GenAge entry for ERCC2 (Homo sapiens)

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Gene name (HAGRID: 11)

HGNC symbol: ERCC2
Aliases: MAG; EM9; MGC102762; MGC126218; MGC126219; TFIIH; XPD
Common name: excision repair cross-complementation group 2

Potential relevance to the human ageing process

Main reason for selection

Entry selected based on evidence directly linking the gene product to ageing in a mammalian model organism

Description

The ERCC2 helicase is primarily involved in DNA repair. It may also be involved in transcription because it is a component of the core TFIIH basal transcription factor [546].

ERCC2-null mice die at embryonic stages [1762]. Mutations in ERCC2 that reduce its activity in mice appear to accelerate ageing and increase cancer incidence. The mutant mice live on average less than a year, display growth retardation, enhanced apoptosis, and start to develop a phenotype resembling premature aging at about 3-4 months of age that becomes increasingly more severe. Combining mutations in ERCC2 with XPA ablation results in a much more severe phenotype [14]. Surprisingly, however, combining different mutations in ERCC2 ameliorates age-related phenotypes and developmental delay in mice [1857]. In humans, several pathologies have been associated with mutations in ERCC2 [191], including trichothiodystrophy and Cockayne syndrome which are characterized by progeroid-like features. As such, ERCC2 may play a role in human ageing.

Cytogenetic information

Cytogenetic band: 19q13.3
Location: 45,351,391 bp to 45,370,587 bp
Orientation: Minus strand

Display region using the UCSC Genome Browser (GRCh38/hg38)

Protein information

Gene Ontology

Process:

GO:0000717; nucleotide-excision repair, DNA duplex unwinding
GO:0001666; response to hypoxia
GO:0001701; in utero embryonic development
GO:0006283; transcription-coupled nucleotide-excision repair
GO:0006289; nucleotide-excision repair
GO:0006293; nucleotide-excision repair, preincision complex stabilization
GO:0006294; nucleotide-excision repair, preincision complex assembly
GO:0006295; nucleotide-excision repair, DNA incision, 3'-to lesion
GO:0006296; nucleotide-excision repair, DNA incision, 5'-to lesion
GO:0006361; transcription initiation from RNA polymerase I promoter
GO:0006362; transcription elongation from RNA polymerase I promoter

And 32 more GO terms

Cellular component:

GO:0000439; core TFIIH complex
GO:0005634; nucleus
GO:0005654; nucleoplasm
GO:0005669; transcription factor TFIID complex
GO:0005675; holo TFIIH complex
GO:0005737; cytoplasm
GO:0005819; spindle
GO:0019907; cyclin-dependent protein kinase activating kinase holoenzyme complex
GO:0071817; MMXD complex

Function:

GO:0003677; DNA binding
GO:0004003; ATP-dependent DNA helicase activity
GO:0004672; protein kinase activity
GO:0005515; protein binding
GO:0005524; ATP binding
GO:0008022; protein C-terminus binding
GO:0008094; DNA-dependent ATPase activity
GO:0008353; RNA polymerase II carboxy-terminal domain kinase activity
GO:0043139; 5'-3' DNA helicase activity
GO:0046872; metal ion binding
GO:0047485; protein N-terminus binding

And 2 more GO terms

Show all GO terms

Protein interactions and network

Protein-protein interacting partners in GenAge: TP53, ERCC6, ERCC3, ERCC5, AR, GTF2H2, RAD52, CDK7
STRING interaction network

Retrieve sequences for ERCC2

ORF: ORF
CDS: CDS

Homologs in model organisms

Caenorhabditis elegans: CELE_Y50D7A.2
Danio rerio: ercc2
Drosophila melanogaster: Xpd
Mus musculus: Ercc2
Rattus norvegicus: Ercc2
Saccharomyces cerevisiae: RAD3
Schizosaccharomyces pombe: rad15

In other databases

GenAge model organism genes

A homolog of this gene for Mus musculus is present as Ercc2

LongevityMap

This gene is present as ERCC2