ERCC2_MOUSE
ID ERCC2_MOUSE Reviewed; 760 AA.
AC O08811; Q8C487; Q9DC01;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 27-JUL-2011, sequence version 2.
DT 03-AUG-2022, entry version 178.
DE RecName: Full=General transcription and DNA repair factor IIH helicase subunit XPD;
DE Short=TFIIH subunit XPD;
DE EC=3.6.4.12;
DE AltName: Full=CXPD;
DE AltName: Full=DNA excision repair protein ERCC-2;
DE AltName: Full=DNA repair protein complementing XP-D cells;
DE AltName: Full=Xeroderma pigmentosum group D-complementing protein;
GN Name=Ercc2; Synonyms=Xpd;
OS Mus musculus (Mouse).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC Murinae; Mus; Mus.
OX NCBI_TaxID=10090;
RN [1]
RP NUCLEOTIDE SEQUENCE [MRNA].
RX PubMed=9426063;
RA de Boer J., Donker I., de Wit J., Hoeijmakers J.H.J., Weeda G.;
RT "Disruption of the mouse xeroderma pigmentosum group D DNA repair/basal
RT transcription gene results in preimplantation lethality.";
RL Cancer Res. 58:89-94(1998).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC STRAIN=C57BL/6J; TISSUE=Lung;
RX PubMed=16141072; DOI=10.1126/science.1112014;
RA Carninci P., Kasukawa T., Katayama S., Gough J., Frith M.C., Maeda N.,
RA Oyama R., Ravasi T., Lenhard B., Wells C., Kodzius R., Shimokawa K.,
RA Bajic V.B., Brenner S.E., Batalov S., Forrest A.R., Zavolan M., Davis M.J.,
RA Wilming L.G., Aidinis V., Allen J.E., Ambesi-Impiombato A., Apweiler R.,
RA Aturaliya R.N., Bailey T.L., Bansal M., Baxter L., Beisel K.W., Bersano T.,
RA Bono H., Chalk A.M., Chiu K.P., Choudhary V., Christoffels A.,
RA Clutterbuck D.R., Crowe M.L., Dalla E., Dalrymple B.P., de Bono B.,
RA Della Gatta G., di Bernardo D., Down T., Engstrom P., Fagiolini M.,
RA Faulkner G., Fletcher C.F., Fukushima T., Furuno M., Futaki S.,
RA Gariboldi M., Georgii-Hemming P., Gingeras T.R., Gojobori T., Green R.E.,
RA Gustincich S., Harbers M., Hayashi Y., Hensch T.K., Hirokawa N., Hill D.,
RA Huminiecki L., Iacono M., Ikeo K., Iwama A., Ishikawa T., Jakt M.,
RA Kanapin A., Katoh M., Kawasawa Y., Kelso J., Kitamura H., Kitano H.,
RA Kollias G., Krishnan S.P., Kruger A., Kummerfeld S.K., Kurochkin I.V.,
RA Lareau L.F., Lazarevic D., Lipovich L., Liu J., Liuni S., McWilliam S.,
RA Madan Babu M., Madera M., Marchionni L., Matsuda H., Matsuzawa S., Miki H.,
RA Mignone F., Miyake S., Morris K., Mottagui-Tabar S., Mulder N., Nakano N.,
RA Nakauchi H., Ng P., Nilsson R., Nishiguchi S., Nishikawa S., Nori F.,
RA Ohara O., Okazaki Y., Orlando V., Pang K.C., Pavan W.J., Pavesi G.,
RA Pesole G., Petrovsky N., Piazza S., Reed J., Reid J.F., Ring B.Z.,
RA Ringwald M., Rost B., Ruan Y., Salzberg S.L., Sandelin A., Schneider C.,
RA Schoenbach C., Sekiguchi K., Semple C.A., Seno S., Sessa L., Sheng Y.,
RA Shibata Y., Shimada H., Shimada K., Silva D., Sinclair B., Sperling S.,
RA Stupka E., Sugiura K., Sultana R., Takenaka Y., Taki K., Tammoja K.,
RA Tan S.L., Tang S., Taylor M.S., Tegner J., Teichmann S.A., Ueda H.R.,
RA van Nimwegen E., Verardo R., Wei C.L., Yagi K., Yamanishi H.,
RA Zabarovsky E., Zhu S., Zimmer A., Hide W., Bult C., Grimmond S.M.,
RA Teasdale R.D., Liu E.T., Brusic V., Quackenbush J., Wahlestedt C.,
RA Mattick J.S., Hume D.A., Kai C., Sasaki D., Tomaru Y., Fukuda S.,
