ERCC2 ERCC excision repair 2, TFIIH core complex helicase subunit [Homo sapiens (human)] - Gene

Summary

Official Symbol: ERCC2provided by HGNC
Official Full Name: ERCC excision repair 2, TFIIH core complex helicase subunitprovided by HGNC
Primary source: HGNC:HGNC:3434
See related: Ensembl:ENSG00000104884 MIM:126340
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: EM9; TTD; XPD; TTD1; COFS2; TFIIH
Summary: The nucleotide excision repair pathway is a mechanism to repair damage to DNA. The protein encoded by this gene is involved in transcription-coupled nucleotide excision repair and is an integral member of the basal transcription factor BTF2/TFIIH complex. The gene product has ATP-dependent DNA helicase activity and belongs to the RAD3/XPD subfamily of helicases. Defects in this gene can result in three different disorders, the cancer-prone syndrome xeroderma pigmentosum complementation group D, trichothiodystrophy, and Cockayne syndrome. Alternatively spliced transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Aug 2008]
Expression: Ubiquitous expression in testis (RPKM 6.4), skin (RPKM 6.1) and 25 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 19q13.32

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
109.20191205	current	GRCh38.p13 (GCF_000001405.39)	19	NC_000019.10 (45349837..45370647, complement)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (45854649..45873845, complement)

Chromosome 19 - NC_000019.10 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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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?

Polymorphisms in XPD is associated with Oral Pre Cancer and Cancer.
Title: Risk Modulation of Oral Pre Cancer and Cancer with Polymorphisms in XPD and XPG Genes in North Indian Population.
Outcome Definition Influences the Relationship Between Genetic Polymorphisms of ERCC1, ERCC2, SLC22A2 and Cisplatin Nephrotoxicity in Adult Testicular Cancer Patients.
Title: Outcome Definition Influences the Relationship Between Genetic Polymorphisms of ERCC1, ERCC2, SLC22A2 and Cisplatin Nephrotoxicity in Adult Testicular Cancer Patients.
The XPD Asp312Asn polymorphism is associated with overall survival, but it is not a biomarker in predicting the response to oxaliplatin-based first-line chemotherapy in patients with metastatic colorectal cancer.
Title: Association of XPD Asp312Asn polymorphism and response to oxaliplatin-based first-line chemotherapy and survival in patients with metastatic colorectal cancer.
XRCC1 and XPD polymorphisms, cooking oil mist, and soot exposure history may be interactively correlated with non-small-cell lung cancer incidence for nonsmoking female patients.
Title: Gene polymorphism of DNA repair gene X-ray repair cross complementing group 1 and xeroderma pigmentosum group D and environment interaction in non-small-cell lung cancer for Chinese nonsmoking female patients.
The results suggest that XPD G751A, hOGG1 C326G and XRCC4 G1394T gene polymorphisms might play an important role in colorectal carcinogenesis and increase the risk of developing colorectal cancer in the Chinese Han population.
Title: Impact of polymorphisms in DNA repair genes XPD, hOGG1 and XRCC4 on colorectal cancer risk in a Chinese Han Population.
Studied association of excision repair cross-complimentary group 2 (ERCC2) polymorpisms with ovarian cancer risk; results showed a significant association between ERCC2 gene rs13181 polymorphism and increased risk of ovarian cancer.
Title: Association between ERCC2 rs13181 polymorphism and ovarian cancer risk: an updated meta-analysis with 4024 subjects.
The aim of the study is to investigate the relation between XPG and XPD gene variants in the DNA repair system and oral squamous cell cancers.
Title: Are XPD and XPG gene variants related to the mechanism of oral squamous cell carcinoma?
a combination of ERCC1 and ERCC2 polymorphisms may predict overall survival among pemetrexed/platinum treated advanced non-squamous non-small-cell lung cancer patients
Title: Combined effect of ERCC1 and ERCC2 polymorphisms on overall survival in non-squamous non-small-cell lung cancer patients treated with first-line pemetrexed/platinum.
Homozygous wild type alleles encoding XPD and CSB proteins with optimal properties were shown to affect human lifespan, risk of developing bladder cancer, its progression and recurrence under certain conditions.
Title: The Involvement of ERCC2/XPD and ERCC6/CSB Wild Type Alleles in Protection Against Aging and Cancer.
ERCC1 (C118T (rs11615) and C8092A (rs3212986)) and ERCC2 (A751C (rs171140) and G312A (rs1799793)) polymorphisms were analysed in 44 patients with osteosarcoma.
Title: The effect of ERCC1 and ERCC2 gene polymorphysims on response to cisplatin based therapy in osteosarcoma patients.

