ID   TOP3A_HUMAN             Reviewed;        1001 AA.
AC   Q13472; Q13473;
DT   01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT   01-NOV-1997, sequence version 1.
DT   07-JUL-2009, entry version 79.
DE   RecName: Full=DNA topoisomerase 3-alpha;
DE            EC=5.99.1.2;
DE   AltName: Full=DNA topoisomerase III alpha;
GN   Name=TOP3A; Synonyms=TOP3;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORMS LONG AND SHORT).
RX   MEDLINE=96195027; PubMed=8622991; DOI=10.1073/pnas.93.8.3653;
RA   Hanai R., Caron P.R., Wang J.C.;
RT   "Human TOP3: a single-copy gene encoding DNA topoisomerase III.";
RL   Proc. Natl. Acad. Sci. U.S.A. 93:3653-3657(1996).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM LONG).
RC   TISSUE=Testis;
RX   PubMed=15489334; DOI=10.1101/gr.2596504;
RG   The MGC Project Team;
RT   "The status, quality, and expansion of the NIH full-length cDNA
RT   project: the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
RN   [3]
RP   IDENTIFICATION IN COMPLEX WITH BLM AND RMI1.
RX   PubMed=15775963; DOI=10.1038/sj.emboj.7600622;
RA   Yin J., Sobeck A., Xu C., Meetei A.R., Hoatlin M., Li L., Wang W.;
RT   "BLAP75, an essential component of Bloom's syndrome protein complexes
RT   that maintain genome integrity.";
RL   EMBO J. 24:1465-1476(2005).
RN   [4]
RP   IDENTIFICATION IN THE RMI COMPLEX.
RX   PubMed=18923082; DOI=10.1101/gad.1708608;
RA   Xu D., Guo R., Sobeck A., Bachrati C.Z., Yang J., Enomoto T.,
RA   Brown G.W., Hoatlin M.E., Hickson I.D., Wang W.;
RT   "RMI, a new OB-fold complex essential for Bloom syndrome protein to
RT   maintain genome stability.";
RL   Genes Dev. 22:2843-2855(2008).
RN   [5]
RP   IDENTIFICATION IN THE RMI COMPLEX.
RX   PubMed=18923083; DOI=10.1101/gad.1725108;
RA   Singh T.R., Ali A.M., Busygina V., Raynard S., Fan Q., Du C.-H.,
RA   Andreassen P.R., Sung P., Meetei A.R.;
RT   "BLAP18/RMI2, a novel OB-fold-containing protein, is an essential
RT   component of the Bloom helicase-double Holliday junction
RT   dissolvasome.";
RL   Genes Dev. 22:2856-2868(2008).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-54 AND SER-771, AND MASS
RP   SPECTROMETRY.
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
CC   -!- FUNCTION: Reduces the number of supercoils in a highly negatively
CC       supercoiled DNA. Essential component of the RMI complex, a complex
CC       that plays an important role in the processing of homologous
CC       recombination intermediates to limit DNA crossover formation in
CC       cells.
CC   -!- CATALYTIC ACTIVITY: ATP-independent breakage of single-stranded
CC       DNA, followed by passage and rejoining.
CC   -!- SUBUNIT: Directly interacts with BLM and RMI1. Component of the
CC       RMI complex, containing at least TOP3A, RMI1 and RMI2. The RMI
CC       complex interacts with BLM.
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=2;
CC       Name=Long;
CC         IsoId=Q13472-1; Sequence=Displayed;
CC       Name=Short;
CC         IsoId=Q13472-2; Sequence=VSP_006524;
CC   -!- TISSUE SPECIFICITY: High expression is found in testis, heart,
CC       skeletal muscle and pancreas.
CC   -!- SIMILARITY: Belongs to the prokaryotic type I/III topoisomerase
CC       family.
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DR   EMBL; U43431; AAB03694.1; -; mRNA.
DR   EMBL; U43431; AAB03695.1; -; mRNA.
DR   EMBL; BC051748; AAH51748.1; -; mRNA.
DR   IPI; IPI00013378; -.
DR   IPI; IPI00221295; -.
DR   RefSeq; NP_004609.1; -.
DR   UniGene; Hs.592115; -.
DR   HSSP; P06612; 1CY9.
DR   PhosphoSite; Q13472; -.
DR   PRIDE; Q13472; -.
DR   Ensembl; ENSG00000177302; Homo sapiens.
DR   GeneID; 7156; -.
DR   KEGG; hsa:7156; -.
DR   NMPDR; fig|9606.3.peg.13244; -.
DR   UCSC; uc002gsx.1; human.
DR   GeneCards; GC17M018117; -.
DR   H-InvDB; HIX0027125; -.
DR   HGNC; HGNC:11992; TOP3A.
DR   HPA; CAB002449; -.
DR   MIM; 601243; gene.
DR   PharmGKB; PA36673; -.
DR   HOGENOM; Q13472; -.
DR   HOVERGEN; Q13472; -.
DR   OMA; Q13472; TVRKEGP.
DR   BRENDA; 5.99.1.2; 247.
DR   NextBio; 28002; -.
DR   ArrayExpress; Q13472; -.
DR   Bgee; Q13472; -.
DR   CleanEx; HS_TOP3A; -.
DR   GermOnline; ENSG00000177302; Homo sapiens.
DR   GO; GO:0005694; C:chromosome; IEA:InterPro.
DR   GO; GO:0016605; C:PML body; IDA:UniProtKB.
DR   GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
DR   GO; GO:0003917; F:DNA topoisomerase type I activity; IEA:EC.
