ERCC2
Domain
Interacts with GTF2H2/p44 via the C-terminus of this protein; mutations in the C-terminal region of XPD do not alter its helicase activity, but prevent its interaction with and helicase stimulation by GTF2H2/p44 (PubMed:9771713).
Function
ATP-dependent 5'-3' DNA helicase (PubMed:31253769, PubMed:8413672, PubMed:9771713). Component of the general transcription and DNA repair factor IIH (TFIIH) core complex, not absolutely essential for minimal transcription in vitro (PubMed:10024882, PubMed:17466626, PubMed:9771713). Required for transcription-coupled nucleotide excision repair (NER) of damaged DNA; recognizes damaged bases (PubMed:17466626, PubMed:23352696, PubMed:9771713). Sequestered in chromatin on UV-damaged DNA (PubMed:23352696). When complexed to CDK-activating kinase (CAK), involved in transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA around the lesion to allow the excision of the damaged oligonucleotide and its replacement by a new DNA fragment. The ATP-dependent helicase activity of XPD/ERCC2 is required for DNA opening. Involved in DNA lesion verification (PubMed:31253769). In transcription, TFIIH has an essential role in transcription initiation. When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape. Phosphorylation of the C-terminal tail (CTD) of the largest subunit of RNA polymerase II by the kinase module CAK controls the initiation of transcription. XPD/ERCC2 acts by forming a bridge between CAK and the core-TFIIH complex. The structure of the TFIIH transcription complex differs from the NER-TFIIH complex; large movements by XPD/ERCC2 and XPB/ERCC3 are stabilized by XPA which allow this subunit to contact ssDNA (PubMed:31253769, PubMed:33902107). Involved in the regulation of vitamin-D receptor activity. As part of the mitotic spindle-associated MMXD complex it plays a role in chromosome segregation. Might have a role in aging process and could play a causative role in the generation of skin cancers.
Involvement in disease
Xeroderma pigmentosum complementation group D
XP-D
An autosomal recessive pigmentary skin disorder characterized by solar hypersensitivity of the skin, high predisposition for developing cancers on areas exposed to sunlight and, in some cases, neurological abnormalities. The skin develops marked freckling and other pigmentation abnormalities. Some XP-D patients present features of Cockayne syndrome, including cachectic dwarfism, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. The phenotype combining xeroderma pigmentosum and Cockayne syndrome traits is referred to as XP-CS complex.
None
The disease is caused by variants affecting the gene represented in this entry.
Trichothiodystrophy 1, photosensitive
TTD1
A form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder. TTD1 patients manifest cutaneous photosensitivity.
None
The disease is caused by variants affecting the gene represented in this entry.
Cerebro-oculo-facio-skeletal syndrome 2
COFS2
A disorder of prenatal onset characterized by microcephaly, congenital cataracts, facial dysmorphism, neurogenic arthrogryposis, growth failure and severe psychomotor retardation. COFS is considered to be part of the nucleotide-excision repair disorders spectrum that include also xeroderma pigmentosum, trichothiodystrophy and Cockayne syndrome.
None
The disease is caused by variants affecting the gene represented in this entry.
Post-translational modifications
ISGylated.
Sequence Similarities
Belongs to the helicase family. RAD3/XPD subfamily.
Cellular localization
- Nucleus
- Cytoplasm
- Cytoskeleton
- Spindle
Alternative names
XPD, XPDC, ERCC2, General transcription and DNA repair factor IIH helicase subunit XPD, TFIIH subunit XPD, Basic transcription factor 2 80 kDa subunit, CXPD, DNA 5'-3' helicase XPD, DNA excision repair protein ERCC-2, DNA repair protein complementing XP-D cells, TFIIH basal transcription factor complex 80 kDa subunit, Xeroderma pigmentosum group D-complementing protein, BTF2 p80, TFIIH 80 kDa subunit, TFIIH p80