RA Kanamori-Katayama M., Suzuki M., Aoki J., Arakawa T., Iida J., Imamura K.,
RA Itoh M., Kato T., Kawaji H., Kawagashira N., Kawashima T., Kojima M.,
RA Kondo S., Konno H., Nakano K., Ninomiya N., Nishio T., Okada M., Plessy C.,
RA Shibata K., Shiraki T., Suzuki S., Tagami M., Waki K., Watahiki A.,
RA Okamura-Oho Y., Suzuki H., Kawai J., Hayashizaki Y.;
RT "The transcriptional landscape of the mammalian genome.";
RL Science 309:1559-1563(2005).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Adams M.D., Myers E.W., Smith H.O., Venter J.C.;
RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases.
RN [4]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Testis;
RX PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL Cell 143:1174-1189(2010).
CC -!- FUNCTION: ATP-dependent 5'-3' DNA helicase, component of the general
CC transcription and DNA repair factor IIH (TFIIH) core complex, which is
CC involved in general and transcription-coupled nucleotide excision
CC repair (NER) of damaged DNA and, when complexed to CAK, in RNA
CC transcription by RNA polymerase II. In NER, TFIIH acts by opening DNA
CC around the lesion to allow the excision of the damaged oligonucleotide
CC and its replacement by a new DNA fragment. The ATP-dependent helicase
CC activity of XPD/ERCC2 is required for DNA opening. In transcription,
CC TFIIH has an essential role in transcription initiation. When the pre-
CC initiation complex (PIC) has been established, TFIIH is required for
CC promoter opening and promoter escape. Phosphorylation of the C-terminal
CC tail (CTD) of the largest subunit of RNA polymerase II by the kinase
CC module CAK controls the initiation of transcription. XPD/ERCC2 acts by
CC forming a bridge between CAK and the core-TFIIH complex. Involved in
CC the regulation of vitamin-D receptor activity. As part of the mitotic
CC spindle-associated MMXD complex it plays a role in chromosome
CC segregation. Might have a role in aging process and could play a
CC causative role in the generation of skin cancers.
CC {ECO:0000250|UniProtKB:P18074}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP + H2O = ADP + H(+) + phosphate; Xref=Rhea:RHEA:13065,
CC ChEBI:CHEBI:15377, ChEBI:CHEBI:15378, ChEBI:CHEBI:30616,
CC ChEBI:CHEBI:43474, ChEBI:CHEBI:456216; EC=3.6.4.12;
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250};
CC -!- COFACTOR:
CC Name=[4Fe-4S] cluster; Xref=ChEBI:CHEBI:49883; Evidence={ECO:0000250};
CC Note=Binds 1 [4Fe-4S] cluster. {ECO:0000250};
CC -!- SUBUNIT: Component of the 7-subunit TFIIH core complex composed of
CC XPB/ERCC3, XPD/ERCC2, GTF2H1, GTF2H2, GTF2H3, GTF2H4 and GTF2H5, which
CC is active in NER. The core complex associates with the 3-subunit CDK-
CC activating kinase (CAK) module composed of CCNH/cyclin H, CDK7 and
CC MNAT1 to form the 10-subunit holoenzyme (holo-TFIIH) active in
CC transcription. The interaction with GTF2H2 results in the stimulation
CC of the 5'-->3' helicase activity. Component of the MMXD complex, which
CC includes CIAO1, ERCC2, CIAO2B, MMS19 and SLC25A5. Interacts with CIAO1
CC and CIAO2B; the interaction WITH CIAO2B is direct. Interacts with
CC ATF7IP. Interacts directly with MMS19. {ECO:0000250|UniProtKB:P18074}.
