Reviewed, UniProtKB/Swiss-Prot P19447 (ERCC3_HUMAN)

Names and origin

Protein names

Recommended name:
    TFIIH basal transcription factor complex helicase XPB subunit
    EC=3.6.1.-
Alternative name(s):
    Basic transcription factor 2 89 kDa subunit
    BTF2-p89
    TFIIH 89 kDa subunit
    DNA repair protein complementing XP-B cells
    Xeroderma pigmentosum group B-complementing protein
    DNA excision repair protein ERCC-3

Gene names

Name:	ERCC3
Synonyms:	XPB, XPBC

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

Protein attributes

Sequence length	782 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

General annotation (Comments)

Function	ATP-dependent 3'-5' DNA helicase, component of the core-TFIIH basal transcription factor, involved in nucleotide excision repair (NER) of DNA and, when complexed to CAK, in RNA transcription by RNA polymerase II. Acts by opening DNA either around the RNA transcription start site or the DNA damage. Ref.8
Subunit structure	One of the six subunits forming the core-TFIIH basal transcription factor. Interacts with PUF60. Interacts with Epstein-Barr virus EBNA2. Ref.9 Ref.10
Subcellular location	Nucleus.
Involvement in disease	Defects in ERCC3 are the cause of xeroderma pigmentosum complementation group B (XP-B) [MIM:610651]; also known as xeroderma pigmentosum II (XP2) or XP group B (XPB) or xeroderma pigmentosum group B combined with Cockayne syndrome (XP-B/CS). 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-B patients present features of Cockayne syndrome, including dwarfism, sensorineural deafness, microcephaly, mental retardation, pigmentary retinopathy, ataxia, decreased nerve conduction velocities. Ref.13 Ref.16 Defects in ERCC3 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. Ref.14
Sequence similarities	Belongs to the helicase family. RAD25/XPB subfamily. Contains 1 helicase ATP-binding domain. Contains 1 helicase C-terminal domain.

Ontologies

Keywords
Biological process	DNA damage DNA repair Host-virus interaction Transcription Transcription regulation
Cellular component	Nucleus
Coding sequence diversity	Polymorphism
Disease	Cockayne syndrome Deafness Disease mutation Dwarfism Ichthyosis Xeroderma pigmentosum
Ligand	ATP-binding DNA-binding Nucleotide-binding
Molecular function	Helicase Hydrolase
PTM	Phosphoprotein
Gene Ontology (GO)
Biological process	DNA topological change Inferred from mutant phenotype. Source: UniProtKB RNA elongation from RNA polymerase II promoter Inferred from Experiment. Source: Reactome cell cycle checkpoint Inferred from mutant phenotype. Source: UniProtKB hair cell differentiation Inferred from mutant phenotype. Source: UniProtKB induction of apoptosis Inferred from direct assay. Source: UniProtKB nucleotide-excision repair, DNA damage removal Inferred from Experiment. Source: Reactome nucleotide-excision repair, DNA duplex unwinding Inferred from mutant phenotype. Source: UniProtKB nucleotide-excision repair, DNA incision Inferred from mutant phenotype. Source: UniProtKB positive regulation of transcription from RNA polymerase II promoter Inferred from direct assay. Source: UniProtKB protein localization Inferred from mutant phenotype. Source: UniProtKB response to oxidative stress Inferred from mutant phenotype. Source: UniProtKB sensory perception of sound Inferred from electronic annotation. Source: UniProtKB-KW transcription initiation from RNA polymerase II promoter Inferred from Experiment. Source: Reactome transcription-coupled nucleotide-excision repair Inferred from direct assay. Source: UniProtKB
Cellular component	holo TFIIH complex Inferred from direct assay. Source: UniProtKB
Molecular function	3'-5' DNA helicase activity Inferred from direct assay. Source: UniProtKB ATP binding Inferred from electronic annotation. Source: UniProtKB-KW ATP-dependent DNA helicase activity Inferred from electronic annotation. Source: InterPro damaged DNA binding Ref.2 Non-traceable author statement. Source: UniProtKB protein C-terminus binding Inferred from physical interaction. Source: UniProtKB protein N-terminus binding Inferred from physical interaction. Source: UniProtKB transcription factor binding Inferred from direct assay. Source: MGI
Complete GO annotation...

