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Details on Person UniProt:P28715 ERCC5

Class:Id	ReferenceGeneProduct:67448
_chainChangeLog	chain:1-1186 added on Sat February 7 2015
_displayName	UniProt:P28715 ERCC5
_timestamp	2026-02-20 21:29:37
chain	chain:1-1186
checksum	B0A844D617C53F2E
comment	FUNCTION Single-stranded structure-specific DNA endonuclease involved in DNA excision repair (PubMed:32522879, PubMed:32821917, PubMed:7651464, PubMed:8078765, PubMed:8090225, PubMed:8206890). Makes the 3'incision in DNA nucleotide excision repair (NER) (PubMed:32522879, PubMed:32821917, PubMed:8078765, PubMed:8090225). Binds and bends DNA repair bubble substrate and breaks base stacking at the single-strand/double-strand DNA junction of the DNA bubble (PubMed:32522879). Plays a role in base excision repair (BER) by promoting the binding of DNA glycosylase NTHL1 to its substrate and increasing NTHL1 catalytic activity that removes oxidized pyrimidines from DNA (PubMed:9927729). Involved in transcription-coupled nucleotide excision repair (TCR) which allows RNA polymerase II-blocking lesions to be rapidly removed from the transcribed strand of active genes (PubMed:16246722). Functions during the initial step of TCR in cooperation with ERCC6/CSB to recognized stalled RNA polymerase II (PubMed:16246722). Also, stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity (PubMed:16246722). Required for DNA replication fork maintenance and preservation of genomic stability (PubMed:26833090, PubMed:32522879). Involved in homologous recombination repair (HRR) induced by DNA replication stress by recruiting RAD51, BRCA2, and PALB2 to the damaged DNA site (PubMed:26833090). In TFIIH stimulates the 5'-3' helicase activity of XPD/ERCC2 and the DNA translocase activity of XPB/ERCC3 (PubMed:31253769). During HRR, binds to the replication fork with high specificity and stabilizes it (PubMed:32522879). Also, acts upstream of HRR, to promote the release of BRCA1 from DNA (PubMed:26833090).COFACTOR Binds 2 magnesium ions per subunit. They probably participate in the reaction catalyzed by the enzyme. May bind an additional third magnesium ion after substrate binding.BIOPHYSICOCHEMICAL PROPERTIES Optimum pH is 6.5-7.SUBUNIT Monomer (PubMed:32522879). Homodimer (PubMed:32522879). Component of the homologous recombination repair (HR) complex composed of ERCC5/XPG, BRCA2, PALB2, DSS1 and RAD51 (PubMed:26833090). Within the complex, interacts with BRCA2 and PALB2 (PubMed:26833090). Interacts with RNA polymerase II (PubMed:16246722). Interacts (via C-terminus) with ERCC6/CSB; the interaction stimulates ERCC6/CSB binding to the DNA repair bubble and ERCC6/CSB ATPase activity (PubMed:16246722). May form a complex composed of RNA polymerase II, ERCC6/CSB and ERCC5/XPG which associates with the DNA repair bubble during transcription-coupled nucleotide excision repair (PubMed:16246722). Interacts with BRCA1; the interaction promotes the release of BRCA1 from DNA (PubMed:26833090). Interacts with PCNA (PubMed:9305916). Interacts with NTHL1; the interaction stimulates NTHL1 activity and NTHL1 binding to its DNA substrate (PubMed:9927729).INTERACTION Colocalizes with RAD51 to nuclear foci in S phase (PubMed:26833090). Localizes to DNA double-strand breaks (DBS) during replication stress (PubMed:26833090). Colocalizes with BRCA2 to nuclear foci following DNA replication stress (PubMed:26833090).ALTERNATIVE PRODUCTS Induced by replication stress caused by DNA double-strand breaks (DBS).DOMAIN Both nuclear localization signals 1 and 2 act as a monopartite signal which binds to the high affinity site on KPNA2/importin-alpha.DOMAIN Both the spacer region (also known as the recognition (R) domain) and C-terminal domain are required for stable binding to the DNA repair bubble (PubMed:16246722). However, both domains are dispensable for incision of DNA bubble structures (PubMed:16246722, PubMed:32522879, PubMed:32821917).DISEASE 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.MISCELLANEOUS Includes a cryptic exon found in intron 6.SIMILARITY Belongs to the XPG/RAD2 endonuclease family. XPG subfamily.CAUTION A paper describing an additional role for this protein in a base excision repair pathway that is not coupled to transcription has been retracted, because some of the experimental data were incorrect.
description	recommendedName: fullName evidence="33"DNA excision repair protein ERCC-5 ecNumber evidence="18 19 21 23 24 25"3.1.-.- alternativeName: DNA repair protein complementing XP-G cells shortName: XPG alternativeName: Xeroderma pigmentosum group G-complementing protein
geneName	ERCC5 ERCM2 XPG XPGC
identifier	P28715
isSequenceChanged	FALSE
keyword	3D-structure Acetylation Alternative splicing Chromosome Cockayne syndrome Deafness Disease variant DNA damage DNA repair DNA-binding Dwarfism Endonuclease Hydrolase Magnesium Metal-binding Nuclease Nucleus Phosphoprotein Proteomics identification Reference proteome Xeroderma pigmentosum
modified	[InstanceEdit:9836292] Weiser, Joel, 2023-05-25 [InstanceEdit:9852000] Weiser, Joel, 2023-11-03 [InstanceEdit:9917590] Weiser, Joel, 2024-08-09 [InstanceEdit:9926675] Weiser, Joel, 2024-11-03 [InstanceEdit:9983091] Weiser, Joel, 2026-02-20
name	ERCC5
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:8991838] ENSEMBL:ENSG00000134899 ERCC5 [Homo sapiens]
secondaryIdentifier	ERCC5_HUMAN A6NGT4 Q5JUS4 Q5JUS5 Q7Z2V3 Q8IZL6 Q8N1B7 Q9HD59 Q9HD60
sequenceLength	1186
species	[Species:48887] Homo sapiens
(isoformParent)	[ReferenceIsoform:384971] UniProt:P28715-2 ERCC5 [Homo sapiens] [ReferenceIsoform:403543] UniProt:P28715-1 ERCC5 [Homo sapiens] [ReferenceIsoform:8969171] UniProt:P28715-3 ERCC5 [Homo sapiens]
(referenceEntity)	[EntityWithAccessionedSequence:67447] ERCC5 [nucleoplasm] [Homo sapiens]
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No pathways have been reviewed or authored by UniProt:P28715 ERCC5 (67448)