ERCC6_HUMAN
ID ERCC6_HUMAN Reviewed; 1493 AA.
AC Q03468; D3DX94; E7EV46; Q5W0L9;
DT 01-OCT-1993, integrated into UniProtKB/Swiss-Prot.
DT 01-OCT-1993, sequence version 1.
DT 03-AUG-2022, entry version 222.
DE RecName: Full=DNA excision repair protein ERCC-6;
DE EC=3.6.4.- {ECO:0000269|PubMed:16246722};
DE AltName: Full=ATP-dependent helicase ERCC6;
DE AltName: Full=Cockayne syndrome protein CSB;
GN Name=ERCC6 {ECO:0000312|HGNC:HGNC:3438}; Synonyms=CSB;
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].
RX PubMed=1339317; DOI=10.1016/0092-8674(92)90390-x;
RA Troelstra C., van Gool A., de Wit J., Vermeulen W., Bootsma D.,
RA Hoeijmakers J.H.J.;
RT "ERCC6, a member of a subfamily of putative helicases, is involved in
RT Cockayne's syndrome and preferential repair of active genes.";
RL Cell 71:939-953(1992).
RN [2]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=8382798; DOI=10.1093/nar/21.3.419;
RA Troelstra C., Hesen V., Bootsma D., Hoeijmakers J.H.J.;
RT "Structure and expression of the excision repair gene ERCC6, involved in
RT the human disorder Cockayne's syndrome group B.";
RL Nucleic Acids Res. 21:419-426(1993).
RN [3]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ASP-399; ALA-425; ASP-446;
RP MET-942; CYS-1002; ARG-1095; VAL-1097; GLY-1213; PRO-1230; LEU-1308;
RP VAL-1322; ARG-1372; ARG-1382; ARG-1410; ARG-1413 AND ILE-1441.
RG NIEHS SNPs program;
RL Submitted (DEC-2002) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=15164054; DOI=10.1038/nature02462;
RA Deloukas P., Earthrowl M.E., Grafham D.V., Rubenfield M., French L.,
RA Steward C.A., Sims S.K., Jones M.C., Searle S., Scott C., Howe K.,
RA Hunt S.E., Andrews T.D., Gilbert J.G.R., Swarbreck D., Ashurst J.L.,
RA Taylor A., Battles J., Bird C.P., Ainscough R., Almeida J.P.,
RA Ashwell R.I.S., Ambrose K.D., Babbage A.K., Bagguley C.L., Bailey J.,
RA Banerjee R., Bates K., Beasley H., Bray-Allen S., Brown A.J., Brown J.Y.,
RA Burford D.C., Burrill W., Burton J., Cahill P., Camire D., Carter N.P.,
RA Chapman J.C., Clark S.Y., Clarke G., Clee C.M., Clegg S., Corby N.,
RA Coulson A., Dhami P., Dutta I., Dunn M., Faulkner L., Frankish A.,
RA Frankland J.A., Garner P., Garnett J., Gribble S., Griffiths C.,
RA Grocock R., Gustafson E., Hammond S., Harley J.L., Hart E., Heath P.D.,
RA Ho T.P., Hopkins B., Horne J., Howden P.J., Huckle E., Hynds C.,
RA Johnson C., Johnson D., Kana A., Kay M., Kimberley A.M., Kershaw J.K.,
RA Kokkinaki M., Laird G.K., Lawlor S., Lee H.M., Leongamornlert D.A.,
RA Laird G., Lloyd C., Lloyd D.M., Loveland J., Lovell J., McLaren S.,
RA McLay K.E., McMurray A., Mashreghi-Mohammadi M., Matthews L., Milne S.,
RA Nickerson T., Nguyen M., Overton-Larty E., Palmer S.A., Pearce A.V.,
RA Peck A.I., Pelan S., Phillimore B., Porter K., Rice C.M., Rogosin A.,
RA Ross M.T., Sarafidou T., Sehra H.K., Shownkeen R., Skuce C.D., Smith M.,
RA Standring L., Sycamore N., Tester J., Thorpe A., Torcasso W., Tracey A.,
RA Tromans A., Tsolas J., Wall M., Walsh J., Wang H., Weinstock K., West A.P.,
RA Willey D.L., Whitehead S.L., Wilming L., Wray P.W., Young L., Chen Y.,
RA Lovering R.C., Moschonas N.K., Siebert R., Fechtel K., Bentley D.,
RA Durbin R.M., Hubbard T., Doucette-Stamm L., Beck S., Smith D.R., Rogers J.;
RT "The DNA sequence and comparative analysis of human chromosome 10.";
RL Nature 429:375-381(2004).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
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 (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
RP REVIEW ON VARIANTS CSB.
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 [7]
RP DISEASE.
RX PubMed=10739753; DOI=10.1086/302867;
RA Meira L.B., Graham J.M. Jr., Greenberg C.R., Busch D.B., Doughty A.T.B.,
RA Ziffer D.W., Coleman D.M., Savre-Train I., Friedberg E.C.;
RT "Manitoba aboriginal kindred with original cerebro-oculo-facio-skeletal
RT syndrome has a mutation in the Cockayne syndrome group B (CSB) gene.";
RL Am. J. Hum. Genet. 66:1221-1228(2000).
RN [8]
RP DISEASE.
RX PubMed=10767341; DOI=10.1093/hmg/9.8.1171;
RA Colella S., Nardo T., Botta E., Lehmann A.R., Stefanini M.;
RT "Identical mutations in the CSB gene associated with either Cockayne
RT syndrome or the DeSanctis-Cacchione variant of xeroderma pigmentosum.";
RL Hum. Mol. Genet. 9:1171-1175(2000).
RN [9]
RP INVOLVEMENT IN UVSS1.
RX PubMed=15486090; DOI=10.1073/pnas.0404587101;
RA Horibata K., Iwamoto Y., Kuraoka I., Jaspers N.G.J., Kurimasa A.,
RA Oshimura M., Ichihashi M., Tanaka K.;
RT "Complete absence of Cockayne syndrome group B gene product gives rise to
RT UV-sensitive syndrome but not Cockayne syndrome.";
RL Proc. Natl. Acad. Sci. U.S.A. 101:15410-15415(2004).
RN [10]
RP SUBUNIT, AND SUBCELLULAR LOCATION.
RX PubMed=16128801; DOI=10.1111/j.1742-4658.2005.04844.x;
RA Christiansen M., Thorslund T., Jochimsen B., Bohr V.A., Stevnsner T.;
RT "The Cockayne syndrome group B protein is a functional dimer.";
RL FEBS J. 272:4306-4314(2005).
RN [11]
RP FUNCTION, SUBUNIT, AND DNA-BINDING.
RX PubMed=15548521; DOI=10.1074/jbc.m409147200;
RA Beerens N., Hoeijmakers J.H., Kanaar R., Vermeulen W., Wyman C.;
RT "The CSB protein actively wraps DNA.";
RL J. Biol. Chem. 280:4722-4729(2005).
RN [12]
RP FUNCTION, CATALYTIC ACTIVITY, AND INTERACTION WITH ERCC5 AND RNA POLYMERASE
RP II.
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 [13]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT networks.";
RL Cell 127:635-648(2006).
RN [14]
RP INTERACTION WITH ERCC8, UBIQUITINATION BY THE CSA COMPLEX, AND PROTEASOMAL
RP DEGRADATION.
RX PubMed=16751180; DOI=10.1101/gad.378206;
RA Groisman R., Kuraoka I., Chevallier O., Gaye N., Magnaldo T., Tanaka K.,
RA Kisselev A.F., Harel-Bellan A., Nakatani Y.;
RT "CSA-dependent degradation of CSB by the ubiquitin-proteasome pathway
RT establishes a link between complementation factors of the Cockayne
RT syndrome.";
RL Genes Dev. 20:1429-1434(2006).
