthaler E.M., Graf E., Zrzavy T., Wieland T., Hotzy C., Kopecky C.,
RA Pferschy S., Schmied C., Leutmezer F., Keilani M., Lill C.M., Hoffjan S.,
RA Epplen J.T., Zettl U.K., Hecker M., Deutschlaender A., Meuth S.G.,
RA Ahram M., Mustafa B., El-Khateeb M., Vilarino-Gueell C., Sadovnick A.D.,
RA Zimprich F., Tomkinson B., Strom T., Kristoferitsch W., Lassmann H.,
RA Zimprich A.;
RT "TPP2 mutation associated with sterile brain inflammation mimicking MS.";
RL Neurol. Genet. 4:e285-e285(2018).
CC -!- FUNCTION: Single-stranded structure-specific DNA endonuclease involved
CC in DNA excision repair (PubMed:8206890, PubMed:8090225, PubMed:8078765,
CC PubMed:7651464, PubMed:32821917, PubMed:32522879). Makes the 3'incision
CC in DNA nucleotide excision repair (NER) (PubMed:8090225,
CC PubMed:8078765, PubMed:32821917, PubMed:32522879). Binds and bends DNA
CC repair bubble substrate and breaks base stacking at the single-
CC strand/double-strand DNA junction of the DNA bubble (PubMed:32522879).
CC Plays a role in base excision repair (BER) by promoting the binding of
CC DNA glycosylase NTHL1 to its substrate and increasing NTHL1 catalytic
CC activity that removes oxidized pyrimidines from DNA (PubMed:9927729).
CC Involved in transcription-coupled nucleotide excision repair (TCR)
CC which allows RNA polymerase II-blocking lesions to be rapidly removed
CC from the transcribed strand of active genes (PubMed:16246722).
CC Functions during the initial step of TCR in cooperation with ERCC6/CSB
CC to recognized stalled RNA polymerase II (PubMed:16246722). Also,
CC stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB
CC ATPase activity (PubMed:16246722). Required for DNA replication fork
CC maintenance and preservation of genomic stability (PubMed:26833090,
CC PubMed:32522879). Involved in homologous recombination repair (HRR)
CC induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2
CC to the damaged DNA site (PubMed:26833090). During HRR, binds to the
CC replication fork with high specificity and stabilizes it
CC (PubMed:32522879). Also, acts upstream of HRR, to promote the release
CC of BRCA1 from DNA (PubMed:26833090). {ECO:0000269|PubMed:16246722,
CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:32522879,
CC ECO:0000269|PubMed:32821917, ECO:0000269|PubMed:7651464,
CC ECO:0000269|PubMed:8078765, ECO:0000269|PubMed:8090225,
CC ECO:0000269|PubMed:8206890, ECO:0000269|PubMed:9927729}.
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:8206890};
CC Note=Binds 2 magnesium ions per subunit. They probably participate in
CC the reaction catalyzed by the enzyme. May bind an additional third
CC magnesium ion after substrate binding. {ECO:0000250};
CC -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC pH dependence:
CC Optimum pH is 6.5-7. {ECO:0000269|PubMed:8206890};
CC -!- SUBUNIT: Monomer (PubMed:32522879). Homodimer (PubMed:32522879).
CC Component of the homologous recombination repair (HR) complex composed
CC of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (PubMed:26833090). Within
CC the complex, interacts with BRCA2 and PALB2 (PubMed:26833090).
CC Interacts with RNA polymerase II (PubMed:16246722). Interacts (via C-
CC terminus) with ERCC6/CSB; the interaction stimulates ERCC6/CSB binding
CC to the DNA repair bubble and ERCC6/CSB ATPase activity
CC (PubMed:16246722). May form a complex composed of RNA polymerase II,
CC ERCC6/CSB and ERCC5/XPG which associates with the DNA repair bubble
CC during transcription-coupled nucleotide excision repair
CC (PubMed:16246722). Interacts with BRCA1; the interaction promotes the
CC release of BRCA1 from DNA (PubMed:26833090). Interacts with PCNA
CC (PubMed:9305916). Interacts with NTHL1; the interaction stimulates
CC NTHL1 activity and NTHL1 binding to its DNA substrate (PubMed:9927729).
CC {ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:26833090,
CC ECO:0000269|PubMed:32522879, ECO:0000269|PubMed:9305916,
CC ECO:0000269|PubMed:9927729}.
