ERCC2_DICDI
ID ERCC2_DICDI Reviewed; 776 AA.
AC Q55G81; O00836;
DT 08-APR-2008, integrated into UniProtKB/Swiss-Prot.
DT 24-MAY-2005, sequence version 1.
DT 03-AUG-2022, entry version 111.
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=DNA excision repair cross-complementing protein-2 homolog;
DE AltName: Full=DNA repair protein D;
DE AltName: Full=TFIIH basal transcription factor complex helicase repD subunit;
GN Name=repD; Synonyms=ercc2; ORFNames=DDB_G0267414;
OS Dictyostelium discoideum (Slime mold).
OC Eukaryota; Amoebozoa; Evosea; Eumycetozoa; Dictyostelia; Dictyosteliales;
OC Dictyosteliaceae; Dictyostelium.
OX NCBI_TaxID=44689;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND DEVELOPMENTAL STAGE.
RC STRAIN=AX4;
RX PubMed=9171087; DOI=10.1093/nar/25.12.2365;
RA Lee S.-K., Yu S.-L., Garcia M.X.U., Alexander H., Alexander S.;
RT "Differential developmental expression of the rep B and rep D xeroderma
RT pigmentosum related DNA helicase genes from Dictyostelium discoideum.";
RL Nucleic Acids Res. 25:2365-2374(1997).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=AX4;
RX PubMed=15875012; DOI=10.1038/nature03481;
RA Eichinger L., Pachebat J.A., Gloeckner G., Rajandream M.A., Sucgang R.,
RA Berriman M., Song J., Olsen R., Szafranski K., Xu Q., Tunggal B.,
RA Kummerfeld S., Madera M., Konfortov B.A., Rivero F., Bankier A.T.,
RA Lehmann R., Hamlin N., Davies R., Gaudet P., Fey P., Pilcher K., Chen G.,
RA Saunders D., Sodergren E.J., Davis P., Kerhornou A., Nie X., Hall N.,
RA Anjard C., Hemphill L., Bason N., Farbrother P., Desany B., Just E.,
RA Morio T., Rost R., Churcher C.M., Cooper J., Haydock S., van Driessche N.,
RA Cronin A., Goodhead I., Muzny D.M., Mourier T., Pain A., Lu M., Harper D.,
RA Lindsay R., Hauser H., James K.D., Quiles M., Madan Babu M., Saito T.,
RA Buchrieser C., Wardroper A., Felder M., Thangavelu M., Johnson D.,
RA Knights A., Loulseged H., Mungall K.L., Oliver K., Price C., Quail M.A.,
RA Urushihara H., Hernandez J., Rabbinowitsch E., Steffen D., Sanders M.,
RA Ma J., Kohara Y., Sharp S., Simmonds M.N., Spiegler S., Tivey A.,
RA Sugano S., White B., Walker D., Woodward J.R., Winckler T., Tanaka Y.,
RA Shaulsky G., Schleicher M., Weinstock G.M., Rosenthal A., Cox E.C.,
RA Chisholm R.L., Gibbs R.A., Loomis W.F., Platzer M., Kay R.R.,
RA Williams J.G., Dear P.H., Noegel A.A., Barrell B.G., Kuspa A.;
RT "The genome of the social amoeba Dictyostelium discoideum.";
RL Nature 435:43-57(2005).
RN [3]
RP INDUCTION BY UV.
RX PubMed=9765592; DOI=10.1016/s0167-4781(98)00103-1;
RA Lee S.-K., Yu S.-L., Alexander H., Alexander S.;
RT "A mutation in repB, the dictyostelium homolog of the human xeroderma
RT pigmentosum B gene, has increased sensitivity to UV-light but normal
RT morphogenesis.";
RL Biochim. Biophys. Acta 1399:161-172(1998).
RN [4]
RP INDUCTION.
