ERCC8_HUMAN
ID ERCC8_HUMAN Reviewed; 396 AA.
AC Q13216; B2RB64; Q6FHX5; Q96GB9;
DT 15-JUL-1998, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 200.
DE RecName: Full=DNA excision repair protein ERCC-8;
DE AltName: Full=Cockayne syndrome WD repeat protein CSA;
GN Name=ERCC8; Synonyms=CKN1, CSA;
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).
RX PubMed=7664335; DOI=10.1016/0092-8674(95)90028-4;
RA Henning K.A., Li L., Iyer N., McDaniel L.D., Reagan M.S., Legerski R.,
RA Schultz R.A., Stefanini M., Lehmann A.R., Mayne L.V., Friedberg E.C.;
RT "The Cockayne syndrome group A gene encodes a WD repeat protein that
RT interacts with CSB protein and a subunit of RNA polymerase II TFIIH.";
RL Cell 82:555-564(1995).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Halleck A., Ebert L., Mkoundinya M., Schick M., Eisenstein S., Neubert P.,
RA Kstrang K., Schatten R., Shen B., Henze S., Mar W., Korn B., Zuo D., Hu Y.,
RA LaBaer J.;
RT "Cloning of human full open reading frames in Gateway(TM) system entry
RT vector (pDONR201).";
RL Submitted (JUN-2004) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RA Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S.,
RA Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y.,
RA Phelan M., Farmer A.;
RT "Cloning of human full-length CDSs in BD Creator(TM) system donor vector.";
RL Submitted (OCT-2004) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANT CYS-200.
RG NIEHS SNPs program;
RL Submitted (JAN-2003) to the EMBL/GenBank/DDBJ databases.
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RC TISSUE=Uterus;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [6]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [7]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC TISSUE=Urinary bladder;
RX PubMed=15489334; DOI=10.1101/gr.2596504;
RG The MGC Project Team;
RT "The status, quality, and expansion of the NIH full-length cDNA project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [8]
RP INTERACTION WITH DDB1, IDENTIFICATION IN THE CSA COMPLEX WITH RBX1; DDB1
RP AND CUL4A, AND INTERACTION OF THE CSA COMPLEX WITH RNA POLYMERASE II AND
RP THE COP9 SIGNALOSOME.
RX PubMed=12732143; DOI=10.1016/s0092-8674(03)00316-7;
RA Groisman R., Polanowska J., Kuraoka I., Sawada J., Saijo M., Drapkin R.,
RA Kisselev A.F., Tanaka K., Nakatani Y.;
RT "The ubiquitin ligase activity in the DDB2 and CSA complexes is
RT differentially regulated by the COP9 signalosome in response to DNA
RT damage.";
RL Cell 113:357-367(2003).
RN [9]
RP INTERACTION WITH ERCC6, AND FUNCTION AS SUBSTRATE-RECOGNITION COMPONENT OF
RP THE CSA COMPLEX.
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 [10]
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 [11]
RP FUNCTION.
RX PubMed=16964240; DOI=10.1038/nature05175;
RA Angers S., Li T., Yi X., MacCoss M.J., Moon R.T., Zheng N.;
RT "Molecular architecture and assembly of the DDB1-CUL4A ubiquitin ligase
RT machinery.";
RL Nature 443:590-593(2006).
RN [12]
RP PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-390; SER-391 AND SER-392, AND
RP 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 [13]
RP 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 [14]
RP SUBCELLULAR LOCATION.
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 [15]
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 [16]
RP X-RAY CRYSTALLOGRAPHY (3.31 ANGSTROMS) IN COMPLEX WITH DDB1, AND SUBUNIT.
RX PubMed=22118460; DOI=10.1016/j.cell.2011.10.035;
RA Fischer E.S., Scrima A., Bohm K., Matsumoto S., Lingaraju G.M., Faty M.,
RA Yasuda T., Cavadini S., Wakasugi M., Hanaoka F., Iwai S., Gut H.,
RA Sugasawa K., Thoma N.H.;
RT "The molecular basis of CRL4DDB2/CSA ubiquitin ligase architecture,
RT targeting, and activation.";
RL Cell 147:1024-1039(2011).