RN [15]
RP IDENTIFICATION IN THE B-WICH COMPLEX.
RX PubMed=16603771; DOI=10.1074/jbc.m600233200;
RA Cavellan E., Asp P., Percipalle P., Oestlund Farrants A.-K.;
RT "The WSTF-SNF2h chromatin remodeling complex interacts with several nuclear
RT proteins in transcription.";
RL J. Biol. Chem. 281:16264-16271(2006).
RN [16]
RP FUNCTION.
RX PubMed=16916636; DOI=10.1016/j.molcel.2006.06.029;
RA Fousteri M., Vermeulen W., van Zeeland A.A., Mullenders L.H.;
RT "Cockayne syndrome A and B proteins differentially regulate recruitment of
RT chromatin remodeling and repair factors to stalled RNA polymerase II in
RT vivo.";
RL Mol. Cell 23:471-482(2006).
RN [17]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=16964243; DOI=10.1038/nbt1240;
RA Beausoleil S.A., Villen J., Gerber S.A., Rush J., Gygi S.P.;
RT "A probability-based approach for high-throughput protein phosphorylation
RT analysis and site localization.";
RL Nat. Biotechnol. 24:1285-1292(2006).
RN [18]
RP INVOLVEMENT IN ARMD5.
RX PubMed=16754848; DOI=10.1073/pnas.0603485103;
RA Tuo J., Ning B., Bojanowski C.M., Lin Z.-N., Ross R.J., Reed G.F., Shen D.,
RA Jiao X., Zhou M., Chew E.Y., Kadlubar F.F., Chan C.-C.;
RT "Synergic effect of polymorphisms in ERCC6 5' flanking region and
RT complement factor H on age-related macular degeneration predisposition.";
RL Proc. Natl. Acad. Sci. U.S.A. 103:9256-9261(2006).
RN [19]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18691976; DOI=10.1016/j.molcel.2008.07.007;
RA Daub H., Olsen J.V., Bairlein M., Gnad F., Oppermann F.S., Korner R.,
RA Greff Z., Keri G., Stemmann O., Mann M.;
RT "Kinase-selective enrichment enables quantitative phosphoproteomics of the
RT kinome across the cell cycle.";
RL Mol. Cell 31:438-448(2008).
RN [20]
RP METHYLATION AT LYS-170; LYS-297; LYS-448 AND LYS-1054.
RX PubMed=18438403; DOI=10.1038/nchembio.88;
RA Rathert P., Dhayalan A., Murakami M., Zhang X., Tamas R., Jurkowska R.,
RA Komatsu Y., Shinkai Y., Cheng X., Jeltsch A.;
RT "Protein lysine methyltransferase G9a acts on non-histone targets.";
RL Nat. Chem. Biol. 4:344-346(2008).
RN [21]
RP ALTERNATIVE SPLICING.
RX PubMed=18369450; DOI=10.1371/journal.pgen.1000031;
RA Newman J.C., Bailey A.D., Fan H.Y., Pavelitz T., Weiner A.M.;
RT "An abundant evolutionarily conserved CSB-PiggyBac fusion protein expressed
RT in Cockayne syndrome.";
RL PLoS Genet. 4:E1000031-E1000031(2008).
RN [22]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158; SER-429; SER-430;
RP SER-1142 AND SER-1348, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA Elledge S.J., Gygi S.P.;
RT "A quantitative atlas of mitotic phosphorylation.";
RL Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN [23]
RP FUNCTION, DOMAIN UBD, UBIQUITIN-BINDING, UBIQUITINATION AT THE C-TERMINUS,
RP AND MUTAGENESIS OF 1427-LEU-LEU-1428.
RX PubMed=20541997; DOI=10.1016/j.molcel.2010.04.017;
RA Anindya R., Mari P.O., Kristensen U., Kool H., Giglia-Mari G.,
RA Mullenders L.H., Fousteri M., Vermeulen W., Egly J.M., Svejstrup J.Q.;
RT "A ubiquitin-binding domain in cockayne syndrome B required for
RT transcription-coupled nucleotide excision repair.";
RL Mol. Cell 38:637-648(2010).
RN [24]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158, AND IDENTIFICATION BY
RP MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
RX PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT site occupancy during mitosis.";
RL Sci. Signal. 3:RA3-RA3(2010).
RN [25]
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 [26]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-429; SER-430; SER-486 AND
RP SER-489, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT "System-wide temporal characterization of the proteome and phosphoproteome
RT of human embryonic stem cell differentiation.";
RL Sci. Signal. 4:RS3-RS3(2011).
RN [27]
RP FUNCTION.
RX PubMed=22483866; DOI=10.1016/j.dnarep.2012.02.004;
RA Bailey A.D., Gray L.T., Pavelitz T., Newman J.C., Horibata K., Tanaka K.,
RA Weiner A.M.;
RT "The conserved Cockayne syndrome B-piggyBac fusion protein (CSB-PGBD3)
RT affects DNA repair and induces both interferon-like and innate antiviral
RT responses in CSB-null cells.";
RL DNA Repair 11:488-501(2012).
RN [28]
RP UBIQUITINATION.
RX PubMed=22466610; DOI=10.1038/ng.2229;
RA Nakazawa Y., Sasaki K., Mitsutake N., Matsuse M., Shimada M., Nardo T.,
RA Takahashi Y., Ohyama K., Ito K., Mishima H., Nomura M., Kinoshita A.,
RA Ono S., Takenaka K., Masuyama R., Kudo T., Slor H., Utani A., Tateishi S.,
RA Yamashita S., Stefanini M., Lehmann A.R., Yoshiura K.I., Ogi T.;
RT "Mutations in UVSSA cause UV-sensitive syndrome and impair RNA polymerase
RT IIo processing in transcription-coupled nucleotide-excision repair.";
RL Nat. Genet. 44:586-592(2012).
RN [29]
RP UBIQUITINATION.
RX PubMed=22466611; DOI=10.1038/ng.2230;
RA Schwertman P., Lagarou A., Dekkers D.H., Raams A., van der Hoek A.C.,
RA Laffeber C., Hoeijmakers J.H., Demmers J.A., Fousteri M., Vermeulen W.,
RA Marteijn J.A.;
RT "UV-sensitive syndrome protein UVSSA recruits USP7 to regulate
RT transcription-coupled repair.";
RL Nat. Genet. 44:598-602(2012).
RN [30]
RP UBIQUITINATION, AND INTERACTION WITH UVSSA.
RX PubMed=22466612; DOI=10.1038/ng.2228;
RA Zhang X., Horibata K., Saijo M., Ishigami C., Ukai A., Kanno S.I.,
RA Tahara H., Neilan E.G., Honma M., Nohmi T., Yasui A., Tanaka K.;
RT "Mutations in UVSSA cause UV-sensitive syndrome and destabilize ERCC6 in
RT transcription-coupled DNA repair.";
RL Nat. Genet. 44:593-597(2012).
RN [31]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-158 AND SER-1348, AND
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma, and Erythroleukemia;
RX PubMed=23186163; DOI=10.1021/pr300630k;
RA Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA Mohammed S.;
RT "Toward a comprehensive characterization of a human cancer cell
RT phosphoproteome.";
RL J. Proteome Res. 12:260-271(2013).
RN [32]
RP FUNCTION, AND INTERACTION WITH SMARCC2; SMARCB1 AND NBAF COMPLEX.