RX PubMed=9649625; DOI=10.1093/nar/26.14.3397;
RA Yu S.-L., Lee S.-K., Alexander H., Alexander S.;
RT "Rapid changes of nucleotide excision repair gene expression following UV-
RT irradiation and cisplatin treatment of Dictyostelium discoideum.";
RL Nucleic Acids Res. 26:3397-3403(1998).
RN [5]
RP INDUCTION, AND DEVELOPMENTAL STAGE.
RX PubMed=11004503; DOI=10.1016/s0167-4781(00)00063-4;
RA Garcia M.X.U., Foote C., van Es S., Devreotes P.N., Alexander S.,
RA Alexander H.;
RT "Differential developmental expression and cell type specificity of
RT Dictyostelium catalases and their response to oxidative stress and UV-
RT light.";
RL Biochim. Biophys. Acta 1492:295-310(2000).
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/repD 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/repD acts by
CC forming a bridge between CAK and the core-TFIIH complex.
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/repB, XPD/repD, gtf2h1, gtf2h2, gtf2h3, gtf2h4 and gtf2h5, which is
CC active in NER. The core complex associates with the 3-subunit CDK-
CC activating kinase (CAK) module composed of cycH/cyclin H, cdk7 and
CC mnat1 to form the 10-subunit holoenzyme (holo-TFIIH) active in
CC transcription. {ECO:0000250|UniProtKB:P18074}.
CC -!- SUBCELLULAR LOCATION: Nucleus {ECO:0000250}.
CC -!- DEVELOPMENTAL STAGE: Levels accumulate after the removal of the food
CC source and increase with the onset of development (expression peaks at
CC 3-4 hours of development and decreases to a low baseline level by 7
CC hours). Expression remain elevated during chemotaxis and formation of
CC multicellular assemblies, and then return to baseline levels for the
CC rest of the development. {ECO:0000269|PubMed:11004503,
CC ECO:0000269|PubMed:9171087}.
CC -!- INDUCTION: Up-regulated in response to DNA damage due to UV light or
CC exposure to cisplatin. Unaffected by exposure to hydrogen peroxide.
CC {ECO:0000269|PubMed:11004503, ECO:0000269|PubMed:9649625,
CC ECO:0000269|PubMed:9765592}.
CC -!- SIMILARITY: Belongs to the helicase family. RAD3/XPD subfamily.
CC {ECO:0000305}.
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DR EMBL; U77066; AAB62733.1; -; Genomic_DNA.
DR EMBL; AAFI02000003; EAL73159.1; -; Genomic_DNA.
DR RefSeq; XP_647302.1; XM_642210.1.
DR AlphaFoldDB; Q55G81; -.
DR SMR; Q55G81; -.
DR STRING; 44689.DDB0191272; -.
DR PaxDb; Q55G81; -.
DR PRIDE; Q55G81; -.
DR EnsemblProtists; EAL73159; EAL73159; DDB_G0267414.
DR GeneID; 8616111; -.
DR KEGG; ddi:DDB_G0267414; -.
DR dictyBase; DDB_G0267414; repD.
DR eggNOG; KOG1131; Eukaryota.
DR HOGENOM; CLU_011312_1_0_1; -.
DR InParanoid; Q55G81; -.
DR OMA; IREQFFR; -.
DR PhylomeDB; Q55G81; -.
DR Reactome; R-DDI-113418; Formation of the Early Elongation Complex.
DR Reactome; R-DDI-5696395; Formation of Incision Complex in GG-NER.
DR Reactome; R-DDI-674695; RNA Polymerase II Pre-transcription Events.
DR Reactome; R-DDI-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-DDI-6782135; Dual incision in TC-NER.
DR Reactome; R-DDI-6782210; Gap-filling DNA repair synthesis and ligation in TC-NER.
DR Reactome; R-DDI-6796648; TP53 Regulates Transcription of DNA Repair Genes.
DR Reactome; R-DDI-72086; mRNA Capping.
DR Reactome; R-DDI-73772; RNA Polymerase I Promoter Escape.
DR Reactome; R-DDI-73776; RNA Polymerase II Promoter Escape.
