ERCC6 ERCC excision repair 6, chromatin remodeling factor [Homo sapiens (human)] - Gene

Summary

Official Symbol: ERCC6provided by HGNC
Official Full Name: ERCC excision repair 6, chromatin remodeling factorprovided by HGNC
Primary source: HGNC:HGNC:3438
See related: Ensembl:ENSG00000225830 MIM:609413
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CSB; CKN2; COFS; ARMD5; COFS1; POF11; RAD26; UVSS1; CSB-PGBD3
Summary: This gene encodes a DNA-binding protein that is important in transcription-coupled excision repair. The encoded protein has ATP-stimulated ATPase activity, interacts with several transcription and excision repair proteins, and may promote complex formation at DNA repair sites. Mutations in this gene are associated with Cockayne syndrome type B and cerebrooculofacioskeletal syndrome 1. Alternative splicing occurs between a splice site from exon 5 of this gene to the 3' splice site upstream of the open reading frame (ORF) of the adjacent gene, piggyback-derived-3 (GeneID:267004), which activates the alternative polyadenylation site downstream of the piggyback-derived-3 ORF. The resulting transcripts encode a fusion protein that shares sequence with the product of each individual gene. [provided by RefSeq, Mar 2016]
Expression: Ubiquitous expression in thyroid (RPKM 2.7), skin (RPKM 2.1) and 25 other tissues See more
Orthologs: mouse all
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Genomic context

Location:: 10q11.23

Exon count:: 23

Annotation release	Status	Assembly	Chr	Location
109.20210226	current	GRCh38.p13 (GCF_000001405.39)	10	NC_000010.11 (49434881..49539538, complement)
105.20201022	previous assembly	GRCh37.p13 (GCF_000001405.25)	10	NC_000010.10 (50642927..50747584, complement)

Chromosome 10 - NC_000010.11 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into Functions

What's a GeneRIF?

USP7-mediated deubiquitination differentially regulates CSB but not UVSSA upon UV radiation-induced DNA damage.
Title: USP7-mediated deubiquitination differentially regulates CSB but not UVSSA upon UV radiation-induced DNA damage.
TCR is initiated by RNAPIIo-bound CSB, which recruits CSA through a newly identified CSA-interaction motif (CIM); once recruited, CSA facilitates the association of UVSSA with stalled RNAPIIo; in addition, UVSSA is the key factor that recruits the TFIIH complex in a manner that is stimulated by CSB and CSA
Title: The cooperative action of CSB, CSA, and UVSSA target TFIIH to DNA damage-stalled RNA polymerase II.
CSB has a role in modulating the competition between HIF-1 and p53 upon hypoxia
Title: CSB modulates the competition between HIF-1 and p53 upon hypoxia.
convergent and divergent roles for CSA and CSB in DNA repair and transcription regulation
Title: Multisystem analyses of two Cockayne syndrome associated proteins CSA and CSB reveal shared and unique functions.
CSA and CSB are positive regulators of ribosomal RNA synthesis via Ncl regulation.
Title: Cockayne syndrome group A and B proteins function in rRNA transcription through nucleolin regulation.
CSB interacts with BRCA1 to promote DNA end resection
Title: CSB interacts with BRCA1 in late S/G2 to promote MRN- and CtIP-mediated DNA end resection.
The results indicate that the CSA, CSB, RNA polymerase II triad is coordinated by ubiquitin and SUMO in response to UV irradiation.
Title: Transcription-coupled nucleotide excision repair is coordinated by ubiquitin and SUMO in response to ultraviolet irradiation.
ROS-induced telomeric R-loops promote repair of telomeric DSBs through CSB-RAD52-POLD3-mediated BIR, a previously unknown pathway protecting telomeres from ROS. ROS-induced telomeric SSBs may not only give rise to DSBs indirectly, but also promote DSB repair by inducing R-loops, revealing an unexpected interplay between distinct ROS-induced DNA lesions.
Title: An R-loop-initiated CSB-RAD52-POLD3 pathway suppresses ROS-induced telomeric DNA breaks.
The study showed that ERCC6 and HTRA1single nucleotide polymorphisms rs3793784 and rs11200638 were associated with increased odds of early and exudative age-related macular degeneration, while the variant in KCTD10 (rs56209061) was found to be protective.
Title: Haplotypes of HTRA1 rs1120638, TIMP3 rs9621532, VEGFA rs833068, CFI rs10033900, ERCC6 rs3793784, and KCTD10 rs56209061 Gene Polymorphisms in Age-Related Macular Degeneration.
Authors show that, after UV irradiation, the cyclin-dependent kinase 9 (CDK9)/cyclin T1 kinase unit is specifically released from the HEXIM1 complex and that this released fraction is degraded in the absence of the Cockayne syndrome group B protein (CSB).
Title: CSB-Dependent Cyclin-Dependent Kinase 9 Degradation and RNA Polymerase II Phosphorylation during Transcription-Coupled Repair.