RX PubMed=24874740; DOI=10.1038/cddis.2014.228;
RA Ciaffardini F., Nicolai S., Caputo M., Canu G., Paccosi E., Costantino M.,
RA Frontini M., Balajee A.S., Proietti-De-Santis L.;
RT "The cockayne syndrome B protein is essential for neuronal differentiation
RT and neuritogenesis.";
RL Cell Death Dis. 5:E1268-E1268(2014).
RN [33]
RP FUNCTION, AND CHARACTERIZATION OF VARIANT CSB ARG-851.
RX PubMed=25820262; DOI=10.15252/embj.201490041;
RA Batenburg N.L., Thompson E.L., Hendrickson E.A., Zhu X.D.;
RT "Cockayne syndrome group B protein regulates DNA double-strand break repair
RT and checkpoint activation.";
RL EMBO J. 34:1399-1416(2015).
RN [34]
RP INTERACTION WITH CAND1; CSTF1; DDX3X; DDX5; DDX17; DDX23; DHX36; HDAC1;
RP HNRNPU; MTA2; PRPF3; PSMD3; RBBP4; SFPQ; SMARCA1; SMARCA2; TOP1; USP7;
RP XRCC5; COPS3; COPS4; COPS6; DDX1; DDX41; GATAD2A; GATAD2B; PRPF4; PSMC5;
RP SF3B2; CTR9; NONO; PSMD12 AND TOP2A.
RX PubMed=26030138; DOI=10.1371/journal.pone.0128558;
RA Nicolai S., Filippi S., Caputo M., Cipak L., Gregan J., Ammerer G.,
RA Frontini M., Willems D., Prantera G., Balajee A.S., Proietti-De-Santis L.;
RT "Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group
RT B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin
RT Dynamics.";
RL PLoS ONE 10:E0128558-E0128558(2015).
RN [35]
RP FUNCTION, INTERACTION WITH RNA POLYMERASE II, SUMOYLATION AT LYS-205,
RP MUTAGENESIS OF LYS-205; LYS-1457; LYS-1487 AND LYS-1489, AND DOMAIN UBD.
RX PubMed=26620705; DOI=10.1074/jbc.m115.683235;
RA Sin Y., Tanaka K., Saijo M.;
RT "The C-terminal Region and SUMOylation of Cockayne Syndrome Group B Protein
RT Play Critical Roles in Transcription-coupled Nucleotide Excision Repair.";
RL J. Biol. Chem. 291:1387-1397(2016).
RN [36]
RP FUNCTION, AND INTERACTION WITH ELOA AND CUL5.
RX PubMed=28292928; DOI=10.1074/jbc.c117.777946;
RA Weems J.C., Slaughter B.D., Unruh J.R., Boeing S., Hall S.M., McLaird M.B.,
RA Yasukawa T., Aso T., Svejstrup J.Q., Conaway J.W., Conaway R.C.;
RT "Cockayne syndrome B protein regulates recruitment of the Elongin A
RT ubiquitin ligase to sites of DNA damage.";
RL J. Biol. Chem. 292:6431-6437(2017).
RN [37]
RP FUNCTION, INTERACTION WITH RIF1, DOMAIN, PHOSPHORYLATION AT SER-10 AND
RP SER-158, MUTAGENESIS OF SER-10; SER-158; LEU-1470; TRP-1486 AND LEU-1488,
RP AND CHARACTERIZATION OF VARIANT CSB ARG-851.
RX PubMed=29203878; DOI=10.1038/s41467-017-02114-x;
RA Batenburg N.L., Walker J.R., Noordermeer S.M., Moatti N., Durocher D.,
RA Zhu X.D.;
RT "ATM and CDK2 control chromatin remodeler CSB to inhibit RIF1 in DSB repair
RT pathway choice.";
RL Nat. Commun. 8:1921-1921(2017).
RN [38]
RP SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-255, AND IDENTIFICATION BY MASS
RP SPECTROMETRY [LARGE SCALE ANALYSIS].
RX PubMed=28112733; DOI=10.1038/nsmb.3366;
RA Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA Nielsen M.L.;
RT "Site-specific mapping of the human SUMO proteome reveals co-modification
RT with phosphorylation.";
RL Nat. Struct. Mol. Biol. 24:325-336(2017).
RN [39]
RP FUNCTION.
RX PubMed=29545921; DOI=10.18632/oncotarget.24342;
RA Pascucci B., Fragale A., Marabitti V., Leuzzi G., Calcagnile A.S.,
RA Parlanti E., Franchitto A., Dogliotti E., D'Errico M.;
RT "CSA and CSB play a role in the response to DNA breaks.";
RL Oncotarget 9:11581-11591(2018).
RN [40]
RP VARIANTS CSB TRP-670; ARG-851; GLY-957 AND LEU-1042, AND VARIANTS THR-255;
RP ASP-399; ARG-1095; VAL-1097; GLY-1213 AND ARG-1413.
RX PubMed=9443879; DOI=10.1086/301686;
RA Mallery D.L., Tanganelli B., Colella S., Steingrimsdottir H.,
RA van Gool A.J., Troelstra C., Stefanini M., Lehmann A.R.;
RT "Molecular analysis of mutations in the CSB (ERCC6) gene in patients with
RT Cockayne syndrome.";
RL Am. J. Hum. Genet. 62:77-85(1998).
RN [41]
RP VARIANTS [LARGE SCALE ANALYSIS] ALA-591; LEU-652; THR-1038; GLN-1119 AND
RP VAL-1119.
RX PubMed=16959974; DOI=10.1126/science.1133427;
RA Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA Velculescu V.E.;
RT "The consensus coding sequences of human breast and colorectal cancers.";
RL Science 314:268-274(2006).
RN [42]
RP VARIANT [LARGE SCALE ANALYSIS] TRP-134.
RX PubMed=18987736; DOI=10.1038/nature07485;
RA Ley T.J., Mardis E.R., Ding L., Fulton B., McLellan M.D., Chen K.,
RA Dooling D., Dunford-Shore B.H., McGrath S., Hickenbotham M., Cook L.,
RA Abbott R., Larson D.E., Koboldt D.C., Pohl C., Smith S., Hawkins A.,
RA Abbott S., Locke D., Hillier L.W., Miner T., Fulton L., Magrini V.,
RA Wylie T., Glasscock J., Conyers J., Sander N., Shi X., Osborne J.R.,
RA Minx P., Gordon D., Chinwalla A., Zhao Y., Ries R.E., Payton J.E.,
RA Westervelt P., Tomasson M.H., Watson M., Baty J., Ivanovich J., Heath S.,
RA Shannon W.D., Nagarajan R., Walter M.J., Link D.C., Graubert T.A.,
RA DiPersio J.F., Wilson R.K.;
RT "DNA sequencing of a cytogenetically normal acute myeloid leukaemia
RT genome.";
RL Nature 456:66-72(2008).
RN [43]
RP VARIANTS CSB TRP-670; ASP-680; CYS-686; LEU-687; ARG-851; GLY-957 AND
RP LEU-1042, VARIANTS COFS1 PRO-871 AND PRO-987, AND VARIANTS ARG-1095 AND
RP GLY-1213.