Submit: New GeneRIF Correction See all GeneRIFs (461)

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
Cerebrooculofacioskeletal syndrome 2 MedGen: C1853102 OMIM: 610756 GeneReviews: Not available	Compare labs
Trichothiodystrophy 1, photosensitive MedGen: C1866504 OMIM: 601675 GeneReviews: Not available	Compare labs
Xeroderma pigmentosum, group D MedGen: C0268138 OMIM: 278730 GeneReviews: Xeroderma Pigmentosum	Compare labs

NHGRI GWAS Catalog

Description
Genome-wide association study reveals novel genetic determinants of DNA repair capacity in lung cancer. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Rev	rev	HIV-1 Rev interacting protein, excision repair cross-complementing rodent repair deficiency, complementation group 2 (ERCC2), is identified by the in-vitro binding experiments involving cytosolic or nuclear extracts from HeLa cells	PubMed
	rev	The interaction of Rev with ERCC2 is increased by the presence of RRE	PubMed
Tat	tat	HIV-1 Tat interacts with the RNA polymerase II holoenzyme and transcription preinitiation complexes, which include TFIIH, during Tat-mediated transactivation of the HIV-1 LTR	PubMed
	tat	Interaction of HIV-1 Tat with TFIIH stimulates phosphorylation of Ser-5 of the RNA polymerase II C-terminal domain (CTD), which in turn also stimulates co-transcriptional capping of HIV-1 mRNA	PubMed
	tat	TFIIH interacts with HIV-1 Tat as a component of the HIV-1 transcription preinitiation complex, but is released from the elongation complex which includes P-TEFb	PubMed
	tat	Amino acids 1-48 of HIV-1 Tat, which includes the Tat activation domain, mediate the binding of Tat to CAK and the TFIIH complex through a direct interaction with CDK7 and possibly other TFIIH subunits, including p62 and ERCC3	PubMed
	tat	CAK/TFIIH is required for HIV-1 Tat-mediated transactivation of the HIV-1 LTR promoter	PubMed
	tat	TFIIH synergizes with HIV-1 Tat to induce transcription elongation from the HIV-1 LTR promoter	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

D19S908 (e-PCR), detects polymorphism
- UniSTS:56071

MARC_23995-23996:1029525921:1 (e-PCR)
- UniSTS:268821

RH15967 (e-PCR)
- UniSTS:68429

GDB:512988 (e-PCR)
- UniSTS:157537

GDB:364012 (e-PCR)
- UniSTS:156797

GDB:364015 (e-PCR)
- UniSTS:156798

GDB:364018 (e-PCR)
- UniSTS:156799

GDB:364021 (e-PCR)
- UniSTS:156800

GDB:364025 (e-PCR)
- UniSTS:156801

GDB:364029 (e-PCR)
- UniSTS:156802

RH80858 (e-PCR)
- UniSTS:83698

Homology

Homologs of the ERCC2 gene: The ERCC2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, fruit fly, mosquito, C.elegans, S.cerevisiae, K.lactis, E.gossypii, S.pombe, M.oryzae, N.crassa, A.thaliana, rice, and frog.
Orthologs from Annotation Pipeline: 244 organisms have orthologs with human gene ERCC2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
4 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
5'-3' DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
ATP binding	IEA Inferred from Electronic Annotation more info
contributes_to DNA-dependent ATPase activity	IDA Inferred from Direct Assay more info	PubMed
DNA-dependent ATPase activity	TAS Traceable Author Statement more info	PubMed
contributes_to RNA polymerase II CTD heptapeptide repeat kinase activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
contributes_to RNA polymerase II CTD heptapeptide repeat kinase activity	IDA Inferred from Direct Assay more info	PubMed
damaged DNA binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
metal ion binding	IEA Inferred from Electronic Annotation more info
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 binding, bridging	IPI Inferred from Physical Interaction more info	PubMed
contributes_to protein kinase activity	IDA Inferred from Direct Assay more info	PubMed

