P18074 (ERCC2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
TFIIH basal transcription factor complex helicase XPD subunit
EC=3.6.4.12

Alternative name(s):
Basic transcription factor 2 80 kDa subunit
Short name=BTF2 p80
CXPD
DNA excision repair protein ERCC-2
DNA repair protein complementing XP-D cells
TFIIH basal transcription factor complex 80 kDa subunit
Short name=TFIIH 80 kDa subunit
Short name=TFIIH p80
Xeroderma pigmentosum group D-complementing protein

Gene names

Name:	ERCC2
Synonyms:	XPD, XPDC

Organism

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

Protein attributes

Sequence length	760 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

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. Ref.8 Ref.12 Ref.13 Ref.16
Catalytic activity	ATP + H2O = ADP + phosphate.
Cofactor	Magnesium. Ref.18 Binds 1 4Fe-4S cluster. Ref.18
Subunit structure	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. Component of the MMXD complex, which includes CIAO1, ERCC2, FAM96B, MMS19 and SLC25A5. Interacts with FAM196B; the interaction is direct. Interacts with ATF7IP. Interacts with Epstein-Barr virus EBNA2. Ref.9 Ref.10 Ref.11 Ref.15 Ref.16
Subcellular location	Nucleus. Cytoplasm › cytoskeleton › spindle Ref.16.
Post-translational modification	ISGylated Probable. Ref.14
Involvement in disease	Xeroderma pigmentosum complementation group D (XP-D) [MIM:278730]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.13 Ref.19 Ref.21 Ref.22 Ref.24 Ref.34 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.20 Ref.23 Ref.25 Ref.26 Ref.27 Ref.35 Cerebro-oculo-facio-skeletal syndrome 2 (COFS2) [MIM:610756]: 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. Note: The disease is caused by mutations affecting the gene represented in this entry. Ref.29
Sequence similarities	Belongs to the helicase family. RAD3/XPD subfamily. Contains 1 helicase ATP-binding domain.
Sequence caution	The sequence AAM45142.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
Biological process	Chromosome partition DNA damage DNA repair Host-virus interaction Transcription Transcription regulation
Cellular component	Cytoplasm Cytoskeleton Nucleus
Coding sequence diversity	Alternative splicing Polymorphism
Disease	Cataract Cockayne syndrome Deafness Disease mutation Dwarfism Ichthyosis Xeroderma pigmentosum
Ligand	4Fe-4S ATP-binding DNA-binding Iron Iron-sulfur Magnesium Metal-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
PTM	Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	7-methylguanosine mRNA capping Traceable author statement. Source: Reactome UV protection Inferred from genetic interaction PubMed 2835663. Source: MGI aging Inferred from electronic annotation. Source: Compara apoptotic process Inferred from electronic annotation. Source: Compara bone mineralization Inferred from electronic annotation. Source: Compara cell cycle checkpoint Inferred from mutant phenotype PubMed 17088560. Source: UniProtKB cell proliferation Inferred from electronic annotation. Source: Compara central nervous system myelin formation Inferred from electronic annotation. Source: Compara chromosome segregation Inferred from mutant phenotype Ref.16. Source: UniProtKB embryonic cleavage Inferred from electronic annotation. Source: Compara erythrocyte maturation