XPA_MOUSE
ID XPA_MOUSE Reviewed; 272 AA.
AC Q64267; A2ALZ7; Q9CVA0;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 14-APR-2009, sequence version 2.
DT 03-AUG-2022, entry version 158.
DE RecName: Full=DNA repair protein complementing XP-A cells homolog;
DE AltName: Full=Xeroderma pigmentosum group A-complementing protein homolog;
GN Name=Xpa; Synonyms=Xpac;
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 [GENOMIC DNA / MRNA] (ISOFORM 1).
RC STRAIN=129/Ola;
RX PubMed=8127648; DOI=10.1093/nar/22.1.11;
RA van Oostrom C.T.M., de Vries A., Verbeek S.J., van Kreijl C.F.,
RA van Steeg H.;
RT "Cloning and characterization of the mouse XPAC gene.";
RL Nucleic Acids Res. 22:11-14(1994).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2).
RC STRAIN=C57BL/6J; TISSUE=Stomach;
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].
RC STRAIN=C57BL/6J;
RX PubMed=19468303; DOI=10.1371/journal.pbio.1000112;
RA Church D.M., Goodstadt L., Hillier L.W., Zody M.C., Goldstein S., She X.,
RA Bult C.J., Agarwala R., Cherry J.L., DiCuccio M., Hlavina W., Kapustin Y.,
RA Meric P., Maglott D., Birtle Z., Marques A.C., Graves T., Zhou S.,
RA Teague B., Potamousis K., Churas C., Place M., Herschleb J., Runnheim R.,
RA Forrest D., Amos-Landgraf J., Schwartz D.C., Cheng Z., Lindblad-Toh K.,
RA Eichler E.E., Ponting C.P.;
RT "Lineage-specific biology revealed by a finished genome assembly of the
RT mouse.";
RL PLoS Biol. 7:E1000112-E1000112(2009).
RN [4]
RP DISRUPTION PHENOTYPE.
RC STRAIN=Hos/HR-1;
RX PubMed=11764287; DOI=10.1046/j.0022-202x.2001.00019.x;
RA Horio T., Miyauchi-Hashimoto H., Kuwamoto K., Horiki S., Okamoto H.,
RA Tanaka K.;
RT "Photobiologic and photoimmunologic characteristics of XPA gene-deficient
RT mice.";
RL J. Investig. Dermatol. Symp. Proc. 6:58-63(2001).
RN [5]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Embryonic brain;
RX PubMed=15345747; DOI=10.1074/mcp.m400085-mcp200;
RA Ballif B.A., Villen J., Beausoleil S.A., Schwartz D., Gygi S.P.;
RT "Phosphoproteomic analysis of the developing mouse brain.";
RL Mol. Cell. Proteomics 3:1093-1101(2004).
RN [6]
RP INDUCTION, AND MISCELLANEOUS.
RC STRAIN=C57BL/6J;
RX PubMed=20304803; DOI=10.1073/pnas.0915085107;
RA Kang T.H., Lindsey-Boltz L.A., Reardon J.T., Sancar A.;
RT "Circadian control of XPA and excision repair of cisplatin-DNA damage by
RT cryptochrome and HERC2 ubiquitin ligase.";
RL Proc. Natl. Acad. Sci. U.S.A. 107:4890-4895(2010).
CC -!- FUNCTION: Involved in DNA excision repair. Initiates repair by binding
CC to damaged sites with various affinities, depending on the photoproduct
CC and the transcriptional state of the region. Required for UV-induced
CC CHEK1 phosphorylation and the recruitment of CEP164 to cyclobutane
CC pyrimidine dimmers (CPD), sites of DNA damage after UV irradiation (By
CC similarity). {ECO:0000250}.
CC -!- SUBUNIT: Interacts with GPN1. Interacts with RPA1 and RPA2; the
CC interaction is direct and associates XPA with the RPA complex.
CC Interacts (via N-terminus) with CEP164 upon UV irradiation. Interacts
CC with HERC2 (By similarity). {ECO:0000250}.
CC -!- SUBCELLULAR LOCATION: Nucleus.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q64267-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q64267-2; Sequence=VSP_036906;
CC -!- INDUCTION: Exhibits a circadian pattern with zenith at around 5 pm and
CC nadir at around 5 am in liver but not in testis, this oscillation is
CC dependent on the circadian clock and on HERC2 regulation.
CC {ECO:0000269|PubMed:20304803}.
CC -!- PTM: Ubiquitinated by HERC2 leading to degradation by the proteasome.
CC {ECO:0000250}.
