ID   TOP3B_HUMAN             Reviewed;         862 AA.
AC   O95985; A0M8Q3; Q9BUP5;
DT   30-MAY-2000, integrated into UniProtKB/Swiss-Prot.
DT   01-MAY-1999, sequence version 1.
DT   27-MAR-2024, entry version 204.
DE   RecName: Full=DNA topoisomerase 3-beta-1;
DE            EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10131};
DE   AltName: Full=DNA topoisomerase III beta-1;
GN   Name=TOP3B; Synonyms=TOP3B1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), ALTERNATIVE SPLICING, AND TISSUE
RP   SPECIFICITY.
RX   PubMed=9927731; DOI=10.1093/nar/27.4.993;
RA   Ng S.-W., Liu Y., Hasselblatt K.T., Mok S.C., Berkowitz R.S.;
RT   "A new human topoisomerase III that interacts with SGS1 protein.";
RL   Nucleic Acids Res. 27:993-1000(1999).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=9074928; DOI=10.1101/gr.7.3.250;
RA   Kawasaki K., Minoshima S., Nakato E., Shibuya K., Shintani A.,
RA   Schmeits J.L., Wang J., Shimizu N.;
RT   "One-megabase sequence analysis of the human immunoglobulin lambda gene
RT   locus.";
RL   Genome Res. 7:250-261(1997).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Hanai R., Li W., Wang J.C.;
RL   Submitted (AUG-1997) to the EMBL/GenBank/DDBJ databases.
RN   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
RA   Riou J.F., Goulaouic H., Grondard L.;
RL   Submitted (FEB-1999) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
RX   PubMed=15461802; DOI=10.1186/gb-2004-5-10-r84;
RA   Collins J.E., Wright C.L., Edwards C.A., Davis M.P., Grinham J.A.,
RA   Cole C.G., Goward M.E., Aguado B., Mallya M., Mokrab Y., Huckle E.J.,
RA   Beare D.M., Dunham I.;
RT   "A genome annotation-driven approach to cloning the human ORFeome.";
RL   Genome Biol. 5:R84.1-R84.11(2004).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ASN-365.
RC   TISSUE=Skin;
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 project:
RT   the Mammalian Gene Collection (MGC).";
RL   Genome Res. 14:2121-2127(2004).
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 than 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 (By similarity). Possesses
CC       negatively supercoiled DNA relaxing activity. {ECO:0000250}.
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   -!- INTERACTION:
CC       O95985; Q6UY14-3: ADAMTSL4; NbExp=3; IntAct=EBI-373403, EBI-10173507;
CC       O95985; Q9Y2T1: AXIN2; NbExp=3; IntAct=EBI-373403, EBI-4400025;
CC       O95985; O76071: CIAO1; NbExp=3; IntAct=EBI-373403, EBI-725145;
CC       O95985; Q14296: FASTK; NbExp=3; IntAct=EBI-373403, EBI-1754067;
CC       O95985; Q6PI77: GPRASP3; NbExp=3; IntAct=EBI-373403, EBI-11519926;
CC       O95985; Q63ZY3: KANK2; NbExp=3; IntAct=EBI-373403, EBI-2556193;
CC       O95985; Q9UJV3-2: MID2; NbExp=6; IntAct=EBI-373403, EBI-10172526;
CC       O95985; Q9UL42: PNMA2; NbExp=3; IntAct=EBI-373403, EBI-302355;
CC       O95985; Q7Z698: SPRED2; NbExp=4; IntAct=EBI-373403, EBI-7082156;
CC       O95985; Q9Y2D8: SSX2IP; NbExp=4; IntAct=EBI-373403, EBI-2212028;
CC       O95985; Q9H7E2-3: TDRD3; NbExp=4; IntAct=EBI-373403, EBI-10969939;
CC       O95985; Q8WV44: TRIM41; NbExp=4; IntAct=EBI-373403, EBI-725997;
CC       O95985; P15622-3: ZNF250; NbExp=3; IntAct=EBI-373403, EBI-10177272;
CC   -!- ALTERNATIVE PRODUCTS:
CC       Event=Alternative splicing; Named isoforms=3;
CC       Name=1;
CC         IsoId=O95985-1; Sequence=Displayed;
CC       Name=2;
CC         IsoId=O95985-2; Sequence=VSP_006525, VSP_006526;
CC       Name=3;
CC         IsoId=O95985-3; Sequence=VSP_006527, VSP_006528;
CC   -!- TISSUE SPECIFICITY: Isoform 1 is found in testis, heart and skeletal
CC       muscle. A 4 kb transcript which probably represents isoform 2 is found
CC       in thymus, kidney and pancreas. {ECO:0000269|PubMed:9927731}.
CC   -!- SIMILARITY: Belongs to the type IA topoisomerase family.
CC       {ECO:0000255|PROSITE-ProRule:PRU01383, ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=BAA20009.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
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DR   EMBL; AF053082; AAD15791.1; -; mRNA.
DR   EMBL; D87012; BAA20009.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; AF017146; AAD01614.1; -; mRNA.
DR   EMBL; AF125216; AAD29670.1; -; mRNA.
DR   EMBL; CR456596; CAG30482.1; -; mRNA.