DR Reactome; R-DDI-73779; RNA Polymerase II Transcription Pre-Initiation And Promoter Opening.
DR Reactome; R-DDI-75953; RNA Polymerase II Transcription Initiation.
DR Reactome; R-DDI-75955; RNA Polymerase II Transcription Elongation.
DR Reactome; R-DDI-76042; RNA Polymerase II Transcription Initiation And Promoter Clearance.
DR Reactome; R-DDI-77075; RNA Pol II CTD phosphorylation and interaction with CE.
DR PRO; PR:Q55G81; -.
DR Proteomes; UP000002195; Chromosome 1.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0005675; C:transcription factor TFIIH holo complex; ISS:dictyBase.
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:dictyBase.
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:0006974; P:cellular response to DNA damage stimulus; IEP:dictyBase.
DR GO; GO:0006289; P:nucleotide-excision repair; ISS:dictyBase.
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:0045951; P:positive regulation of mitotic recombination; IBA:GO_Central.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISS:dictyBase.
DR Gene3D; 3.40.50.300; -; 3.
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 2: Evidence at transcript level;
KW 4Fe-4S; ATP-binding; DNA damage; DNA repair; DNA-binding; Helicase;
KW Hydrolase; Iron; Iron-sulfur; Magnesium; Metal-binding; Nucleotide-binding;
KW Nucleus; Reference proteome; Transcription; Transcription regulation.
FT CHAIN 1..776
FT /note="General transcription and DNA repair factor IIH
FT helicase subunit XPD"
FT /id="PRO_0000328565"
FT DOMAIN 7..277
FT /note="Helicase ATP-binding"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00541"
FT REGION 736..776
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT MOTIF 228..231
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 115
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 133
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 150
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT BINDING 184
FT /ligand="[4Fe-4S] cluster"
FT /ligand_id="ChEBI:CHEBI:49883"
FT /evidence="ECO:0000250"
FT CONFLICT 319..321
FT /note="AEH -> PSI (in Ref. 1; AAB62733)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 776 AA; 88278 MW; 3A779094B8ECD525 CRC64;
MKFYIEDLLV YFPYSYIYPE QYSYMVALKR SLDNGGPCIL EMPSGTGKTV SLLSLISSYQ
VKNPSIKLIY CSRTVPEIEQ ATEEARRVLQ YRNSEMGEES PKTLCMSMSS RRNLCIQPRV
SEERDGKVVD ALCRELTSSW NRESPTSEKC KFFENFESNG KEILLEGVYS LEDLKEYGLK
HQMCPYFLSR HMLNFANIVI FSYQYLLDPK IASLISSSFP SNSIVVFDEA HNIDNVCINA
LSINIDNKLL DTSSKNIAKI NKQIEDIKKV DEKRLKDEYQ RLVNGLARSG STRADETTSD
PVLPNDVIQE AVPGNIRKAE HFISLLRRVV DYLKSRLKSQ MLLSESPLAF LQGLYHATQI
SSRTLRFCSS RLSSLLRTLR INDVNQFSGI SLIADFATLV GTYNNGFLII IEPYYQRQNN
TYDQIFQFCC LDASIGMKPI FDKYRSVVIT SGTLSPLDIY TKMLNFRPTV VERLTMSLNR
NCICPCILTR GSDQISISTK FDVRSDTAVV RNYGALLVEV SAIVPDGIIC FFTSYSYMEQ
IVSVWNEMGL LNNILTNKLI FVETSDPAES ALALQNYKKA CDSGRGAVLL SVARGKVSEG
IDFDNQYGRC VILYGIPYIN TESKVLRARL EFLRDRYQIR ENEFLTFDAM RTASQCVGRV
IRGKSDYGIM IFADKRYNRL DKRNKLPQWI LQFCQPQHLN LSTDMAISLS KTFLREMGQP
FSREEQLGKS LWSLEHVEKQ STSKPPQQQN SAINSTITTS TTTTTTTSTI SETHLT