RX PubMed=19894250; DOI=10.1002/humu.21154;
RA Laugel V., Dalloz C., Durand M., Sauvanaud F., Kristensen U., Vincent M.C.,
RA Pasquier L., Odent S., Cormier-Daire V., Gener B., Tobias E.S.,
RA Tolmie J.L., Martin-Coignard D., Drouin-Garraud V., Heron D., Journel H.,
RA Raffo E., Vigneron J., Lyonnet S., Murday V., Gubser-Mercati D.,
RA Funalot B., Brueton L., Sanchez Del Pozo J., Munoz E., Gennery A.R.,
RA Salih M., Noruzinia M., Prescott K., Ramos L., Stark Z., Fieggen K.,
RA Chabrol B., Sarda P., Edery P., Bloch-Zupan A., Fawcett H., Pham D.,
RA Egly J.M., Lehmann A.R., Sarasin A., Dollfus H.;
RT "Mutation update for the CSB/ERCC6 and CSA/ERCC8 genes involved in Cockayne
RT syndrome.";
RL Hum. Mutat. 31:113-126(2010).
CC -!- FUNCTION: Essential factor involved in transcription-coupled nucleotide
CC excision repair which allows RNA polymerase II-blocking lesions to be
CC rapidly removed from the transcribed strand of active genes
CC (PubMed:20541997, PubMed:26620705, PubMed:16246722). Upon DNA-binding,
CC it locally modifies DNA conformation by wrapping the DNA around itself,
CC thereby modifying the interface between stalled RNA polymerase II and
CC DNA (PubMed:15548521). It is required for transcription-coupled repair
CC complex formation (PubMed:16916636). It recruits the CSA complex
CC (DCX(ERCC8) complex), nucleotide excision repair proteins and EP300 to
CC the sites of RNA polymerase II-blocking lesions (PubMed:16916636).
CC Plays an important role in regulating the choice of the DNA double-
CC strand breaks (DSBs) repair pathway and G2/M checkpoint activation;
CC DNA-dependent ATPase activity is essential for this function
CC (PubMed:25820262). Regulates the DNA repair pathway choice by
CC inhibiting non-homologous end joining (NHEJ), thereby promoting the
CC homologous recombination (HR)-mediated repair of DSBs during the S/G2
CC phases of the cell cycle (PubMed:25820262). Mediates the activation of
CC the ATM- and CHEK2-dependent DNA damage responses thus preventing
CC premature entry of cells into mitosis following the induction of DNA
CC DSBs (PubMed:25820262). Acts as a chromatin remodeler at DSBs; DNA-
CC dependent ATPase-dependent activity is essential for this function.
CC Remodels chromatin by evicting histones from chromatin flanking DSBs,
CC limiting RIF1 accumulation at DSBs thereby promoting BRCA1-mediated HR
CC (PubMed:29203878). Required for stable recruitment of ELOA and CUL5 to
CC DNA damage sites (PubMed:28292928). Involved in UV-induced
CC translocation of ERCC8 to the nuclear matrix (PubMed:26620705).
CC Essential for neuronal differentiation and neuritogenesis; regulates
CC transcription and chromatin remodeling activities required during
CC neurogenesis (PubMed:24874740). {ECO:0000269|PubMed:15548521,
CC ECO:0000269|PubMed:16246722, ECO:0000269|PubMed:16916636,
CC ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:22483866,
CC ECO:0000269|PubMed:24874740, ECO:0000269|PubMed:25820262,
CC ECO:0000269|PubMed:26620705, ECO:0000269|PubMed:28292928,
CC ECO:0000269|PubMed:29203878}.
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;
CC Evidence={ECO:0000269|PubMed:16246722};
CC -!- SUBUNIT: Homodimer (PubMed:16128801, PubMed:15548521). Binds DNA
CC (PubMed:15548521). Interacts with ERCC8 (PubMed:16751180). Interacts
CC with RNA polymerase II; interaction is enhanced by UV irradiation
CC (PubMed:26620705). Component of the B-WICH complex, at least composed
CC of SMARCA5/SNF2H, BAZ1B/WSTF, SF3B1, DEK, MYO1C, ERCC6, MYBBP1A and
CC DDX21 (PubMed:16603771). Interacts with KIAA1530/UVSSA
CC (PubMed:22466612). Interacts with ELOA and CUL5; the interaction is
CC induced by DNA damaging agents or by inhibitors of RNA polymerase II
CC elongation (PubMed:28292928). Interacts (via WHD region) with RIF1
CC (PubMed:29203878). Interacts with SMARCC2/BAF170, SMARCB1/BAF47 and the
CC neuron-specific chromatin remodeling complex (nBAF
CC complex)(PubMed:24874740). Interacts with ERCC5/XPG (via C-terminus);
CC the interaction stimulates ERCC6/CSB binding to the DNA repair bubble
CC and ERCC6/CSB ATPase activity (PubMed:16246722). May form a complex
CC composed of RNA polymerase II, ERCC6/CSB and ERCC5/XPG which associates
CC with the DNA repair bubble during transcription-coupled nucleotide
CC excision repair (PubMed:16246722). Interacts with CAND1, CSTF1, DDX3X,
CC DDX5, DDX17, DDX23, DHX36, HDAC1, HNRNPU, MTA2, PRPF3, PSMD3, RBBP4,
CC SFPQ, SMARCA1, SMARCA2, TOP1, USP7, XRCC5, COPS3, COPS4, COPS6, DDX1,
CC DDX41, GATAD2A, GATAD2B, PRPF4, PSMC5, SF3B2, CTR9, NONO, PSMD12 and
CC TOP2A (PubMed:26030138). {ECO:0000269|PubMed:15548521,
CC ECO:0000269|PubMed:16128801, ECO:0000269|PubMed:16246722,
CC ECO:0000269|PubMed:16603771, ECO:0000269|PubMed:16751180,
CC ECO:0000269|PubMed:22466612, ECO:0000269|PubMed:24874740,
CC ECO:0000269|PubMed:26030138, ECO:0000269|PubMed:26620705,
CC ECO:0000269|PubMed:28292928, ECO:0000269|PubMed:29203878}.
CC -!- INTERACTION:
CC Q03468; P00519: ABL1; NbExp=8; IntAct=EBI-295284, EBI-375543;
CC Q03468; Q13216-1: ERCC8; NbExp=2; IntAct=EBI-295284, EBI-596556;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000269|PubMed:16128801}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=CSB {ECO:0000303|PubMed:18369450};
CC IsoId=Q03468-1; Sequence=Displayed;
CC Name=CSB-PGBD3 {ECO:0000303|PubMed:18369450};
CC IsoId=P0DP91-1, Q03468-2;
CC Sequence=External;
CC -!- DOMAIN: A C-terminal ubiquitin-binding domain (UBD) is essential for
CC transcription-coupled nucleotide excision repair activity, interaction
CC with RNA polymerase II, association with chromatin after UV irradiation
CC and for mediating the UV-induced translocation of ERRC8 to the nuclear
CC matrix. {ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:26620705}.
CC -!- DOMAIN: The N-terminal domain exerts an inhibitory effect on the
CC helicase ATP-binding domain in such a manner that its ATPase activity
CC is restricted (PubMed:29203878). Phosphorylation at Ser-10 and Ser-158
CC promotes the intramolecular interaction of the N-terminal domain with
CC the helicase ATP-binding domain, thereby probably releasing the
CC inhibitory effect of the N-terminal domain on its ATPase activity
CC (PubMed:29203878). {ECO:0000269|PubMed:29203878}.
CC -!- PTM: Phosphorylated in a cell cycle-dependent manner at Ser-158 by
CC cyclin A-CDK2 and at Ser-10 by ATM in response to DNA damage
CC (PubMed:29203878). Phosphorylation at these two sites promotes the
CC intramolecular interaction of the N-terminal domain with the helicase
CC ATP-binding domain, thereby probably releasing the inhibitory effect of
CC the N-terminal domain on its ATPase activity (PubMed:29203878).
CC Phosphorylation is essential for its chromatin remodeling activity
CC (PubMed:29203878). {ECO:0000269|PubMed:29203878}.