DR   GO; GO:0005515; F:protein binding; IPI:UniProtKB.
DR   GO; GO:0008270; F:zinc ion binding; IEA:UniProtKB-KW.
DR   GO; GO:0006265; P:DNA topological change; IEA:InterPro.
DR   GO; GO:0006268; P:DNA unwinding during replication; IEA:InterPro.
DR   GO; GO:0007126; P:meiosis; TAS:ProtInc.
DR   InterPro; IPR003601; Topo_IA_2.
DR   InterPro; IPR013497; Topo_IA_cen.
DR   InterPro; IPR013824; Topo_IA_cen_sub1.
DR   InterPro; IPR013826; Topo_IA_cen_sub3.
DR   InterPro; IPR000380; Topo_IA_core.
DR   InterPro; IPR003602; Topo_IA_DNA_bd.
DR   InterPro; IPR013498; Topo_IA_Znf.
DR   InterPro; IPR006171; Toprim_domain.
DR   InterPro; IPR006154; Toprim_sub.
DR   InterPro; IPR001878; Znf_CCHC.
DR   InterPro; IPR010666; Znf_GRF.
DR   Gene3D; G3DSA:1.10.460.10; Topo_IA_cen_sub1; 1.
DR   Gene3D; G3DSA:1.10.290.10; Topo_IA_cen_sub3; 1.
DR   PANTHER; PTHR11390; Topo_IA; 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   SMART; SM00343; ZnF_C2HC; 1.
DR   PROSITE; PS00396; TOPOISOMERASE_I_PROK; 1.
PE   1: Evidence at protein level;
KW   Alternative splicing; ATP-binding; Complete proteome; DNA-binding;
KW   Isomerase; Metal-binding; Nucleotide-binding; Phosphoprotein;
KW   Polymorphism; Repeat; Topoisomerase; Zinc; Zinc-finger.
FT   CHAIN         1   1001       DNA topoisomerase 3-alpha.
FT                                /FTId=PRO_0000145190.
FT   REPEAT      812    839       1.
FT   REPEAT      896    923       2.
FT   ZN_FING     658    685       C4-type (Potential).
FT   REGION      812    923       2 X 27 AA approximate repeats.
FT   ACT_SITE    362    362       For DNA cleavage activity (By
FT                                similarity).
FT   MOD_RES      54     54       Phosphoserine.
FT   MOD_RES     771    771       Phosphoserine.
FT   VAR_SEQ       1     25       Missing (in isoform Short).
FT                                /FTId=VSP_006524.
FT   VARIANT     459    459       D -> N (in dbSNP:rs28671051).
FT                                /FTId=VAR_052588.
FT   VARIANT     596    596       C -> Y.
FT                                /FTId=VAR_007529.
FT   VARIANT     742    742       D -> N (in dbSNP:rs9909732).
FT                                /FTId=VAR_052589.
FT   VARIANT     773    773       N -> D (in dbSNP:rs9911283).
FT                                /FTId=VAR_052590.
SQ   SEQUENCE   1001 AA;  112372 MW;  06558C749569E0C2 CRC64;
     MIFPVARYAL RWLRRPEDRA FSRAAMEMAL RGVRKVLCVA EKNDAAKGIA DLLSNGRMRR
     REGLSKFNKI YEFDYHLYGQ NVTMVMTSVS GHLLAHDFQM QFRKWQSCNP LVLFEAEIEK
     YCPENFVDIK KTLERETRQC QALVIWTDCD REGENIGFEI IHVCKAVKPN LQVLRARFSE
     ITPHAVRTAC ENLTEPDQRV SDAVDVRQEL DLRIGAAFTR FQTLRLQRIF PEVLAEQLIS
     YGSCQFPTLG FVVERFKAIQ AFVPEIFHRI KVTHDHKDGI VEFNWKRHRL FNHTACLVLY
     QLCVEDPMAT VVEVRSKPKS KWRPQALDTV ELEKLASRKL RINAKETMRI AEKLYTQGYI
     SYPRTETNIF PRDLNLTVLV EQQTPDPRWG AFAQSILERG GPTPRNGNKS DQAHPPIHPT
     KYTNNLQGDE QRLYEFIVRH FLACCSQDAQ GQETTVEIDI AQERFVAHGL MILARNYLDV
     YPYDHWSDKI LPVYEQGSHF QPSTVEMVDG ETSPPKLLTE ADLIALMEKH GIGTDATHAE
     HIETIKARMY VGLTPDKRFL PGHLGMGLVE GYDSMGYEMS KPDLRAELEA DLKLICDGKK
     DKFVVLRQQV QKYKQVFIEA VAKAKKLDEA LAQYFGNGTE LAQQEDIYPA MPEPIRKCPQ
     CNKDMVLKTK KNGGFYLSCM GFPECRSAVW LPDSVLEASR DSSVCPVCQP HPVYRLKLKF
     KRGSLPPTMP LEFVCCIGGC DDTLREILDL RFSGGPPRAS QPSGRLQANQ SLNRMDNSQH
     PQPADSRQTG SSKALAQTLP PPTAAGESNS VTCNCGQEAV LLTVRKEGPN RGRQFFKCNG
     GSCNFFLWAD SPNPGAGGPP ALAYRPLGAS LGCPPGPGIH LGGFGNPGDG SGSGTSCLCS
     QPSVTRTVQK DGPNKGRQFH TCAKPREQQC GFFQWVDENT APGTSGAPSW TGDRGRTLES
     EARSKRPRAS SSDMGSTAKK PRKCSLCHQP GHTRPFCPQN R
//