Inferred from electronic annotation. Source: Compara extracellular matrix organization Inferred from electronic annotation. Source: Compara hair cell differentiation Inferred from mutant phenotype PubMed 11335038. Source: UniProtKB hair follicle maturation Inferred from electronic annotation. Source: Compara hematopoietic stem cell differentiation Inferred from electronic annotation. Source: Compara in utero embryonic development Inferred from electronic annotation. Source: Compara induction of apoptosis Inferred from mutant phenotype PubMed 8675009. Source: UniProtKB multicellular organism growth Inferred from electronic annotation. Source: Compara negative regulation of apoptotic process Inferred from electronic annotation. Source: Compara nucleotide-excision repair, DNA damage removal Traceable author statement. Source: Reactome nucleotide-excision repair, DNA incision Inferred from mutant phenotype PubMed 8692841. Source: UniProtKB positive regulation of DNA binding Inferred from electronic annotation. Source: Compara positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay PubMed 8692841. Source: UniProtKB positive regulation of viral transcription Traceable author statement. Source: Reactome post-embryonic development Inferred from electronic annotation. Source: Compara protein phosphorylation Inferred from direct assay Ref.10. Source: GOC response to hypoxia Inferred from electronic annotation. Source: Compara response to oxidative stress Inferred from mutant phenotype PubMed 17614221. Source: UniProtKB skin development Inferred from electronic annotation. Source: Compara spinal cord development Inferred from electronic annotation. Source: Compara termination of RNA polymerase I transcription Traceable author statement. Source: Reactome transcription elongation from RNA polymerase I promoter Traceable author statement. Source: Reactome transcription elongation from RNA polymerase II promoter Traceable author statement. Source: Reactome transcription initiation from RNA polymerase I promoter Traceable author statement. Source: Reactome transcription initiation from RNA polymerase II promoter Traceable author statement. Source: Reactome transcription-coupled nucleotide-excision repair Inferred from direct assay PubMed 8663148. Source: UniProtKB viral reproduction Traceable author statement. Source: Reactome virus-host interaction Inferred from electronic annotation. Source: UniProtKB-KW
Cellular_component	MMXD complex Inferred from direct assay Ref.16. Source: UniProtKB SSL2-core TFIIH complex Inferred from electronic annotation. Source: Compara cytoplasm Inferred from direct assay Ref.16. Source: UniProtKB holo TFIIH complex Inferred from direct assay Ref.10. Source: UniProtKB
Molecular_function	4 iron, 4 sulfur cluster binding Inferred from electronic annotation. Source: UniProtKB-KW 5'-3' DNA helicase activity Inferred from direct assay PubMed 11445587PubMed 8663148. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent DNA helicase activity Inferred from electronic annotation. Source: InterPro DNA binding Inferred from electronic annotation. Source: UniProtKB-KW DNA-dependent ATPase activity Traceable author statement PubMed 8663148. Source: UniProtKB metal ion binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]