CC -!- INTERACTION:
CC P28715; P24522: GADD45A; NbExp=2; IntAct=EBI-765885, EBI-448167;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16246722,
CC ECO:0000269|PubMed:26833090, ECO:0000269|PubMed:7651464}. Chromosome
CC {ECO:0000269|PubMed:26833090}. Note=Colocalizes with RAD51 to nuclear
CC foci in S phase (PubMed:26833090). Localizes to DNA double-strand
CC breaks (DBS) during replication stress (PubMed:26833090). Colocalizes
CC with BRCA2 to nuclear foci following DNA replication stress
CC (PubMed:26833090). {ECO:0000269|PubMed:26833090}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=1;
CC IsoId=P28715-1; Sequence=Displayed;
CC Name=2;
CC IsoId=P28715-2; Sequence=VSP_035380;
CC Name=3;
CC IsoId=P28715-3; Sequence=VSP_053828, VSP_053829;
CC -!- INDUCTION: Induced by replication stress caused by DNA double-strand
CC breaks (DBS). {ECO:0000269|PubMed:26833090}.
CC -!- DOMAIN: Both nuclear localization signals 1 and 2 act as a monopartite
CC signal which binds to the high affinity site on KPNA2/importin-alpha.
CC {ECO:0000269|PubMed:26812207}.
CC -!- DOMAIN: Both the spacer region (also known as the recognition (R)
CC domain) and C-terminal domain are required for stable binding to the
CC DNA repair bubble (PubMed:16246722). However, both domains are
CC dispensable for incision of DNA bubble structures (PubMed:16246722,
CC PubMed:32821917, PubMed:32522879). {ECO:0000269|PubMed:16246722,
CC ECO:0000269|PubMed:32522879, ECO:0000269|PubMed:32821917}.
CC -!- DISEASE: Xeroderma pigmentosum complementation group G (XP-G)
CC [MIM:278780]: 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-G patients
CC present features of Cockayne syndrome, cachectic dwarfism, pigmentary
CC retinopathy, ataxia, decreased nerve conduction velocities. The
CC phenotype combining xeroderma pigmentosum and Cockayne syndrome traits
CC is referred to as XP-CS complex. {ECO:0000269|PubMed:10447254,
CC ECO:0000269|PubMed:11228268, ECO:0000269|PubMed:11841555,
CC ECO:0000269|PubMed:12060391, ECO:0000269|PubMed:23255472,
CC ECO:0000269|PubMed:7951246}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cerebro-oculo-facio-skeletal syndrome 3 (COFS3) [MIM:616570]:
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:24700531}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- MISCELLANEOUS: [Isoform 3]: Includes a cryptic exon found in intron 6.
CC {ECO:0000305}.
CC -!- SIMILARITY: Belongs to the XPG/RAD2 endonuclease family. XPG subfamily.
CC {ECO:0000305}.
CC -!- CAUTION: A paper describing an additional role for this protein in a
CC base excision repair pathway that is not coupled to transcription has
CC been retracted, because some of the experimental data were incorrect.
CC {ECO:0000269|PubMed:9096355, ECO:0000305|PubMed:17179216}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/XPGID300.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ercc5/";
CC ---------------------------------------------------------------------------
CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms
CC Distributed under the Creative Commons Attribution (CC BY 4.0) License
CC ---------------------------------------------------------------------------
DR EMBL; X69978; CAA49598.1; -; mRNA.
DR EMBL; D16305; BAA03812.1; -; mRNA.
DR EMBL; L20046; AAC37533.1; -; mRNA.
DR EMBL; AF255436; AAF89178.1; -; Genomic_DNA.
DR EMBL; AF255431; AAF89178.1; JOINED; Genomic_DNA.
DR EMBL; AF255433; AAF89178.1; JOINED; Genomic_DNA.
DR EMBL; AF255434; AAF89178.1; JOINED; Genomic_DNA.
DR EMBL; AF255435; AAF89178.1; JOINED; Genomic_DNA.
DR EMBL; AF255442; AAF89179.1; -; Genomic_DNA.
DR EMBL; AF255431; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF255433; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF255434; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF255435; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF255436; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF255437; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF255438; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF255439; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF255440; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF255441; AAF89179.1; JOINED; Genomic_DNA.
DR EMBL; AF462447; AAP97715.1; -; mRNA.
DR EMBL; AF550128; AAN46091.1; -; Genomic_DNA.