Submit: New GeneRIF Correction See all GeneRIFs (134)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

Associated conditions

Description	Tests
Age-related macular degeneration 5 MedGen: C3151063 OMIM: 613761 GeneReviews: Not available	Compare labs
Cerebrooculofacioskeletal syndrome 1 MedGen: C0220722 OMIM: 214150 GeneReviews: Not available	Compare labs
Cockayne syndrome B MedGen: C0751038 OMIM: 133540 GeneReviews: Cockayne Syndrome	Compare labs
DE SANCTIS-CACCHIONE SYNDROME MedGen: C0265201 OMIM: 278800 GeneReviews: Not available	Compare labs
Premature ovarian failure 11 MedGen: C4310783 OMIM: 616946 GeneReviews: Not available	Compare labs
UV-sensitive syndrome 1 MedGen: C3551173 OMIM: 600630 GeneReviews: Not available	Compare labs

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

RH104261 (e-PCR)
- UniSTS:98586

G60405 (e-PCR)
- UniSTS:137511

D10S1321E (e-PCR)
- UniSTS:151349

RH26695 (e-PCR)
- UniSTS:89910

D10S1553 (e-PCR)
- UniSTS:19011

D10S1378E (e-PCR)
- UniSTS:151374

ERCC6_1944 (e-PCR)
- UniSTS:280657

D10S1766 (e-PCR)
- UniSTS:67929

SHGC-37683 (e-PCR)
- UniSTS:2923

SHGC-67307 (e-PCR)
- UniSTS:89991

RH66662 (e-PCR)
- UniSTS:58254

RH44808 (e-PCR)
- UniSTS:61612

STS-L04791 (e-PCR)
- UniSTS:8116

RH92205 (e-PCR)
- UniSTS:92088

D10S238E (e-PCR)
- UniSTS:147404

SHGC-149029 (e-PCR)
- UniSTS:182235

RH98308 (e-PCR)
- UniSTS:85980

D10S2351 (e-PCR)
- UniSTS:23293

Homology

Homologs of the ERCC6 gene: The ERCC6 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, chicken, and zebrafish.
Orthologs from Annotation Pipeline: 330 organisms have orthologs with human gene ERCC6
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
ATP binding	IDA Inferred from Direct Assay more info	PubMed
DNA binding	IDA Inferred from Direct Assay more info	PubMed
NOT DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
DNA-dependent ATPase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
DNA-dependent ATPase activity	IDA Inferred from Direct Assay more info	PubMed
DNA-dependent ATPase activity	IMP Inferred from Mutant Phenotype more info	PubMed
chromatin binding	IDA Inferred from Direct Assay more info	PubMed
chromatin binding	IMP Inferred from Mutant Phenotype more info	PubMed
protein C-terminus binding	IPI Inferred from Physical Interaction more info	PubMed
protein N-terminus binding	IPI Inferred from Physical Interaction more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed
protein tyrosine kinase activator activity	IDA Inferred from Direct Assay more info	PubMed
protein-containing complex binding	IDA Inferred from Direct Assay more info	PubMed
sequence-specific DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed

Process	Evidence Code	Pubs
ATP-dependent chromatin remodeling	IMP Inferred from Mutant Phenotype more info	PubMed
DNA damage checkpoint	IMP Inferred from Mutant Phenotype more info	PubMed
DNA duplex unwinding	IEA Inferred from Electronic Annotation more info
activation of JNKK activity	IEA Inferred from Electronic Annotation more info
activation of JUN kinase activity	IEA Inferred from Electronic Annotation more info
base-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed
double-strand break repair via classical nonhomologous end joining	IDA Inferred from Direct Assay more info	PubMed
intrinsic apoptotic signaling pathway in response to DNA damage	IEA Inferred from Electronic Annotation more info
multicellular organism growth	IEA Inferred from Electronic Annotation more info
negative regulation of double-strand break repair via nonhomologous end joining	IMP Inferred from Mutant Phenotype more info	PubMed
neurogenesis	IMP Inferred from Mutant Phenotype more info	PubMed
neuron differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
neuron projection development	IMP Inferred from Mutant Phenotype more info	PubMed
photoreceptor cell maintenance	IEA Inferred from Electronic Annotation more info
positive regulation of DNA repair	IGI Inferred from Genetic Interaction more info	PubMed
positive regulation of DNA repair	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of DNA-templated transcription, elongation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of double-strand break repair via homologous recombination	IMP Inferred from Mutant Phenotype more info	PubMed
positive regulation of gene expression, epigenetic	TAS Traceable Author Statement more info
positive regulation of protein tyrosine kinase activity	IEA Inferred from Electronic Annotation more info
positive regulation of transcription initiation from RNA polymerase II promoter	IEA Inferred from Electronic Annotation more info
pyrimidine dimer repair	IEA Inferred from Electronic Annotation more info
regulation of DNA-templated transcription, elongation	IDA Inferred from Direct Assay more info	PubMed
response to UV	IDA Inferred from Direct Assay more info	PubMed
response to UV-B	IEA Inferred from Electronic Annotation more info
response to X-ray	IEA Inferred from Electronic Annotation more info
response to gamma radiation	IEA Inferred from Electronic Annotation more info
response to oxidative stress	IDA Inferred from Direct Assay more info	PubMed
response to oxidative stress	IGI Inferred from Genetic Interaction more info	PubMed
response to superoxide	IEA Inferred from Electronic Annotation more info
response to toxic substance	IEA Inferred from Electronic Annotation more info
single strand break repair	IDA Inferred from Direct Assay more info	PubMed
transcription by RNA polymerase II	NAS Non-traceable Author Statement more info	PubMed
transcription elongation from RNA polymerase I promoter	IEA Inferred from Electronic Annotation more info
transcription-coupled nucleotide-excision repair	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transcription-coupled nucleotide-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed
transcription-coupled nucleotide-excision repair	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
nucleolus	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	IDA Inferred from Direct Assay more info	PubMed
nucleoplasm	TAS Traceable Author Statement more info
nucleus	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleus	IDA Inferred from Direct Assay more info	PubMed
site of DNA damage	IDA Inferred from Direct Assay more info	PubMed
transcription elongation factor complex	IDA Inferred from Direct Assay more info	PubMed

General protein information

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Preferred Names: DNA excision repair protein ERCC-6; ERCC6-PGBD3 fusion protein

Names: ATP-dependent helicase ERCC6; Chimeric CSB-PGBD3 protein; Chimeric ERCC6-PGBD3 protein; Cockayne syndrome group B protein; cockayne syndrome protein CSB; excision repair cross-complementation group 6; excision repair cross-complementing rodent repair deficiency, complementation group 6

NP_000115.1

EC 3.6.4.-

NP_001263987.1

EC 3.6.4.-

NP_001263988.1

EC 3.6.4.-

NP_001333369.1

EC 3.6.4.-

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_009442.1 RefSeqGene

Range

4979..89622

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_465

mRNA and Protein(s)

NM_000124.4 → NP_000115.1 DNA excision repair protein ERCC-6 isoform 2

See identical proteins and their annotated locations for NP_000115.1

Status: REVIEWED

Description

Transcript Variant: This variant (3) represents the longest transcript and encodes the longer protein (isoform 2).

