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Identification
HMDB Protein ID HMDBP08717
Secondary Accession Numbers
  • 14439
Name TFIIH basal transcription factor complex helicase XPD subunit
Synonyms
  1. BTF2 p80
  2. Basic transcription factor 2 80 kDa subunit
  3. CXPD
  4. DNA excision repair protein ERCC-2
  5. DNA repair protein complementing XP-D cells
  6. TFIIH 80 kDa subunit
  7. TFIIH basal transcription factor complex 80 kDa subunit
  8. TFIIH p80
  9. Xeroderma pigmentosum group D-complementing protein
Gene Name ERCC2
Protein Type Unknown
Biological Properties
General Function Involved in DNA binding
Specific 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. 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.
Pathways
  • Basal transcription factors
  • Nucleotide Excision Repair
  • Nucleotide excision repair
Reactions
Adenosine triphosphate + Water → ADP + Phosphate details
GO Classification
Biological Process
transcription-coupled nucleotide-excision repair
extracellular matrix organization
apoptotic process
negative regulation of apoptotic process
cell proliferation
response to oxidative stress
in utero embryonic development
positive regulation of DNA binding
chromosome segregation
7-methylguanosine mRNA capping
cell cycle checkpoint
central nervous system myelin formation
embryonic cleavage
erythrocyte maturation
hair cell differentiation
hair follicle maturation
hematopoietic stem cell differentiation
nucleotide-excision repair, DNA damage removal
nucleotide-excision repair, DNA incision
spinal cord development
termination of RNA polymerase I transcription
transcription elongation from RNA polymerase I promoter
transcription initiation from RNA polymerase I promoter
bone mineralization
induction of apoptosis
virus-host interaction
viral reproduction
positive regulation of transcription from RNA polymerase II promoter
protein phosphorylation
aging
multicellular organism growth
skin development
UV protection
response to hypoxia
positive regulation of viral transcription
transcription elongation from RNA polymerase II promoter
post-embryonic development
transcription initiation from RNA polymerase II promoter
Cellular Component
cytoplasm
holo TFIIH complex
MMXD complex
SSL2-core TFIIH complex
Component
organelle
membrane-bounded organelle
intracellular membrane-bounded organelle
nucleus
Function
binding
catalytic activity
hydrolase activity
nucleoside binding
purine nucleoside binding
adenyl nucleotide binding
adenyl ribonucleotide binding
atp binding
atp-dependent helicase activity
dna helicase activity
atp-dependent dna helicase activity
atpase activity
atpase activity, coupled
nucleic acid binding
dna binding
nucleoside-triphosphatase activity
helicase activity
hydrolase activity, acting on acid anhydrides
hydrolase activity, acting on acid anhydrides, in phosphorus-containing anhydrides
pyrophosphatase activity
Molecular Function
5'-3' DNA helicase activity
metal ion binding
ATP binding
4 iron, 4 sulfur cluster binding
ATP-dependent DNA helicase activity
DNA-dependent ATPase activity
DNA binding
Process
nucleotide-excision repair
metabolic process
nitrogen compound metabolic process
cellular nitrogen compound metabolic process
