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XPD |
Protein FULL name:
TFIIH basal transcription factor complex helicase subunit, Basic transcription factor 2 80 kDa subunit, TFIIH basal transcription factor complex 80 kDa subunit, DNA repair protein complementing XP-D cells, Xeroderma pigmentosum group D-complementing protein, CXPD, DNA excision repair protein ERCC-2.,
Protein SHORT name:
XPD, CXPD, ERCC2, ERCC-2
XPD (Homo sapiens) is product of expression of ERCC2 gene.
Human diseases related to this protein:
- XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP E (#601675 )
- TRICHOTHIODYSTROPHY, PHOTOSENSITIVE (#601675 )
- XERODERMA PIGMENTOSUM, COMPLEMENTATION GROUP D (#278730 )
XPD is involved in:
NER in Homo sapiens
Keywords:
FUNCTION: ATP-dependent 5'-3' DNA helicase, component of the core- TFIIH basal transcription factor. Involved in nucleotide excision repair (NER) of DNA by opening DNA around the damage, and in RNA transcription by RNA polymerase II by anchoring the CDK-activating kinase (CAK) complex, composed of CDK7, cyclin H and MAT1, to the core-TFIIH complex. Involved in the regulation of vitamin-D receptor activity. Might also have a role in aging process and could play a causative role in the generation of skin cancers.
CATALYTIC ACTIVITY: ATP + H(2)O = ADP + phosphate.
COFACTOR: Magnesium.
SUBUNIT: One of the six subunits forming the core-TFIIH basal transcription factor which associates with the CAK complex composed of CDK7, CCNH/cyclin H and MNAT1 to form the TFIIH basal transcription factor. The interaction with GTF2H2 results in the stimulation of the 5'-->3' helicase activity. Interacts with Epstein-Barr virus EBNA2.
SUBCELLULAR LOCATION: Nucleus.
DISEASE: Defects in ERCC2 are the cause of xeroderma pigmentosum complementation group D (XP-D) [MIM:278730]; also known as XP group D (XPD). Xeroderma pigmentosum is 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. Some XP-D patients present features of Cockayne syndrome, including dwarfism, sensorineural deafness, microcephaly, mental retardation, pigmentary retinopathy, ataxia, decreased nerve conduction velocities.
DISEASE: Defects in ERCC2 are a cause of trichothiodystrophy photosensitive (TTDP) [MIM:601675]. TTDP is an autosomal recessive disease characterized by sulfur-deficient brittle hair and nails, ichthyosis, mental retardation, impaired sexual development, abnormal facies and cutaneous photosensitivity correlated with a nucleotide excision repair (NER) defect. Neonates with trichothiodystrophy and ichthyosis are usually born with a collodion membrane. The severity of the ichthyosis after the membrane is shed is variable, ranging from a mild to severe lamellar ichthyotic phenotype. There are no reports of skin cancer associated with TTDP.
DISEASE: Defects in ERCC2 are the cause of cerebro-oculo-facio- skeletal syndrome type 2 (COFS2) [MIM:610756]. COFS is a degenerative autosomal recessive disorder of prenatal onset affecting the brain, eye and spinal cord. After birth, it leads to brain atrophy, hypoplasia of the corpus callosum, hypotonia, cataracts, microcornea, optic atrophy, progressive joint contractures and growth failure. Facial dysmorphism is a constant feature. Abnormalities of the skull, eyes, limbs, heart and kidney also occur.
SIMILARITY: Belongs to the helicase family. RAD3/XPD subfamily.
SIMILARITY: Contains 1 helicase ATP-binding domain.