Binary interactions

With	Entry	#Exp.	IntAct	Notes
PSMC5	P62195	1	EBI-1183307,EBI-357745
Psmc5	P62196	5	EBI-1183307,EBI-357713	From a different organism.

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 782	782	TFIIH basal transcription factor complex helicase XPB subunit		PRO_0000101987
Regions
	Domain	327 – 488	162	Helicase ATP-binding
	Domain	542 – 702	161	Helicase C-terminal
	Nucleotide binding	340 – 347	8	ATP By similarity
	Motif	6 – 18	13	Nuclear localization signal Potential
	Motif	441 – 444	4	DEVH box
	Compositional bias	20 – 28	9	Asp/Glu-rich (acidic)
	Compositional bias	256 – 265	10	Asp/Glu-rich (acidic)
	Compositional bias	697 – 700	4	Asp/Glu-rich (acidic)
	Compositional bias	721 – 728	8	Asp/Glu-rich (acidic)
Amino acid modifications
	Modified residue	370	1	Phosphoserine Ref.12
Natural variations
	Natural variant	99	1	F → S in XP-B; combined with features of Cockayne syndrome; mild. Ref.13 Ref.16		VAR_003632
	Natural variant	117	1	K → R: dbSNP rs1805161. Ref.15		VAR_014766
	Natural variant	119	1	T → P in TTDP; mild. Ref.14		VAR_008186
	Natural variant	402	1	G → C: dbSNP rs1805162. Ref.15		VAR_014767
	Natural variant	418	1	K → Q in a breast cancer sample; somatic mutation. Ref.17		VAR_035942
	Natural variant	704	1	S → L: dbSNP rs4150521. Ref.4		VAR_017294
	Natural variant	735	1	S → P: dbSNP rs4150522. Ref.4		VAR_014344
Experimental info
	Mutagenesis	346	1	K → R: No transcriptional activity of the reconstituted TFIIH complex. Ref.8

Sequences

	Sequence		Length	Mass (Da)
	P19447-1 [UniParc]. Last modified February 1, 1991. Version 1. Checksum: F5F4D3A89A7DF826	FASTA	782	89,278
	10 20 30 40 50 60 MGKRDRADRD KKKSRKRHYE DEEDDEEDAP GNDPQEAVPS AAGKQVDESG TKVDEYGAKD 70 80 90 100 110 120 YRLQMPLKDD HTSRPLWVAP DGHIFLEAFS PVYKYAQDFL VAIAEPVCRP THVHEYKLTA 130 140 150 160 170 180 YSLYAAVSVG LQTSDITEYL RKLSKTGVPD GIMQFIKLCT VSYGKVKLVL KHNRYFVESC 190 200 210 220 230 240 HPDVIQHLLQ DPVIRECRLR NSEGEATELI TETFTSKSAI SKTAESSGGP STSRVTDPQG 250 260 270 280 290 300 KSDIPMDLFD FYEQMDKDEE EEEETQTVSF EVKQEMIEEL QKRCIHLEYP LLAEYDFRND 310 320 330 340 350 360 SVNPDINIDL KPTAVLRPYQ EKSLRKMFGN GRARSGVIVL PCGAGKSLVG VTAACTVRKR 370 380 390 400 410 420 CLVLGNSAVS VEQWKAQFKM WSTIDDSQIC RFTSDAKDKP IGCSVAISTY SMLGHTTKRS 430 440 450 460 470 480 WEAERVMEWL KTQEWGLMIL DEVHTIPAKM FRRVLTIVQA HCKLGLTATL VREDDKIVDL 490 500 510 520 530 540 NFLIGPKLYE ANWMELQNNG YIAKVQCAEV WCPMSPEFYR EYVAIKTKKR ILLYTMNPNK 550 560 570 580 590 600 FRACQFLIKF HERRNDKIIV FADNVFALKE YAIRLNKPYI YGPTSQGERM QILQNFKHNP 610 620 630 640 650 660 KINTIFISKV GDTSFDLPEA NVLIQISSHG GSRRQEAQRL GRVLRAKKGM VAEEYNAFFY 670 680 690 700 710 720 SLVSQDTQEM AYSTKRQRFL VDQGYSFKVI TKLAGMEEED LAFSTKEEQQ QLLQKVLAAT 730 740 750 760 770 780 DLDAEEEVVA GEFGSRSSQA SRRFGTMSSM SGADDTVYME YHSSRSKAPS KHVHPLFKRF RK

