UniProtKB - O08811 (ERCC2_MOUSE)
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Protein
General transcription and DNA repair factor IIH helicase subunit XPD
Gene
Ercc2
Organism
Mus musculus (Mouse)
Status
Functioni
ATP-dependent 5'-3' 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 ATP-dependent helicase activity of XPD/ERCC2 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. 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. XPD/ERCC2 acts by forming a bridge between CAK and 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.By similarity
Catalytic activityi
ATP + H2O = ADP + phosphate.
Cofactori
Protein has several cofactor binding sites:- Mg2+By similarity
- [4Fe-4S] clusterBy similarityNote: Binds 1 [4Fe-4S] cluster.By similarity
Sites
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Metal bindingi | 116 | Iron-sulfur (4Fe-4S)By similarity | 1 | |
Metal bindingi | 134 | Iron-sulfur (4Fe-4S)By similarity | 1 | |
Metal bindingi | 155 | Iron-sulfur (4Fe-4S)By similarity | 1 | |
Metal bindingi | 190 | Iron-sulfur (4Fe-4S)By similarity | 1 |
Regions
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Nucleotide bindingi | 42 – 49 | ATPPROSITE-ProRule annotation | 8 |
GO - Molecular functioni
- 4 iron, 4 sulfur cluster binding Source: UniProtKB-KW
- 5'-3' DNA helicase activity Source: UniProtKB
- ATP binding Source: UniProtKB-KW
- ATP-dependent DNA helicase activity Source: InterPro
- DNA binding Source: UniProtKB-KW
- metal ion binding Source: UniProtKB-KW
- protein C-terminus binding Source: MGI
- protein N-terminus binding Source: MGI
- RNA polymerase II carboxy-terminal domain kinase activity Source: Ensembl
GO - Biological processi
- aging Source: MGI
- apoptotic process Source: UniProtKB
- bone mineralization Source: MGI
- cell proliferation Source: MGI
- central nervous system myelin formation Source: MGI
- chromosome segregation Source: UniProtKB
- DNA repair Source: MGI
- embryonic cleavage Source: MGI
- embryonic organ development Source: Ensembl
- erythrocyte maturation Source: MGI
- extracellular matrix organization Source: MGI
- hair cell differentiation Source: MGI
- hair cycle process Source: MGI
- hair follicle maturation Source: MGI
- hematopoietic stem cell differentiation Source: MGI
- in utero embryonic development Source: MGI
- multicellular organism growth Source: MGI
- nucleotide-excision repair Source: MGI
- nucleotide-excision repair, DNA incision Source: MGI
- positive regulation of DNA binding Source: MGI
- positive regulation of transcription, DNA-templated Source: MGI
- positive regulation of transcription by RNA polymerase II Source: MGI
- post-embryonic development Source: MGI
- regulation of mitotic cell cycle phase transition Source: MGI
- response to hypoxia Source: Ensembl
- response to oxidative stress Source: MGI
- response to UV Source: MGI
- skin development Source: MGI
- spinal cord development Source: MGI
- transcription by RNA polymerase II Source: UniProtKB
- transcription-coupled nucleotide-excision repair Source: UniProtKB
- UV protection Source: MGI
Keywordsi
Molecular function | DNA-binding, Helicase, Hydrolase |
Biological process | Chromosome partition, DNA damage, DNA repair, Transcription, Transcription regulation |
Ligand | 4Fe-4S, ATP-binding, Iron, Iron-sulfur, Magnesium, Metal-binding, Nucleotide-binding |
Enzyme and pathway databases