Process	Evidence Code	Pubs
7-methylguanosine mRNA capping	TAS Traceable Author Statement more info
UV protection	IGI Inferred from Genetic Interaction more info	PubMed
aging	IEA Inferred from Electronic Annotation more info
apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
bone mineralization	IEA Inferred from Electronic Annotation more info
cell proliferation	IEA Inferred from Electronic Annotation more info
central nervous system myelin formation	IEA Inferred from Electronic Annotation more info
chromosome segregation	IMP Inferred from Mutant Phenotype more info	PubMed
embryonic cleavage	IEA Inferred from Electronic Annotation more info
embryonic organ development	IEA Inferred from Electronic Annotation more info
erythrocyte maturation	IEA Inferred from Electronic Annotation more info
extracellular matrix organization	IEA Inferred from Electronic Annotation more info
global genome nucleotide-excision repair	TAS Traceable Author Statement more info
hair cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
hair follicle maturation	IEA Inferred from Electronic Annotation more info
hematopoietic stem cell differentiation	IEA Inferred from Electronic Annotation more info
in utero embryonic development	IEA Inferred from Electronic Annotation more info
maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	IEA Inferred from Electronic Annotation more info
multicellular organism growth	IEA Inferred from Electronic Annotation more info
nucleotide-excision repair	IGI Inferred from Genetic Interaction more info	PubMed
nucleotide-excision repair	NAS Non-traceable Author Statement more info	PubMed
nucleotide-excision repair, DNA duplex unwinding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleotide-excision repair, DNA duplex unwinding	TAS Traceable Author Statement more info
nucleotide-excision repair, DNA incision	IBA Inferred from Biological aspect of Ancestor more info	PubMed
nucleotide-excision repair, DNA incision	IMP Inferred from Mutant Phenotype more info	PubMed
nucleotide-excision repair, DNA incision	TAS Traceable Author Statement more info
nucleotide-excision repair, DNA incision, 3'-to lesion	TAS Traceable Author Statement more info
nucleotide-excision repair, DNA incision, 5'-to lesion	TAS Traceable Author Statement more info
nucleotide-excision repair, preincision complex assembly	TAS Traceable Author Statement more info
nucleotide-excision repair, preincision complex stabilization	TAS Traceable Author Statement more info
positive regulation of DNA binding	IEA Inferred from Electronic Annotation more info
positive regulation of mitotic recombination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
positive regulation of transcription, DNA-templated	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of transcription, DNA-templated	IDA Inferred from Direct Assay more info	PubMed
post-embryonic development	IEA Inferred from Electronic Annotation more info
protein phosphorylation	IEA Inferred from Electronic Annotation more info
regulation of mitotic cell cycle phase transition	IMP Inferred from Mutant Phenotype more info	PubMed
regulation of mitotic recombination	IBA Inferred from Biological aspect of Ancestor more info	PubMed
response to UV	IBA Inferred from Biological aspect of Ancestor more info	PubMed
response to hypoxia	IEA Inferred from Electronic Annotation more info
response to oxidative stress	IBA Inferred from Biological aspect of Ancestor more info	PubMed
response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
spinal cord development	IEA Inferred from Electronic Annotation more info
termination of RNA polymerase I transcription	TAS Traceable Author Statement more info
transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info	PubMed
transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
transcription elongation from RNA polymerase I promoter	TAS Traceable Author Statement more info
transcription elongation from RNA polymerase II promoter	TAS Traceable Author Statement more info
transcription initiation from RNA polymerase I promoter	TAS Traceable Author Statement more info
transcription initiation from RNA polymerase II promoter	TAS Traceable Author Statement more info
transcription-coupled nucleotide-excision repair	IDA Inferred from Direct Assay more info	PubMed
transcription-coupled nucleotide-excision repair	TAS Traceable Author Statement more info
viral process	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
CAK-ERCC2 complex	IDA Inferred from Direct Assay more info	PubMed
MMXD complex	IDA Inferred from Direct Assay more info	PubMed
cytoplasm	IDA Inferred from Direct Assay more info	PubMed
cytosol	IDA Inferred from Direct Assay more info
nucleoplasm	IDA Inferred from Direct Assay more info
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
spindle	IDA Inferred from Direct Assay more info	PubMed
transcription factor TFIID complex	IDA Inferred from Direct Assay more info	PubMed
transcription factor TFIIH core complex	IEA Inferred from Electronic Annotation more info
transcription factor TFIIH holo complex	IDA Inferred from Direct Assay more info	PubMed
transcription factor TFIIH holo complex	TAS Traceable Author Statement more info	PubMed