CC -!- SUBCELLULAR LOCATION: Nucleus. Cytoplasm, cytoskeleton, spindle
CC {ECO:0000250}.
CC -!- PTM: ISGylated. {ECO:0000250}.
CC -!- SIMILARITY: Belongs to the helicase family. RAD3/XPD subfamily.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAB23443.1; Type=Erroneous initiation; Note=Truncated N-terminus.; Evidence={ECO:0000305};
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DR EMBL; U97572; AAB58296.1; -; mRNA.
DR EMBL; AK004652; BAB23443.1; ALT_INIT; mRNA.
DR EMBL; AK082761; BAC38607.1; -; mRNA.
DR EMBL; CH466639; EDL23140.1; -; Genomic_DNA.
DR CCDS; CCDS20900.1; -.
DR RefSeq; NP_031975.2; NM_007949.4.
DR AlphaFoldDB; O08811; -.
DR SMR; O08811; -.
DR BioGRID; 199500; 1.
DR IntAct; O08811; 1.
DR MINT; O08811; -.
DR STRING; 10090.ENSMUSP00000054380; -.
DR iPTMnet; O08811; -.
DR PhosphoSitePlus; O08811; -.
DR EPD; O08811; -.
DR MaxQB; O08811; -.
DR PaxDb; O08811; -.
DR PRIDE; O08811; -.
DR ProteomicsDB; 275672; -.
DR Antibodypedia; 17895; 288 antibodies from 37 providers.
DR DNASU; 13871; -.
DR Ensembl; ENSMUST00000062831; ENSMUSP00000054380; ENSMUSG00000030400.
DR GeneID; 13871; -.
DR KEGG; mmu:13871; -.
DR UCSC; uc009flq.1; mouse.
DR CTD; 2068; -.
DR MGI; MGI:95413; Ercc2.
DR VEuPathDB; HostDB:ENSMUSG00000030400; -.
DR eggNOG; KOG1131; Eukaryota.
DR GeneTree; ENSGT00950000182970; -.
DR InParanoid; O08811; -.
DR OMA; IREQFFR; -.
DR OrthoDB; 186062at2759; -.
DR PhylomeDB; O08811; -.
DR TreeFam; TF101232; -.
DR Reactome; R-MMU-112382; Formation of RNA Pol II elongation complex.
DR Reactome; R-MMU-113418; Formation of the Early Elongation Complex.
DR Reactome; R-MMU-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-MMU-5696400; Dual Incision in GG-NER.
DR Reactome; R-MMU-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-MMU-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-MMU-6782135; Dual incision in TC-NER.
DR Reactome; R-MMU-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-MMU-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-MMU-72086; mRNA Capping.
DR Reactome; R-MMU-73762; RNA Polymerase I Transcription Initiation.
DR Reactome; R-MMU-73772; RNA Polymerase I Promoter Escape.
DR Reactome; R-MMU-73776; RNA Polymerase II Promoter Escape.
DR Reactome; R-MMU-73779; RNA Polymerase II Transcription Pre-Initiation And Promoter Opening.
DR Reactome; R-MMU-73863; RNA Polymerase I Transcription Termination.
DR Reactome; R-MMU-75953; RNA Polymerase II Transcription Initiation.
DR Reactome; R-MMU-75955; RNA Polymerase II Transcription Elongation.
DR Reactome; R-MMU-76042; RNA Polymerase II Transcription Initiation And Promoter Clearance.
DR Reactome; R-MMU-77075; RNA Pol II CTD phosphorylation and interaction with CE.
DR BioGRID-ORCS; 13871; 32 hits in 115 CRISPR screens.
DR PRO; PR:O08811; -.
DR Proteomes; UP000000589; Chromosome 7.
DR RNAct; O08811; protein.
DR Bgee; ENSMUSG00000030400; Expressed in spermatocyte and 148 other tissues.
DR ExpressionAtlas; O08811; baseline and differential.
DR Genevisible; O08811; MM.
