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 27-MAR-2024, entry version 209. 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: SKIC8; 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="https://atlasgeneticsoncology.org/gene/301/CSA"; 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"; 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; 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 CCDS; CCDS93715.1; -. [Q13216-2] 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 PDB; 8B3D; EM; 2.60 A; a=1-396. DR PDB; 8B3F; EM; 3.10 A; a=1-396. DR PDB; 8B3I; EM; 3.50 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 PDBsum; 8B3D; -. DR PDBsum; 8B3F; -. DR PDBsum; 8B3I; -. DR AlphaFoldDB; Q13216; -. DR EMDB; EMD-13004; -. DR EMDB; EMD-13009; -. DR EMDB; EMD-13010; -. DR EMDB; EMD-13015; -. DR EMDB; EMD-13016; -. DR EMDB; EMD-15825; -. DR EMDB; EMD-15826; -. DR EMDB; EMD-15829; -. DR SMR; Q13216; -. DR BioGRID; 107581; 115. DR ComplexPortal; CPX-2757; CRL4-ERCC8 E3 ubiquitin ligase complex, CUL4A variant. DR ComplexPortal; CPX-2758; CRL4-ERCC8 E3 ubiquitin ligase complex, CUL4B variant. DR CORUM; Q13216; -. DR DIP; DIP-291N; -. DR IntAct; Q13216; 26. DR MINT; Q13216; -. DR STRING; 9606.ENSP00000265038; -. DR GlyGen; Q13216; 1 site, 1 O-linked glycan (1 site). 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; 9606-ENSP00000265038; -. DR PeptideAtlas; Q13216; -. DR ProteomicsDB; 59228; -. [Q13216-1] DR ProteomicsDB; 59229; -. [Q13216-2] DR Pumba; Q13216; -. DR Antibodypedia; 11400; 394 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 AGR; HGNC:3439; -. 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; CMTAVKA; -. DR OrthoDB; 1364175at2759; -. 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 SIGNOR; Q13216; -. DR UniPathway; UPA00143; -. DR BioGRID-ORCS; 1161; 29 hits in 1198 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 136 other cell types or tissues. DR ExpressionAtlas; Q13216; baseline and differential. 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:DNA damage response; 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; YVTN repeat-like/Quinoprotein amine dehydrogenase; 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; IPR019775; WD40_repeat_CS. DR InterPro; IPR036322; WD40_repeat_dom_sf. DR InterPro; IPR001680; WD40_rpt. DR PANTHER; PTHR46202; DNA EXCISION REPAIR PROTEIN ERCC-8; 1. DR PANTHER; PTHR46202:SF1; DNA EXCISION REPAIR PROTEIN ERCC-8; 1. DR Pfam; PF00400; WD40; 4. DR PRINTS; PR00320; GPROTEINBRPT. DR SMART; SM00320; WD40; 5. DR SUPFAM; SSF50978; WD40 repeat-like; 1. DR PROSITE; PS00678; WD_REPEATS_1; 2. DR PROSITE; PS50082; WD_REPEATS_2; 5. DR PROSITE; PS50294; WD_REPEATS_REGION; 1. DR Genevisible; Q13216; HS. 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:8B3D" FT HELIX 15..28 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 30..32 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 34..38 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 46..51 FT /evidence="ECO:0007829|PDB:8B3D" FT TURN 53..55 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 58..63 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 68..72 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 77..80 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 82..84 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 86..90 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 102..107 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 114..119 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 122..128 FT /evidence="ECO:0007829|PDB:8B3D" FT TURN 129..132 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 133..139 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 144..149 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 158..172 FT /evidence="ECO:0007829|PDB:8B3D" FT TURN 173..176 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 180..182 FT /evidence="ECO:0007829|PDB:6FCV" FT STRAND 191..194 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 196..198 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 201..205 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 211..215 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 219..225 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 227..233 FT /evidence="ECO:0007829|PDB:7OOB" FT STRAND 237..239 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 243..246 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 248..253 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 257..264 FT /evidence="ECO:0007829|PDB:8B3D" FT TURN 265..267 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 268..273 FT /evidence="ECO:0007829|PDB:8B3D" FT TURN 274..276 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 302..305 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 307..312 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 315..320 FT /evidence="ECO:0007829|PDB:8B3D" FT TURN 321..323 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 326..330 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 337..343 FT /evidence="ECO:0007829|PDB:8B3D" FT TURN 344..347 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 348..353 FT /evidence="ECO:0007829|PDB:8B3D" FT STRAND 358..363 FT /evidence="ECO:0007829|PDB:8B3D" 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 //