ERCC2_CRIGR
ID ERCC2_CRIGR Reviewed; 760 AA.
AC Q60452;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1996, sequence version 1.
DT 03-AUG-2022, entry version 129.
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 Cricetulus griseus (Chinese hamster) (Cricetulus barabensis griseus).
OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea;
OC Cricetidae; Cricetinae; Cricetulus.
OX NCBI_TaxID=10029;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RC TISSUE=Lung;
RX PubMed=7851887; DOI=10.1006/geno.1994.1547;
RA Kirchner J.M., Salazar E.P., Lamerdin J.E., Montgomery M.A., Carrano A.V.,
RA Weber C.A.;
RT "Cloning and molecular characterization of the Chinese hamster ERCC2
RT nucleotide excision repair gene.";
RL Genomics 23:592-599(1994).
RN [2]
RP ERRATUM OF PUBMED:7851887.
RX PubMed=7558017; DOI=10.1006/geno.1995.1067;
RA Kirchner J.M., Salazar E.P., Lamerdin J.E., Montgomery M.A., Carrano A.V.,
RA Weber C.A.;
RL Genomics 27:387-387(1995).
RN [3]
RP MUTAGENESIS OF CYS-116 AND GLY-615, AND VARIANT GLN-286.
RC TISSUE=Ovary;
RX PubMed=8052270; DOI=10.1016/0165-7992(94)90012-4;
RA Weber C.A., Kirchner J.M., Salazar E.P., Takayama K.;
RT "Molecular analysis of CXPD mutations in the repair-deficient hamster
RT mutants UV5 and UVL-13.";
RL Mutat. Res. 324:147-152(1994).
RN [4]
RP ERRATUM OF PUBMED:8052270.
RX PubMed=7596368; DOI=10.1016/0165-7992(95)90033-0;
RA Weber C.A., Kirchner J.M., Salazar E.P., Takayama K.;
RL Mutat. Res. 347:53-53(1995).
RN [5]
RP MUTAGENESIS OF THR-46; LYS-48; ARG-75; ARG-683 AND ARG-722.
RX PubMed=11182546; DOI=10.1016/s0921-8777(00)00077-x;
RA Kadkhodayan S., Coin F., Salazar E.P., George J.W., Egly J.-M.,
RA Thompson L.H.;
RT "Codominance associated with overexpression of certain XPD mutations.";
RL Mutat. Res. 485:153-168(2001).
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}.
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DR EMBL; U04968; AAC13749.1; -; Genomic_DNA.
DR EMBL; U04967; AAC13749.1; JOINED; Genomic_DNA.
DR PIR; A55732; A55732.
DR AlphaFoldDB; Q60452; -.
DR SMR; Q60452; -.
DR STRING; 10029.NP_001231320.1; -.
DR eggNOG; KOG1131; Eukaryota.
DR GO; GO:0070516; C:CAK-ERCC2 complex; ISS:UniProtKB.
DR GO; GO:0005737; C:cytoplasm; ISS:UniProtKB.
DR GO; GO:0071817; C:MMXD complex; ISS:UniProtKB.
DR GO; GO:0005634; C:nucleus; ISS:UniProtKB.
DR GO; GO:0005819; C:spindle; ISS:UniProtKB.
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:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0008022; F:protein C-terminus binding; ISS:UniProtKB.
DR GO; GO:0047485; F:protein N-terminus binding; ISS:UniProtKB.
DR GO; GO:0006915; P:apoptotic process; ISS:UniProtKB.
DR GO; GO:0007059; P:chromosome segregation; ISS:UniProtKB.
DR GO; GO:0035315; P:hair cell differentiation; ISS:UniProtKB.
DR GO; GO:0006289; P:nucleotide-excision repair; ISS:UniProtKB.
DR GO; GO:1901990; P:regulation of mitotic cell cycle phase transition; ISS:UniProtKB.
DR GO; GO:0006979; P:response to oxidative stress; ISS:UniProtKB.
DR GO; GO:0006366; P:transcription by RNA polymerase II; ISS:UniProtKB.
DR GO; GO:0006283; P:transcription-coupled nucleotide-excision repair; ISS:UniProtKB.
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 Transcription; Transcription regulation; Ubl conjugation.
FT CHAIN 1..760
FT /note="General transcription and DNA repair factor IIH
FT helicase subunit XPD"
FT /id="PRO_0000101979"
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 MOTIF 682..695
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
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 VARIANT 286
FT /note="R -> Q"
FT /evidence="ECO:0000269|PubMed:8052270"
FT MUTAGEN 46
FT /note="T->I: NER deficiency, no change in basal
FT transcription activity."
FT /evidence="ECO:0000269|PubMed:11182546"
FT MUTAGEN 48
FT /note="K->R: NER deficiency."
FT /evidence="ECO:0000269|PubMed:11182546"
FT MUTAGEN 75
FT /note="R->W: NER deficiency associated to slight deficiency
FT in basal transcription."
FT /evidence="ECO:0000269|PubMed:11182546"
FT MUTAGEN 116
FT /note="C->Y: NER deficiency."
FT /evidence="ECO:0000269|PubMed:8052270"
FT MUTAGEN 615
FT /note="G->E: NER deficiency."
FT /evidence="ECO:0000269|PubMed:8052270"
FT MUTAGEN 683
FT /note="R->W: No effect."
FT /evidence="ECO:0000269|PubMed:11182546"
FT MUTAGEN 722
FT /note="R->W: No effect."
FT /evidence="ECO:0000269|PubMed:11182546"
FT MUTAGEN 725
FT /note="A->P: No effect."
SQ SEQUENCE 760 AA; 86752 MW; 0B888C2F06C95C49 CRC64;
MKLNVDGLLV YFPYDYIYPE QFSYMLELKR TLDAKGHGVL EMPSGTGKTV SLLALIVAYQ
RAFPLEVTKL IYCSRTVPEI EKVIEELRKL LSFYEQQEGE KLPFLGLALS SRKNLCIHPE
VTPLRFGKDV DGKCHSLTAS YVRAQYQQDA SLPHCRFYEE FDAHGRQVPL PAGIYNLDDL
KALGQRQGWC PYFLARYSIL HANVVVYSYH YLLDPKIADL VSKELARKAV VVFDEAHNID
NVCIDSMSVN LTRRTLDRCQ SNLDTLQKTV LRIKETDEQR LRDEYRRLVE GLREASAARE
TDAHLANPVL PDEVLQEAVP GSIRTAEHFL GFLRRLLEYV KWRLRVQHVV QESPPAFLSG
LAQRVCIQRK PLRFCAERLR SLLHTLEIAD LADFSPLTLL ANFATLVSTY AKGFTIIIEP
FDDRTPTIAN PILHFSCMDA 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 RRVEQIAQQL