DR EMBL; AL157769; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC031522; AAH31522.1; -; mRNA.
DR EMBL; X71341; CAA50481.1; -; Genomic_DNA.
DR EMBL; X71342; CAA50481.1; JOINED; Genomic_DNA.
DR CCDS; CCDS32004.1; -. [P28715-1]
DR PIR; I58009; I58009.
DR PIR; S35993; S35993.
DR RefSeq; NP_000114.2; NM_000123.3. [P28715-1]
DR PDB; 5EKF; X-ray; 2.00 A; B/C=1054-1077.
DR PDB; 5EKG; X-ray; 2.80 A; B/C=1168-1186.
DR PDB; 6TUR; X-ray; 2.90 A; AAA/BBB/CCC/DDD=1-747, AAA/BBB/CCC/DDD=750-990.
DR PDB; 6TUS; X-ray; 2.50 A; A/B=1-747, A/B=750-990.
DR PDB; 6TUW; X-ray; 3.50 A; A=1-747, A=750-990.
DR PDB; 6TUX; X-ray; 3.10 A; A/B=1-747, A/B=750-986.
DR PDB; 6VBH; X-ray; 2.00 A; A=766-987.
DR PDBsum; 5EKF; -.
DR PDBsum; 5EKG; -.
DR PDBsum; 6TUR; -.
DR PDBsum; 6TUS; -.
DR PDBsum; 6TUW; -.
DR PDBsum; 6TUX; -.
DR PDBsum; 6VBH; -.
DR AlphaFoldDB; P28715; -.
DR SMR; P28715; -.
DR BioGRID; 108385; 42.
DR DIP; DIP-750N; -.
DR ELM; P28715; -.
DR IntAct; P28715; 14.
DR STRING; 9606.ENSP00000347978; -.
DR BindingDB; P28715; -.
DR ChEMBL; CHEMBL4736; -.
DR GlyGen; P28715; 2 sites, 1 O-linked glycan (2 sites).
DR iPTMnet; P28715; -.
DR PhosphoSitePlus; P28715; -.
DR BioMuta; ERCC5; -.
DR DMDM; 205371791; -.
DR EPD; P28715; -.
DR jPOST; P28715; -.
DR MassIVE; P28715; -.
DR MaxQB; P28715; -.
DR PaxDb; P28715; -.
DR PeptideAtlas; P28715; -.
DR PRIDE; P28715; -.
DR ProteomicsDB; 54495; -. [P28715-1]
DR ProteomicsDB; 54496; -. [P28715-2]
DR ProteomicsDB; 81837; -.
DR Antibodypedia; 11224; 384 antibodies from 30 providers.
DR DNASU; 2073; -.
DR Ensembl; ENST00000652225.2; ENSP00000498881.2; ENSG00000134899.24. [P28715-1]
DR GeneID; 2073; -.
DR KEGG; hsa:2073; -.
DR MANE-Select; ENST00000652225.2; ENSP00000498881.2; NM_000123.4; NP_000114.3.
DR UCSC; uc001vpw.4; human. [P28715-1]
DR CTD; 2073; -.
DR DisGeNET; 2073; -.
DR GeneCards; ERCC5; -.
DR GeneReviews; ERCC5; -.
DR HGNC; HGNC:3437; ERCC5.
DR HPA; ENSG00000134899; Low tissue specificity.
DR MalaCards; ERCC5; -.
DR MIM; 133530; gene.
DR MIM; 278780; phenotype.
DR MIM; 616570; phenotype.
DR neXtProt; NX_P28715; -.
DR OpenTargets; ENSG00000134899; -.
DR Orphanet; 1466; COFS syndrome.
DR Orphanet; 910; Xeroderma pigmentosum.
DR Orphanet; 220295; Xeroderma pigmentosum-Cockayne syndrome complex.
DR PharmGKB; PA27851; -.
DR VEuPathDB; HostDB:ENSG00000134899; -.
DR eggNOG; KOG2520; Eukaryota.
DR GeneTree; ENSGT00510000048601; -.
DR HOGENOM; CLU_003018_2_0_1; -.
DR InParanoid; P28715; -.
DR OMA; EDSTCEN; -.
DR OrthoDB; 1094524at2759; -.
DR PhylomeDB; P28715; -.
DR TreeFam; TF101235; -.
DR PathwayCommons; P28715; -.
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-6782135; Dual incision in TC-NER.
DR SignaLink; P28715; -.