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Molecular cloning and biological characterization of the human excision repair gene ERCC-3." Weeda G., van Ham R.C.A., Masurel R., Westerveld A., Odijk H., de Wit J., Bootsma D., van der Eb A.J., Hoeijmakers J.H.J. Mol. Cell. Biol. 10:2570-2581(1990) [PubMed: 2111438] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[2]	"A presumed DNA helicase encoded by ERCC-3 is involved in the human repair disorders Xeroderma pigmentosum and Cockayne's syndrome." Weeda G., van Ham R.C.A., Vermeulen W., Bootsma D., van der Eb A.J., Hoeijmakers J.H.J. Cell 62:777-791(1990) [PubMed: 2167179] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[3]	"Structure and expression of the human XPBC/ERCC-3 gene involved in DNA repair disorders xeroderma pigmentosum and Cockayne's syndrome." Weeda G., Ma L., van Ham R.C.A., van der Eb A.J., Hoeijmakers J.H.J. Nucleic Acids Res. 19:6301-6308(1991) [PubMed: 1956789] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[4]	NIEHS SNPs program Submitted (OCT-2002) to the EMBL/GenBank/DDBJ databases Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS LEU-704 AND PRO-735.
[5]	"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: 15489334] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA]. Tissue: Placenta.
[6]	"Correction of xeroderma pigmentosum repair defect by basal transcription factor BTF2 (TFIIH)." van Vuuren A.J., Vermeulen W., Ma L., Weeda G., Appeldoorn E., Jaspers N.G.J., van der Eb A.J., Bootsma D., Hoeijmakers J.H.J., Humbert S., Schaeffer L., Egly J.-M. EMBO J. 13:1645-1653(1994) [PubMed: 8157004] [Abstract] Cited for: INVOLVEMENT IN TRANSCRIPTION.
[7]	"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: 7724549] [Abstract] Cited for: INTERACTION WITH EBV EBNA2.
[8]	"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: 10024882] [Abstract] Cited for: MUTAGENESIS OF LYS-346, FUNCTION.
[9]	"The FBP interacting repressor targets TFIIH to inhibit activated transcription." Liu J., He L., Collins I., Ge H., Libutti D., Li J., Egly J.-M., Levens D. Mol. Cell 5:331-341(2000) [PubMed: 10882074] [Abstract] Cited for: INTERACTION WITH PUF60.
[10]	"Defective interplay of activators and repressors with TFIH in xeroderma pigmentosum." Liu J., Akoulitchev S., Weber A., Ge H., Chuikov S., Libutti D., Wang X.W., Conaway J.W., Harris C.C., Conaway R.C., Reinberg D., Levens D. Cell 104:353-363(2001) [PubMed: 11239393] [Abstract] Cited for: INTERACTION WITH PUF60.
[11]	"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: 10447254] [Abstract] Cited for: REVIEW ON VARIANTS XP-B.
[12]	"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks." Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M. Cell 127:635-648(2006) [PubMed: 17081983] [Abstract] Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-370, MASS SPECTROMETRY. Tissue: Epithelium.
[13]	"Clinical heterogeneity within xeroderma pigmentosum associated with mutations in the DNA repair and transcription gene ERCC3." Vermeulen W., Scott R.J., Rodgers S., Mueller H.J., Cole J., Arlett C.F., Kleijer W.J., Bootsma D., Hoeijmakers J.H.J., Weeda G. Am. J. Hum. Genet. 54:191-200(1994) [PubMed: 8304337] [Abstract] Cited for: VARIANT XP-B SER-99.