General protein information

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Preferred Names: general transcription and DNA repair factor IIH helicase subunit XPD

Names: BTF2 p80; CXPD; DNA excision repair protein ERCC-2; DNA repair protein complementing XP-D cells; TFIIH 80 kDa subunit; TFIIH basal transcription factor complex 80 kDa subunit; TFIIH basal transcription factor complex helicase XPB subunit; TFIIH basal transcription factor complex helicase XPD subunit; TFIIH basal transcription factor complex helicase subunit; TFIIH p80; TFIIH subunit XPD; basic transcription factor 2 80 kDa subunit; excision repair cross-complementation group 2; excision repair cross-complementing rodent repair deficiency, complementation group 2; xeroderma pigmentosum complementary group D; xeroderma pigmentosum group D-complementing protein

NP_000391.1

EC 3.6.4.12

NP_001124339.1

EC 3.6.4.12

XP_011524913.1

EC 3.6.4.12

XP_016881956.1

EC 3.6.4.12

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_007067.2 RefSeqGene

Range

5001..24197

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_461

mRNA and Protein(s)

NM_000400.4 → NP_000391.1 general transcription and DNA repair factor IIH helicase subunit XPD isoform 1

See identical proteins and their annotated locations for NP_000391.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) encodes the longer isoform (1).

Source sequence(s)

BC108255, CN388234, DA409300, L47234

Consensus CDS

CCDS33049.1

UniProtKB/Swiss-Prot

P18074

Related

ENSP00000375809.3, ENST00000391945.9

Conserved Domains (1) summary

TIGR00604
Location:7 → 708

rad3; DNA repair helicase (rad3)
NM_001130867.1 → NP_001124339.1 general transcription and DNA repair factor IIH helicase subunit XPD isoform 2

See identical proteins and their annotated locations for NP_001124339.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) has an additional segment in the 5' region, which results in a downstream AUG start codon, and lacks multiple 3' exons but has an alternate 3' exon, as compared to variant 1. The resulting isoform (2) has a shorter N-terminus and a distinct and shorter C-terminus, as compared to isoform 1.

Source sequence(s)

AL535248, BC008346, BG719746, BT006883, DA409300

Consensus CDS

CCDS46112.1

UniProtKB/Swiss-Prot

P18074

Related

ENSP00000431229.2, ENST00000485403.6

Conserved Domains (2) summary

smart00488
Location:1 → 256

DEXDc2; DEAD-like helicases superfamily

pfam06777
Location:248 → 389

HBB; Helical and beta-bridge domain

RefSeqs of Annotated Genomes: Homo sapiens Updated Annotation Release 109.20191205

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p13 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p13 Primary Assembly

Range

45349837..45370647 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011526611.2 → XP_011524913.1 general transcription and DNA repair factor IIH helicase subunit XPD isoform X1

Conserved Domains (4) summary

smart00488
Location:8 → 254

DEXDc2; DEAD-like helicases superfamily

smart00491
Location:516 → 660

HELICc2; helicase superfamily c-terminal domain

TIGR00604
Location:7 → 682

rad3; DNA repair helicase (rad3)

pfam06777
Location:246 → 387

HBB; Helical and beta-bridge domain
XM_017026467.1 → XP_016881956.1 general transcription and DNA repair factor IIH helicase subunit XPD isoform X2

Related

ENSP00000375805.2, ENST00000391941.6