Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

General transcription and DNA repair factor IIH helicase subunit XPB

Gene

ERCC3

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

ATP-dependent 3'-5' 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 ATPase activity of XPB/ERCC3, but not its helicase activity, 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. The ATP-dependent helicase activity of XPB/ERCC3 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.2 Publications

Catalytic activityi

ATP + H2O = ADP + phosphate.

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Nucleotide bindingi340 – 347ATPPROSITE-ProRule annotation8

GO - Molecular functioni

  • 3'-5' DNA helicase activity Source: UniProtKB
  • ATPase activity Source: UniProtKB
  • ATP binding Source: UniProtKB-KW
  • ATP-dependent DNA helicase activity Source: InterPro
  • damaged DNA binding Source: UniProtKB
  • DNA binding Source: UniProtKB
  • helicase activity Source: Reactome
  • protein C-terminus binding Source: UniProtKB
  • protein N-terminus binding Source: UniProtKB
  • transcription factor binding Source: MGI

GO - Biological processi

  • 7-methylguanosine mRNA capping Source: Reactome
  • apoptotic process Source: UniProtKB
  • DNA repair Source: UniProtKB
  • DNA topological change Source: UniProtKB
  • embryonic organ development Source: Ensembl
  • global genome nucleotide-excision repair Source: Reactome
  • hair cell differentiation Source: UniProtKB
  • nucleotide-excision repair Source: UniProtKB
  • nucleotide-excision repair, DNA duplex unwinding Source: UniProtKB
  • nucleotide-excision repair, DNA incision Source: UniProtKB
  • nucleotide-excision repair, DNA incision, 5'-to lesion Source: Reactome
  • nucleotide-excision repair, preincision complex assembly Source: Reactome
  • nucleotide-excision repair, preincision complex stabilization Source: Reactome
  • positive regulation of apoptotic process Source: UniProtKB
  • positive regulation of transcription by RNA polymerase II Source: UniProtKB
  • protein localization Source: UniProtKB
  • protein phosphorylation Source: GOC
  • regulation of mitotic cell cycle phase transition Source: UniProtKB
  • response to hypoxia Source: Ensembl
  • response to oxidative stress Source: UniProtKB
  • response to UV Source: UniProtKB
  • termination of RNA polymerase I transcription Source: Reactome
  • transcription by RNA polymerase II Source: UniProtKB
  • transcription-coupled nucleotide-excision repair Source: UniProtKB
  • transcription elongation from RNA polymerase II promoter Source: Reactome
  • transcription initiation from RNA polymerase II promoter Source: Reactome
  • transcription initiation from RNA polymerase I promoter Source: Reactome
  • UV protection Source: Ensembl
  • viral process Source: UniProtKB-KW

Keywordsi

Molecular functionDNA-binding, Helicase, Hydrolase
Biological processDNA damage, DNA repair, Host-virus interaction, Transcription, Transcription regulation
LigandATP-binding, Nucleotide-binding

Enzyme and pathway databases

ReactomeiR-HSA-112382 Formation of RNA Pol II elongation complex
R-HSA-113418 Formation of the Early Elongation Complex
R-HSA-167152 Formation of HIV elongation complex in the absence of HIV Tat
R-HSA-167158 Formation of the HIV-1 Early Elongation Complex
R-HSA-167160 RNA Pol II CTD phosphorylation and interaction with CE during HIV infection
R-HSA-167161 HIV Transcription Initiation
R-HSA-167162 RNA Polymerase II HIV Promoter Escape
R-HSA-167172 Transcription of the HIV genome
R-HSA-167200 Formation of HIV-1 elongation complex containing HIV-1 Tat
R-HSA-167246 Tat-mediated elongation of the HIV-1 transcript
R-HSA-427413 NoRC negatively regulates rRNA expression
R-HSA-5696395 Formation of Incision Complex in GG-NER
R-HSA-5696400 Dual Incision in GG-NER
R-HSA-674695 RNA Polymerase II Pre-transcription Events
R-HSA-6781823 Formation of TC-NER Pre-Incision Complex
R-HSA-6781827 Transcription-Coupled Nucleotide Excision Repair (TC-NER)
R-HSA-6782135 Dual incision in TC-NER
R-HSA-6782210 Gap-filling DNA repair synthesis and ligation in TC-NER
R-HSA-6796648 TP53 Regulates Transcription of DNA Repair Genes
R-HSA-72086 mRNA Capping
R-HSA-73762 RNA Polymerase I Transcription Initiation
R-HSA-73772 RNA Polymerase I Promoter Escape
R-HSA-73776 RNA Polymerase II Promoter Escape
R-HSA-73777 RNA Polymerase I Chain Elongation
R-HSA-73779 RNA Polymerase II Transcription Pre-Initiation And Promoter Opening
R-HSA-73863 RNA Polymerase I Transcription Termination
R-HSA-75953 RNA Polymerase II Transcription Initiation
R-HSA-75955 RNA Polymerase II Transcription Elongation
R-HSA-76042 RNA Polymerase II Transcription Initiation And Promoter Clearance
R-HSA-77075 RNA Pol II CTD phosphorylation and interaction with CE
SIGNORiP19447