Isoform 1 (identifier: P18074-1)

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

Isoform 2 (identifier: P18074-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-24: Missing.
     414-429: FTIIIEPFDDRTPTIA → QAQHCGSSRNQKRSHP
     430-760: Missing.

Note: No experimental confirmation available.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 760	760	TFIIH basal transcription factor complex helicase XPD subunit		PRO_0000101980
Regions
	Domain	7 – 283	277	Helicase ATP-binding
	Nucleotide binding	42 – 49	8	ATP By similarity
	Region	438 – 637	200	Mediates interaction with MMS19
	Motif	234 – 237	4	DEAH box
	Motif	682 – 695	14	Nuclear localization signal Potential
Sites
	Metal binding	116	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	134	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	155	1	Iron-sulfur (4Fe-4S) By similarity
	Metal binding	190	1	Iron-sulfur (4Fe-4S) Probable
Natural variations
	Alternative sequence	1 – 24	24	Missing in isoform 2.		VSP_043132
	Alternative sequence	414 – 429	16	FTIII…TPTIA → QAQHCGSSRNQKRSHP in isoform 2.		VSP_043133
	Alternative sequence	430 – 760	331	Missing in isoform 2.		VSP_043134
	Natural variant	47	1	G → R in XP-D.		VAR_008187
	Natural variant	76	1	T → A in XP-D.		VAR_017282
	Natural variant	112	1	R → H in TTDP and XP-D. Ref.20 Ref.27 Ref.34		VAR_003622
	Natural variant	199	1	I → M. Corresponds to variant rs1799791 [ dbSNP | Ensembl ].		VAR_011412
	Natural variant	201	1	H → Y. Corresponds to variant rs1799792 [ dbSNP | Ensembl ].		VAR_011413
	Natural variant	234	1	D → N in XP-D.		VAR_008188
	Natural variant	259	1	C → Y in TTDP. Ref.27		VAR_008189
	Natural variant	312	1	D → N. Ref.3 Ref.31 Ref.32 Ref.34 Corresponds to variant rs1799793 [ dbSNP | Ensembl ].		VAR_011414
	Natural variant	461	1	L → V in XP-D and TTDP. Ref.19 Ref.25 Ref.27		VAR_003623
	Natural variant	482	1	Missing in TTDP. Ref.27		VAR_008190
	Natural variant	485	1	L → P in XP-D; the corresponding mutation in fission yeast causes complete loss of activity. Ref.34		VAR_017283
	Natural variant	487	1	R → G in TTDP.		VAR_017284
	Natural variant	488 – 493	6	Missing in TTDP; mild.		VAR_003624
	Natural variant	511	1	R → Q in XP-D.		VAR_017285
	Natural variant	541	1	S → R in XP-D; mild. Ref.24		VAR_003625
	Natural variant	542	1	Y → C in XP-D.		VAR_008191
	Natural variant	582 – 583	2	EK → VSE in XP-D.		VAR_017286
	Natural variant	592	1	R → P in TTDP.		VAR_017287
	Natural variant	594	1	A → P in TTDP.		VAR_017288
	Natural variant	601	1	R → L in XP-D.		VAR_008192
	Natural variant	601	1	R → W in XP-D.		VAR_017289
	Natural variant	602	1	G → D in XP-D; combined with features of Cockayne syndrome.		VAR_003627
	Natural variant	616	1	R → C. Ref.30		VAR_011415
	Natural variant	616	1	R → P in XP-D and TTDP. Ref.20		VAR_003626
	Natural variant	616	1	R → W in XP-D and COFS2. Ref.29		VAR_008193
	Natural variant	658	1	R → C in TTDP. Ref.23 Ref.35		VAR_008194
	Natural variant	658	1	R → G in TTDP.		VAR_017290
	Natural variant	658	1	R → H in TTDP.		VAR_008195
	Natural variant	663	1	C → R in TTDP.		VAR_017291
	Natural variant	666	1	R → W in XP-D.		VAR_017292
	Natural variant	673	1	D → G in TTDP. Ref.27		VAR_008196
	Natural variant	675	1	G → R in XP-D/CS; severe form. Ref.21		VAR_003628
	Natural variant	681	1	D → N in XP-D and COFS2. Ref.29		VAR_017293
	Natural variant	683	1	R → Q in XP-D; CNS.		VAR_008197
	Natural variant	683	1	R → W in XP-D; CNS; vitamin D-mediated activation of CYP24A1 is impaired in patient fibroblasts due to altered TFIIH-dependent phosphorylation of ETS1, subsequent impaired cooperation of ETS1 with VDR and altered VDR recruitment to CYP24A1 promoter. Ref.13 Corresponds to variant rs41556519 [ dbSNP | Ensembl ].		VAR_008198
	Natural variant	713	1	G → R in TTDP. Ref.23 Ref.35		VAR_008199
	Natural variant	716 – 730	15	Missing in XP-D and TTDP.		VAR_003629
	Natural variant	722	1	R → W in TTDP. Ref.20 Ref.27		VAR_003630
	Natural variant	725	1	A → P in TTDP. Ref.25		VAR_003631
	Natural variant	751	1	K → Q May be linked to a reduced activity. Ref.3 Ref.5 Ref.6 Ref.31 Ref.32 Ref.34 Corresponds to variant rs13181 [ dbSNP | Ensembl ].		VAR_011416
Experimental info
	Mutagenesis	48	1	K → R: Decreased transcriptional activity of the reconstituted TFIIH complex. Ref.12
	Mutagenesis	190	1	C → S: Reduced iron-sulfur-binding. Iron-sulfur-binding is further decreased in absence of MMS19. Ref.18