RN [17]
RP VARIANT CSA PRO-205.
RX PubMed=14661080; DOI=10.1007/s10038-003-0107-2;
RA Cao H., Williams C., Carter M., Hegele R.A.;
RT "CKN1 (MIM 216400): mutations in Cockayne syndrome type A and a new common
RT polymorphism.";
RL J. Hum. Genet. 49:61-63(2004).
RN [18]
RP VARIANT CSA VAL-160.
RX PubMed=15744458; DOI=10.1007/s10038-004-0228-2;
RA Ridley A.J., Colley J., Wynford-Thomas D., Jones C.J.;
RT "Characterisation of novel mutations in Cockayne syndrome type A and
RT xeroderma pigmentosum group C subjects.";
RL J. Hum. Genet. 50:151-154(2005).
RN [19]
RP VARIANT UVSS2 CYS-361.
RX PubMed=19329487; DOI=10.1073/pnas.0902113106;
RA Nardo T., Oneda R., Spivak G., Vaz B., Mortier L., Thomas P., Orioli D.,
RA Laugel V., Stary A., Hanawalt P.C., Sarasin A., Stefanini M.;
RT "A UV-sensitive syndrome patient with a specific CSA mutation reveals
RT separable roles for CSA in response to UV and oxidative DNA damage.";
RL Proc. Natl. Acad. Sci. U.S.A. 106:6209-6214(2009).
RN [20]
RP VARIANTS CSA THR-160; CYS-194; SER-202 AND GLY-266.
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: Substrate-recognition component of the CSA complex, a DCX
CC (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in
CC transcription-coupled nucleotide excision repair. The CSA complex
CC (DCX(ERCC8) complex) promotes the ubiquitination and subsequent
CC proteasomal degradation of ERCC6 in a UV-dependent manner; ERCC6
CC degradation is essential for the recovery of RNA synthesis after
CC transcription-coupled repair. It is required for the recruitment of
CC XAB2, HMGN1 and TCEA1/TFIIS to a transcription-coupled repair complex
CC which removes RNA polymerase II-blocking lesions from the transcribed
CC strand of active genes. Plays a role in DNA single-strand and double-
CC strand breaks (DSSBs) repair; involved in repair of DSSBs by non-
CC homologous end joining (NHEJ) (PubMed:29545921).
CC {ECO:0000269|PubMed:16751180, ECO:0000269|PubMed:16916636,
CC ECO:0000269|PubMed:16964240, ECO:0000269|PubMed:29545921}.
CC -!- PATHWAY: Protein modification; protein ubiquitination.
CC -!- SUBUNIT: Part of the CSA complex (DCX(ERCC8) complex), a DCX E3
CC ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and
CC CUL4A; the CSA complex interacts with RNA polymerase II; upon UV
CC irradiation it interacts with the COP9 signalosome and preferentially
CC with the hyperphosphorylated form of RNA polymerase II. Interacts with
CC ERCC6 and KIAA1530/UVSSA. Interacts with a subunit of RNA polymerase II
CC TFIIH. Interacts directly with DDB1 (PubMed:22118460).
CC {ECO:0000269|PubMed:12732143, ECO:0000269|PubMed:16751180,
CC ECO:0000269|PubMed:22118460, ECO:0000269|PubMed:22466612}.