DR GO; GO:0070516; C:CAK-ERCC2 complex; ISO:MGI.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0005829; C:cytosol; ISO:MGI.
DR GO; GO:0071817; C:MMXD complex; ISS:UniProtKB.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0005819; C:spindle; ISS:UniProtKB.
DR GO; GO:0005669; C:transcription factor TFIID complex; ISO:MGI.
DR GO; GO:0000439; C:transcription factor TFIIH core complex; ISO:MGI.
DR GO; GO:0005675; C:transcription factor TFIIH holo complex; ISS:UniProtKB.
DR GO; GO:0051539; F:4 iron, 4 sulfur cluster binding; IEA:UniProtKB-KW.
DR GO; GO:0043139; F:5'-3' DNA helicase activity; ISS:UniProtKB.
DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR GO; GO:0016887; F:ATP hydrolysis activity; IEA:RHEA.
DR GO; GO:0003684; F:damaged DNA binding; IBA:GO_Central.
DR GO; GO:0003678; F:DNA helicase activity; IBA:GO_Central.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; ISO:MGI.
DR GO; GO:0047485; F:protein N-terminus binding; ISO:MGI.
DR GO; GO:0030674; F:protein-macromolecule adaptor activity; ISO:MGI.
DR GO; GO:0007568; P:aging; IMP:MGI.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0030282; P:bone mineralization; IMP:MGI.
DR GO; GO:0032289; P:central nervous system myelin formation; IMP:MGI.
DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB.
DR GO; GO:0006281; P:DNA repair; IMP:MGI.
DR GO; GO:0040016; P:embryonic cleavage; IMP:MGI.
DR GO; GO:0043249; P:erythrocyte maturation; IMP:MGI.
DR GO; GO:0030198; P:extracellular matrix organization; IMP:MGI.
DR GO; GO:0035315; P:hair cell differentiation; IMP:MGI.
DR GO; GO:0022405; P:hair cycle process; IMP:MGI.
DR GO; GO:0048820; P:hair follicle maturation; IMP:MGI.
DR GO; GO:0060218; P:hematopoietic stem cell differentiation; IMP:MGI.
DR GO; GO:0071425; P:hematopoietic stem cell proliferation; IMP:MGI.
DR GO; GO:0001701; P:in utero embryonic development; IMP:MGI.
DR GO; GO:0000462; P:maturation of SSU-rRNA from tricistronic rRNA transcript (SSU-rRNA, 5.8S rRNA, LSU-rRNA); IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IMP:MGI.
DR GO; GO:0006289; P:nucleotide-excision repair; IMP:MGI.
DR GO; GO:0000717; P:nucleotide-excision repair, DNA duplex unwinding; IBA:GO_Central.
DR GO; GO:0033683; P:nucleotide-excision repair, DNA incision; IBA:GO_Central.
DR GO; GO:0043388; P:positive regulation of DNA binding; IMP:MGI.
DR GO; GO:0045951; P:positive regulation of mitotic recombination; IBA:GO_Central.
DR GO; GO:0009791; P:post-embryonic development; IMP:MGI.
DR GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; ISO:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0009411; P:response to UV; IMP:MGI.
DR GO; GO:0042274; P:ribosomal small subunit biogenesis; IMP:MGI.
DR GO; GO:0043588; P:skin development; IMP:MGI.
DR GO; GO:0021510; P:spinal cord development; IMP:MGI.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006362; P:transcription elongation from RNA polymerase I promoter; IMP:MGI.
DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:0009650; P:UV protection; IMP:MGI.
DR Gene3D; 3.40.50.300; -; 2.
DR InterPro; IPR006555; ATP-dep_Helicase_C.
DR InterPro; IPR010614; DEAD_2.
DR InterPro; IPR045028; DinG/Rad3-like.
DR InterPro; IPR002464; DNA/RNA_helicase_DEAH_CS.
DR InterPro; IPR010643; HBB.
DR InterPro; IPR014013; Helic_SF1/SF2_ATP-bd_DinG/Rad3.
DR InterPro; IPR006554; Helicase-like_DEXD_c2.