Names & Taxonomyi

Protein namesi
Recommended name:
General transcription and DNA repair factor IIH helicase subunit XPB (EC:3.6.4.12)
Short name:
TFIIH subunit XPB
Alternative name(s):
Basic transcription factor 2 89 kDa subunit
Short name:
BTF2 p89
DNA excision repair protein ERCC-3
DNA repair protein complementing XP-B cells
TFIIH basal transcription factor complex 89 kDa subunit
Short name:
TFIIH 89 kDa subunit
Short name:
TFIIH p89
Xeroderma pigmentosum group B-complementing protein
Gene namesi
Name:ERCC3
Synonyms:XPB, XPBC
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

EuPathDBiHostDB:ENSG00000163161.12
HGNCiHGNC:3435 ERCC3
MIMi133510 gene
neXtProtiNX_P19447

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Keywords - Cellular componenti

Nucleus

Pathology & Biotechi

Involvement in diseasei

Xeroderma pigmentosum complementation group B (XP-B)3 Publications
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionAn 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-B 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.
See also OMIM:610651
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00363299F → S in XP-B; combined with features of Cockayne syndrome; mild. 2 PublicationsCorresponds to variant dbSNP:rs121913045EnsemblClinVar.1
Trichothiodystrophy 2, photosensitive (TTD2)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionA form of trichothiodystrophy, an autosomal recessive disease characterized by sulfur-deficient brittle hair and multisystem variable abnormalities. The spectrum of clinical features varies from mild disease with only hair involvement to severe disease with cutaneous, neurologic and profound developmental defects. Ichthyosis, intellectual and developmental disabilities, decreased fertility, abnormal characteristics at birth, ocular abnormalities, short stature, and infections are common manifestations. There are both photosensitive and non-photosensitive forms of the disorder.
See also OMIM:616390
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_008186119T → P in TTD2; mild. 1 PublicationCorresponds to variant dbSNP:rs121913046EnsemblClinVar.1

Mutagenesis

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Mutagenesisi346K → R: No transcriptional activity of the reconstituted TFIIH complex. 1 Publication1
Mutagenesisi782Missing : Impairs protein folding. 1 Publication1

Keywords - Diseasei

Cockayne syndrome, Deafness, Disease mutation, Dwarfism, Ichthyosis, Xeroderma pigmentosum

Organism-specific databases

DisGeNETi2071
GeneReviewsiERCC3
MalaCardsiERCC3
MIMi610651 phenotype
616390 phenotype
OpenTargetsiENSG00000163161
Orphaneti33364 Trichothiodystrophy
276252 Xeroderma pigmentosum complementation group B
PharmGKBiPA27849

Polymorphism and mutation databases

BioMutaiERCC3
DMDMi119541

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00001019871 – 782General transcription and DNA repair factor IIH helicase subunit XPBAdd BLAST782

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei686PhosphoserineCombined sources1

Keywords - PTMi

Phosphoprotein

Proteomic databases

EPDiP19447
MaxQBiP19447
PaxDbiP19447
PeptideAtlasiP19447
PRIDEiP19447

PTM databases

iPTMnetiP19447
PhosphoSitePlusiP19447

Expressioni

Gene expression databases

BgeeiENSG00000163161
CleanExiHS_ERCC3
ExpressionAtlasiP19447 baseline and differential
GenevisibleiP19447 HS

Organism-specific databases

HPAiCAB037153
HPA046077

Interactioni

Subunit structurei

Component of the 7-subunit TFIIH core complex composed of XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which is active in NER. The core complex associates with the 3-subunit CDK-activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in transcription. Interacts with PUF60. Interacts with ATF7IP. Interacts with Epstein-Barr virus EBNA2.4 Publications
(Microbial infection) Interacts with Epstein-Barr virus EBNA2.1 Publication