CC -!- DISRUPTION PHENOTYPE: Deficient mice cannot repair UV-induced DNA
CC damage and easily develop skin cancers by UV irradiation. They develop
CC stronger longer-lasting acute inflammation, they show a more severe UV-
CC induced damage of keratinocytes and Langerhans cells as well as the
CC enhancement of local and systemic immunosuppression. PGE2 and COX2
CC expression is greatly increased after UVB irradiation, this causes the
CC enhancement of inflammation and immunosuppression. Natural killer cell
CC activity is also significantly decreased.
CC {ECO:0000269|PubMed:11764287}.
CC -!- MISCELLANEOUS: Plays an essential role in the repair of cisplatin
CC induced damage by nucleotide excision repair. Cisplatin is one of the
CC most commnly used anticancer drugs.
CC -!- SIMILARITY: Belongs to the XPA family. {ECO:0000305}.
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DR EMBL; X74345; CAA52392.1; -; Genomic_DNA.
DR EMBL; X74346; CAA52392.1; JOINED; Genomic_DNA.
DR EMBL; X74347; CAA52392.1; JOINED; Genomic_DNA.
DR EMBL; X74348; CAA52392.1; JOINED; Genomic_DNA.
DR EMBL; X74349; CAA52392.1; JOINED; Genomic_DNA.
DR EMBL; X74350; CAA52392.1; JOINED; Genomic_DNA.
DR EMBL; X74351; CAA52393.1; -; mRNA.
DR EMBL; AK008962; BAB25992.1; -; mRNA.
DR EMBL; AL806523; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR CCDS; CCDS18146.1; -. [Q64267-1]
DR PIR; S41498; S41498.
DR RefSeq; NP_035858.2; NM_011728.2. [Q64267-1]
DR AlphaFoldDB; Q64267; -.
DR SMR; Q64267; -.
DR BioGRID; 204604; 1.
DR STRING; 10090.ENSMUSP00000030013; -.
DR iPTMnet; Q64267; -.
DR PhosphoSitePlus; Q64267; -.
DR EPD; Q64267; -.
DR jPOST; Q64267; -.
DR MaxQB; Q64267; -.
DR PaxDb; Q64267; -.
DR PeptideAtlas; Q64267; -.
DR PRIDE; Q64267; -.
DR ProteomicsDB; 299714; -. [Q64267-1]
DR ProteomicsDB; 299715; -. [Q64267-2]
DR Antibodypedia; 3603; 494 antibodies from 36 providers.
DR DNASU; 22590; -.
DR Ensembl; ENSMUST00000030013; ENSMUSP00000030013; ENSMUSG00000028329. [Q64267-1]
DR Ensembl; ENSMUST00000142380; ENSMUSP00000121850; ENSMUSG00000028329. [Q64267-2]
DR GeneID; 22590; -.
DR KEGG; mmu:22590; -.
DR UCSC; uc008stm.2; mouse. [Q64267-1]
DR UCSC; uc008stn.1; mouse. [Q64267-2]
DR CTD; 7507; -.
DR MGI; MGI:99135; Xpa.
DR VEuPathDB; HostDB:ENSMUSG00000028329; -.
DR eggNOG; KOG4017; Eukaryota.
DR GeneTree; ENSGT00390000002721; -.
DR HOGENOM; CLU_053731_1_0_1; -.
DR InParanoid; Q64267; -.
DR OMA; VWKRETV; -.
DR OrthoDB; 1542306at2759; -.
DR TreeFam; TF101241; -.
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-6781823; Formation of TC-NER Pre-Incision Complex.
DR Reactome; R-MMU-6782135; Dual incision in TC-NER.
DR BioGRID-ORCS; 22590; 1 hit in 109 CRISPR screens.
DR ChiTaRS; Xpa; mouse.
DR PRO; PR:Q64267; -.
DR Proteomes; UP000000589; Chromosome 4.
DR RNAct; Q64267; protein.
DR Bgee; ENSMUSG00000028329; Expressed in granulocyte and 235 other tissues.
DR ExpressionAtlas; Q64267; baseline and differential.
DR Genevisible; Q64267; MM.
DR GO; GO:0005737; C:cytoplasm; ISO:MGI.
DR GO; GO:0005662; C:DNA replication factor A complex; ISO:MGI.
DR GO; GO:0045171; C:intercellular bridge; ISO:MGI.
DR GO; GO:0005654; C:nucleoplasm; ISO:MGI.
DR GO; GO:0000110; C:nucleotide-excision repair factor 1 complex; IBA:GO_Central.
DR GO; GO:0005634; C:nucleus; IDA:MGI.
DR GO; GO:0003684; F:damaged DNA binding; ISS:UniProtKB.
DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW.
DR GO; GO:0019904; F:protein domain specific binding; ISO:MGI.
DR GO; GO:0042803; F:protein homodimerization activity; ISO:MGI.
DR GO; GO:1990837; F:sequence-specific double-stranded DNA binding; ISO:MGI.
DR GO; GO:0006284; P:base-excision repair; IBA:GO_Central.