Reactomei | R-MMU-112382. Formation of RNA Pol II elongation complex. R-MMU-113418. Formation of the Early Elongation Complex. R-MMU-5696395. Formation of Incision Complex in GG-NER. R-MMU-5696400. Dual Incision in GG-NER. R-MMU-674695. RNA Polymerase II Pre-transcription Events. R-MMU-6781823. Formation of TC-NER Pre-Incision Complex. R-MMU-6782135. Dual incision in TC-NER. R-MMU-6782210. Gap-filling DNA repair synthesis and ligation in TC-NER. R-MMU-6796648. TP53 Regulates Transcription of DNA Repair Genes. R-MMU-72086. mRNA Capping. R-MMU-73762. RNA Polymerase I Transcription Initiation. R-MMU-73772. RNA Polymerase I Promoter Escape. R-MMU-73776. RNA Polymerase II Promoter Escape. R-MMU-73777. RNA Polymerase I Chain Elongation. R-MMU-73779. RNA Polymerase II Transcription Pre-Initiation And Promoter Opening. R-MMU-73863. RNA Polymerase I Transcription Termination. R-MMU-75953. RNA Polymerase II Transcription Initiation. R-MMU-75955. RNA Polymerase II Transcription Elongation. R-MMU-76042. RNA Polymerase II Transcription Initiation And Promoter Clearance. R-MMU-77075. RNA Pol II CTD phosphorylation and interaction with CE. |
Names & Taxonomyi
Protein namesi | Recommended name: General transcription and DNA repair factor IIH helicase subunit XPD (EC:3.6.4.12)Short name: TFIIH subunit XPD Alternative name(s): CXPD DNA excision repair protein ERCC-2 DNA repair protein complementing XP-D cells Xeroderma pigmentosum group D-complementing protein |
Gene namesi | Name:Ercc2 Synonyms:Xpd |
Organismi | Mus musculus (Mouse) |
Taxonomic identifieri | 10090 [NCBI] |
Taxonomic lineagei | Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Myomorpha › Muroidea › Muridae › Murinae › Mus › Mus |
Proteomesi |
|
Organism-specific databases
MGIi | MGI:95413. Ercc2. |
PTM / Processingi
Molecule processing
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
ChainiPRO_0000101981 | 1 – 760 | General transcription and DNA repair factor IIH helicase subunit XPDAdd BLAST | 760 |
Post-translational modificationi
ISGylated.By similarity
Keywords - PTMi
Ubl conjugationProteomic databases
EPDi | O08811. |
MaxQBi | O08811. |
PaxDbi | O08811. |
PRIDEi | O08811. |
PTM databases
iPTMneti | O08811. |
PhosphoSitePlusi | O08811. |
Expressioni
Gene expression databases
Bgeei | ENSMUSG00000030400. |
ExpressionAtlasi | O08811. baseline and differential. |
Genevisiblei | O08811. MM. |
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. 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.By similarity
GO - Molecular functioni
- protein C-terminus binding Source: MGI
- protein N-terminus binding Source: MGI
Protein-protein interaction databases
BioGridi | 199500. 1 interactor. |
IntActi | O08811. 1 interactor. |
MINTi | O08811. |
STRINGi | 10090.ENSMUSP00000054380. |
Family & Domainsi
Domains and Repeats
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Domaini | 7 – 283 | Helicase ATP-bindingPROSITE-ProRule annotationAdd BLAST | 277 |
Region
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Regioni | 438 – 637 | Mediates interaction with MMS19By similarityAdd BLAST | 200 |
Motif
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Motifi | 234 – 237 | DEAH box | 4 |
Sequence similaritiesi
Phylogenomic databases
eggNOGi | KOG1131. Eukaryota. COG1199. LUCA. |
GeneTreei | ENSGT00550000075092. |
HOGENOMi | HOG000205390. |
HOVERGENi | HBG051498. |
InParanoidi | O08811. |
KOi | K10844. |
OMAi | PSVVRNY. |
OrthoDBi | EOG091G0262. |
TreeFami | TF101232. |
Family and domain databases
InterProi | View protein in InterPro IPR006555. ATP-dep_Helicase_C. IPR010614. DEAD_2. IPR002464. DNA/RNA_helicase_DEAH_CS. IPR010643. HBB. IPR014013. Helic_SF1/SF2_ATP-bd_DinG/Rad3. IPR006554. Helicase-like_DEXD_c2. IPR027417. P-loop_NTPase. IPR013020. Rad3/Chl1-like. IPR001945. RAD3/XPD. |
PANTHERi | PTHR11472:SF1. PTHR11472:SF1. 1 hit. |
Pfami | View protein in Pfam PF06733. DEAD_2. 1 hit. PF06777. HBB. 1 hit. PF13307. Helicase_C_2. 1 hit. |
PRINTSi | PR00852. XRODRMPGMNTD. |
SMARTi | View protein in SMART SM00488. DEXDc2. 1 hit. SM00491. HELICc2. 1 hit. |
SUPFAMi | SSF52540. SSF52540. 4 hits. |
TIGRFAMsi | TIGR00604. rad3. 1 hit. |
PROSITEi | View protein in PROSITE PS00690. DEAH_ATP_HELICASE. 1 hit. PS51193. HELICASE_ATP_BIND_2. 1 hit. |
i Sequence
Sequence statusi: Complete.