DR SIGNOR; P28715; -.
DR BioGRID-ORCS; 2073; 25 hits in 1076 CRISPR screens.
DR GeneWiki; ERCC5; -.
DR GenomeRNAi; 2073; -.
DR Pharos; P28715; Tchem.
DR PRO; PR:P28715; -.
DR Proteomes; UP000005640; Chromosome 13.
DR RNAct; P28715; protein.
DR Bgee; ENSG00000134899; Expressed in granulocyte and 97 other tissues.
DR ExpressionAtlas; P28715; baseline and differential.
DR Genevisible; P28715; HS.
DR GO; GO:0005694; C:chromosome; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000109; C:nucleotide-excision repair complex; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0000405; F:bubble DNA binding; IDA:UniProtKB.
DR GO; GO:0003684; F:damaged DNA binding; IDA:UniProtKB.
DR GO; GO:0003690; F:double-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0004520; F:endodeoxyribonuclease activity; IDA:UniProtKB.
DR GO; GO:0004519; F:endonuclease activity; IDA:UniProtKB.
DR GO; GO:0008047; F:enzyme activator activity; IDA:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0042803; F:protein homodimerization activity; IPI:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; IPI:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0000993; F:RNA polymerase II complex binding; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0006285; P:base-excision repair, AP site formation; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0043066; P:negative regulation of apoptotic process; IMP:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; IDA:UniProtKB.
DR GO; GO:0006295; P:nucleotide-excision repair, DNA incision, 3'-to lesion; IBA:GO_Central.
DR GO; GO:0006296; P:nucleotide-excision repair, DNA incision, 5'-to lesion; TAS:Reactome.
DR GO; GO:0050790; P:regulation of catalytic activity; IDA:UniProtKB.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR GO; GO:0010225; P:response to UV-C; IMP:UniProtKB.
DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:0009650; P:UV protection; IGI:MGI.
DR InterPro; IPR036279; 5-3_exonuclease_C_sf.
DR InterPro; IPR008918; HhH2.
DR InterPro; IPR029060; PIN-like_dom_sf.
DR InterPro; IPR006086; XPG-I_dom.
DR InterPro; IPR006084; XPG/Rad2.
DR InterPro; IPR001044; XPG/Rad2_eukaryotes.
DR InterPro; IPR019974; XPG_CS.
DR InterPro; IPR006085; XPG_DNA_repair_N.
DR Pfam; PF00867; XPG_I; 1.
DR Pfam; PF00752; XPG_N; 1.
DR PRINTS; PR00853; XPGRADSUPER.
DR PRINTS; PR00066; XRODRMPGMNTG.
DR SMART; SM00279; HhH2; 1.
DR SMART; SM00484; XPGI; 1.
DR SMART; SM00485; XPGN; 1.
DR SUPFAM; SSF47807; SSF47807; 1.
DR SUPFAM; SSF88723; SSF88723; 1.
DR TIGRFAMs; TIGR00600; rad2; 1.
DR PROSITE; PS00841; XPG_1; 1.
DR PROSITE; PS00842; XPG_2; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Acetylation; Alternative splicing; Chromosome;
KW Cockayne syndrome; Deafness; Disease variant; DNA damage; DNA repair;
KW DNA-binding; Dwarfism; Endonuclease; Hydrolase; Magnesium; Metal-binding;
KW Nuclease; Nucleus; Phosphoprotein; Reference proteome;
KW Xeroderma pigmentosum.