SEQUENCE CAUTION: Sequence=AAM45142.1; Type=Erroneous gene model prediction;
WEB RESOURCE: Name=Allelic variations of the XP genes; [LINK]
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; [LINK]
WEB RESOURCE: Name=GeneReviews; [LINK]
WEB RESOURCE: Name=NIEHS-SNPs; [LINK]
This protein can be a part of a given complexes:
| NCBI GenPept GI number(s): |
119540 15834617 |
| Species: | Homo sapiens |
Links to other databases:
| Database | ID | Link |
| Uniprot | P18074 |
P18074 |
| PFAM: |
PF06733 PF06777 |
PF06733 PF06777 |
| InterPro: |
IPR010614 IPR002464 IPR013020 IPR010643 IPR014013 IPR006554 IPR006555 IPR001945 |
IPR010614 IPR002464 IPR013020 IPR010643 IPR014013 IPR006554 IPR006555 IPR001945 |
| CATH: | - | - |
| SCOP: | - | - |
| PDB: | - | - |
Protein sequence:
|
MKLNVDGLLVYFPYDYIYPEQFSYMRELKRTLDAKGHGVLEMPSGTGKTV SLLALIMAYQRAYPLEVTKLIYCSRTVPEIEKVIEELRKLLNFYEKQEGE KLPFLGLALSSRKNLCIHPEVTPLRFGKDVDGKCHSLTASYVRAQYQHDT SLPHCRFYEEFDAHGREVPLPAGIYNLDDLKALGRRQGWCPYFLARYSIL HANVVVYSYHYLLDPKIADLVSKELARKAVVVFDEAHNIDNVCIDSMSVN LTRRTLDRCQGNLETLQKTVLRIKETDEQRLRDEYRRLVEGLREASAARE TDAHLANPVLPDEVLQEAVPGSIRTAEHFLGFLRRLLEYVKWRLRVQHVV QESPPAFLSGLAQRVCIQRKPLRFCAERLRSLLHTLEITDLADFSPLTLL ANFATLVSTYAKGFTIIIEPFDDRTPTIANPILHFSCMDASLAIKPVFER FQSVIITSGTLSPLDIYPKILDFHPVTMATFTMTLARVCLCPMIIGRGND QVAISSKFETREDIAVIRNYGNLLLEMSAVVPDGIVAFFTSYQYMESTVA SWYEQGILENIQRNKLLFIETQDGAETSVALEKYQEACENGRGAILLSVA RGKVSEGIDFVHHYGRAVIMFGVPYVYTQSRILKARLEYLRDQFQIREND FLTFDAMRHAAQCVGRAIRGKTDYGLMVFADKRFARGDKRGKLPRWIQEH LTDANLNLTVDEGVQVAKYFLRQMAQPFHREDQLGLSLLSLEQLESEETL KRIEQIAQQL |
XPD (Homo sapiens) belongs to following protein families:
References:
| Title | Authors | Journal |
| ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3. | Weber CA, Salazar EP, Stewart SA, Thompson LH | EMBO J May 1, 1990 |
| Correction of xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: involvement of the human ERCC2 DNA repair gene. | Flejter WL, McDaniel LD, Johns D, Friedberg EC, Schultz RA | Proc Natl Acad Sci U S A Feb. 1, 1992 |
| Human xeroderma pigmentosum group D gene encodes a DNA helicase. | Sung P, Bailly V, Weber C, Thompson LH, Prakash L, Prakash S | Nature Oct. 28, 1993 |
| Mutations in the xeroderma pigmentosum group D DNA repair/transcription gene in patients with trichothiodystrophy. | Broughton BC, Steingrimsdottir H, Weber CA, Lehmann AR | Nat Genet June 1, 1994 |
| Structural and mutational analysis of the xeroderma pigmentosum group D (XPD) gene. | Frederick GD, Amirkhan RH, Schultz RA, Friedberg EC | Hum Mol Genet Oct. 1, 1994 |
| Molecular and cellular analysis of the DNA repair defect in a patient in xeroderma pigmentosum complementation group D who has the clinical features of xeroderma pigmentosum and Cockayne syndrome. | Broughton BC, Thompson AF, Harcourt SA, Vermeulen W, Hoeijmakers JH, Botta E, Stefanini M, King MD, Weber CA, Cole J, et al. | Am J Hum Genet Feb. 1, 1995 |
| The 62- and 80-kDa subunits of transcription factor IIH mediate the interaction with Epstein-Barr virus nuclear protein 2. | Tong X, Drapkin R, Reinberg D, Kieff E | Proc Natl Acad Sci U S A April 11, 1995 |
| Defects in the DNA repair and transcription gene ERCC2 in the cancer-prone disorder xeroderma pigmentosum group D. | Takayama K, Salazar EP, Lehmann A, Stefanini M, Thompson LH, Weber CA | Cancer Res Dec. 1, 1995 |
| Defects in the DNA repair and transcription gene ERCC2(XPD) in trichothiodystrophy. | Takayama K, Salazar EP, Broughton BC, Lehmann AR, Sarasin A, Thompson LH, Weber CA | Am J Hum Genet Jan. 1, 1996 |
| Sequence analysis of the ERCC2 gene regions in human, mouse, and hamster reveals three linked genes. | Lamerdin JE, Stilwagen SA, Ramirez MH, Stubbs L, Carrano AV | Genomics June 15, 1996 |
