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; AllianceGenome:HGNC:3434
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
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Genomic context

Location:: 19q13.32

Exon count:: 25

Annotation release	Status	Assembly	Chr	Location
RS_2023_10	current	GRCh38.p14 (GCF_000001405.40)	19	NC_000019.10 (45349837..45370573, complement)
RS_2023_10	current	T2T-CHM13v2.0 (GCF_009914755.1)	19	NC_060943.1 (48177079..48197811, complement)
105.20220307	previous assembly	GRCh37.p13 (GCF_000001405.25)	19	NC_000019.9 (45853095..45873831, 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?

NOP2-mediated m5C methylation of XPD is associated with hepatocellular carcinoma progression.
Title: NOP2-mediated m5C methylation of XPD is associated with hepatocellular carcinoma progression.
Lesion recognition by XPC, TFIIH and XPA in DNA excision repair.
Title: Lesion recognition by XPC, TFIIH and XPA in DNA excision repair.
Involvement of ERCC1 (rs3212986) and ERCC2 (rs1799793, rs13181) polymorphisms of DNA repair genes in breast cancer occurrence in Burkina Faso.
Title: Involvement of ERCC1 (rs3212986) and ERCC2 (rs1799793, rs13181) polymorphisms of DNA repair genes in breast cancer occurrence in Burkina Faso.
TFIIH mutations can impact on translational fidelity of the ribosome.
Title: TFIIH mutations can impact on translational fidelity of the ribosome.
A disease-associated XPA allele interferes with TFIIH binding and primarily affects transcription-coupled nucleotide excision repair.
Title: A disease-associated XPA allele interferes with TFIIH binding and primarily affects transcription-coupled nucleotide excision repair.
TFIIH stabilization recovers the DNA repair and transcription dysfunctions in thermo-sensitive trichothiodystrophy.
Title: TFIIH stabilization recovers the DNA repair and transcription dysfunctions in thermo-sensitive trichothiodystrophy.
Debilitating hip degeneration in trichothiodystrophy: Association with ERCC2/XPD mutations, osteosclerosis, osteopenia, coxa valga, contractures, and osteonecrosis.
Title: Debilitating hip degeneration in trichothiodystrophy: Association with ERCC2/XPD mutations, osteosclerosis, osteopenia, coxa valga, contractures, and osteonecrosis.
DNA repair gene (XRCC1 and XPD) polymorphism and risk of primary ovarian failure.
Title: DNA repair gene (XRCC1 and XPD) polymorphism and risk of primary ovarian failure.
Phosphorylation of XPD drives its mitotic role independently of its DNA repair and transcription functions.
Title: Phosphorylation of XPD drives its mitotic role independently of its DNA repair and transcription functions.
Association of genetic polymorphisms in DNA repair genes ERCC2 Asp312Asn (rs1799793), ERCC2 Lys 751 Gln (rs13181), XRCC1 Arg399 Gln (rs25487) and XRCC3 Thr 241Met (rs861539) with the susceptibility of lung cancer in Saudi population.
Title: Association of genetic polymorphisms in DNA repair genes ERCC2 Asp312Asn (rs1799793), ERCC2 Lys 751 Gln (rs13181), XRCC1 Arg399 Gln (rs25487) and XRCC3 Thr 241Met (rs861539) with the susceptibility of lung cancer in Saudi population.

Submit: New GeneRIF Correction See all GeneRIFs (500)

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

EBI GWAS Catalog

Description
Genome-wide association study reveals novel genetic determinants of DNA repair capacity in lung cancer. EBI GWAS Catalog EBI GWAS 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