DR InterPro; IPR027417; P-loop_NTPase.
DR InterPro; IPR013020; Rad3/Chl1-like.
DR InterPro; IPR001945; RAD3/XPD.
DR PANTHER; PTHR11472; PTHR11472; 1.
DR PANTHER; PTHR11472:SF1; PTHR11472:SF1; 1.
DR Pfam; PF06733; DEAD_2; 1.
DR Pfam; PF06777; HBB; 1.
DR Pfam; PF13307; Helicase_C_2; 1.
DR PRINTS; PR00852; XRODRMPGMNTD.
DR SMART; SM00488; DEXDc2; 1.
DR SMART; SM00491; HELICc2; 1.
DR SUPFAM; SSF52540; SSF52540; 1.
DR TIGRFAMs; TIGR00604; rad3; 1.
DR PROSITE; PS00690; DEAH_ATP_HELICASE; 1.
DR PROSITE; PS51193; HELICASE_ATP_BIND_2; 1.
PE 1: Evidence at protein level;
KW 4Fe-4S; ATP-binding; Chromosome partition; Cytoplasm; Cytoskeleton;
KW DNA damage; DNA repair; DNA-binding; Helicase; Hydrolase; Iron;
KW Iron-sulfur; Magnesium; Metal-binding; Nucleotide-binding; Nucleus;
KW Reference proteome; Transcription; Transcription regulation;
KW Ubl conjugation.
FT CHAIN 1..760
FT /note="General transcription and DNA repair factor IIH
FT helicase subunit XPD"
FT /id="PRO_0000101981"
FT DOMAIN 7..283
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT REGION 438..637
FT /note="Mediates interaction with MMS19"
FT /evidence="ECO:0000250"
FT MOTIF 234..237
FT /note="DEAH box"
FT BINDING 42..49
FT /ligand="ATP"
FT /ligand_id="ChEBI:CHEBI:30616"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT BINDING 116
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 134
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 155
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 190
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT CONFLICT 285
FT /note="Y -> C (in Ref. 2; BAB23443)"
FT /evidence="ECO:0000305"
FT CONFLICT 595
FT /note="I -> V (in Ref. 1; AAB58296)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 760 AA; 86842 MW; 02B2E116792D4E44 CRC64;
MKLNVDGLLV YFPYDYIYPE QFSYMLELKR TLDAKGHGVL EMPSGTGKTV SLLALIVAYQ
RAYPLEVTKL IYCSRTVPEI EKVIEELRKL LSFYEQQEGE KLPFLGLALS SRKNLCIHPE
VTPLRFGKDV DGKCHSLTAS YVRAQYQQDA SLPHCRFYEE FDIHGRQMPL PAGIYNLDDL
KALGQRQGWC PYFLARYSIL HANVVVYSYH YLLDPKIADL VSKELARKAV VVFDEAHNID
NVCIDSMSVN LTRRTLDRCQ SNLDTLQKTV LRIKETDEQR LRDEYRRLVE GLREASVARE
TDAHLANPVL PDEVLQEAVP GSIRTAEHFL GFLRRLLEYV KWRLRVQHVV QESPPAFLSG
LAQRVCIQRK PLRFCAERLR SLLHTLEIAD LADFSPLTLL ANFATLVSTY AKGFTIIIEP
FDDRTPTIAN PVLHFSCMDA SLAIKPVFER FQSVIITSGT LSPLDIYPKI LDFHPVTMAT
FTMTLARVCL CPMIIGRGND QVAISSKFET REDIAVIRNY GNLLLEMSAV VPDGIVAFFT
SYQYMESTVA SWYEQGILEN IQRNKLLFIE TQDGAETSVA LEKYQEACEN GRGAILLSVA
RGKVSEGIDF VHHYGRAVIM FGVPYVYTQS RILKARLEYL RDQFQIREND FLTFDAMRHA
AQCVGRAIRG KTDYGLMVFA DKRFARADKR GKLPRWIQEH LTDSNLNLTV DEGVQVAKYF
LRQMAQPFHR EDQLGLSLLS LEQLQSEETL QRIEQIAQQL