CC -!- PTM: Ubiquitinated at the C-terminus. Ubiquitination by the CSA complex
CC leads to ERCC6 proteasomal degradation in a UV-dependent manner.
CC Stabilized following interaction with KIAA1530/UVSSA, which promotes
CC recruitment of deubiquitinating enzyme USP7, leading to
CC deubiquitination of ERCC6 thereby preventing UV-induced degradation of
CC ERCC6 by the proteasome. {ECO:0000269|PubMed:16751180,
CC ECO:0000269|PubMed:20541997, ECO:0000269|PubMed:22466610,
CC ECO:0000269|PubMed:22466611, ECO:0000269|PubMed:22466612}.
CC -!- PTM: Sumoylation at Lys-205 in an UV-radiation-dependent manner is
CC essential for its transcription-coupled nucleotide excision repair
CC activity. {ECO:0000269|PubMed:26620705}.
CC -!- DISEASE: Cockayne syndrome B (CSB) [MIM:133540]: A rare disorder
CC characterized by cutaneous sensitivity to sunlight, abnormal and slow
CC growth, cachectic dwarfism, progeroid appearance, progressive
CC pigmentary retinopathy and sensorineural deafness. There is delayed
CC neural development and severe progressive neurologic degeneration
CC resulting in intellectual disability. Two clinical forms are
CC recognized: in the classical form or Cockayne syndrome type 1, the
CC symptoms are progressive and typically become apparent within the first
CC few years or life; the less common Cockayne syndrome type 2 is
CC characterized by more severe symptoms that manifest prenatally.
CC Cockayne syndrome shows some overlap with certain forms of xeroderma
CC pigmentosum. Unlike xeroderma pigmentosum, patients with Cockayne
CC syndrome do not manifest increased freckling and other pigmentation
CC abnormalities in the skin and have no significant increase in skin
CC cancer. {ECO:0000269|PubMed:10447254, ECO:0000269|PubMed:19894250,
CC ECO:0000269|PubMed:25820262, ECO:0000269|PubMed:29203878,
CC ECO:0000269|PubMed:9443879}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Cerebro-oculo-facio-skeletal syndrome 1 (COFS1) [MIM:214150]:
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:19894250}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: De Sanctis-Cacchione syndrome (DSC) [MIM:278800]: An autosomal
CC recessive syndrome consisting of xeroderma pigmentosum associated with
CC severe neurological and developmental involvement. In addition to the
CC clinical signs of xeroderma pigmentosum, patients present with
CC intellectual disability, dwarfism, gonadal hypoplasia, microcephaly and
CC various neurologic complications of early onset. Note=The disease is
CC caused by variants affecting the gene represented in this entry.
CC -!- DISEASE: Macular degeneration, age-related, 5 (ARMD5) [MIM:613761]: A
CC form of age-related macular degeneration, a multifactorial eye disease
CC and the most common cause of irreversible vision loss in the developed
CC world. In most patients, the disease is manifest as ophthalmoscopically
CC visible yellowish accumulations of protein and lipid that lie beneath
CC the retinal pigment epithelium and within an elastin-containing
CC structure known as Bruch membrane. {ECO:0000269|PubMed:16754848}.
CC Note=Disease susceptibility is associated with variants affecting the
CC gene represented in this entry.
CC -!- DISEASE: UV-sensitive syndrome 1 (UVSS1) [MIM:600630]: An autosomal
CC recessive disorder characterized by cutaneous photosensitivity and mild
CC freckling in the absence of neurological abnormalities or skin tumors.
CC {ECO:0000269|PubMed:15486090}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the SNF2/RAD54 helicase family. {ECO:0000305}.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CSBID302.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ercc6/";
CC ---------------------------------------------------------------------------
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DR EMBL; L04791; AAA52397.1; -; mRNA.
DR EMBL; AY204752; AAO13487.1; -; Genomic_DNA.
DR EMBL; AC073366; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; AL138760; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471187; EAW93094.1; -; Genomic_DNA.
DR EMBL; CH471187; EAW93097.1; -; Genomic_DNA.
DR CCDS; CCDS7229.1; -. [Q03468-1]
DR PIR; A44224; A44224.
DR RefSeq; NP_000115.1; NM_000124.3. [Q03468-1]
DR RefSeq; NP_001333369.1; NM_001346440.1. [Q03468-1]
DR PDB; 4CVO; X-ray; 1.85 A; A=84-160.
DR PDB; 7OO3; EM; 2.80 A; b=1-1493.
DR PDB; 7OOB; EM; 2.70 A; b=1-1493.
DR PDB; 7OOP; EM; 2.90 A; b=1-1493.
DR PDB; 7OPC; EM; 3.00 A; b=1-1493.
DR PDB; 7OPD; EM; 3.00 A; b=1-1493.
DR PDBsum; 4CVO; -.
DR PDBsum; 7OO3; -.
DR PDBsum; 7OOB; -.
DR PDBsum; 7OOP; -.
DR PDBsum; 7OPC; -.
DR PDBsum; 7OPD; -.
DR AlphaFoldDB; Q03468; -.
DR SMR; Q03468; -.
DR BioGRID; 108386; 214.
DR ComplexPortal; CPX-1099; B-WICH chromatin remodelling complex.
DR CORUM; Q03468; -.
DR DIP; DIP-193N; -.
DR IntAct; Q03468; 26.
DR MINT; Q03468; -.
DR STRING; 9606.ENSP00000348089; -.
DR iPTMnet; Q03468; -.
DR PhosphoSitePlus; Q03468; -.
DR BioMuta; ERCC6; -.
DR DMDM; 416959; -.
DR EPD; Q03468; -.
DR jPOST; Q03468; -.
DR MassIVE; Q03468; -.
DR MaxQB; Q03468; -.
DR PaxDb; Q03468; -.
DR PeptideAtlas; Q03468; -.
DR PRIDE; Q03468; -.
DR ProteomicsDB; 18566; -.
DR ProteomicsDB; 58213; -.
DR Antibodypedia; 34972; 412 antibodies from 35 providers.
DR DNASU; 2074; -.
DR Ensembl; ENST00000355832.10; ENSP00000348089.5; ENSG00000225830.16. [Q03468-1]
DR GeneID; 2074; -.
DR KEGG; hsa:2074; -.
DR MANE-Select; ENST00000355832.10; ENSP00000348089.5; NM_000124.4; NP_000115.1.
DR UCSC; uc001jhs.6; human. [Q03468-1]
DR UCSC; uc001jhu.4; human.
DR CTD; 2074; -.
DR DisGeNET; 2074; -.
DR GeneCards; ERCC6; -.
DR GeneReviews; ERCC6; -.
DR HGNC; HGNC:3438; ERCC6.
DR HPA; ENSG00000225830; Low tissue specificity.
DR MalaCards; ERCC6; -.
DR MIM; 133540; phenotype.
DR MIM; 214150; phenotype.
DR MIM; 278800; phenotype.
DR MIM; 600630; phenotype.
DR MIM; 609413; gene.
DR MIM; 613761; phenotype.
DR neXtProt; NX_Q03468; -.
DR OpenTargets; ENSG00000225830; -.
DR Orphanet; 90321; Cockayne syndrome type 1.
DR Orphanet; 90322; Cockayne syndrome type 2.
DR Orphanet; 90324; Cockayne syndrome type 3.
DR Orphanet; 1466; COFS syndrome.
DR Orphanet; 619; NON RARE IN EUROPE: Primary ovarian failure.
DR Orphanet; 178338; UV-sensitive syndrome.
DR PharmGKB; PA27852; -.
DR VEuPathDB; HostDB:ENSG00000225830; -.