nucleobase, nucleoside, nucleotide and nucleic acid metabolic process
macromolecule metabolic process
cellular macromolecule metabolic process
dna metabolic process
dna repair
Cellular Location
  1. Nucleus
Gene Properties
Chromosome Location 19
Locus 19q13.3
SNPs ERCC2
Gene Sequence
>2283 bp
ATGAAGCTCAACGTGGACGGGCTCCTGGTCTACTTCCCGTACGACTACATCTACCCCGAG
CAGTTCTCCTACATGCGGGAGCTCAAACGCACGCTGGACGCCAAGGGTCATGGAGTCCTG
GAGATGCCCTCAGGCACCGGGAAGACAGTATCCCTGTTGGCCCTGATCATGGCATACCAG
AGAGCATATCCGCTGGAGGTGACCAAACTCATCTACTGCTCAAGAACTGTGCCAGAGATT
GAGAAGGTGATTGAAGAGCTTCGAAAGTTGCTCAACTTCTATGAGAAGCAGGAGGGCGAG
AAGCTGCCGTTTCTGGGACTGGCTCTGAGCTCCCGCAAAAACTTGTGTATTCACCCTGAG
GTGACACCCCTGCGCTTTGGGAAGGACGTCGATGGGAAATGCCACAGCCTCACAGCCTCC
TATGTGCGGGCGCAGTACCAGCATGACACCAGCCTGCCCCACTGCCGATTCTATGAGGAA
TTTGATGCCCATGGGCGTGAGGTGCCCCTCCCCGCTGGCATCTACAACCTGGATGACCTG
AAGGCCCTGGGGCGGCGCCAGGGCTGGTGCCCATACTTCCTTGCTCGATACTCAATCCTG
CATGCCAATGTGGTGGTTTATAGCTACCACTACCTCCTGGACCCCAAGATTGCAGACCTG
GTGTCCAAGGAACTGGCCCGCAAGGCCGTCGTGGTCTTCGACGAGGCCCACAACATTGAC
AACGTCTGCATCGACTCCATGAGCGTCAACCTCACCCGCCGGACCCTTGACCGGTGCCAG
GGCAACCTGGAGACCCTGCAGAAGACGGTGCTCAGGATCAAAGAGACAGACGAGCAGCGC
CTGCGGGACGAGTACCGGCGTCTGGTGGAGGGGCTGCGGGAGGCCAGCGCCGCCCGGGAG
ACGGACGCCCACCTGGCCAACCCCGTGCTGCCCGACGAAGTGCTGCAGGAGGCAGTGCCT
GGCTCCATCCGCACGGCCGAGCATTTCCTGGGCTTCCTGAGGCGGCTGCTGGAGTACGTG
AAGTGGCGGCTGCGTGTGCAGCATGTGGTGCAGGAGAGCCCGCCCGCCTTCCTGAGCGGC
CTGGCCCAGCGCGTGTGCATCCAGCGCAAGCCCCTCAGATTCTGTGCTGAACGCCTCCGG
TCCCTGCTGCATACTCTGGAGATCACCGACCTTGCTGACTTCTCCCCGCTCACCCTCCTT
GCTAACTTTGCCACCCTTGTCAGCACCTACGCCAAAGGCTTCACCATCATCATCGAGCCC
TTTGACGACAGAACCCCGACCATTGCCAACCCCATCCTGCACTTCAGCTGCATGGACGCC
TCGCTGGCCATCAAACCCGTATTTGAGCGTTTCCAGTCTGTCATCATCACATCTGGGACA
CTGTCCCCGCTGGACATCTACCCCAAGATCCTGGACTTCCACCCCGTCACCATGGCAACC
TTCACCATGACGCTGGCACGGGTCTGCCTCTGCCCTATGATCATCGGCCGTGGCAATGAC
CAGGTGGCCATCAGCTCCAAATTTGAGACCCGGGAGGATATTGCTGTGATCCGGAACTAT
GGGAACCTCCTGCTGGAGATGTCCGCTGTGGTCCCTGATGGCATCGTGGCCTTCTTCACC
AGCTACCAGTACATGGAGAGCACCGTGGCCTCCTGGTATGAGCAGGGGATCCTTGAGAAC
ATCCAGAGGAACAAGCTGCTCTTTATTGAGACCCAGGATGGTGCCGAAACCAGTGTCGCC
CTGGAGAAGTACCAGGAGGCCTGCGAGAATGGCCGCGGGGCCATCCTGCTGTCAGTGGCC
CGGGGCAAAGTGTCCGAGGGAATCGACTTTGTGCACCACTACGGGCGGGCCGTCATCATG
TTTGGCGTCCCCTACGTCTACACACAGAGCCGCATTCTCAAGGCGCGGCTGGAATACCTG
CGGGACCAGTTCCAGATTCGTGAGAATGACTTTCTTACCTTCGATGCCATGCGCCACGCG
GCCCAGTGTGTGGGTCGGGCCATCAGGGGCAAGACGGACTACGGCCTCATGGTCTTTGCC
GACAAGCGGTTTGCCCGTGGGGACAAGCGGGGGAAGCTGCCCCGCTGGATCCAGGAGCAC
CTCACAGATGCCAACCTCAACCTGACCGTGGACGAGGGTGTCCAGGTGGCCAAGTACTTC
CTGCGGCAGATGGCACAGCCCTTCCACCGGGAGGATCAGCTGGGCCTGTCCCTGCTCAGC
CTGGAGCAGCTAGAATCAGAGGAGACGCTGAAGAGGATAGAGCAGATTGCTCAGCAGCTC
TGA
Protein Properties
Number of Residues 760
Molecular Weight 86908.305
Theoretical pI 7.151
Pfam Domain Function
Signals Not Available
Transmembrane Regions Not Available
Protein Sequence
>TFIIH basal transcription factor complex helicase XPD subunit
MKLNVDGLLVYFPYDYIYPEQFSYMRELKRTLDAKGHGVLEMPSGTGKTVSLLALIMAYQ
RAYPLEVTKLIYCSRTVPEIEKVIEELRKLLNFYEKQEGEKLPFLGLALSSRKNLCIHPE
VTPLRFGKDVDGKCHSLTASYVRAQYQHDTSLPHCRFYEEFDAHGREVPLPAGIYNLDDL
KALGRRQGWCPYFLARYSILHANVVVYSYHYLLDPKIADLVSKELARKAVVVFDEAHNID
NVCIDSMSVNLTRRTLDRCQGNLETLQKTVLRIKETDEQRLRDEYRRLVEGLREASAARE