Sequences

	Sequence		Length	Mass (Da)
	Isoform 1 [UniParc]. Last modified November 1, 1990. Version 1. Checksum: 746C0888CDF2E331	FASTA	760	86,909
	10 20 30 40 50 60 MKLNVDGLLV YFPYDYIYPE QFSYMRELKR TLDAKGHGVL EMPSGTGKTV SLLALIMAYQ 70 80 90 100 110 120 RAYPLEVTKL IYCSRTVPEI EKVIEELRKL LNFYEKQEGE KLPFLGLALS SRKNLCIHPE 130 140 150 160 170 180 VTPLRFGKDV DGKCHSLTAS YVRAQYQHDT SLPHCRFYEE FDAHGREVPL PAGIYNLDDL 190 200 210 220 230 240 KALGRRQGWC PYFLARYSIL HANVVVYSYH YLLDPKIADL VSKELARKAV VVFDEAHNID 250 260 270 280 290 300 NVCIDSMSVN LTRRTLDRCQ GNLETLQKTV LRIKETDEQR LRDEYRRLVE GLREASAARE 310 320 330 340 350 360 TDAHLANPVL PDEVLQEAVP GSIRTAEHFL GFLRRLLEYV KWRLRVQHVV QESPPAFLSG 370 380 390 400 410 420 LAQRVCIQRK PLRFCAERLR SLLHTLEITD LADFSPLTLL ANFATLVSTY AKGFTIIIEP 430 440 450 460 470 480 FDDRTPTIAN PILHFSCMDA SLAIKPVFER FQSVIITSGT LSPLDIYPKI LDFHPVTMAT 490 500 510 520 530 540 FTMTLARVCL CPMIIGRGND QVAISSKFET REDIAVIRNY GNLLLEMSAV VPDGIVAFFT 550 560 570 580 590 600 SYQYMESTVA SWYEQGILEN IQRNKLLFIE TQDGAETSVA LEKYQEACEN GRGAILLSVA 610 620 630 640 650 660 RGKVSEGIDF VHHYGRAVIM FGVPYVYTQS RILKARLEYL RDQFQIREND FLTFDAMRHA 670 680 690 700 710 720 AQCVGRAIRG KTDYGLMVFA DKRFARGDKR GKLPRWIQEH LTDANLNLTV DEGVQVAKYF 730 740 750 760 LRQMAQPFHR EDQLGLSLLS LEQLESEETL KRIEQIAQQL
	Isoform 2 [UniParc]. Checksum: D56A486AC3C9D222	FASTA	405	46,274
	10 20 30 40 50 60 MRELKRTLDA KGHGVLEMPS GTGKTVSLLA LIMAYQRAYP LEVTKLIYCS RTVPEIEKVI 70 80 90 100 110 120 EELRKLLNFY EKQEGEKLPF LGLALSSRKN LCIHPEVTPL RFGKDVDGKC HSLTASYVRA 130 140 150 160 170 180 QYQHDTSLPH CRFYEEFDAH GREVPLPAGI YNLDDLKALG RRQGWCPYFL ARYSILHANV 190 200 210 220 230 240 VVYSYHYLLD PKIADLVSKE LARKAVVVFD EAHNIDNVCI DSMSVNLTRR TLDRCQGNLE 250 260 270 280 290 300 TLQKTVLRIK ETDEQRLRDE YRRLVEGLRE ASAARETDAH LANPVLPDEV LQEAVPGSIR 310 320 330 340 350 360 TAEHFLGFLR RLLEYVKWRL RVQHVVQESP PAFLSGLAQR VCIQRKPLRF CAERLRSLLH 370 380 390 400 TLEITDLADF SPLTLLANFA TLVSTYAKGQ AQHCGSSRNQ KRSHP