CC -!- INTERACTION:
CC Q13216; Q9HCS7: XAB2; NbExp=3; IntAct=EBI-295260, EBI-295232;
CC Q13216-1; Q03468: ERCC6; NbExp=2; IntAct=EBI-596556, EBI-295284;
CC Q13216-2; P54253: ATXN1; NbExp=3; IntAct=EBI-16466949, EBI-930964;
CC Q13216-2; Q9UNS2: COPS3; NbExp=3; IntAct=EBI-16466949, EBI-350590;
CC Q13216-2; P14136: GFAP; NbExp=3; IntAct=EBI-16466949, EBI-744302;
CC Q13216-2; O43464: HTRA2; NbExp=3; IntAct=EBI-16466949, EBI-517086;
CC Q13216-2; Q8WXH2: JPH3; NbExp=3; IntAct=EBI-16466949, EBI-1055254;
CC Q13216-2; O60333-2: KIF1B; NbExp=3; IntAct=EBI-16466949, EBI-10975473;
CC Q13216-2; O15069: NACAD; NbExp=3; IntAct=EBI-16466949, EBI-7108375;
CC Q13216-2; O75925: PIAS1; NbExp=3; IntAct=EBI-16466949, EBI-629434;
CC Q13216-2; D3DTS7: PMP22; NbExp=3; IntAct=EBI-16466949, EBI-25882629;
CC Q13216-2; P60891: PRPS1; NbExp=3; IntAct=EBI-16466949, EBI-749195;
CC Q13216-2; Q96D59: RNF183; NbExp=3; IntAct=EBI-16466949, EBI-743938;
CC Q13216-2; Q9GZS3: WDR61; NbExp=3; IntAct=EBI-16466949, EBI-358545;
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000305}. Nucleus matrix
CC {ECO:0000269|PubMed:26620705}. Note=UV-induced translocation to the
CC nuclear matrix is dependent on ERCC6. {ECO:0000269|PubMed:26620705}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q13216-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q13216-2; Sequence=VSP_013914, VSP_013915;
CC -!- DISEASE: Cockayne syndrome A (CSA) [MIM:216400]: 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:14661080, ECO:0000269|PubMed:15744458,
CC ECO:0000269|PubMed:19894250}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: UV-sensitive syndrome 2 (UVSS2) [MIM:614621]: 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:19329487}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC Haematology;
CC URL="http://atlasgeneticsoncology.org/Genes/CSAID301.html";
CC -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC URL="http://egp.gs.washington.edu/data/ckn1/";
CC -!- WEB RESOURCE: Name=Mendelian genes excision repair cross-complementing
CC rodent repair deficiency, complementation group 8 (ERCC8); Note=Leiden
CC Open Variation Database (LOVD);
CC URL="https://databases.lovd.nl/shared/genes/ERCC8";
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DR EMBL; U28413; AAA82605.1; -; mRNA.
DR EMBL; CR536563; CAG38800.1; -; mRNA.
DR EMBL; BT020021; AAV38824.1; -; mRNA.
DR EMBL; AY213194; AAO21128.1; -; Genomic_DNA.
DR EMBL; AK314511; BAG37111.1; -; mRNA.
DR EMBL; CH471123; EAW55004.1; -; Genomic_DNA.
DR EMBL; BC009793; AAH09793.1; -; mRNA.
DR CCDS; CCDS3978.1; -. [Q13216-1]
DR PIR; A57090; A57090.
DR RefSeq; NP_000073.1; NM_000082.3. [Q13216-1]
DR RefSeq; NP_001007235.1; NM_001007234.2. [Q13216-2]
DR PDB; 4A11; X-ray; 3.31 A; B=1-396.
DR PDB; 6FCV; X-ray; 2.92 A; B=1-396.
DR PDB; 7OO3; EM; 2.80 A; a=1-396.
DR PDB; 7OOB; EM; 2.70 A; a=1-396.
DR PDB; 7OOP; EM; 2.90 A; a=1-396.
DR PDB; 7OPC; EM; 3.00 A; a=1-396.
DR PDB; 7OPD; EM; 3.00 A; a=1-396.
DR PDBsum; 4A11; -.
DR PDBsum; 6FCV; -.
DR PDBsum; 7OO3; -.
DR PDBsum; 7OOB; -.
