ERCC3
entrez
2071
canonical
uniprot
P19447
canonical
ensembl
ENSG00000163161
resolver
ensp
ENSP00000285398
resolver
ensp
ENSP00000560248
resolver
enst
ENST00000285398
resolver
genesymbol
ERCC3
resolver
genesymbol_syn
XPB
resolver
genesymbol_syn
XPBC
resolver
hgnc
HGNC:3435
resolver
uniprot
B3KRG2
resolver
uniprot
B3KTH1
resolver
uniprot
Q53QM0
resolver
uniprot_entry
B3KRG2_HUMAN
resolver
uniprot_entry
B3KTH1_HUMAN
resolver
uniprot_entry
ERCC3_HUMAN
resolver
uniprot_sec
Q53QM0
resolver
activity_regulation
ACTIVITY REGULATION: Phosphorylation on Ser-751 by CK2 controls the 5'-excision activity of ERCC1-XPF endonuclease; phosphorylated protein inhibits the excision activity and thus NER (PubMed:15549133). ATPase activity is stimulated by TFIIH subunit p52 (GTF2H4) (PubMed:17466626). DNA translocase activity by this subunit in TFIIH is stimulated by XPA, ERCC5/XPG and XFP plus ERCC1; translocase activity is sensitive to triptolide which targets this enzyme (PubMed:31253769). {ECO:0000269|PubMed:15549133, ECO:0000269|PubMed:17466626, ECO:0000269|PubMed:31253769}.
uniprot
proteins
amino_acid_sequence
MGKRDRADRDKKKSRKRHYEDEEDDEEDAPGNDPQEAVPSAAGKQVDESGTKVDEYGAKDYRLQMPLKDDHTSRPLWVAPDGHIFLEAFSPVYKYAQDFLVAIAEPVCRPTHVHEYKLTAYSLYAAVSVGLQTSDITEYLRKLSKTGVPDGIMQFIKLCTVSYGKVKLVLKHNRYFVESCHPDVIQHLLQDPVIRECRLRNSEGEATELITETFTSKSAISKTAESSGGPSTSRVTDPQGKSDIPMDLFDFYEQMDKDEEEEEETQTVSFEVKQEMIEELQKRCIHLEYPLLAEYDFRNDSVNPDINIDLKPTAVLRPYQEKSLRKMFGNGRARSGVIVLPCGAGKSLVGVTAACTVRKRCLVLGNSAVSVEQWKAQFKMWSTIDDSQICRFTSDAKDKPIGCSVAISTYSMLGHTTKRSWEAERVMEWLKTQEWGLMILDEVHTIPAKMFRRVLTIVQAHCKLGLTATLVREDDKIVDLNFLIGPKLYEANWMELQNNGYIAKVQCAEVWCPMSPEFYREYVAIKTKKRILLYTMNPNKFRACQFLIKFHERRNDKIIVFADNVFALKEYAIRLNKPYIYGPTSQGERMQILQNFKHNPKINTIFISKVGDTSFDLPEANVLIQISSHGGSRRQEAQRLGRVLRAKKGMVAEEYNAFFYSLVSQDTQEMAYSTKRQRFLVDQGYSFKVITKLAGMEEEDLAFSTKEEQQQLLQKVLAATDLDAEEEVVAGEFGSRSSQASRRFGTMSSMSGADDTVYMEYHSSRSKAPSKHVHPLFKRFRK
uniprot
proteins
disease_involvement
DISEASE: Xeroderma pigmentosum complementation group B (XP-B) [MIM:610651]: 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-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. {ECO:0000269|PubMed:10447254, ECO:0000269|PubMed:16947863, ECO:0000269|PubMed:17466626, ECO:0000269|PubMed:30894545, ECO:0000269|PubMed:8304337}. Note=The disease is caused by variants affecting the gene represented in this entry.; DISEASE: Trichothiodystrophy 2, photosensitive (TTD2) [MIM:616390]: A 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. {ECO:0000269|PubMed:17466626, ECO:0000269|PubMed:9012405}. Note=The disease is caused by variants affecting the gene represented in this entry.