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables 4 iron, 4 sulfur cluster binding	IEA Inferred from Electronic Annotation more info
enables 5'-3' DNA helicase activity	IDA Inferred from Direct Assay more info	PubMed
enables 5'-3' DNA helicase activity	TAS Traceable Author Statement more info
enables ATP binding	IEA Inferred from Electronic Annotation more info
enables ATP hydrolysis activity	IEA Inferred from Electronic Annotation more info
enables DNA helicase activity	IBA Inferred from Biological aspect of Ancestor more info
enables damaged DNA binding	IBA Inferred from Biological aspect of Ancestor more info
enables metal ion binding	IEA Inferred from Electronic Annotation more info
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables protein-macromolecule adaptor activity	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
involved_in DNA duplex unwinding	IEA Inferred from Electronic Annotation more info
involved_in UV protection	IEA Inferred from Electronic Annotation more info
involved_in apoptotic process	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in bone mineralization	IEA Inferred from Electronic Annotation more info
involved_in central nervous system myelin formation	IEA Inferred from Electronic Annotation more info
involved_in chromosome segregation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in determination of adult lifespan	IEA Inferred from Electronic Annotation more info
involved_in embryonic cleavage	IEA Inferred from Electronic Annotation more info
involved_in embryonic organ development	IEA Inferred from Electronic Annotation more info
involved_in erythrocyte maturation	IEA Inferred from Electronic Annotation more info
involved_in extracellular matrix organization	IEA Inferred from Electronic Annotation more info
involved_in hair cell differentiation	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in hair follicle maturation	IEA Inferred from Electronic Annotation more info
involved_in hematopoietic stem cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in hematopoietic stem cell proliferation	IEA Inferred from Electronic Annotation more info
involved_in in utero embryonic development	IEA Inferred from Electronic Annotation more info
involved_in insulin-like growth factor receptor signaling pathway	IEA Inferred from Electronic Annotation more info
involved_in intrinsic apoptotic signaling pathway by p53 class mediator	IEA Inferred from Electronic Annotation more info
involved_in maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA)	IEA Inferred from Electronic Annotation more info
involved_in multicellular organism growth	IEA Inferred from Electronic Annotation more info
involved_in nucleotide-excision repair	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in nucleotide-excision repair	NAS Non-traceable Author Statement more info	PubMed
involved_in positive regulation of mitotic recombination	IBA Inferred from Biological aspect of Ancestor more info
involved_in post-embryonic development	IEA Inferred from Electronic Annotation more info
involved_in regulation of mitotic cell cycle phase transition	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in response to hypoxia	IEA Inferred from Electronic Annotation more info
involved_in response to oxidative stress	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in spinal cord development	IEA Inferred from Electronic Annotation more info
involved_in transcription by RNA polymerase II	IBA Inferred from Biological aspect of Ancestor more info
involved_in transcription by RNA polymerase II	IDA Inferred from Direct Assay more info	PubMed
involved_in transcription by RNA polymerase II	TAS Traceable Author Statement more info	PubMed
involved_in transcription elongation by RNA polymerase I	IEA Inferred from Electronic Annotation more info
involved_in transcription-coupled nucleotide-excision repair	IDA Inferred from Direct Assay more info	PubMed
involved_in transcription-coupled nucleotide-excision repair	TAS Traceable Author Statement more info

Component	Evidence Code	Pubs
part_of CAK-ERCC2 complex	IDA Inferred from Direct Assay more info	PubMed
part_of MMXD complex	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	IDA Inferred from Direct Assay more info	PubMed
located_in cytosol	IDA Inferred from Direct Assay more info
located_in nucleoplasm	IDA Inferred from Direct Assay more info
located_in nucleoplasm	TAS Traceable Author Statement more info
is_active_in nucleus	IBA Inferred from Biological aspect of Ancestor more info
located_in nucleus	IDA Inferred from Direct Assay more info	PubMed
located_in spindle	IDA Inferred from Direct Assay more info	PubMed
part_of transcription factor TFIID complex	IDA Inferred from Direct Assay more info	PubMed
part_of transcription factor TFIIH core complex	IDA Inferred from Direct Assay more info	PubMed
part_of transcription factor TFIIH holo complex	IDA Inferred from Direct Assay more info	PubMed
part_of 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_047294349.1

EC 3.6.4.12

XP_054176156.1

EC 3.6.4.12

XP_054176157.1

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, Q2TB78, Q2YDY2, Q7KZU6, Q8N721

UniProtKB/TrEMBL

A0A804HK53

Related

ENSP00000375809.4, ENST00000391945.10

Conserved Domains (1) summary

TIGR00604
Location:7 → 708

rad3; DNA repair helicase (rad3)
NM_001130867.2 → 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/TrEMBL

A0A804HL97

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: GCF_000001405.40-RS_2023_10

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

Reference GRCh38.p14 Primary Assembly

Genomic

NC_000019.10 Reference GRCh38.p14 Primary Assembly

Range

45349837..45370573 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_011526611.3 → XP_011524913.1 general transcription and DNA repair factor IIH helicase subunit XPD isoform X1

UniProtKB/TrEMBL

A0A804HK53

Related

ENST00000682508.1

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_047438393.1 → XP_047294349.1 general transcription and DNA repair factor IIH helicase subunit XPD isoform X2

UniProtKB/TrEMBL

A0A804HL97

Related

ENSP00000508260.1, ENST00000684458.1

RNA

XR_007066680.1 RNA Sequence
XR_001753633.3 RNA Sequence

Related

ENST00000684218.1

Alternate T2T-CHM13v2.0

Genomic

NC_060943.1 Alternate T2T-CHM13v2.0

Range

48177079..48197811 complement

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_054320181.1 → XP_054176156.1 general transcription and DNA repair factor IIH helicase subunit XPD isoform X1

UniProtKB/TrEMBL

A0A804HK53
XM_054320182.1 → XP_054176157.1 general transcription and DNA repair factor IIH helicase subunit XPD isoform X2

UniProtKB/TrEMBL

A0A804HL97