TDAHLANPVLPDEVLQEAVPGSIRTAEHFLGFLRRLLEYVKWRLRVQHVVQESPPAFLSG
LAQRVCIQRKPLRFCAERLRSLLHTLEITDLADFSPLTLLANFATLVSTYAKGFTIIIEP
FDDRTPTIANPILHFSCMDASLAIKPVFERFQSVIITSGTLSPLDIYPKILDFHPVTMAT
FTMTLARVCLCPMIIGRGNDQVAISSKFETREDIAVIRNYGNLLLEMSAVVPDGIVAFFT
SYQYMESTVASWYEQGILENIQRNKLLFIETQDGAETSVALEKYQEACENGRGAILLSVA
RGKVSEGIDFVHHYGRAVIMFGVPYVYTQSRILKARLEYLRDQFQIRENDFLTFDAMRHA
AQCVGRAIRGKTDYGLMVFADKRFARGDKRGKLPRWIQEHLTDANLNLTVDEGVQVAKYF
LRQMAQPFHREDQLGLSLLSLEQLESEETLKRIEQIAQQL
GenBank ID Protein 82568960
UniProtKB/Swiss-Prot ID P18074
UniProtKB/Swiss-Prot Entry Name ERCC2_HUMAN
PDB IDs Not Available
GenBank Gene ID BC108255
GeneCard ID ERCC2
GenAtlas ID ERCC2
HGNC ID HGNC:3434
References
General References
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  2. Kershnar E, Wu SY, Chiang CM: 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. J Biol Chem. 1998 Dec 18;273(51):34444-53. [PubMed:9852112 ]
  3. Takeuchi T, Inoue S, Yokosawa H: Identification and Herc5-mediated ISGylation of novel target proteins. Biochem Biophys Res Commun. 2006 Sep 22;348(2):473-7. Epub 2006 Jul 28. [PubMed:16884686 ]
  4. Tirode F, Busso D, Coin F, Egly JM: Reconstitution of the transcription factor TFIIH: assignment of functions for the three enzymatic subunits, XPB, XPD, and cdk7. Mol Cell. 1999 Jan;3(1):87-95. [PubMed:10024882 ]
  5. Weber CA, Salazar EP, Stewart SA, Thompson LH: ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3. EMBO J. 1990 May;9(5):1437-47. [PubMed:2184031 ]
  6. Lamerdin JE, Stilwagen SA, Ramirez MH, Stubbs L, Carrano AV: Sequence analysis of the ERCC2 gene regions in human, mouse, and hamster reveals three linked genes. Genomics. 1996 Jun 15;34(3):399-409. [PubMed:8786141 ]
  7. Flejter WL, McDaniel LD, Johns D, Friedberg EC, Schultz RA: Correction of xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: involvement of the human ERCC2 DNA repair gene. Proc Natl Acad Sci U S A. 1992 Jan 1;89(1):261-5. [PubMed:1729695 ]
  8. Sung P, Bailly V, Weber C, Thompson LH, Prakash L, Prakash S: Human xeroderma pigmentosum group D gene encodes a DNA helicase. Nature. 1993 Oct 28;365(6449):852-5. [PubMed:8413672 ]
  9. Tong X, Drapkin R, Reinberg D, Kieff E: The 62- and 80-kDa subunits of transcription factor IIH mediate the interaction with Epstein-Barr virus nuclear protein 2. Proc Natl Acad Sci U S A. 1995 Apr 11;92(8):3259-63. [PubMed:7724549 ]
  10. Coin F, Marinoni JC, Rodolfo C, Fribourg S, Pedrini AM, Egly JM: Mutations in the XPD helicase gene result in XP and TTD phenotypes, preventing interaction between XPD and the p44 subunit of TFIIH. Nat Genet. 1998 Oct;20(2):184-8. [PubMed:9771713 ]
  11. Drane P, Compe E, Catez P, Chymkowitch P, Egly JM: Selective regulation of vitamin D receptor-responsive genes by TFIIH. Mol Cell. 2004 Oct 22;16(2):187-97. [PubMed:15494306 ]
  12. Frederick GD, Amirkhan RH, Schultz RA, Friedberg EC: Structural and mutational analysis of the xeroderma pigmentosum group D (XPD) gene. Hum Mol Genet. 1994 Oct;3(10):1783-8. [PubMed:7849702 ]
  13. Broughton BC, Steingrimsdottir H, Weber CA, Lehmann AR: Mutations in the xeroderma pigmentosum group D DNA repair/transcription gene in patients with trichothiodystrophy. Nat Genet. 1994 Jun;7(2):189-94. [PubMed:7920640 ]