FT CHAIN 1..1186
FT /note="DNA excision repair protein ERCC-5"
FT /id="PRO_0000154031"
FT REGION 1..78
FT /note="N-domain"
FT /evidence="ECO:0000305|PubMed:32522879"
FT REGION 31..67
FT /note="DNA-binding; may bind to the undamaged single-strand
FT DNA of the DNA repair bubble"
FT /evidence="ECO:0000269|PubMed:32821917,
FT ECO:0000312|PDB:6TUW, ECO:0007744|PDB:6TUX"
FT REGION 79..785
FT /note="Spacer region"
FT /evidence="ECO:0000269|PubMed:16246722"
FT REGION 306..342
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 354..385
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 404..473
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 510..533
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 667..724
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 786..881
FT /note="I-domain"
FT /evidence="ECO:0000305|PubMed:32522879"
FT REGION 820..836
FT /note="DNA-binding; may bind to the undamaged single-strand
FT DNA of the DNA repair bubble"
FT /evidence="ECO:0000269|PubMed:32821917,
FT ECO:0000312|PDB:6TUW, ECO:0007744|PDB:6TUX"
FT REGION 848..880
FT /note="DNA-binding; H2TH (helix-2turn-helix) motif which
FT binds double-stranded DNA"
FT /evidence="ECO:0000269|PubMed:32821917,
FT ECO:0000312|PDB:6TUW, ECO:0007744|PDB:6TUX"
FT REGION 912..918
FT /note="DNA-binding; may bind double-stranded DNA"
FT /evidence="ECO:0000269|PubMed:32821917,
FT ECO:0000312|PDB:6TUW, ECO:0007744|PDB:6TUX"
FT REGION 981..1009
FT /note="Interaction with PCNA"
FT /evidence="ECO:0000269|PubMed:9305916"
FT REGION 1011..1186
FT /note="Interaction with ERCC6/CSB"
FT /evidence="ECO:0000269|PubMed:16246722"
FT REGION 1056..1081
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1095..1186
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 1057..1074
FT /note="Nuclear localization signal 1"
FT /evidence="ECO:0000305|PubMed:26812207"
FT MOTIF 1169..1186
FT /note="Nuclear localization signal 2"
FT /evidence="ECO:0000305|PubMed:26812207"
FT COMPBIAS 443..458
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 676..724
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1095..1150
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1168..1186
FT /note="Basic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 30
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT BINDING 77
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT BINDING 789
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT BINDING 791
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="1"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT BINDING 810
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT BINDING 812
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT BINDING 861
FT /ligand="Mg(2+)"
FT /ligand_id="ChEBI:CHEBI:18420"
FT /ligand_label="2"
FT /evidence="ECO:0000250|UniProtKB:P39748"
FT MOD_RES 8
FT /note="N6-acetyllysine"
FT /evidence="ECO:0007744|PubMed:19608861"
FT MOD_RES 384
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35689"
FT MOD_RES 705
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P35689"
FT VAR_SEQ 1..767
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000305"
FT /id="VSP_035380"
FT VAR_SEQ 225..232
FT /note="ESDDFSQY -> VYLPLLQP (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_053828"
FT VAR_SEQ 233..1186
FT /note="Missing (in isoform 3)"
FT /evidence="ECO:0000305"
FT /id="VSP_053829"
FT VARIANT 28
FT /note="A -> D (in XP-G; patient cells show a strong DNA
FT repair defect in response to UV light but not in response
FT to oxidative stress; decreased nucleotide-excision repair
FT activity; dbSNP:rs267607281)"
FT /evidence="ECO:0000269|PubMed:23255472"
FT /id="VAR_075773"
FT VARIANT 72
FT /note="P -> H (in XP-G; combined with features of Cockayne
FT syndrome; dbSNP:rs121434574)"
FT /evidence="ECO:0000269|PubMed:11228268"
FT /id="VAR_015280"
FT VARIANT 145
FT /note="V -> I (in dbSNP:rs4987063)"
FT /id="VAR_020431"
FT VARIANT 181
FT /note="H -> R (in dbSNP:rs4150295)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023120"
