TOP3A_MOUSE
ID TOP3A_MOUSE Reviewed; 1003 AA.
AC O70157;
DT 30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT 01-AUG-1998, sequence version 1.
DT 03-AUG-2022, entry version 180.
DE RecName: Full=DNA topoisomerase 3-alpha;
DE EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10131};
DE AltName: Full=DNA topoisomerase III alpha;
GN Name=Top3a; Synonyms=Top3;
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].
RC STRAIN=BALB/cJ; TISSUE=Testis;
RX PubMed=9540825; DOI=10.1016/s0167-4781(97)00192-9;
RA Seki T., Seki M., Katada T., Enomoto T.;
RT "Isolation of a cDNA encoding mouse DNA topoisomerase III which is highly
RT expressed at the mRNA level in the testis.";
RL Biochim. Biophys. Acta 1396:127-131(1998).
CC -!- FUNCTION: Releases the supercoiling and torsional tension of DNA
CC introduced during the DNA replication and transcription by transiently
CC cleaving and rejoining one strand of the DNA duplex. Introduces a
CC single-strand break via transesterification at a target site in duplex
CC DNA. The scissile phosphodiester is attacked by the catalytic tyrosine
CC of the enzyme, resulting in the formation of a DNA-(5'-phosphotyrosyl)-
CC enzyme intermediate and the expulsion of a 3'-OH DNA strand. The free
CC DNA strand then undergoes passage around the unbroken strand thus
CC removing DNA supercoils. Finally, in the religation step, the DNA 3'-OH
CC attacks the covalent intermediate to expel the active-site tyrosine and
CC restore the DNA phosphodiester backbone. As an essential component of
CC the RMI complex it is involved in chromosome separation and the
CC processing of homologous recombination intermediates to limit DNA
CC crossover formation in cells. Has DNA decatenation activity. It is
CC required for mtDNA decatenation and segregation after completion of
CC replication, in a process that does not require BLM, RMI1 and RMI2.
CC {ECO:0000250|UniProtKB:Q13472}.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=ATP-independent breakage of single-stranded DNA, followed by
CC passage and rejoining.; EC=5.6.2.1; Evidence={ECO:0000255|PROSITE-
CC ProRule:PRU10131};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC -!- SUBUNIT: Binds ssDNA. Interacts (via N-terminal region) with BLM; the
CC interaction is direct. Directly interacts with RMI1. Component of the
CC RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI complex
CC interacts with BLM. {ECO:0000250|UniProtKB:Q13472}.
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000250|UniProtKB:Q13472}.
CC -!- TISSUE SPECIFICITY: Highly expressed in testis.
CC -!- SIMILARITY: Belongs to the type IA topoisomerase family. {ECO:0000305}.
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DR EMBL; AB006074; BAA25662.1; -; mRNA.
DR CCDS; CCDS24797.1; -.
DR PIR; T13951; T13951.
DR RefSeq; NP_033436.1; NM_009410.2.
DR AlphaFoldDB; O70157; -.
DR SMR; O70157; -.
DR BioGRID; 204278; 14.
DR ComplexPortal; CPX-3303; BTR double Holliday Junction dissolution complex.
DR IntAct; O70157; 9.
DR STRING; 10090.ENSMUSP00000002891; -.
DR iPTMnet; O70157; -.
DR PhosphoSitePlus; O70157; -.
DR EPD; O70157; -.
DR PaxDb; O70157; -.
DR PeptideAtlas; O70157; -.
DR PRIDE; O70157; -.
DR ProteomicsDB; 259156; -.
DR Antibodypedia; 43348; 83 antibodies from 19 providers.
DR DNASU; 21975; -.
DR Ensembl; ENSMUST00000002891; ENSMUSP00000002891; ENSMUSG00000002814.
DR GeneID; 21975; -.
DR KEGG; mmu:21975; -.
DR UCSC; uc007jgl.1; mouse.
DR CTD; 7156; -.
DR MGI; MGI:1197527; Top3a.
DR VEuPathDB; HostDB:ENSMUSG00000002814; -.
DR eggNOG; KOG1956; Eukaryota.
DR GeneTree; ENSGT00940000156701; -.
DR InParanoid; O70157; -.
DR OMA; EHICFEV; -.
DR OrthoDB; 373433at2759; -.
DR PhylomeDB; O70157; -.
DR TreeFam; TF105287; -.
DR Reactome; R-MMU-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-MMU-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-MMU-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-MMU-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-MMU-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-MMU-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-MMU-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-MMU-69473; G2/M DNA damage checkpoint.
DR BioGRID-ORCS; 21975; 27 hits in 71 CRISPR screens.
DR ChiTaRS; Top3a; mouse.
DR PRO; PR:O70157; -.
DR Proteomes; UP000000589; Chromosome 11.
DR RNAct; O70157; protein.
DR Bgee; ENSMUSG00000002814; Expressed in spermatocyte and 184 other tissues.
DR ExpressionAtlas; O70157; baseline and differential.
DR Genevisible; O70157; MM.
DR GO; GO:0005759; C:mitochondrial matrix; IEA:UniProtKB-SubCell.
DR GO; GO:0005654; C:nucleoplasm; TAS:Reactome.
DR GO; GO:0005634; C:nucleus; IBA:GO_Central.
DR GO; GO:0016605; C:PML body; ISO:MGI.
DR GO; GO:0031422; C:RecQ family helicase-topoisomerase III complex; ISO:MGI.
DR GO; GO:0003916; F:DNA topoisomerase activity; IBA:GO_Central.
DR GO; GO:0003917; F:DNA topoisomerase type I (single strand cut, ATP-independent) activity; ISS:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; ISO:MGI.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0051304; P:chromosome separation; ISS:UniProtKB.
