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 27-MAR-2024, entry version 241. 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="https://atlasgeneticsoncology.org/gene/300/XPG"; 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; 58. DR DIP; DIP-750N; -. DR ELM; P28715; -. DR IntAct; P28715; 14. DR STRING; 9606.ENSP00000498881; -. DR BindingDB; P28715; -. DR ChEMBL; CHEMBL4736; -. DR GlyCosmos; P28715; 2 sites, 1 glycan. 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; 9606-ENSP00000347978; -. DR PeptideAtlas; P28715; -. DR ProteomicsDB; 54495; -. [P28715-1] DR ProteomicsDB; 54496; -. [P28715-2] DR ProteomicsDB; 81837; -. DR Pumba; P28715; -. DR Antibodypedia; 11224; 414 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 AGR; HGNC:3437; -. 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; KNEPANP; -. DR OrthoDB; 26655at2759; -. 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 1163 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 99 other cell types or tissues. DR ExpressionAtlas; P28715; baseline and differential. 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:0004520; F:DNA endonuclease activity; IDA:UniProtKB. DR GO; GO:0003690; F:double-stranded DNA binding; 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: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: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 CDD; cd09904; H3TH_XPG; 1. DR CDD; cd09868; PIN_XPG_RAD2; 2. DR Gene3D; 1.10.150.20; 5' to 3' exonuclease, C-terminal subdomain; 1. DR Gene3D; 3.40.50.1010; 5'-nuclease; 2. 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 NCBIfam; TIGR00600; rad2; 1. DR PANTHER; PTHR16171:SF7; DNA EXCISION REPAIR PROTEIN ERCC-5; 1. DR PANTHER; PTHR16171; DNA REPAIR PROTEIN COMPLEMENTING XP-G CELLS-RELATED; 1. 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; 5' to 3' exonuclease, C-terminal subdomain; 1. DR SUPFAM; SSF88723; PIN domain-like; 1. DR PROSITE; PS00841; XPG_1; 1. DR PROSITE; PS00842; XPG_2; 1. DR Genevisible; P28715; HS. 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; uncertain significance; 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 YDNA 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 YDNA incision activity; when associated with 955-A-A-956 FT 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 YDNA incision activity; when associated with 955-A-A-956 FT 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 //