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Details on Person UniProt:Q13216 ERCC8

Class:IdReferenceGeneProduct:52836
_chainChangeLogchain:1-396 added on Fri February 6 2015
_displayNameUniProt:Q13216 ERCC8
_timestamp2025-05-21 21:36:29
chainchain:1-396
checksumEC962D56226D717B
commentFUNCTION Substrate-recognition component of the CSA complex, a DCX (DDB1-CUL4-X-box) E3 ubiquitin-protein ligase complex, involved in transcription-coupled nucleotide excision repair (TC-NER), a process during which RNA polymerase II-blocking lesions are rapidly removed from the transcribed strand of active genes (PubMed:12732143, PubMed:16751180, PubMed:16964240, PubMed:32142649, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). Following recruitment to lesion-stalled RNA polymerase II (Pol II), the CSA complex mediates ubiquitination of Pol II subunit POLR2A/RPB1 at 'Lys-1268', a critical TC-NER checkpoint, governing RNA Pol II stability and initiating DNA damage excision by TFIIH recruitment (PubMed:12732143, PubMed:16751180, PubMed:16964240, PubMed:32142649, PubMed:32355176, PubMed:34526721, PubMed:38316879, PubMed:38600235, PubMed:38600236). The CSA complex also promotes the ubiquitination and subsequent proteasomal degradation of ERCC6/CSB in a UV-dependent manner; ERCC6 degradation is essential for the recovery of RNA synthesis after transcription-coupled repair (PubMed:16751180). Also plays a role in DNA double-strand breaks (DSSBs) repair by non-homologous end joining (NHEJ) (PubMed:29545921).PATHWAY Protein modification; protein ubiquitination.SUBUNIT Part of the CSA complex (also named DCX(ERCC8) complex), a DCX E3 ubiquitin-protein ligase complex containing ERCC8, RBX1, DDB1 and CUL4A; the CSA complex interacts with RNA polymerase II; upon UV irradiation it interacts with the COP9 signalosome and preferentially with the hyperphosphorylated form of RNA polymerase II (PubMed:12732143, PubMed:22118460, PubMed:32355176, PubMed:34526721, PubMed:38316879). Interacts with ERCC6/CSB (via CIM motif); promoting recruitment to lesion-stalled RNA polymerase II (Pol II) (PubMed:16751180, PubMed:32355176, PubMed:7664335). Interacts with KIAA1530/UVSSA (PubMed:22466612). Interacts with a subunit of RNA polymerase II TFIIH (PubMed:7664335).INTERACTION Recruited to lesion-stalled RNA polymerase II (Pol II) sites by ERCC6/CSB (PubMed:32355176). UV-induced translocation to the nuclear matrix is dependent on ERCC6/CSB (PubMed:26620705).ALTERNATIVE PRODUCTS The disease is caused by variants affecting the gene represented in this entry.DISEASE The disease is caused by variants affecting the gene represented in this entry.CAUTION PubMed:16916636 was retracted due to image manipulations.ONLINE INFORMATION Leiden Open Variation Database (LOVD)
descriptionrecommendedName: fullName evidence="26"DNA excision repair protein ERCC-8 alternativeName: fullName evidence="25"Cockayne syndrome WD repeat protein CSA
geneNameERCC8
CKN1
CSA
identifierQ13216
isSequenceChangedFALSE
keyword3D-structure
Alternative splicing
Chromosome
Cockayne syndrome
Deafness
Disease variant
DNA damage
DNA repair
Dwarfism
Nucleus
Phosphoprotein
Proteomics identification
Reference proteome
Repeat
Ubl conjugation pathway
WD repeat
modified[InstanceEdit:9836292] Weiser, Joel, 2023-05-25
[InstanceEdit:9852000] Weiser, Joel, 2023-11-03
[InstanceEdit:9926675] Weiser, Joel, 2024-11-03
[InstanceEdit:9939033] Weiser, Joel, 2025-02-21
[InstanceEdit:9948485] Weiser, Joel, 2025-05-21
nameERCC8
referenceDatabase[ReferenceDatabase:2] UniProt
referenceGene[ReferenceDNASequence:8999463] ENSEMBL:ENSG00000049167 ERCC8 [Homo sapiens]
secondaryIdentifierERCC8_HUMAN
B2RB64
Q6FHX5
Q96GB9
sequenceLength396
species[Species:48887] Homo sapiens
(isoformParent)[ReferenceIsoform:228434] UniProt:Q13216-2 ERCC8 [Homo sapiens]
[ReferenceIsoform:405574] UniProt:Q13216-1 ERCC8 [Homo sapiens]
(referenceEntity)[EntityWithAccessionedSequence:52835] ERCC8 [nucleoplasm] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:Q13216 ERCC8 (52836)