Binary interactionsi

Show more details

GO - Molecular functioni

  • protein C-terminus binding Source: UniProtKB
  • protein N-terminus binding Source: UniProtKB
  • transcription factor binding Source: MGI

Protein-protein interaction databases

BioGridi108383, 61 interactors
CORUMiP19447
DIPiDIP-83N
IntActiP19447, 37 interactors
MINTiP19447
STRINGi9606.ENSP00000285398

Structurei

Secondary structure

1782
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi505 – 512Combined sources8
Helixi516 – 524Combined sources9
Helixi528 – 530Combined sources3
Helixi531 – 536Combined sources6
Helixi538 – 552Combined sources15
Turni553 – 555Combined sources3
Beta strandi558 – 561Combined sources4
Helixi565 – 574Combined sources10
Helixi586 – 598Combined sources13
Beta strandi604 – 607Combined sources4
Helixi609 – 611Combined sources3
Turni612 – 614Combined sources3
Beta strandi620 – 626Combined sources7
Helixi633 – 643Combined sources11
Beta strandi651 – 654Combined sources4
Beta strandi656 – 664Combined sources9
Helixi668 – 670Combined sources3
Helixi671 – 682Combined sources12
Beta strandi686 – 692Combined sources7
Helixi696 – 698Combined sources3
Helixi706 – 718Combined sources13
Helixi721 – 724Combined sources4

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
4ERNX-ray1.80A494-782[»]
5IVWelectron microscopy10.00V1-782[»]
5IY6electron microscopy7.20V1-782[»]
5IY7electron microscopy8.60V1-782[»]
5IY8electron microscopy7.90V1-782[»]
5IY9electron microscopy6.30V1-782[»]
5OF4electron microscopy4.40A265-782[»]
ProteinModelPortaliP19447
SMRiP19447
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini327 – 488Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST162
Domaini542 – 702Helicase C-terminalPROSITE-ProRule annotationAdd BLAST161

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi6 – 18Nuclear localization signalSequence analysisAdd BLAST13
Motifi441 – 444DEVH box4

Compositional bias

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Compositional biasi20 – 28Asp/Glu-rich (acidic)9
Compositional biasi256 – 265Asp/Glu-rich (acidic)10
Compositional biasi697 – 700Asp/Glu-rich (acidic)4
Compositional biasi721 – 728Asp/Glu-rich (acidic)8

Sequence similaritiesi

Belongs to the helicase family. RAD25/XPB subfamily.Curated

Phylogenomic databases

eggNOGiKOG1123 Eukaryota
COG1061 LUCA
GeneTreeiENSGT00390000002204
HOGENOMiHOG000160172
HOVERGENiHBG051499
InParanoidiP19447
KOiK10843
OMAiTKHVHPL
OrthoDBiEOG091G0291
PhylomeDBiP19447
TreeFamiTF101233

Family and domain databases

CDDicd00079 HELICc, 1 hit
InterProiView protein in InterPro
IPR032438 ERCC3_RAD25_C
IPR006935 Helicase/UvrB_N
IPR014001 Helicase_ATP-bd
IPR001650 Helicase_C
IPR027417 P-loop_NTPase
IPR001161 XPB/Ssl2
IPR032830 XPB/Ssl2_N
PfamiView protein in Pfam
PF16203 ERCC3_RAD25_C, 1 hit
PF13625 Helicase_C_3, 1 hit
PF04851 ResIII, 1 hit
SMARTiView protein in SMART
SM00487 DEXDc, 1 hit
SM00490 HELICc, 1 hit
SUPFAMiSSF52540 SSF52540, 3 hits
TIGRFAMsiTIGR00603 rad25, 1 hit
PROSITEiView protein in PROSITE
PS51192 HELICASE_ATP_BIND_1, 1 hit
PS51194 HELICASE_CTER, 1 hit

Sequencei

Sequence statusi: Complete.