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"ERCC2: cDNA cloning and molecular characterization of a human nucleotide excision repair gene with high homology to yeast RAD3." Weber C.A., Salazar E.P., Stewart S.A., Thompson L.H. EMBO J. 9:1437-1447(1990) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). Tissue: Fibroblast.
[2]	"Sequence analysis of the ERCC2 gene regions in human, mouse, and hamster reveals three linked genes." Lamerdin J.E., Stilwagen S.A., Ramirez M.H., Stubbs L., Carrano A.V. Genomics 34:399-409(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Tissue: Fibroblast.
[3]	NIEHS SNPs program Submitted (MAR-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ASN-312 AND GLN-751.
[4]	"Cloning of human full-length CDSs in BD Creator(TM) system donor vector." Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A. Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
[5]	Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C. Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA], VARIANT GLN-751.
[6]	"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)." The MGC Project Team Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT GLN-751. Tissue: Testis.
[7]	"Correction of Xeroderma pigmentosum complementation group D mutant cell phenotypes by chromosome and gene transfer: involvement of the human ERCC2 DNA repair gene." Fletjer W.L., McDaniel L.D., Johns D., Friedberg E.C., Schultz R.A. Proc. Natl. Acad. Sci. U.S.A. 89:261-265(1992) [PubMed] [Europe PMC] [Abstract] Cited for: CHARACTERIZATION.
[8]	"Human Xeroderma pigmentosum group D gene encodes a DNA helicase." Sung P., Bailly V., Weber C.A., Thompson L.H., Prakash L., Prakash S. Nature 365:852-855(1993) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION.
[9]	"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. 92:3259-3263(1995) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH EBV EBNA2.
[10]	"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 S.-Y., Chiang C.-M. J. Biol. Chem. 273:34444-34453(1998) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION IN THE TFIIH BASAL TRANSCRIPTION FACTOR.
[11]	"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 J.-C., Rodolfo C., Fribourg S., Pedrini A.M., Egly J.-M. Nat. Genet. 20:184-188(1998) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH GTF2H2.
[12]	"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 J.-M. Mol. Cell 3:87-95(1999) [PubMed] [Europe PMC] [Abstract] Cited for: MUTAGENESIS OF LYS-48, FUNCTION.
[13]	"Selective regulation of vitamin D receptor-responsive genes by TFIIH." Drane P., Compe E., Catez P., Chymkowitch P., Egly J.-M. Mol. Cell 16:187-197(2004) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, POSSIBLE PATHOLOGICAL MECHANISM OF VARIANT XP-D TRP-683.
[14]	"Identification and Herc5-mediated ISGylation of novel target proteins." Takeuchi T., Inoue S., Yokosawa H. Biochem. Biophys. Res. Commun. 348:473-477(2006) [PubMed] [Europe PMC] [Abstract] Cited for: ISGYLATION.
[15]	"MCAF1/AM is involved in Sp1-mediated maintenance of cancer-associated telomerase activity." Liu L., Ishihara K., Ichimura T., Fujita N., Hino S., Tomita S., Watanabe S., Saitoh N., Ito T., Nakao M. J. Biol. Chem. 284:5165-5174(2009) [PubMed] [Europe PMC] [Abstract] Cited for: INTERACTION WITH ATF7IP.
[16]	"MMXD, a TFIIH-independent XPD-MMS19 protein complex involved in chromosome segregation." Ito S., Tan L.J., Andoh D., Narita T., Seki M., Hirano Y., Narita K., Kuraoka I., Hiraoka Y., Tanaka K. Mol. Cell 39:632-640(2010) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, IDENTIFICATION IN MMXD COMPLEX, INTERACTION WITH FAM196B, SUBCELLULAR LOCATION.
[17]	"Initial characterization of the human central proteome." Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J. BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]	"MMS19 links cytoplasmic iron-sulfur cluster assembly to DNA metabolism." Gari K., Leon Ortiz A.M., Borel V., Flynn H., Skehel J.M., Boulton S.J. Science 337:243-245(2012) [PubMed] [Europe PMC] [Abstract] Cited for: IRON-SULFUR-BINDING, COFACTOR, MUTAGENESIS OF CYS-190.
[19]	"Structural and mutational analysis of the xeroderma pigmentosum group D (XPD) gene." Frederick G.D., Amirkhan R.H., Schultz R.A., Friedberg E.C. Hum. Mol. Genet. 3:1783-1788(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XP-D VAL-461.
[20]	"Mutations in the xeroderma pigmentosum group D DNA repair/transcription gene in patients with trichothiodystrophy." Broughton B.C., Steingrimsdottir H., Weber C.A., Lehmann A.R. Nat. Genet. 7:189-194(1994) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TTDP HIS-112; PRO-616; TRP-722 AND 488-VAL--MET-493 DEL.