  14. Broughton BC, Thompson AF, Harcourt SA, Vermeulen W, Hoeijmakers JH, Botta E, Stefanini M, King MD, Weber CA, Cole J, et al.: 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. Am J Hum Genet. 1995 Jan;56(1):167-74. [PubMed:7825573 ]
  15. Takayama K, Salazar EP, Lehmann A, Stefanini M, Thompson LH, Weber CA: Defects in the DNA repair and transcription gene ERCC2 in the cancer-prone disorder xeroderma pigmentosum group D. Cancer Res. 1995 Dec 1;55(23):5656-63. [PubMed:7585650 ]
  16. Takayama K, Salazar EP, Broughton BC, Lehmann AR, Sarasin A, Thompson LH, Weber CA: Defects in the DNA repair and transcription gene ERCC2(XPD) in trichothiodystrophy. Am J Hum Genet. 1996 Feb;58(2):263-70. [PubMed:8571952 ]
  17. Kobayashi T, Kuraoka I, Saijo M, Nakatsu Y, Tanaka A, Someda Y, Fukuro S, Tanaka K: Mutations in the XPD gene leading to xeroderma pigmentosum symptoms. Hum Mutat. 1997;9(4):322-31. [PubMed:9101292 ]
  18. Takayama K, Danks DM, Salazar EP, Cleaver JE, Weber CA: DNA repair characteristics and mutations in the ERCC2 DNA repair and transcription gene in a trichothiodystrophy patient. Hum Mutat. 1997;9(6):519-25. [PubMed:9195225 ]
  19. Taylor EM, Broughton BC, Botta E, Stefanini M, Sarasin A, Jaspers NG, Fawcett H, Harcourt SA, Arlett CF, Lehmann AR: Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene. Proc Natl Acad Sci U S A. 1997 Aug 5;94(16):8658-63. [PubMed:9238033 ]
  20. Botta E, Nardo T, Broughton BC, Marinoni S, Lehmann AR, Stefanini M: 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. Am J Hum Genet. 1998 Oct;63(4):1036-48. [PubMed:9758621 ]
  21. Cleaver JE, Thompson LH, Richardson AS, States JC: A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy. Hum Mutat. 1999;14(1):9-22. [PubMed:10447254 ]
  22. Graham JM Jr, Anyane-Yeboa K, Raams A, Appeldoorn E, Kleijer WJ, Garritsen VH, Busch D, Edersheim TG, Jaspers NG: Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy. Am J Hum Genet. 2001 Aug;69(2):291-300. Epub 2001 Jul 3. [PubMed:11443545 ]
  23. Caggana M, Kilgallen J, Conroy JM, Wiencke JK, Kelsey KT, Miike R, Chen P, Wrensch MR: Associations between ERCC2 polymorphisms and gliomas. Cancer Epidemiol Biomarkers Prev. 2001 Apr;10(4):355-60. [PubMed:11319176 ]
  24. Spitz MR, Wu X, Wang Y, Wang LE, Shete S, Amos CI, Guo Z, Lei L, Mohrenweiser H, Wei Q: Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients. Cancer Res. 2001 Feb 15;61(4):1354-7. [PubMed:11245433 ]
  25. Hemminki K, Xu G, Angelini S, Snellman E, Jansen CT, Lambert B, Hou SM: XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ. Carcinogenesis. 2001 Aug;22(8):1185-8. [PubMed:11470747 ]
  26. Lehmann AR: The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases. Genes Dev. 2001 Jan 1;15(1):15-23. [PubMed:11156600 ]
  27. 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: Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene. Hum Mol Genet. 2001 Oct 15;10(22):2539-47. [PubMed:11709541 ]
  28. Vermeulen W, Rademakers S, Jaspers NG, Appeldoorn E, Raams A, Klein B, Kleijer WJ, Hansen LK, Hoeijmakers JH: A temperature-sensitive disorder in basal transcription and DNA repair in humans. Nat Genet. 2001 Mar;27(3):299-303. [PubMed:11242112 ]