P19447-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MGKRDRADRD KKKSRKRHYE DEEDDEEDAP GNDPQEAVPS AAGKQVDESG
60 70 80 90 100
TKVDEYGAKD YRLQMPLKDD HTSRPLWVAP DGHIFLEAFS PVYKYAQDFL
110 120 130 140 150
VAIAEPVCRP THVHEYKLTA YSLYAAVSVG LQTSDITEYL RKLSKTGVPD
160 170 180 190 200
GIMQFIKLCT VSYGKVKLVL KHNRYFVESC HPDVIQHLLQ DPVIRECRLR
210 220 230 240 250
NSEGEATELI TETFTSKSAI SKTAESSGGP STSRVTDPQG KSDIPMDLFD
260 270 280 290 300
FYEQMDKDEE EEEETQTVSF EVKQEMIEEL QKRCIHLEYP LLAEYDFRND
310 320 330 340 350
SVNPDINIDL KPTAVLRPYQ EKSLRKMFGN GRARSGVIVL PCGAGKSLVG
360 370 380 390 400
VTAACTVRKR CLVLGNSAVS VEQWKAQFKM WSTIDDSQIC RFTSDAKDKP
410 420 430 440 450
IGCSVAISTY SMLGHTTKRS WEAERVMEWL KTQEWGLMIL DEVHTIPAKM
460 470 480 490 500
FRRVLTIVQA HCKLGLTATL VREDDKIVDL NFLIGPKLYE ANWMELQNNG
510 520 530 540 550
YIAKVQCAEV WCPMSPEFYR EYVAIKTKKR ILLYTMNPNK FRACQFLIKF
560 570 580 590 600
HERRNDKIIV FADNVFALKE YAIRLNKPYI YGPTSQGERM QILQNFKHNP
610 620 630 640 650
KINTIFISKV GDTSFDLPEA NVLIQISSHG GSRRQEAQRL GRVLRAKKGM
660 670 680 690 700
VAEEYNAFFY SLVSQDTQEM AYSTKRQRFL VDQGYSFKVI TKLAGMEEED
710 720 730 740 750
LAFSTKEEQQ QLLQKVLAAT DLDAEEEVVA GEFGSRSSQA SRRFGTMSSM
760 770 780
SGADDTVYME YHSSRSKAPS KHVHPLFKRF RK
Length:782
Mass (Da):89,278
Last modified:February 1, 1991 - v1
Checksum:iF5F4D3A89A7DF826
GO

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural variantiVAR_00363299F → S in XP-B; combined with features of Cockayne syndrome; mild. 2 PublicationsCorresponds to variant dbSNP:rs121913045EnsemblClinVar.1
Natural variantiVAR_014766117K → R1 PublicationCorresponds to variant dbSNP:rs1805161EnsemblClinVar.1
Natural variantiVAR_008186119T → P in TTD2; mild. 1 PublicationCorresponds to variant dbSNP:rs121913046EnsemblClinVar.1
Natural variantiVAR_014767402G → C1 PublicationCorresponds to variant dbSNP:rs1805162Ensembl.1
Natural variantiVAR_035942418K → Q in a breast cancer sample; somatic mutation. 1 Publication1
Natural variantiVAR_017294704S → L1 PublicationCorresponds to variant dbSNP:rs4150521EnsemblClinVar.1
Natural variantiVAR_014344735S → P1 PublicationCorresponds to variant dbSNP:rs4150522Ensembl.1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M31899 mRNA Translation: AAA52396.1
AY163769 Genomic DNA Translation: AAN46739.1
AC110926 Genomic DNA Translation: AAY15069.1
CH471103 Genomic DNA Translation: EAW95313.1
BC008820 mRNA Translation: AAH08820.1
CCDSiCCDS2144.1
PIRiA35661
RefSeqiNP_000113.1, NM_000122.1
UniGeneiHs.469872

Genome annotation databases

EnsembliENST00000285398; ENSP00000285398; ENSG00000163161
GeneIDi2071
KEGGihsa:2071
UCSCiuc002toh.1 human

Keywords - Coding sequence diversityi

Polymorphism

Similar proteinsi

Entry informationi

Entry nameiERCC3_HUMAN
AccessioniPrimary (citable) accession number: P19447
Secondary accession number(s): Q53QM0
Entry historyiIntegrated into UniProtKB/Swiss-Prot: February 1, 1991
Last sequence update: February 1, 1991
Last modified: May 23, 2018
This is version 207 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny 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.

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. SIMILARITY comments
    Index of protein domains and families

Cookie policy

We would like to use anonymized google analytics cookies to gather statistics on how uniprot.org is used in aggregate. Learn more

UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health