[21]	"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 B.C., Thompson A.F., Harcourt S.A., Vermeulen W., Hoeijmakers J.H.J., Botta E., Stefanini M., King M.D., Weber C.A., Cole J., Arlett C.F., Lehmann A.R. Am. J. Hum. Genet. 56:167-174(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XP-D ARG-675.
[22]	"Defects in the DNA repair and transcription gene ERCC2 in the cancer-prone disorder xeroderma pigmentosum group D." Takayama K., Salazar E.P., Lehmann A.R., Stefanini M., Thompson L.H., Weber C.A. Cancer Res. 55:5656-5663(1995) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XP-D.
[23]	"Defects in the DNA repair and transcription gene ERCC2(XPD) in trichothiodystrophy." Takayama K., Salazar E.P., Broughton B.C., Lehmann A.R., Sarasin A., Thompson L.H., Weber C.A. Am. J. Hum. Genet. 58:263-270(1996) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TTDP CYS-658 AND ARG-713.
[24]	"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. 9:322-331(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT XP-D ARG-541.
[25]	"DNA repair characteristics and mutations in the ERCC2 DNA repair and transcription gene in a trichothiodystrophy patient." Takayama K., Danks D.M., Salazar E.P., Cleaver J.E., Weber C.A. Hum. Mutat. 9:519-525(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TTDP VAL-461; 716-VAL--ARG-730 DEL AND PRO-725.
[26]	"Xeroderma pigmentosum and trichothiodystrophy are associated with different mutations in the XPD (ERCC2) repair/transcription gene." Taylor E.M., Broughton B.C., Botta E., Stefanini M., Sarasin A., Jaspers N.G.J., Fawcett H., Harcourt S.A., Arlett C.F., Lehmann A.R. Proc. Natl. Acad. Sci. U.S.A. 94:8658-8663(1997) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TTDP/XP.
[27]	"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 B.C., Marinoni S., Lehmann A.R., Stefanini M. Am. J. Hum. Genet. 63:1036-1048(1998) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TTDP HIS-112; TYR-259; VAL-461; THR-482 DEL; GLY-673 AND TRP-722.
[28]	"A summary of mutations in the UV-sensitive disorders: xeroderma pigmentosum, Cockayne syndrome, and trichothiodystrophy." Cleaver J.E., Thompson L.H., Richardson A.S., States J.C. Hum. Mutat. 14:9-22(1999) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS XP-D.
[29]	"Cerebro-oculo-facio-skeletal syndrome with a nucleotide excision-repair defect and a mutated XPD gene, with prenatal diagnosis in a triplet pregnancy." Graham J.M. Jr., Anyane-Yeboa K., Raams A., Appeldoorn E., Kleijer W.J., Garritsen V.H., Busch D., Edersheim T.G., Jaspers N.G.J. Am. J. Hum. Genet. 69:291-300(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS COFS2 TRP-616 AND ASN-681.
[30]	"Associations between ercc2 polymorphisms and gliomas." Caggana M., Kilgallen J., Conroy J.M., Wiencke J.K., Kelsey K.T., Miike R., Chen P., Wrensch M.R. Cancer Epidemiol. Biomarkers Prev. 10:355-360(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANT CYS-616.
[31]	"Modulation of nucleotide excision repair capacity by XPD polymorphisms in lung cancer patients." Spitz M.R., Wu X., Wang Y., Wang L.E., Shete S., Amos C.I., Guo Z., Lei L., Mohrenweiser H., Wei Q. Cancer Res. 61:1354-1357(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASN-312 AND GLN-751.
[32]	"XPD exon 10 and 23 polymorphisms and DNA repair in human skin in situ." Hemminki K., Xu G., Angelini S., Snellman E., Jansen C.T., Lambert B., Hou S.M. Carcinogenesis 22:1185-1188(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS ASN-312 AND GLN-751.
[33]	"The xeroderma pigmentosum group D (XPD) gene: one gene, two functions, three diseases." Lehmann A.R. Genes Dev. 15:15-23(2001) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW ON VARIANTS.
[34]	"Two individuals with features of both xeroderma pigmentosum and trichothiodystrophy highlight the complexity of the clinical outcomes of mutations in the XPD gene." Broughton B.C., Berneburg M., Fawcett H., Taylor E.M., Arlett C.F., Nardo T., Stefanini M., Menefee E., Price V.H., Queille S., Sarasin A., Bohnert E., Krutmann J., Davidson R., Kraemer K.H., Lehmann A.R. Hum. Mol. Genet. 10:2539-2547(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS XP-D HIS-112; PRO-485 AND 582-GLU-LYS-583 DELINS VAL-SER-GLU, VARIANTS ASN-312 AND GLN-751.
[35]	"A temperature-sensitive disorder in basal transcription and DNA repair in humans." Vermeulen W., Rademakers S., Jaspers N.G.J., Appeldoorn E., Raams A., Klein B., Kleijer W.J., Hansen L.K., Hoeijmakers J.H.J. Nat. Genet. 27:299-303(2001) [PubMed] [Europe PMC] [Abstract] Cited for: VARIANTS TTDP CYS-658 AND ARG-713.
+	Additional computationally mapped references.