FT VARIANT 254
FT /note="M -> V (in dbSNP:rs1047769)"
FT /evidence="ECO:0000269|PubMed:7510366,
FT ECO:0000269|PubMed:8413238, ECO:0000269|Ref.5,
FT ECO:0000269|Ref.6"
FT /id="VAR_007732"
FT VARIANT 256
FT /note="Q -> R (in dbSNP:rs4150313)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_020432"
FT VARIANT 311
FT /note="S -> C (in dbSNP:rs2307491)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_014829"
FT VARIANT 399
FT /note="E -> K (in dbSNP:rs4150315)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023121"
FT VARIANT 529
FT /note="C -> S (in dbSNP:rs2227869)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_020433"
FT VARIANT 590
FT /note="V -> I (in dbSNP:rs4150318)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023122"
FT VARIANT 597
FT /note="V -> L (in dbSNP:rs4150319)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023123"
FT VARIANT 670
FT /note="F -> L (in dbSNP:rs1803542)"
FT /id="VAR_046373"
FT VARIANT 680
FT /note="Q -> R (in dbSNP:rs4987168)"
FT /id="VAR_020434"
FT VARIANT 792
FT /note="A -> V (in XP-G; mild form; dbSNP:rs121434571)"
FT /evidence="ECO:0000269|PubMed:7951246"
FT /id="VAR_007733"
FT VARIANT 858
FT /note="L -> P (in XP-G; reduced stability and greatly
FT impaired endonuclease activity; dbSNP:rs121434575)"
FT /evidence="ECO:0000269|PubMed:11841555"
FT /id="VAR_017097"
FT VARIANT 874
FT /note="A -> T (in XP-G; mild form; residual activity;
FT dbSNP:rs121434576)"
FT /evidence="ECO:0000269|PubMed:12060391"
FT /id="VAR_017096"
FT VARIANT 879
FT /note="N -> S (in dbSNP:rs4150342)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_020435"
FT VARIANT 968
FT /note="W -> C (in XP-G; patient cells show a strong DNA
FT repair defect in response to UV light but not in response
FT to oxidative stress; decreased nucleotide-excision repair
FT activity; dbSNP:rs267607280)"
FT /evidence="ECO:0000269|PubMed:23255472"
FT /id="VAR_075774"
FT VARIANT 1009
FT /note="R -> H (in dbSNP:rs4150387)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023124"
FT VARIANT 1053
FT /note="G -> R (in dbSNP:rs9514066)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7510366, ECO:0000269|PubMed:8413238,
FT ECO:0000269|PubMed:8483504, ECO:0000269|Ref.5,
FT ECO:0000269|Ref.6"
FT /id="VAR_046374"
FT VARIANT 1078
FT /note="S -> A (found in a patient diagnosed with multiple
FT sclerosis; unknown pathological significance;
FT dbSNP:rs760347832)"
FT /evidence="ECO:0000269|PubMed:30533531"
FT /id="VAR_085644"
FT VARIANT 1080
FT /note="G -> Q (requires 2 nucleotide substitutions;
FT dbSNP:rs587778291)"
FT /evidence="ECO:0000269|Ref.6"
FT /id="VAR_023125"
FT VARIANT 1080
FT /note="G -> R (in dbSNP:rs9514067)"
FT /evidence="ECO:0000269|PubMed:15489334,
FT ECO:0000269|PubMed:7510366, ECO:0000269|PubMed:8413238,
FT ECO:0000269|PubMed:8483504, ECO:0000269|Ref.5,
FT ECO:0000269|Ref.6"
FT /id="VAR_046375"
FT VARIANT 1104
FT /note="D -> H (in dbSNP:rs17655)"
FT /evidence="ECO:0000269|PubMed:8483504"
FT /id="VAR_007734"
FT VARIANT 1119
FT /note="A -> V (in dbSNP:rs2227871)"
FT /id="VAR_020436"
FT MUTAGEN 67..68
FT /note="FF->AA: Slight reduction in endonuclease activity.
FT Increased affinity for bubble DNA."
FT /evidence="ECO:0000269|PubMed:32522879"
FT MUTAGEN 955..956
FT /note="LD->AA: Reduced protein stability, two-fold decrease
FT in 15-nt bubble DNA incision activity and smaller decrease
FT in Y DNA incision activity; when associated with A-978 and
FT A-981."
FT /evidence="ECO:0000269|PubMed:32522879"
FT MUTAGEN 978
FT /note="F->A: Reduced protein stability, two-fold decrease
FT in 15-nt bubble DNA incision activity and smaller decrease
FT in Y DNA incision activity; when associated with 955-A-A-
FT 956 and A-981."
FT /evidence="ECO:0000269|PubMed:32522879"
FT MUTAGEN 981
FT /note="L->A: Reduced protein stability, two-fold decrease
FT in 15-nt bubble DNA incision activity and smaller decrease
FT in Y DNA incision activity; when associated with 955-A-A-
FT 956 and A-978."
