Protein: General transcription and DNA repair factor IIH helicase subunit XPD (TFIIH subunit XPD) (EC 5.6.2.3) (Basic transcription factor 2 80 kDa subunit) (BTF2 p80) (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) (TFIIH 80 kDa subunit) (TFIIH p80) (Xeroderma pigmentosum group D-complementing protein) (P18074)
Organism: Homo sapiens (Human)
Function: ATP-dependent 5'-3' DNA helicase, component of the general transcription and DNA repair factor IIH (TFIIH) core complex, which is involved in general and transcription-coupled nucleotide excision repair (NER) of damaged DNA and, when complexed to CAK, in RNA 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. 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. 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.
Subcellular location: Nucleus {ECO:0000269|PubMed:20797633, ECO:0000269|PubMed:23352696, ECO:0000269|PubMed:23585563}. Cytoplasm, cytoskeleton, spindle {ECO:0000269|PubMed:20797633}.
Sequence: MKLNVDGLLVYFPYDYIYPEQFSYMRELKRTLDAKGHGVLEMPSGTGKTVSLLALIMAYQRAYPLEVTKLIYCSRTVPEIEKVIEELRKLLNFYEKQEGEKLPFLGLALSSRKNLCIHPEVTPLRFGKDVDGKCHSLTASYVRAQYQHDTSLPHCRFYEEFDAHGREVPLPAGIYNLDDLKALGRRQGWCPYFLARYSILHANVVVYSYHYLLDPKIADLVSKELARKAVVVFDEAHNIDNVCIDSMSVNLTRRTLDRCQGNLETLQKTVLRIKETDEQRLRDEYRRLVEGLREASAARETDAHLANPVLPDEVLQEAVPGSIRTAEHFLGFLRRLLEYVKWRLRVQHVVQESPPAFLSGLAQRVCIQRKPLRFCAERLRSLLHTLEITDLADFSPLTLLANFATLVSTYAKGFTIIIEPFDDRTPTIANPILHFSCMDASLAIKPVFERFQSVIITSGTLSPLDIYPKILDFHPVTMATFTMTLARVCLCPMIIGRGNDQVAISSKFETREDIAVIRNYGNLLLEMSAVVPDGIVAFFTSYQYMESTVASWYEQGILENIQRNKLLFIETQDGAETSVALEKYQEACENGRGAILLSVARGKVSEGIDFVHHYGRAVIMFGVPYVYTQSRILKARLEYLRDQFQIRENDFLTFDAMRHAAQCVGRAIRGKTDYGLMVFADKRFARGDKRGKLPRWIQEHLTDANLNLTVDEGVQVAKYFLRQMAQPFHREDQLGLSLLSLEQLESEETLKRIEQIAQQL
InterPro domains: - IPR010643: Helical and beta-bridge domain (domain) [271-413]
- IPR013020: ATP-dependent helicase Rad3/Chl1-like (family) [8-708]
- IPR006554: Helicase-like, DEXD box c2 type (domain) [8-280]
- IPR006555: ATP-dependent helicase, C-terminal (domain) [525-699]
- IPR002464: DNA/RNA helicase, ATP-dependent, DEAH-box type, conserved site (conserved_site) [229-238]
- IPR045028: Helicase superfamily 1/2, DinG/Rad3-like (family) [7-721]
- IPR010614: RAD3-like helicase, DEAD (domain) [72-256]
- IPR027417: P-loop containing nucleoside triphosphate hydrolase (homologous_superfamily) [16-695]
- IPR001945: RAD3/XPD (family) [8-727]
- IPR014013: Helicase superfamily 1/2, ATP-binding domain, DinG/Rad3-type (domain) [7-283]
Interaction partners: - Cyclin-H
- General transcription factor IIE subunit 1
- DNA repair protein complementing XP-A cells
- General transcription and DNA repair factor IIH helicase/translocase subunit XPB
- Cyclin-dependent kinase 7
- General transcription factor IIH subunit 5
- General transcription factor IIH subunit 3
- Transcription initiation factor IIE subunit beta
- General transcription factor IIH subunit 4
- General transcription factor IIH subunit 2
Gene Ontology annotations:
Molecular Function (MF): GO:0003674 (molecular function), GO:0005488 (binding), GO:0140223 (general transcription initiation factor activity), GO:0036094 (small molecule binding), GO:1901363 (heterocyclic compound binding), GO:0043167 (ion binding), GO:0097159 (organic cyclic compound binding), GO:0097367 (carbohydrate derivative binding), GO:0005515 (protein binding), GO:1901265 (nucleoside phosphate binding), GO:0043168 (anion binding), GO:0000166 (nucleotide binding), GO:0032553 (ribonucleotide binding), GO:0035639 (purine ribonucleoside triphosphate binding), GO:0032555 (purine ribonucleotide binding), GO:0017076 (purine nucleotide binding), GO:0005524 (ATP binding), GO:0032559 (adenyl ribonucleotide binding), GO:0030554 (adenyl nucleotide binding)
Biological Process (BP): GO:0008150 (biological process), GO:0008152 (metabolic process), GO:0009987 (cellular process), GO:0009058 (biosynthetic process), GO:0044237 (cellular metabolic process), GO:0071704 (organic substance metabolic process), GO:0044238 (primary metabolic process), GO:0006807 (nitrogen compound metabolic process), GO:0044249 (cellular biosynthetic process), GO:0006725 (cellular aromatic compound metabolic process), GO:1901360 (organic cyclic compound metabolic process), GO:0034641 (cellular nitrogen compound metabolic process), GO:1901576 (organic substance biosynthetic process), GO:0006139 (nucleobase-containing compound metabolic process), GO:0043170 (macromolecule metabolic process), GO:0046483 (heterocycle metabolic process), GO:0009059 (macromolecule biosynthetic process), GO:1901362 (organic cyclic compound biosynthetic process), GO:0044271 (cellular nitrogen compound biosynthetic process), GO:0090304 (nucleic acid metabolic process), GO:0019438 (aromatic compound biosynthetic process), GO:0010467 (gene expression), GO:0018130 (heterocycle biosynthetic process), GO:0034654 (nucleobase-containing compound biosynthetic process), GO:0016070 (RNA metabolic process), GO:0032774 (RNA biosynthetic process), GO:0097659 (nucleic acid-templated transcription), GO:0006351 (DNA-templated transcription), GO:0006366 (transcription by RNA polymerase II)
Cellular Component (CC): GO:0005575 (cellular component), GO:0032991 (protein-containing complex), GO:0110165 (cellular anatomical entity), GO:0005622 (intracellular anatomical structure), GO:0043226 (organelle), GO:0005829 (cytosol), GO:0140513 (nuclear protein-containing complex), GO:0005737 (cytoplasm), GO:0005667 (transcription regulator complex), GO:0031974 (membrane-enclosed lumen), GO:0005654 (nucleoplasm), GO:0090575 (RNA polymerase II transcription regulator complex), GO:0043233 (organelle lumen), GO:0043229 (intracellular organelle), GO:0043227 (membrane-bounded organelle), GO:0043231 (intracellular membrane-bounded organelle), GO:0070013 (intracellular organelle lumen), GO:0031981 (nuclear lumen), GO:0005634 (nucleus)