Web resources

Allelic variations of the XP genes

Atlas of Genetics and Cytogenetics in Oncology and Haematology

GeneReviews

NIEHS-SNPs

Cross-references

Sequence databases
EMBL GenBank DDBJ	X52221 mRNA. Translation: CAA36463.1. X52222 mRNA. Translation: CAA36464.1. L47234 Genomic DNA. Translation: AAL48323.1. AY092780 Genomic DNA. Translation: AAM45142.1. Sequence problems. BT006883 mRNA. Translation: AAP35529.1. CH471126 Genomic DNA. Translation: EAW57341.1. BC108255 mRNA. Translation: AAI08256.1. BC110523 mRNA. Translation: AAI10524.1.
IPI	IPI00029728. IPI00984321.
PIR	S10888.
RefSeq	NP_000391.1. NM_000400.3. NP_001124339.1. NM_001130867.1.
UniGene	Hs.487294.
3D structure databases
ProteinModelPortal	P18074.
ModBase	Search...
Protein-protein interaction databases
DIP	DIP-644N.
STRING	9606.ENSP00000375809.
PTM databases
PhosphoSite	P18074.
Polymorphism databases
DMDM	119540.
Proteomic databases
PaxDb	P18074.
PRIDE	P18074.
Protocols and materials databases
DNASU	2068.
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENST00000391940; ENSP00000375804; ENSG00000104884. ENST00000391945; ENSP00000375809; ENSG00000104884. ENST00000485403; ENSP00000431229; ENSG00000104884.
GeneID	2068.
KEGG	hsa:2068.
UCSC	uc002pbj.2. human.
Organism-specific databases
CTD	2068.
GeneCards	GC19M045854.
HGNC	HGNC:3434. ERCC2.
HPA	CAB005375.
MIM	126340. gene. 278730. phenotype. 601675. phenotype. 610756. phenotype.
neXtProt	NX_P18074.
Orphanet	231256. Beta-thalassemia - trichothiodystrophy. 1466. COFS syndrome. 453. IBIDS syndrome. 670. PIBIDS syndrome. 276258. Xeroderma pigmentosum complementation group D. 220295. Xeroderma pigmentosum/Cockayne syndrome complex.
PharmGKB	PA27848.
GenAtlas	Search...
Phylogenomic databases
eggNOG	COG1199.
HOGENOM	HOG000205390.
HOVERGEN	HBG051498.
InParanoid	P18074.
KO	K10844.
OMA	KDVDGKC.
OrthoDB	EOG4BVRT2.
PhylomeDB	P18074.
Enzyme and pathway databases
Reactome	REACT_116125. Disease. REACT_1675. mRNA Processing. REACT_1788. Transcription. REACT_216. DNA Repair. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P18074.
Bgee	P18074.
CleanEx	HS_ERCC2.
Genevestigator	P18074.
GermOnline	ENSG00000104884. Homo sapiens.
Family and domain databases
InterPro	IPR006555. ATP-dep_Helicase_C. IPR010614. DEAD_2. IPR002464. DNA/RNA_helicase_DEAH_CS. IPR013020. DNA_helicase_DNA-repair_Rad3. IPR010643. DUF1227. IPR014013. Helic_SF1/SF2_ATP-bd_DinG/Rad3. IPR006554. Helicase-like_DEXD_c2. IPR001945. XPGD_DNA_repair. [Graphical view]
Pfam	PF06733. DEAD_2. 1 hit. PF06777. DUF1227. 1 hit. PF13307. Helicase_C_2. 1 hit. [Graphical view]
PRINTS	PR00852. XRODRMPGMNTD.
SMART	SM00488. DEXDc2. 1 hit. SM00491. HELICc2. 1 hit. [Graphical view]
TIGRFAMs	TIGR00604. rad3. 1 hit.
PROSITE	PS00690. DEAH_ATP_HELICASE. 1 hit. PS51193. HELICASE_ATP_BIND_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
ChiTaRS	ERCC2. human.
GenomeRNAi	2068.
NextBio	8409.
SOURCE	Search...

Entry information

Entry name

ERCC2_HUMAN

Accession

Primary (citable) accession number: P18074
Secondary accession number(s): Q2TB78 , Q2YDY2, Q7KZU6, Q8N721

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1990
Last sequence update:	November 1, 1990
Last modified:	May 1, 2013
This is version 164 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.