uniprot
proteins
ec_number
5.6.2.4
uniprot
proteins
function
FUNCTION: ATP-dependent 3'-5' DNA helicase/translocase (PubMed:17466626, PubMed:27193682, PubMed:33902107, PubMed:8465201, PubMed:8663148). Binds dsDNA rather than ssDNA, unzipping it in a translocase rather than classical helicase activity (PubMed:27193682, PubMed:33902107). Component of the general transcription and DNA repair factor IIH (TFIIH) core complex (PubMed:10024882, PubMed:17466626, PubMed:8157004, PubMed:8465201). When complexed to CDK-activating kinase (CAK), involved in RNA transcription by RNA polymerase II. The ATPase activity of XPB/ERCC3, but not its helicase activity, is required for DNA opening; it may wrap around the damaged DNA wedging it open, causing localized melting that allows XPD/ERCC2 helicase to anchor (PubMed:10024882, PubMed:17466626). In transcription, TFIIH has an essential role in transcription initiation (PubMed:30894545, PubMed:8157004). When the pre-initiation complex (PIC) has been established, TFIIH is required for promoter opening and promoter escape (PubMed:8157004). The ATP-dependent helicase activity of XPB/ERCC3 is required for promoter opening and promoter escape (PubMed:10024882). In transcription pre-initiation complexes induces and propagates a DNA twist to open DNA (PubMed:27193682, PubMed:33902107). Also involved in transcription-coupled nucleotide excision repair (NER) of damaged DNA (PubMed:17466626, PubMed:2111438, PubMed:8157004). 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 structure of the TFIIH transcription complex differs from the NER-TFIIH complex; large movements by XPD/ERCC2 and XPB/ERCC3 are stabilized by XPA (PubMed:31253769, PubMed:33902107). XPA retains XPB/ERCC3 at the 5' end of a DNA bubble (mimicking DNA damage) (PubMed:31253769). {ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:17466626, ECO:0000269|PubMed:30894545, ECO:0000269|PubMed:31253769, ECO:0000269|PubMed:33902107, ECO:0000269|PubMed:7724549, ECO:0000269|PubMed:8157004, ECO:0000269|PubMed:8663148, ECO:0000305|PubMed:8465201}.
uniprot
proteins
mass_dalton
89278
uniprot
proteins
mutagenesis
MUTAGEN 346; /note="K->R: Dominant-negative effect on transcription and NER, induces chromatin collapse, probably has no ATPase activity. No transcriptional activity of the reconstituted TFIIH complex. TFHHI is inactive in DNA repair and in transcription."; /evidence="ECO:0000269|PubMed:10024882, ECO:0000269|PubMed:17466626, ECO:0000269|PubMed:8157004"; MUTAGEN 469; /note="T->A: Very low 3'-5' helicase activity, wild-type ATPase activity, opens damaged DNA, nearly wild-type NER activity in vivo, 50% decreased transcription in vitro."; /evidence="ECO:0000269|PubMed:17466626"; MUTAGEN 638; /note="Q->A: Very low 3'-5' helicase activity, wild-type ATPase activity, wild-type damaged DNA removal, 80% decreased transcription (all in vitro)."; /evidence="ECO:0000269|PubMed:17466626"; MUTAGEN 751; /note="S->A: Restores NER in XPB/ERCC3-defective cells, does not inhibit 5'-incision by ERCC1-XPF, wild-type transcription and helicase activities."; /evidence="ECO:0000269|PubMed:15549133"; MUTAGEN 751; /note="S->E: Does not restore NER in XPB/ERCC3-defective cells, inhibits 5'-incision by ERCC1-XPF, wild-type transcription and helicase activities."; /evidence="ECO:0000269|PubMed:15549133"; MUTAGEN 782; /note="Missing: Impairs protein folding."; /evidence="ECO:0000269|PubMed:23385459
uniprot
proteins
post_translational_modification
PTM: Phosphorylation on Ser-751 by CK2 controls the 5'-excision activity of ERCC1-XPF endonuclease; phosphorylated protein inhibits the excision activity and thus NER (PubMed:15549133). Dephosphorylation reactivates the 5'-excision step (PubMed:15549133). Phosphorylation has no effect on transcription or the 3'-5' helicase activity (PubMed:15549133). {ECO:0000269|PubMed:15549133}.
uniprot
proteins
protein_family
Helicase family
uniprot
proteins
protein_family
RAD25/XPB subfamily
uniprot
proteins
pubmed
10024882
uniprot
proteins
pubmed
10447254
uniprot
proteins
pubmed
10862089
uniprot
proteins
pubmed
10882074
uniprot
proteins
pubmed
11239393
uniprot
proteins
pubmed
15489334
uniprot
proteins
pubmed
15549133
uniprot
proteins
pubmed
15815621
uniprot
proteins
pubmed
16947863
uniprot
proteins
pubmed
16959974
uniprot
proteins
pubmed
17466626
uniprot
proteins
pubmed
19106100
uniprot
proteins
pubmed
1956789
uniprot
proteins
pubmed
2111438
uniprot
proteins
pubmed
2167179
uniprot
proteins
pubmed
23186163
uniprot
proteins
pubmed
23385459
uniprot
proteins
pubmed
24275569
uniprot
proteins
pubmed
27193682
uniprot
proteins
pubmed
30894545
uniprot
proteins
pubmed
31253769
uniprot
proteins
pubmed
33902107
uniprot
proteins
pubmed
7724549
uniprot
proteins
pubmed
8157004
uniprot
proteins
pubmed
8304337
uniprot
proteins
pubmed
8465201
uniprot
proteins
pubmed
8663148
uniprot
proteins
pubmed
9012405
uniprot
proteins
pubmed
9852112
uniprot
proteins
sequence_length
782
uniprot
proteins
subcellular_location
SUBCELLULAR LOCATION: Nucleus.
uniprot
proteins