DR eggNOG; KOG0387; Eukaryota.
DR GeneTree; ENSGT00940000158057; -.
DR HOGENOM; CLU_000315_7_2_1; -.
DR InParanoid; Q03468; -.
DR OMA; HSVVKHD; -.
DR OrthoDB; 372069at2759; -.
DR PhylomeDB; Q03468; -.
DR TreeFam; TF101236; -.
DR TreeFam; TF328011; -.
DR PathwayCommons; Q03468; -.
DR Reactome; R-HSA-427389; ERCC6 (CSB) and EHMT2 (G9a) positively regulate rRNA expression.
DR Reactome; R-HSA-5250924; B-WICH complex positively regulates rRNA expression.
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-73762; RNA Polymerase I Transcription Initiation.
DR SignaLink; Q03468; -.
DR SIGNOR; Q03468; -.
DR BioGRID-ORCS; 2074; 26 hits in 1068 CRISPR screens.
DR ChiTaRS; ERCC6; human.
DR GeneWiki; ERCC6; -.
DR GenomeRNAi; 2074; -.
DR Pharos; Q03468; Tbio.
DR PRO; PR:Q03468; -.
DR Proteomes; UP000005640; Chromosome 10.
DR RNAct; Q03468; protein.
DR Bgee; ENSG00000225830; Expressed in oocyte and 175 other tissues.
DR ExpressionAtlas; Q03468; baseline and differential.
DR Genevisible; Q03468; HS.
DR GO; GO:0110016; C:B-WICH complex; IDA:ComplexPortal.
DR GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR GO; GO:0090734; C:site of DNA damage; IDA:UniProtKB.
DR GO; GO:0008023; C:transcription elongation factor complex; IDA:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IDA:UniProtKB.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0008094; F:ATP-dependent activity, acting on DNA; IDA:UniProtKB.
DR GO; GO:0140658; F:ATP-dependent chromatin remodeler activity; IMP:GO_Central.
DR GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR GO; GO:0004386; F:helicase activity; 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:0030296; F:protein tyrosine kinase activator activity; IDA:MGI.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0070063; F:RNA polymerase binding; IDA:UniProtKB.
DR GO; GO:0006284; P:base-excision repair; IMP:UniProtKB.
DR GO; GO:0006338; P:chromatin remodeling; IC:ComplexPortal.
DR GO; GO:0000077; P:DNA damage checkpoint signaling; IMP:UniProtKB.
DR GO; GO:0042262; P:DNA protection; IEA:Ensembl.
DR GO; GO:0006281; P:DNA repair; IMP:UniProtKB.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; IDA:UniProtKB.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IEA:Ensembl.
DR GO; GO:0007254; P:JNK cascade; IEA:Ensembl.
DR GO; GO:0035264; P:multicellular organism growth; IEA:Ensembl.
DR GO; GO:2001033; P:negative regulation of double-strand break repair via nonhomologous end joining; IMP:UniProtKB.
DR GO; GO:0022008; P:neurogenesis; IMP:UniProtKB.
DR GO; GO:0030182; P:neuron differentiation; IMP:UniProtKB.
DR GO; GO:0031175; P:neuron projection development; IMP:UniProtKB.
DR GO; GO:0045494; P:photoreceptor cell maintenance; IEA:Ensembl.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0032786; P:positive regulation of DNA-templated transcription, elongation; IDA:UniProtKB.
DR GO; GO:1905168; P:positive regulation of double-strand break repair via homologous recombination; IMP:UniProtKB.
DR GO; GO:0035066; P:positive regulation of histone acetylation; IC:ComplexPortal.
DR GO; GO:0045943; P:positive regulation of transcription by RNA polymerase I; IC:ComplexPortal.
DR GO; GO:0045944; P:positive regulation of transcription by RNA polymerase II; IC:ComplexPortal.
DR GO; GO:0045945; P:positive regulation of transcription by RNA polymerase III; IDA:ComplexPortal.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0006290; P:pyrimidine dimer repair; IEA:Ensembl.
DR GO; GO:0032784; P:regulation of DNA-templated transcription, elongation; IDA:UniProtKB.
DR GO; GO:0034243; P:regulation of transcription elongation from RNA polymerase II promoter; IEA:Ensembl.
DR GO; GO:0010332; P:response to gamma radiation; IEA:Ensembl.
DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0000303; P:response to superoxide; IEA:Ensembl.
DR GO; GO:0009636; P:response to toxic substance; IEA:Ensembl.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
DR GO; GO:0010224; P:response to UV-B; IEA:Ensembl.
DR GO; GO:0010165; P:response to X-ray; IEA:Ensembl.
DR GO; GO:0000012; P:single strand break repair; IDA:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; NAS: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; IMP:UniProtKB.
DR Gene3D; 3.40.50.10810; -; 1.
DR Gene3D; 3.40.50.300; -; 1.
DR InterPro; IPR014001; Helicase_ATP-bd.
DR InterPro; IPR001650; Helicase_C.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR038718; SNF2-like_sf.
DR InterPro; IPR000330; SNF2_N.
DR Pfam; PF00271; Helicase_C; 1.
DR Pfam; PF00176; SNF2-rel_dom; 1.
DR SMART; SM00487; DEXDc; 1.
DR SMART; SM00490; HELICc; 1.
DR SUPFAM; SSF52540; SSF52540; 2.
DR PROSITE; PS51192; HELICASE_ATP_BIND_1; 1.
DR PROSITE; PS51194; HELICASE_CTER; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Age-related macular degeneration; Alternative splicing;
KW ATP-binding; Cataract; Cockayne syndrome; Deafness; Disease variant;
KW DNA damage; DNA repair; DNA-binding; Dwarfism; Helicase; Hydrolase;
KW Intellectual disability; Isopeptide bond; Methylation; Neurogenesis;
KW Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome;
KW Transcription; Transcription regulation; Ubl conjugation;
KW Xeroderma pigmentosum.