Source sequence(s)

AB209504, AC073366, AL138760, DA457690, L04791

Consensus CDS

CCDS7229.1

UniProtKB/Swiss-Prot

Q03468

UniProtKB/TrEMBL

Q59FF6

Related

ENSP00000348089.5, ENST00000355832.10

Conserved Domains (3) summary

cd00046
Location:527 → 677

DEXDc; DEAD-like helicases superfamily. A diverse family of proteins involved in ATP-dependent RNA or DNA unwinding. This domain contains the ATP-binding region.

cd00079
Location:830 → 960

HELICc; Helicase superfamily c-terminal domain; associated with DEXDc-, DEAD-, and DEAH-box proteins, yeast initiation factor 4A, Ski2p, and Hepatitis C virus NS3 helicases; this domain is found in a wide variety of helicases and helicase related proteins; may ...

pfam00176
Location:510 → 812

SNF2_N; SNF2 family N-terminal domain
NM_001277058.2 → NP_001263987.1 ERCC6-PGBD3 fusion protein isoform 1

See identical proteins and their annotated locations for NP_001263987.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) contains an alternate 3' terminal exon, compared to variant 3. It is generated as a result of splicing of ERCC6 exon 5 to the 3' splice site upstream of the PGBD3 ORF that activates the alternative polyadenylation site downstream of the PGBD3 ORF. The resulting protein (isoform 1, ERCC6-PGBD3 fusion protein) is shorter and has a distinct C-terminus, compared to isoform 2.

Source sequence(s)

AC073366, AK291018, AL138760

Consensus CDS

CCDS60529.1

UniProtKB/Swiss-Prot

P0DP91

UniProtKB/TrEMBL

A8K4Q3

Related

ENSP00000387966.2, ENST00000447839.6

Conserved Domains (1) summary

pfam13843
Location:609 → 967

DDE_Tnp_1_7; Transposase IS4
NM_001277059.2 → NP_001263988.1 ERCC6-PGBD3 fusion protein isoform 1

See identical proteins and their annotated locations for NP_001263988.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR and contains an alternate 3' terminal exon, compared to variant 3. It is generated as a result of splicing of ERCC6 exon 5 to the 3' splice site upstream of the PGBD3 ORF that activates the alternative polyadenylation site downstream of the PGBD3 ORF. The resulting protein (isoform 1, ERCC6-PGBD3 fusion protein) is shorter and has a distinct C-terminus, compared to isoform 2.

Source sequence(s)

AK291018, AL138760, BC034479

Consensus CDS

CCDS60529.1

UniProtKB/Swiss-Prot

P0DP91

UniProtKB/TrEMBL

A8K4Q3

Related

ENSP00000423550.1, ENST00000515869.1

Conserved Domains (1) summary

pfam13843
Location:609 → 967

DDE_Tnp_1_7; Transposase IS4
NM_001346440.2 → NP_001333369.1 DNA excision repair protein ERCC-6 isoform 2

Status: REVIEWED

Description

Transcript Variant: This variant (4 ) uses an alternate splice site in the 5' UTR, compared to variant 3, and encodes isoform 2. Variants 3 and 4 encode the same protein (isoform 2).

Source sequence(s)

AC073366, AL138760, DA457690, L04791

Consensus CDS

CCDS7229.1

UniProtKB/Swiss-Prot

Q03468