DR PDBsum; 7OOP; -.
DR PDBsum; 7OPC; -.
DR PDBsum; 7OPD; -.
DR AlphaFoldDB; Q13216; -.
DR SMR; Q13216; -.
DR BioGRID; 107581; 75.
DR CORUM; Q13216; -.
DR DIP; DIP-291N; -.
DR IntAct; Q13216; 27.
DR MINT; Q13216; -.
DR STRING; 9606.ENSP00000265038; -.
DR iPTMnet; Q13216; -.
DR PhosphoSitePlus; Q13216; -.
DR BioMuta; ERCC8; -.
DR DMDM; 3121917; -.
DR EPD; Q13216; -.
DR jPOST; Q13216; -.
DR MassIVE; Q13216; -.
DR MaxQB; Q13216; -.
DR PaxDb; Q13216; -.
DR PeptideAtlas; Q13216; -.
DR PRIDE; Q13216; -.
DR ProteomicsDB; 59228; -. [Q13216-1]
DR ProteomicsDB; 59229; -. [Q13216-2]
DR Antibodypedia; 11400; 348 antibodies from 26 providers.
DR DNASU; 1161; -.
DR Ensembl; ENST00000647486.2; ENSP00000494466.2; ENSG00000049167.16. [Q13216-2]
DR Ensembl; ENST00000675229.1; ENSP00000502154.1; ENSG00000049167.16. [Q13216-2]
DR Ensembl; ENST00000676185.1; ENSP00000501614.1; ENSG00000049167.16. [Q13216-1]
DR GeneID; 1161; -.
DR KEGG; hsa:1161; -.
DR MANE-Select; ENST00000676185.1; ENSP00000501614.1; NM_000082.4; NP_000073.1.
DR UCSC; uc003jsm.4; human. [Q13216-1]
DR CTD; 1161; -.
DR DisGeNET; 1161; -.
DR GeneCards; ERCC8; -.
DR GeneReviews; ERCC8; -.
DR HGNC; HGNC:3439; ERCC8.
DR HPA; ENSG00000049167; Low tissue specificity.
DR MalaCards; ERCC8; -.
DR MIM; 216400; phenotype.
DR MIM; 609412; gene.
DR MIM; 614621; phenotype.
DR neXtProt; NX_Q13216; -.
DR OpenTargets; ENSG00000049167; -.
DR Orphanet; 90321; Cockayne syndrome type 1.
DR Orphanet; 90322; Cockayne syndrome type 2.
DR Orphanet; 90324; Cockayne syndrome type 3.
DR Orphanet; 178338; UV-sensitive syndrome.
DR PharmGKB; PA27853; -.
DR VEuPathDB; HostDB:ENSG00000049167; -.
DR eggNOG; KOG4283; Eukaryota.
DR GeneTree; ENSGT00390000009065; -.
DR HOGENOM; CLU_032951_2_2_1; -.
DR InParanoid; Q13216; -.
DR OMA; MTAVKAF; -.
DR OrthoDB; 1318335at2759; -.
DR PhylomeDB; Q13216; -.
DR TreeFam; TF101237; -.
DR PathwayCommons; Q13216; -.
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-8951664; Neddylation.
DR SignaLink; Q13216; -.
DR UniPathway; UPA00143; -.
DR BioGRID-ORCS; 1161; 28 hits in 1119 CRISPR screens.
DR ChiTaRS; ERCC8; human.
DR GeneWiki; ERCC8_(gene); -.
DR GenomeRNAi; 1161; -.
DR Pharos; Q13216; Tbio.
DR PRO; PR:Q13216; -.
DR Proteomes; UP000005640; Chromosome 5.
DR RNAct; Q13216; protein.
DR Bgee; ENSG00000049167; Expressed in adrenal tissue and 135 other tissues.
DR ExpressionAtlas; Q13216; baseline and differential.
DR Genevisible; Q13216; HS.