DR GO; GO:0006265; P:DNA topological change; ISS:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; ISO:MGI.
DR GO; GO:0032042; P:mitochondrial DNA metabolic process; ISO:MGI.
DR GO; GO:0071139; P:resolution of recombination intermediates; ISO:MGI.
DR CDD; cd00186; TOP1Ac; 1.
DR CDD; cd03362; TOPRIM_TopoIA_TopoIII; 1.
DR Gene3D; 1.10.290.10; -; 1.
DR Gene3D; 1.10.460.10; -; 1.
DR Gene3D; 2.70.20.10; -; 1.
DR InterPro; IPR000380; Topo_IA.
DR InterPro; IPR003601; Topo_IA_2.
DR InterPro; IPR023406; Topo_IA_AS.
DR InterPro; IPR013497; Topo_IA_cen.
DR InterPro; IPR013824; Topo_IA_cen_sub1.
DR InterPro; IPR013825; Topo_IA_cen_sub2.
DR InterPro; IPR013826; Topo_IA_cen_sub3.
DR InterPro; IPR023405; Topo_IA_core_domain.
DR InterPro; IPR003602; Topo_IA_DNA-bd_dom.
DR InterPro; IPR013498; Topo_IA_Znf.
DR InterPro; IPR006171; TOPRIM_domain.
DR InterPro; IPR034144; TOPRIM_TopoIII.
DR InterPro; IPR010666; Znf_GRF.
DR PANTHER; PTHR11390; PTHR11390; 1.
DR Pfam; PF01131; Topoisom_bac; 1.
DR Pfam; PF01751; Toprim; 1.
DR Pfam; PF01396; zf-C4_Topoisom; 1.
DR Pfam; PF06839; zf-GRF; 2.
DR PRINTS; PR00417; PRTPISMRASEI.
DR SMART; SM00437; TOP1Ac; 1.
DR SMART; SM00436; TOP1Bc; 1.
DR SMART; SM00493; TOPRIM; 1.
DR SUPFAM; SSF56712; SSF56712; 1.
DR PROSITE; PS00396; TOPOISOMERASE_I_PROK; 1.
DR PROSITE; PS50880; TOPRIM; 1.
PE 2: Evidence at transcript level;
KW DNA-binding; Isomerase; Magnesium; Metal-binding; Mitochondrion;
KW Reference proteome; Repeat; Topoisomerase; Zinc; Zinc-finger.
FT CHAIN 1..1003
FT /note="DNA topoisomerase 3-alpha"
FT /id="PRO_0000145191"
FT DOMAIN 35..179
FT /note="Toprim"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT ZN_FING 658..685
FT /note="C4-type"
FT /evidence="ECO:0000255"
FT ZN_FING 813..853
FT /note="GRF-type 1"
FT ZN_FING 898..941
FT /note="GRF-type 2"
FT REGION 400..426
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 856..888
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 946..991
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 856..878
FT /note="Polar residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT ACT_SITE 362
FT /note="O-(5'-phospho-DNA)-tyrosine intermediate"
FT /evidence="ECO:0000250"
SQ SEQUENCE 1003 AA; 112358 MW; 254C738E746EE495 CRC64;
MIFPVTLLAF QWHRRPGGRA LSRAAMEVAF RGVRKVLCVA EKNDAAKGIA DLLSNGRMRR
KEGLSKFNKI YEFDYHLYGQ NVTMIMTSVS GHLLAHDFQM QFRKWQSCNP LVLFEAEIEK
YCPENFIDIK KTLERETHHC QALVIWTDCD REGENIGFEI IHVCKAVKPN LRVLRARFSE
ITPHAVRTAC ENLTEPDQRV SDAVDVRQEL DLRIGAAFTR FQTLRLQRIF PEVLAEQLIS
YGSCQFPTLG FVVERFKAIQ AFVPEVFHKI KVTHDHKDGT VEFNWKRYRL FNHTACLVLY
QLCMEDPMAT VVEVRSKPKS KWRPQALDTV ELEKLASRKL RINAKETMRI AEKLYTQGYI
SYPRTETNIF PKDLNLVALV EQQTVDPHWG AFAQTILERG GPTPRNGSKS DQAHPPIHPT
KYTSGLQGDD RRLYEFIVRH FLACCSQDAQ GQETTVEIDI AQERFVAHGL IILARNYLDV
YPYDHWSDKL LPVYEQGSHF QPSTVEMVDG ETSPPQLLTE ADLIALMEKH GIGTDATHAE
HIETIKARMY VGLTSDKRFL PGHLGMGLVE GYDSMGYEMS KPDLRAELEA DLKLICEGKK
DKFQVLRQQV QKYKQVFIEA VAKAKKLDEA LSQYLGERTE MAQQEEIYPA MPEPVRKCPQ
CNKDMVLKTK KSGGFYLSCM GFPECRSAVW FPDSVLEASR DNSVCSVCQP PPVYRLKLKF
KRGSLPPAMP LEFVGCIGGC DETLKEIFGL RFPRALPRAS QPSGHLQASQ ALNRMDSSQH
NLSQPLVNRH TRPSKTVAQA LLPPTTAGES NSVTCNCGRE AVLLTVRKQG PNQGRHFYKC
SNGDCNFFLW ADSSHSTGGG TPTSASGPPG SSVGCPSSVG SHMDGFGSLG SDSDGGTPCL
CGQPAVTRTV QKDGPNKGRQ FHTCAKPREQ QCGFFQWVDE NVAPGSFAAP AWPGGRGKAQ
RPEAASKRPR AGSSDAGSTV KKPRKCSLCH QPGHTRTFCP QNR