FT CHAIN 1..1493
FT /note="DNA excision repair protein ERCC-6"
FT /id="PRO_0000074314"
FT DOMAIN 519..695
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT DOMAIN 843..1002
FT /note="Helicase C-terminal"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00542"
FT REGION 1..510
FT /note="N-terminal domain; essential for its chromatin
FT remodeling activity"
FT /evidence="ECO:0000269|PubMed:29203878"
FT REGION 1..39
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 287..323
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 344..453
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1042..1147
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1181..1247
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1318..1384
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 1400..1428
FT /note="Ubiquitin-binding domain (UBD)"
FT /evidence="ECO:0000269|PubMed:20541997"
FT REGION 1429..1493
FT /note="Winged-helix domain (WHD)"
FT /evidence="ECO:0000305|PubMed:29203878"
FT REGION 1446..1493
FT /note="Essential for its interaction with RNA polymerase
FT II, transcription-coupled nucleotide excision repair
FT activity, association with chromatin after UV irradiation
FT and for mediating the UV-induced translocation of ERRC8 to
FT the nuclear matrix"
FT /evidence="ECO:0000269|PubMed:26620705"
FT MOTIF 646..649
FT /note="DEAH box"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT COMPBIAS 1..31
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 363..396
FT /note="Acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 405..422
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1095..1110
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1124..1142
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1181..1202
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1211..1247
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1335..1353
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 1354..1375
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT BINDING 532..539
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT MOD_RES 10
FT /note="Phosphoserine; by ATM"
FT /evidence="ECO:0000269|PubMed:29203878"
FT MOD_RES 158
FT /note="Phosphoserine; by CDK2"
FT /evidence="ECO:0000269|PubMed:29203878,
FT ECO:0007744|PubMed:16964243, ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:18691976, ECO:0007744|PubMed:20068231,
FT ECO:0007744|PubMed:23186163"
FT MOD_RES 170
FT /note="N6-methylated lysine; by EHMT2"
FT /evidence="ECO:0000269|PubMed:18438403"
FT MOD_RES 297
FT /note="N6-methylated lysine; by EHMT2"
FT /evidence="ECO:0000269|PubMed:18438403"
FT MOD_RES 429
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 430
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:21406692"
FT MOD_RES 448
FT /note="N6-methylated lysine; by EHMT2"
FT /evidence="ECO:0000269|PubMed:18438403"
FT MOD_RES 486
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 489
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 1054
FT /note="N6-methylated lysine; by EHMT2"
FT /evidence="ECO:0000269|PubMed:18438403"
FT MOD_RES 1142
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648"
FT MOD_RES 1348
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:18669648,
FT ECO:0007744|PubMed:23186163"
FT CROSSLNK 205
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO3)"
FT /evidence="ECO:0000269|PubMed:26620705"
FT CROSSLNK 255
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0007744|PubMed:28112733"
FT VARIANT 134
FT /note="R -> W (in dbSNP:rs148095899)"
FT /evidence="ECO:0000269|PubMed:18987736"
FT /id="VAR_054153"
FT VARIANT 255
FT /note="K -> T"
FT /evidence="ECO:0000269|PubMed:9443879"
FT /id="VAR_001216"
FT VARIANT 399
FT /note="G -> D (in dbSNP:rs2228528)"
FT /evidence="ECO:0000269|PubMed:9443879, ECO:0000269|Ref.3"
FT /id="VAR_001217"
FT VARIANT 425
FT /note="D -> A (in dbSNP:rs4253046)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016301"
FT VARIANT 446
FT /note="G -> D (in dbSNP:rs4253047)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016302"
FT VARIANT 591
FT /note="P -> A (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1184760254)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036021"
FT VARIANT 652
FT /note="R -> L (in a colorectal cancer sample; somatic
FT mutation; dbSNP:rs1365187961)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036022"
FT VARIANT 670
FT /note="R -> W (in CSB; dbSNP:rs202080674)"
FT /evidence="ECO:0000269|PubMed:19894250,
FT ECO:0000269|PubMed:9443879"
FT /id="VAR_001218"
FT VARIANT 680
FT /note="N -> D (in CSB; dbSNP:rs1554788393)"
FT /evidence="ECO:0000269|PubMed:19894250"
FT /id="VAR_063511"
FT VARIANT 686
FT /note="W -> C (in CSB; dbSNP:rs751292948)"
FT /evidence="ECO:0000269|PubMed:19894250"
FT /id="VAR_063512"
FT VARIANT 687
FT /note="S -> L (in CSB; dbSNP:rs1026438103)"
FT /evidence="ECO:0000269|PubMed:19894250"
FT /id="VAR_063513"
FT VARIANT 851
FT /note="W -> R (in CSB; DNA-dependent ATPase-dead mutant;
FT loss of chromatin remodeling activity; loss of its ability
FT to inhibit non-homologous end joining-mediated repair and
FT promote homologous recombination-mediated repair of DNA
FT double-strand breaks; loss of its ability to suppress
FT premature exit from G2/M checkpoint; abrogation of its UV-
FT induced chromatin association; dbSNP:rs368728467)"
FT /evidence="ECO:0000269|PubMed:19894250,
FT ECO:0000269|PubMed:25820262, ECO:0000269|PubMed:29203878,
FT ECO:0000269|PubMed:9443879"
FT /id="VAR_001219"
FT VARIANT 871
FT /note="L -> P (in COFS1)"
FT /evidence="ECO:0000269|PubMed:19894250"
FT /id="VAR_063514"
FT VARIANT 942
FT /note="T -> M (in dbSNP:rs2228525)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016303"
FT VARIANT 957
FT /note="V -> G (in CSB)"
FT /evidence="ECO:0000269|PubMed:19894250,
FT ECO:0000269|PubMed:9443879"
FT /id="VAR_001220"
FT VARIANT 987
FT /note="L -> P (in COFS1; dbSNP:rs121917905)"
FT /evidence="ECO:0000269|PubMed:19894250"
FT /id="VAR_063515"
FT VARIANT 1002
FT /note="Y -> C (in dbSNP:rs4253206)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016304"
FT VARIANT 1038
FT /note="R -> T (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036023"
FT VARIANT 1042
FT /note="P -> L (in CSB)"
FT /evidence="ECO:0000269|PubMed:19894250,
FT ECO:0000269|PubMed:9443879"
FT /id="VAR_001221"
FT VARIANT 1095
FT /note="P -> R (in dbSNP:rs4253208)"
FT /evidence="ECO:0000269|PubMed:19894250,
FT ECO:0000269|PubMed:9443879, ECO:0000269|Ref.3"
FT /id="VAR_001222"
FT VARIANT 1097
FT /note="M -> V (in dbSNP:rs2228526)"
FT /evidence="ECO:0000269|PubMed:9443879, ECO:0000269|Ref.3"
FT /id="VAR_001223"
FT VARIANT 1119
FT /note="E -> Q (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036024"
FT VARIANT 1119
FT /note="E -> V (in a breast cancer sample; somatic
FT mutation)"
FT /evidence="ECO:0000269|PubMed:16959974"
FT /id="VAR_036025"
FT VARIANT 1213
FT /note="R -> G (in dbSNP:rs2228527)"
FT /evidence="ECO:0000269|PubMed:19894250,
FT ECO:0000269|PubMed:9443879, ECO:0000269|Ref.3"
FT /id="VAR_001224"
FT VARIANT 1220
FT /note="T -> I (in dbSNP:rs34704611)"
FT /id="VAR_037436"
FT VARIANT 1230
FT /note="R -> P (in dbSNP:rs4253211)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016305"
FT VARIANT 1308
FT /note="V -> L (in dbSNP:rs2229761)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016306"
FT VARIANT 1322
FT /note="G -> V (in dbSNP:rs4253219)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016307"
FT VARIANT 1355
FT /note="D -> E (in dbSNP:rs34917815)"
FT /id="VAR_037437"
FT VARIANT 1372
FT /note="G -> R (in dbSNP:rs4253227)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016308"
FT VARIANT 1382
FT /note="G -> R (in dbSNP:rs4253228)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016309"
FT VARIANT 1410
FT /note="G -> R (in dbSNP:rs4253229)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016310"
FT VARIANT 1413
FT /note="Q -> R (in dbSNP:rs2228529)"
FT /evidence="ECO:0000269|PubMed:9443879, ECO:0000269|Ref.3"
FT /id="VAR_001225"
FT VARIANT 1441
FT /note="T -> I (in dbSNP:rs4253230)"
FT /evidence="ECO:0000269|Ref.3"
FT /id="VAR_016311"
FT MUTAGEN 10
FT /note="S->A: Non-phosphorylatable by ATM. Loss of chromatin
FT remodeling activity and its ability to promote the
FT intramolecular interaction of the N-terminal domain with
FT the helicase ATP-binding domain."
FT /evidence="ECO:0000269|PubMed:29203878"
FT MUTAGEN 10
FT /note="S->D: Phosphomimetic mutant. No loss of chromatin
FT remodeling activity and its ability to promote the
FT intramolecular interaction of the N-terminal domain with
FT the helicase ATP-binding domain."
FT /evidence="ECO:0000269|PubMed:29203878"
FT MUTAGEN 158
FT /note="S->A: Non-phosphorylatable by CDK2. Loss of
FT chromatin remodeling activity and its ability to promote
FT the intramolecular interaction of the N-terminal domain
FT with the helicase ATP-binding domain."