[14]	"A mutation in the XPB/ERCC3 DNA repair transcription gene, associated with trichothiodystrophy." Weeda G., Eveno E., Donker I., Vermeulen W., Chevallier-Lagente O., Taieb A., Stary A., Hoeijmakers J.H.J., Mezzina M., Sarasin A. Am. J. Hum. Genet. 60:320-329(1997) [PubMed: 9012405] [Abstract] Cited for: VARIANT TTDP PRO-119.
[15]	"Identification of four single nucleotide polymorphisms in DNA repair genes: XPA and XPB (ERCC3) in Polish population." Butkiewicz D., Rusin M., Harris C.C., Chorazy M. Hum. Mutat. 15:577-578(2000) [PubMed: 10862089] [Abstract] Cited for: VARIANTS ARG-117 AND CYS-402.
[16]	"Phenotypic heterogeneity in the XPB DNA helicase gene (ERCC3): xeroderma pigmentosum without and with Cockayne syndrome." Oh K.-S., Khan S.G., Jaspers N.G.J., Raams A., Ueda T., Lehmann A., Friedmann P.S., Emmert S., Gratchev A., Lachlan K., Lucassan A., Baker C.C., Kraemer K.H. Hum. Mutat. 27:1092-1103(2006) [PubMed: 16947863] [Abstract] Cited for: VARIANT XP-B SER-99.
[17]	"The consensus coding sequences of human breast and colorectal cancers." Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E. Science 314:268-274(2006) [PubMed: 16959974] [Abstract] Cited for: VARIANT [LARGE SCALE ANALYSIS] GLN-418.
+	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
EMBLGenBankDDBJ	M31899 mRNA. Translation: AAA52396.1. AY163769 Genomic DNA. Translation: AAN46739.1. BC008820 mRNA. Translation: AAH08820.1.
IPI	IPI00747053.
PIR	A35661.
RefSeq	NP_000113.1.
UniGene	Hs.469872
3D structure databases
ModBase	Search...
Protein-protein interaction databases
DIP	DIP:83N.
IntAct	P19447. 4 interactions.
PTM databases
PhosphoSite	P19447.
Proteomic databases
PRIDE	P19447.
Genome annotation databases
Ensembl	ENSG00000163161. Homo sapiens. [Contig view]
GeneID	2071.
KEGG	hsa:2071.
Organism-specific databases
GeneCards	GC02M127731.
H-InvDB	HIX0002431.
HGNC	HGNC:3435. ERCC3.
MIM	133510. gene. 601675. phenotype. 610651. phenotype.
Orphanet	453. IBIDS syndrome. 670. PIBIDS syndrome. 910. Xeroderma pigmentosum.
PharmGKB	PA27849.
GenAtlas	Search...
Phylogenomic databases
HOVERGEN	P19447.
OMA	P19447. IKLCTVS.
Enzyme and pathway databases
Reactome	REACT_1675. mRNA Processing. REACT_1788. Transcription. REACT_216. DNA Repair. REACT_6185. HIV Infection. REACT_71. Gene Expression.
Gene expression databases
ArrayExpress	P19447.
Bgee	P19447.
CleanEx	HS_ERCC3.
GermOnline	ENSG00000163161. Homo sapiens.
Family and domain databases
InterPro	IPR014001. DEAD-like_N. IPR001650. DNA/RNA_helicase_C. IPR014021. Helicase_SF1/SF2_ATP-bd. IPR006935. Restrct_endonuc_I_R/III_Res. IPR001161. XPGB_DNA_repair. [Graphical view]
Pfam	PF00271. Helicase_C. 1 hit. PF04851. ResIII. 1 hit. [Graphical view]
PRINTS	PR00851. XRODRMPGMNTB.
SMART	SM00487. DEXDc. 1 hit. SM00490. HELICc. 1 hit. [Graphical view]
TIGRFAMs	TIGR00603. rad25. 1 hit.
PROSITE	PS51192. HELICASE_ATP_BIND_1. 1 hit. PS51194. HELICASE_CTER. 1 hit. [Graphical view]
ProtoNet	Search...
Other Resources
NextBio	8425.
SOURCE	Search...

Entry information

Entry name

ERCC3_HUMAN

Accession

Primary (citable) accession number: P19447

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1991
Last sequence update:	February 1, 1991
Last modified:	June 16, 2009
This is version 115 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation project

HPI (Human Proteome Initiative)