DR GO; GO:0080008; C:Cul4-RING E3 ubiquitin ligase complex; IMP:UniProtKB.
DR GO; GO:0031464; C:Cul4A-RING E3 ubiquitin ligase complex; IDA:UniProtKB.
DR GO; GO:0016363; C:nuclear matrix; IDA:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0000109; C:nucleotide-excision repair complex; IDA:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0032991; C:protein-containing complex; IDA:UniProtKB.
DR GO; GO:0044877; F:protein-containing complex binding; IDA:UniProtKB.
DR GO; GO:0006974; P:cellular response to DNA damage stimulus; IDA:UniProtKB.
DR GO; GO:0097680; P:double-strand break repair via classical nonhomologous end joining; IDA:UniProtKB.
DR GO; GO:0045739; P:positive regulation of DNA repair; IMP:UniProtKB.
DR GO; GO:0043161; P:proteasome-mediated ubiquitin-dependent protein catabolic process; IDA:UniProtKB.
DR GO; GO:0051865; P:protein autoubiquitination; IDA:UniProtKB.
DR GO; GO:0000209; P:protein polyubiquitination; IDA:UniProtKB.
DR GO; GO:0090262; P:regulation of transcription-coupled nucleotide-excision repair; IMP:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; IDA:UniProtKB.
DR GO; GO:0009411; P:response to UV; IDA:UniProtKB.
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:0006283; P:transcription-coupled nucleotide-excision repair; IDA:MGI.
DR Gene3D; 2.130.10.10; -; 1.
DR InterPro; IPR020472; G-protein_beta_WD-40_rep.
DR InterPro; IPR042238; Rad28/ERCC8/Ckn1/ATCSA-1.
DR InterPro; IPR015943; WD40/YVTN_repeat-like_dom_sf.
DR InterPro; IPR001680; WD40_repeat.
DR InterPro; IPR019775; WD40_repeat_CS.
DR InterPro; IPR036322; WD40_repeat_dom_sf.
DR PANTHER; PTHR46202; PTHR46202; 1.
DR Pfam; PF00400; WD40; 4.
DR PRINTS; PR00320; GPROTEINBRPT.
DR SMART; SM00320; WD40; 5.
DR SUPFAM; SSF50978; SSF50978; 1.
DR PROSITE; PS00678; WD_REPEATS_1; 2.
DR PROSITE; PS50082; WD_REPEATS_2; 5.
DR PROSITE; PS50294; WD_REPEATS_REGION; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Cockayne syndrome; Deafness;
KW Disease variant; DNA damage; DNA repair; Dwarfism; Nucleus; Phosphoprotein;
KW Reference proteome; Repeat; Ubl conjugation pathway; WD repeat.
FT CHAIN 1..396
FT /note="DNA excision repair protein ERCC-8"
FT /id="PRO_0000050970"
FT REPEAT 33..73
FT /note="WD 1"
FT REPEAT 88..129
FT /note="WD 2"
FT REPEAT 133..173
FT /note="WD 3"
FT REPEAT 177..216
FT /note="WD 4"
FT REPEAT 235..274
FT /note="WD 5"
FT REPEAT 281..321
FT /note="WD 6"
FT REPEAT 325..363
FT /note="WD 7"
FT REGION 371..396
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOD_RES 390
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 391
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT MOD_RES 392
FT /note="Phosphoserine"
FT /evidence="ECO:0007744|PubMed:21406692"
FT VAR_SEQ 185..205
FT /note="HRQEILAVSWSPRYDYILATA -> IFILFQTATTLSKRFNKKKRY (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013914"
FT VAR_SEQ 206..396
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:15489334"
FT /id="VSP_013915"
FT VARIANT 150
FT /note="S -> C (in dbSNP:rs167037)"
FT /id="VAR_053392"
FT VARIANT 160
FT /note="A -> T (in CSA; dbSNP:rs281875222)"
FT /evidence="ECO:0000269|PubMed:19894250"
FT /id="VAR_063507"
FT VARIANT 160
FT /note="A -> V (in CSA; dbSNP:rs121434325)"
FT /evidence="ECO:0000269|PubMed:15744458"
FT /id="VAR_025380"
FT VARIANT 194
FT /note="W -> C (in CSA; dbSNP:rs281875223)"
FT /evidence="ECO:0000269|PubMed:19894250"
FT /id="VAR_063508"
FT VARIANT 200
FT /note="Y -> C (in dbSNP:rs4647105)"
FT /evidence="ECO:0000269|Ref.4"
FT /id="VAR_016319"
FT VARIANT 202