FT /evidence="ECO:0000269|PubMed:29203878"
FT MUTAGEN 158
FT /note="S->D: Phosphomimetic mutant. No loss of chromatin
FT remodeling activity and its ability to promote the
FT intramolecular interaction of the N-terminal domain with
FT the helicase ATP-binding domain."
FT /evidence="ECO:0000269|PubMed:29203878"
FT MUTAGEN 205
FT /note="K->R: Loss of sumoylation and defects in
FT transcription-coupled nucleotide excision repair."
FT /evidence="ECO:0000269|PubMed:26620705"
FT MUTAGEN 1427..1428
FT /note="LL->GG: Fails to bind polyubiquitin chains."
FT /evidence="ECO:0000269|PubMed:20541997"
FT MUTAGEN 1457
FT /note="K->R: No loss of sumoylation; when associated with
FT R-1487 and R-1489."
FT /evidence="ECO:0000269|PubMed:26620705"
FT MUTAGEN 1470
FT /note="L->G: Loss of interaction with RIF1; when associated
FT with G-1486 and G-1488."
FT /evidence="ECO:0000269|PubMed:29203878"
FT MUTAGEN 1486
FT /note="W->G: Loss of interaction with RIF1; when associated
FT with G-1470 and G-1488."
FT /evidence="ECO:0000269|PubMed:29203878"
FT MUTAGEN 1487
FT /note="K->R: No loss of sumoylation; when associated with
FT R-1457 and R-1489. No loss of sumoylation; when associated
FT with R-1489."
FT /evidence="ECO:0000269|PubMed:26620705"
FT MUTAGEN 1488
FT /note="L->G: Loss of interaction with RIF1; when associated
FT with G-1470 and G-1486."
FT /evidence="ECO:0000269|PubMed:29203878"
FT MUTAGEN 1489
FT /note="K->R: No loss of sumoylation; when associated with
FT R-1457 and R-1487. No loss of sumoylation; when associated
FT with R-1487."
FT /evidence="ECO:0000269|PubMed:26620705"
FT HELIX 93..96
FT /evidence="ECO:0007829|PDB:4CVO"
FT HELIX 102..104
FT /evidence="ECO:0007829|PDB:4CVO"
FT HELIX 109..155
FT /evidence="ECO:0007829|PDB:4CVO"
FT STRAND 494..496
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 501..506
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 509..524
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 528..530
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 539..551
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 564..566
FT /evidence="ECO:0007829|PDB:7OOP"
FT STRAND 569..573
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 575..577
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 578..588
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 594..602
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 607..617
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 620..624
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 625..630
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 632..635
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 641..646
FT /evidence="ECO:0007829|PDB:7OO3"
FT HELIX 648..651
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 654..656
FT /evidence="ECO:0007829|PDB:7OO3"
FT HELIX 657..662
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 671..673
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 679..681
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 682..692
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 700..706
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 708..713
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 721..738
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 739..741
FT /evidence="ECO:0007829|PDB:7OOB"
FT TURN 747..749
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 751..753
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 759..766
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 770..780
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 783..789
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 795..807
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 809..813
FT /evidence="ECO:0007829|PDB:7OO3"
FT HELIX 835..837
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 839..853
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 858..863
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 865..877
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 882..884
FT /evidence="ECO:0007829|PDB:7OO3"
FT HELIX 891..893
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 894..903
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 909..913
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 914..917
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 928..931
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 938..945
FT /evidence="ECO:0007829|PDB:7OOB"
FT TURN 946..948
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 957..964
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 968..987
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 998..1002
FT /evidence="ECO:0007829|PDB:7OO3"
FT STRAND 1012..1014
FT /evidence="ECO:0007829|PDB:7OO3"
FT HELIX 1017..1021
FT /evidence="ECO:0007829|PDB:7OO3"
FT HELIX 1388..1398
FT /evidence="ECO:0007829|PDB:7OOB"
SQ SEQUENCE 1493 AA; 168416 MW; 285257E2AEC071AC CRC64;
MPNEGIPHSS QTQEQDCLQS QPVSNNEEMA IKQESGGDGE VEEYLSFRSV GDGLSTSAVG
CASAAPRRGP ALLHIDRHQI QAVEPSAQAL ELQGLGVDVY DQDVLEQGVL QQVDNAIHEA
SRASQLVDVE KEYRSVLDDL TSCTTSLRQI NKIIEQLSPQ AATSRDINRK LDSVKRQKYN
KEQQLKKITA KQKHLQAILG GAEVKIELDH ASLEEDAEPG PSSLGSMLMP VQETAWEELI
RTGQMTPFGT QIPQKQEKKP RKIMLNEASG FEKYLADQAK LSFERKKQGC NKRAARKAPA
PVTPPAPVQN KNKPNKKARV LSKKEERLKK HIKKLQKRAL QFQGKVGLPK ARRPWESDMR
PEAEGDSEGE ESEYFPTEEE EEEEDDEVEG AEADLSGDGT DYELKPLPKG GKRQKKVPVQ
EIDDDFFPSS GEEAEAASVG EGGGGGRKVG RYRDDGDEDY YKQRLRRWNK LRLQDKEKRL
KLEDDSEESD AEFDEGFKVP GFLFKKLFKY QQTGVRWLWE LHCQQAGGIL GDEMGLGKTI
QIIAFLAGLS YSKIRTRGSN YRFEGLGPTV IVCPTTVMHQ WVKEFHTWWP PFRVAILHET
GSYTHKKEKL IRDVAHCHGI LITSYSYIRL MQDDISRYDW HYVILDEGHK IRNPNAAVTL
ACKQFRTPHR IILSGSPMQN NLRELWSLFD FIFPGKLGTL PVFMEQFSVP ITMGGYSNAS
PVQVKTAYKC ACVLRDTINP YLLRRMKSDV KMSLSLPDKN EQVLFCRLTD EQHKVYQNFV
DSKEVYRILN GEMQIFSGLI ALRKICNHPD LFSGGPKNLK GLPDDELEED QFGYWKRSGK
MIVVESLLKI WHKQGQRVLL FSQSRQMLDI LEVFLRAQKY TYLKMDGTTT IASRQPLITR
YNEDTSIFVF LLTTRVGGLG VNLTGANRVV IYDPDWNPST DTQARERAWR IGQKKQVTVY
RLLTAGTIEE KIYHRQIFKQ FLTNRVLKDP KQRRFFKSND LYELFTLTSP DASQSTETSA
IFAGTGSDVQ TPKCHLKRRI QPAFGADHDV PKRKKFPASN ISVNDATSSE EKSEAKGAEV
NAVTSNRSDP LKDDPHMSSN VTSNDRLGEE TNAVSGPEEL SVISGNGECS NSSGTGKTSM
PSGDESIDEK LGLSYKRERP SQAQTEAFWE NKQMENNFYK HKSKTKHHSV AEEETLEKHL
RPKQKPKNSK HCRDAKFEGT RIPHLVKKRR YQKQDSENKS EAKEQSNDDY VLEKLFKKSV
GVHSVMKHDA IMDGASPDYV LVEAEANRVA QDALKALRLS RQRCLGAVSG VPTWTGHRGI
SGAPAGKKSR FGKKRNSNFS VQHPSSTSPT EKCQDGIMKK EGKDNVPEHF SGRAEDADSS
SGPLASSSLL AKMRARNHLI LPERLESESG HLQEASALLP TTEHDDLLVE MRNFIAFQAH
TDGQASTREI LQEFESKLSA SQSCVFRELL RNLCTFHRTS GGEGIWKLKP EYC