FT /evidence="ECO:0000269|PubMed:32522879"
FT CONFLICT 55
FT /note="L -> P (in Ref. 2; BAA03812)"
FT /evidence="ECO:0000305"
FT CONFLICT 120..122
FT /note="KTA -> QTS (in Ref. 2; BAA03812)"
FT /evidence="ECO:0000305"
FT CONFLICT 126
FT /note="K -> Q (in Ref. 2; BAA03812)"
FT /evidence="ECO:0000305"
FT CONFLICT 264..266
FT /note="RQY -> SSH (in Ref. 2; BAA03812)"
FT /evidence="ECO:0000305"
FT CONFLICT 760
FT /note="I -> F (in Ref. 2; BAA03812)"
FT /evidence="ECO:0000305"
FT CONFLICT 796
FT /note="I -> V (in Ref. 2; BAA03812)"
FT /evidence="ECO:0000305"
FT CONFLICT 864..872
FT /note="EGIPTVGCV -> GNTNCGLC (in Ref. 2; BAA03812)"
FT /evidence="ECO:0000305"
FT CONFLICT 959
FT /note="R -> S (in Ref. 2; BAA03812)"
FT /evidence="ECO:0000305"
FT STRAND 713..715
FT /evidence="ECO:0007829|PDB:6TUS"
FT HELIX 716..724
FT /evidence="ECO:0007829|PDB:6TUX"
FT TURN 755..757
FT /evidence="ECO:0007829|PDB:6TUX"
FT HELIX 766..779
FT /evidence="ECO:0007829|PDB:6VBH"
FT STRAND 783..785
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 790..799
FT /evidence="ECO:0007829|PDB:6VBH"
FT STRAND 802..804
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 812..815
FT /evidence="ECO:0007829|PDB:6VBH"
FT STRAND 820..823
FT /evidence="ECO:0007829|PDB:6VBH"
FT STRAND 830..836
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 837..844
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 848..858
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 871..880
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 887..901
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 913..919
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 930..937
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 955..966
FT /evidence="ECO:0007829|PDB:6VBH"
FT HELIX 970..985
FT /evidence="ECO:0007829|PDB:6VBH"
SQ SEQUENCE 1186 AA; 133108 MW; B0A844D617C53F2E CRC64;
MGVQGLWKLL ECSGRQVSPE ALEGKILAVD ISIWLNQALK GVRDRHGNSI ENPHLLTLFH
RLCKLLFFRI RPIFVFDGDA PLLKKQTLVK RRQRKDLASS DSRKTTEKLL KTFLKRQAIK
TAFRSKRDEA LPSLTQVRRE NDLYVLPPLQ EEEKHSSEEE DEKEWQERMN QKQALQEEFF
HNPQAIDIES EDFSSLPPEV KHEILTDMKE FTKRRRTLFE AMPEESDDFS QYQLKGLLKK
NYLNQHIEHV QKEMNQQHSG HIRRQYEDEG GFLKEVESRR VVSEDTSHYI LIKGIQAKTV
AEVDSESLPS SSKMHGMSFD VKSSPCEKLK TEKEPDATPP SPRTLLAMQA ALLGSSSEEE
LESENRRQAR GRNAPAAVDE GSISPRTLSA IKRALDDDED VKVCAGDDVQ TGGPGAEEMR
INSSTENSDE GLKVRDGKGI PFTATLASSS VNSAEEHVAS TNEGREPTDS VPKEQMSLVH
VGTEAFPISD ESMIKDRKDR LPLESAVVRH SDAPGLPNGR ELTPASPTCT NSVSKNETHA
EVLEQQNELC PYESKFDSSL LSSDDETKCK PNSASEVIGP VSLQETSSIV SVPSEAVDNV
ENVVSFNAKE HENFLETIQE QQTTESAGQD LISIPKAVEP MEIDSEESES DGSFIEVQSV
ISDEELQAEF PETSKPPSEQ GEEELVGTRE GEAPAESESL LRDNSERDDV DGEPQEAEKD
AEDSLHEWQD INLEELETLE SNLLAQQNSL KAQKQQQERI AATVTGQMFL ESQELLRLFG
IPYIQAPMEA EAQCAILDLT DQTSGTITDD SDIWLFGARH VYRNFFNKNK FVEYYQYVDF
HNQLGLDRNK LINLAYLLGS DYTEGIPTVG CVTAMEILNE FPGHGLEPLL KFSEWWHEAQ
KNPKIRPNPH DTKVKKKLRT LQLTPGFPNP AVAEAYLKPV VDDSKGSFLW GKPDLDKIRE
FCQRYFGWNR TKTDESLFPV LKQLDAQQTQ LRIDSFFRLA QQEKEDAKRI KSQRLNRAVT
CMLRKEKEAA ASEIEAVSVA MEKEFELLDK AKGKTQKRGI TNTLEESSSL KRKRLSDSKG
KNTCGGFLGE TCLSESSDGS SSEDAESSSL MNVQRRTAAK EPKTSASDSQ NSVKEAPVKN
GGATTSSSSD SDDDGGKEKM VLVTARSVFG KKRRKLRRAR GRKRKT