DR GO; GO:0006281; P:DNA repair; IMP:MGI.
DR GO; GO:0008630; P:intrinsic apoptotic signaling pathway in response to DNA damage; IMP:MGI.
DR GO; GO:0035264; P:multicellular organism growth; IGI:MGI.
DR GO; GO:0006289; P:nucleotide-excision repair; IMP:MGI.
DR GO; GO:1901255; P:nucleotide-excision repair involved in interstrand cross-link repair; IBA:GO_Central.
DR GO; GO:0000715; P:nucleotide-excision repair, DNA damage recognition; IBA:GO_Central.
DR GO; GO:0033683; P:nucleotide-excision repair, DNA incision; ISO:MGI.
DR GO; GO:0060261; P:positive regulation of transcription initiation from RNA polymerase II promoter; IGI:MGI.
DR GO; GO:0034504; P:protein localization to nucleus; ISO:MGI.
DR GO; GO:0010506; P:regulation of autophagy; IMP:MGI.
DR GO; GO:0006979; P:response to oxidative stress; IMP:MGI.
DR GO; GO:0009636; P:response to toxic substance; IMP:MGI.
DR GO; GO:0009411; P:response to UV; IMP:MGI.
DR GO; GO:0009650; P:UV protection; ISO:MGI.
DR GO; GO:0070914; P:UV-damage excision repair; IBA:GO_Central.
DR Gene3D; 3.90.530.10; -; 1.
DR InterPro; IPR009061; DNA-bd_dom_put_sf.
DR InterPro; IPR000465; XPA.
DR InterPro; IPR022656; XPA_C.
DR InterPro; IPR022658; XPA_CS.
DR InterPro; IPR037129; XPA_sf.
DR InterPro; IPR022652; Znf_XPA_CS.
DR PANTHER; PTHR10142; PTHR10142; 1.
DR Pfam; PF05181; XPA_C; 1.
DR Pfam; PF01286; XPA_N; 1.
DR SUPFAM; SSF46955; SSF46955; 1.
DR TIGRFAMs; TIGR00598; rad14; 1.
DR PROSITE; PS00752; XPA_1; 1.
DR PROSITE; PS00753; XPA_2; 1.
PE 1: Evidence at protein level;
KW Acetylation; Alternative splicing; DNA damage; DNA repair; DNA-binding;
KW Isopeptide bond; Metal-binding; Nucleus; Phosphoprotein;
KW Reference proteome; Ubl conjugation; Zinc; Zinc-finger.
FT INIT_MET 1
FT /note="Removed"
FT /evidence="ECO:0000250|UniProtKB:P23025"
FT CHAIN 2..272
FT /note="DNA repair protein complementing XP-A cells homolog"
FT /id="PRO_0000208649"
FT ZN_FING 104..128
FT REGION 1..22
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 4..96
FT /note="Interaction with CEP164 and required for UV
FT resistance"
FT /evidence="ECO:0000250"
FT MOTIF 28..49
FT /note="Nuclear localization signal"
FT /evidence="ECO:0000255"
FT MOD_RES 2
FT /note="N-acetylalanine"
FT /evidence="ECO:0000250|UniProtKB:P23025"
FT MOD_RES 195
FT /note="Phosphoserine"
FT /evidence="ECO:0000250|UniProtKB:P23025"
FT CROSSLNK 63
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P23025"
FT CROSSLNK 144
FT /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT G-Cter in SUMO2)"
FT /evidence="ECO:0000250|UniProtKB:P23025"
FT VAR_SEQ 224..272
FT /note="ELRRAIRSSVWKRETTTHQHKYGPEENLEDDMYRKTCTLCGHELTYEKM ->
FT GKWPDFLSRRSQSTVSVGKERGVNAGLRALVYEAWVNPHGTSLIKAIVFM (in
FT isoform 2)"
FT /evidence="ECO:0000303|PubMed:16141072"
FT /id="VSP_036906"
FT CONFLICT 244
FT /note="K -> E (in Ref. 1; CAA52392/CAA52393)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 272 AA; 31398 MW; 9061C9528F9E63CB CRC64;
MATAEEKQTS PEPVAADEPA QLPAAVRASV ERKRQRALML RQARLAARPY PAAAATGGVA
SVKAAPKMID TKGGFILEEE EEKHEIGNIV HEPGPVMEFD YTICEECGKE FMDSYLMNHF
DLPTCDSCRD ADDKHKLITK TEAKQEYLLK DCDLEKREPA LRFLVKKNPR HSQWGDMKLY
LKLQVVKRAL EVWGSQEALE DAKEVRQENR EKMKQKKFDK KVKELRRAIR SSVWKRETTT
HQHKYGPEEN LEDDMYRKTC TLCGHELTYE KM