O08811-1 [UniParc]FASTAAdd to basket
10 20 30 40 50
MKLNVDGLLV YFPYDYIYPE QFSYMLELKR TLDAKGHGVL EMPSGTGKTV
60 70 80 90 100
SLLALIVAYQ RAYPLEVTKL IYCSRTVPEI EKVIEELRKL LSFYEQQEGE
110 120 130 140 150
KLPFLGLALS SRKNLCIHPE VTPLRFGKDV DGKCHSLTAS YVRAQYQQDA
160 170 180 190 200
SLPHCRFYEE FDIHGRQMPL PAGIYNLDDL KALGQRQGWC PYFLARYSIL
210 220 230 240 250
HANVVVYSYH YLLDPKIADL VSKELARKAV VVFDEAHNID NVCIDSMSVN
260 270 280 290 300
LTRRTLDRCQ SNLDTLQKTV LRIKETDEQR LRDEYRRLVE GLREASVARE
310 320 330 340 350
TDAHLANPVL PDEVLQEAVP GSIRTAEHFL GFLRRLLEYV KWRLRVQHVV
360 370 380 390 400
QESPPAFLSG LAQRVCIQRK PLRFCAERLR SLLHTLEIAD LADFSPLTLL
410 420 430 440 450
ANFATLVSTY AKGFTIIIEP FDDRTPTIAN PVLHFSCMDA SLAIKPVFER
460 470 480 490 500
FQSVIITSGT LSPLDIYPKI LDFHPVTMAT FTMTLARVCL CPMIIGRGND
510 520 530 540 550
QVAISSKFET REDIAVIRNY GNLLLEMSAV VPDGIVAFFT SYQYMESTVA
560 570 580 590 600
SWYEQGILEN IQRNKLLFIE TQDGAETSVA LEKYQEACEN GRGAILLSVA
610 620 630 640 650
RGKVSEGIDF VHHYGRAVIM FGVPYVYTQS RILKARLEYL RDQFQIREND
660 670 680 690 700
FLTFDAMRHA AQCVGRAIRG KTDYGLMVFA DKRFARADKR GKLPRWIQEH
710 720 730 740 750
LTDSNLNLTV DEGVQVAKYF LRQMAQPFHR EDQLGLSLLS LEQLQSEETL
760
QRIEQIAQQL
Sequence cautioni
The sequence BAB23443 differs from that shown. Reason: Erroneous initiation. Translation N-terminally extended.Curated
Experimental Info
Feature key | Position(s) | DescriptionActions | Graphical view | Length |
---|---|---|---|---|
Sequence conflicti | 285 | Y → C in BAB23443 (PubMed:16141072).Curated | 1 | |
Sequence conflicti | 595 | I → V in AAB58296 (PubMed:9426063).Curated | 1 |
Sequence databases
Select the link destinations: EMBLi GenBanki DDBJi Links Updated | U97572 mRNA. Translation: AAB58296.1. AK004652 mRNA. Translation: BAB23443.1. Different initiation. AK082761 mRNA. Translation: BAC38607.1. CH466639 Genomic DNA. Translation: EDL23140.1. |
CCDSi | CCDS20900.1. |
RefSeqi | NP_031975.2. NM_007949.4. |
UniGenei | Mm.36524. |
Genome annotation databases
Ensembli | ENSMUST00000062831; ENSMUSP00000054380; ENSMUSG00000030400. |
GeneIDi | 13871. |
KEGGi | mmu:13871. |
UCSCi | uc009flq.1. mouse. |
Similar proteinsi
Entry informationi
Entry namei | ERCC2_MOUSE | |
Accessioni | O08811Primary (citable) accession number: O08811 Secondary accession number(s): Q8C487, Q9DC01 | |
Entry historyi | Integrated into UniProtKB/Swiss-Prot: | November 1, 1997 |
Last sequence update: | July 27, 2011 | |
Last modified: | March 28, 2018 | |
This is version 152 of the entry and version 2 of the sequence. See complete history. | ||
Entry statusi | Reviewed (UniProtKB/Swiss-Prot) | |
Annotation program | Chordata Protein Annotation Program |