| Mutations in the XPD gene leading to xeroderma pigmentosum symptoms. | Kobayashi T, Kuraoka I, Saijo M, Nakatsu Y, Tanaka A, Someda Y, Fukuro S, Tanaka K | Hum Mutat Jan. 1, 1997 |
| DNA repair characteristics and mutations in the ERCC2 DNA repair and transcription gene in a trichothiodystrophy patient. | Takayama K, Danks DM, Salazar EP, Cleaver JE, Weber CA | Hum Mutat Jan. 1, 1997 |
| Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene. | Taylor EM, Broughton BC, Botta E, Stefanini M, Sarasin A, Jaspers NG, Fawcett H, Harcourt SA, Arlett CF, Lehmann AR | Proc Natl Acad Sci U S A Aug. 5, 1997 |
| Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH. | Coin F, Marinoni JC, Rodolfo C, Fribourg S, Pedrini AM, Egly JM | Nat Genet Oct. 1, 1998 |
| Analysis of mutations in the XPD gene in Italian patients with trichothiodystrophy: site of mutation correlates with repair deficiency, but gene dosage appears to determine clinical severity. | Botta E, Nardo T, Broughton BC, Marinoni S, Lehmann AR, Stefanini M | Am J Hum Genet Oct. 1, 1998 |
| Immunoaffinity purification and functional characterization of human transcription factor IIH and RNA polymerase II from clonal cell lines that conditionally express epitope-tagged subunits of the multiprotein complexes. | Kershnar E, Wu SY, Chiang CM | J Biol Chem Dec. 18, 1998 |
| A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. | Cleaver JE, Thompson LH, Richardson AS, States JC | Hum Mutat Jan. 1, 1999 |
| Reconstitution of the transcription factor TFIIH: assignment of functions for the three enzymatic subunits, XPB, XPD, and cdk7. | Tirode F, Busso D, Coin F, Egly JM | Mol Cell Feb. 1, 1999 |
| Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. | Spitz MR, Wu X, Wang Y, Wang LE, Shete S, Amos CI, Guo Z, Lei L, Mohrenweiser H, Wei Q | Cancer Res Jan. 15, 2001 |
| The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases. | Lehmann AR | Genes Dev Feb. 1, 2001 |
| A temperature-sensitive disorder in basal transcription and DNA repair in humans. | Vermeulen W, Rademakers S, Jaspers NG, Appeldoorn E, Raams A, Klein B, Kleijer WJ, Hansen LK, Hoeijmakers JH | Nat Genet March 1, 2001 |
| Associations between ERCC2 polymorphisms and gliomas. | Caggana M, Kilgallen J, Conroy JM, Wiencke JK, Kelsey KT, Miike R, Chen P, Wrensch MR | Cancer Epidemiol Biomarkers Prev April 1, 2001 |
| Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy. | Graham JM Jr, Anyane-Yeboa K, Raams A, Appeldoorn E, Kleijer WJ, Garritsen VH, Busch D, Edersheim TG, Jaspers NG | Am J Hum Genet Aug. 1, 2001 |
| XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. | Hemminki K, Xu G, Angelini S, Snellman E, Jansen CT, Lambert B, Hou SM | Carcinogenesis Aug. 1, 2001 |
| Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene. | Broughton BC, Berneburg M, Fawcett H, Taylor EM, Arlett CF, Nardo T, Stefanini M, Menefee E, Price VH, Queille S, Sarasin A, Bohnert E, Krutmann J, Davidson R, Kraemer KH, Lehmann AR | Hum Mol Genet Oct. 15, 2001 |
| The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). | Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J | Genome Res Oct. 1, 2004 |
| Selective regulation of vitamin D receptor-responsive genes by TFIIH. | Drane P, Compe E, Catez P, Chymkowitch P, Egly JM | Mol Cell Oct. 22, 2004 |
| Identification and Herc5-mediated ISGylation of novel target proteins. | Takeuchi T, Inoue S, Yokosawa H | Biochem Biophys Res Commun Sept. 22, 2006 |
Last modification of this entry: Oct. 19, 2010.
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