FT /note="L -> S (in CSA; dbSNP:rs281875224)"
FT /evidence="ECO:0000269|PubMed:19894250"
FT /id="VAR_063509"
FT VARIANT 205
FT /note="A -> P (in CSA; dbSNP:rs121434326)"
FT /evidence="ECO:0000269|PubMed:14661080"
FT /id="VAR_025381"
FT VARIANT 266
FT /note="D -> G (in CSA; dbSNP:rs281875225)"
FT /evidence="ECO:0000269|PubMed:19894250"
FT /id="VAR_063510"
FT VARIANT 361
FT /note="W -> C (in UVSS2; dbSNP:rs281875221)"
FT /evidence="ECO:0000269|PubMed:19329487"
FT /id="VAR_068177"
FT HELIX 2..9
FT /evidence="ECO:0007829|PDB:7OOB"
FT HELIX 15..28
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 30..32
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 36..38
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 46..51
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 53..56
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 58..63
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 68..72
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 77..80
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 82..84
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 86..90
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 102..107
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 112..119
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 122..128
FT /evidence="ECO:0007829|PDB:7OOB"
FT TURN 129..132
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 133..139
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 144..149
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 158..172
FT /evidence="ECO:0007829|PDB:7OOB"
FT TURN 173..176
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 180..182
FT /evidence="ECO:0007829|PDB:6FCV"
FT STRAND 189..194
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 196..198
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 201..206
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 211..215
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 219..221
FT /evidence="ECO:0007829|PDB:7OO3"
FT STRAND 223..225
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 227..233
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 237..239
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 243..246
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 248..253
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 257..264
FT /evidence="ECO:0007829|PDB:7OOB"
FT TURN 265..267
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 268..273
FT /evidence="ECO:0007829|PDB:7OOB"
FT TURN 274..276
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 302..305
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 307..312
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 315..320
FT /evidence="ECO:0007829|PDB:7OOB"
FT TURN 321..323
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 326..331
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 337..343
FT /evidence="ECO:0007829|PDB:7OOB"
FT TURN 344..347
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 348..353
FT /evidence="ECO:0007829|PDB:7OOB"
FT STRAND 358..363
FT /evidence="ECO:0007829|PDB:7OOB"
SQ SEQUENCE 396 AA; 44055 MW; EC962D56226D717B CRC64;
MLGFLSARQT GLEDPLRLRR AESTRRVLGL ELNKDRDVER IHGGGINTLD IEPVEGRYML
SGGSDGVIVL YDLENSSRQS YYTCKAVCSI GRDHPDVHRY SVETVQWYPH DTGMFTSSSF
DKTLKVWDTN TLQTADVFNF EETVYSHHMS PVSTKHCLVA VGTRGPKVQL CDLKSGSCSH
ILQGHRQEIL AVSWSPRYDY ILATASADSR VKLWDVRRAS GCLITLDQHN GKKSQAVESA
NTAHNGKVNG LCFTSDGLHL LTVGTDNRMR LWNSSNGENT LVNYGKVCNN SKKGLKFTVS
CGCSSEFVFV PYGSTIAVYT VYSGEQITML KGHYKTVDCC VFQSNFQELY SGSRDCNILA
WVPSLYEPVP DDDETTTKSQ LNPAFEDAWS SSDEEG