DR   EMBL; BC002432; AAH02432.1; -; mRNA.
DR   CCDS; CCDS13797.1; -. [O95985-1]
DR   RefSeq; NP_001269041.1; NM_001282112.1. [O95985-1]
DR   RefSeq; NP_001269042.1; NM_001282113.1. [O95985-1]
DR   RefSeq; NP_003926.1; NM_003935.4. [O95985-1]
DR   RefSeq; XP_005261868.1; XM_005261811.1.
DR   RefSeq; XP_006724412.1; XM_006724349.1.
DR   RefSeq; XP_006724413.1; XM_006724350.1.
DR   RefSeq; XP_011528784.1; XM_011530482.1.
DR   PDB; 5GVC; X-ray; 2.44 A; A/B=1-612.
DR   PDB; 5GVE; X-ray; 3.61 A; A=1-612.
DR   PDBsum; 5GVC; -.
DR   PDBsum; 5GVE; -.
DR   AlphaFoldDB; O95985; -.
DR   SMR; O95985; -.
DR   BioGRID; 114452; 1476.
DR   ComplexPortal; CPX-1621; TDRD3-TOP3B type IA topoisomerase complex.
DR   CORUM; O95985; -.
DR   IntAct; O95985; 54.
DR   MINT; O95985; -.
DR   STRING; 9606.ENSP00000381773; -.
DR   iPTMnet; O95985; -.
DR   PhosphoSitePlus; O95985; -.
DR   BioMuta; TOP3B; -.
DR   EPD; O95985; -.
DR   jPOST; O95985; -.
DR   MassIVE; O95985; -.
DR   MaxQB; O95985; -.
DR   PaxDb; 9606-ENSP00000381773; -.
DR   PeptideAtlas; O95985; -.
DR   ProteomicsDB; 51161; -. [O95985-1]
DR   ProteomicsDB; 51162; -. [O95985-2]
DR   ProteomicsDB; 51163; -. [O95985-3]
DR   Pumba; O95985; -.
DR   Antibodypedia; 3974; 235 antibodies from 28 providers.
DR   DNASU; 8940; -.
DR   Ensembl; ENST00000357179.10; ENSP00000349705.5; ENSG00000100038.20. [O95985-1]
DR   Ensembl; ENST00000398793.6; ENSP00000381773.2; ENSG00000100038.20. [O95985-1]
DR   GeneID; 8940; -.
DR   KEGG; hsa:8940; -.
DR   MANE-Select; ENST00000357179.10; ENSP00000349705.5; NM_001282112.2; NP_001269041.1.
DR   UCSC; uc002zvs.5; human. [O95985-1]
DR   AGR; HGNC:11993; -.
DR   CTD; 8940; -.
DR   DisGeNET; 8940; -.
DR   GeneCards; TOP3B; -.
DR   HGNC; HGNC:11993; TOP3B.
DR   HPA; ENSG00000100038; Low tissue specificity.
DR   MIM; 603582; gene.
DR   neXtProt; NX_O95985; -.
DR   OpenTargets; ENSG00000100038; -.
DR   PharmGKB; PA36674; -.
DR   VEuPathDB; HostDB:ENSG00000100038; -.
DR   eggNOG; KOG1957; Eukaryota.
DR   GeneTree; ENSGT00940000156516; -.
DR   HOGENOM; CLU_002929_1_0_1; -.
DR   InParanoid; O95985; -.
DR   OMA; KGKTAYG; -.
DR   OrthoDB; 166270at2759; -.
DR   PhylomeDB; O95985; -.
DR   TreeFam; TF105288; -.
DR   PathwayCommons; O95985; -.
DR   SignaLink; O95985; -.
DR   BioGRID-ORCS; 8940; 23 hits in 1163 CRISPR screens.
DR   ChiTaRS; TOP3B; human.
DR   GeneWiki; TOP3B; -.
DR   GenomeRNAi; 8940; -.
DR   Pharos; O95985; Tbio.
DR   PRO; PR:O95985; -.
DR   Proteomes; UP000005640; Chromosome 22.
DR   RNAct; O95985; Protein.
DR   Bgee; ENSG00000100038; Expressed in paraflocculus and 108 other cell types or tissues.
DR   ExpressionAtlas; O95985; baseline and differential.
DR   GO; GO:0000793; C:condensed chromosome; IEA:Ensembl.
DR   GO; GO:0140225; C:DNA topoisomerase III-beta-TDRD3 complex; IPI:ComplexPortal.
DR   GO; GO:0005634; C:nucleus; IDA:ComplexPortal.
DR   GO; GO:0003677; F:DNA binding; TAS:ProtInc.
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; IEA:UniProtKB-EC.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0007059; P:chromosome segregation; IEA:Ensembl.
DR   GO; GO:0006265; P:DNA topological change; IBA:GO_Central.
DR   CDD; cd00186; TOP1Ac; 1.
DR   CDD; cd03362; TOPRIM_TopoIA_TopoIII; 1.
DR   Gene3D; 3.40.50.140; -; 1.
DR   Gene3D; 1.10.460.10; Topoisomerase I, domain 2; 1.
DR   Gene3D; 2.70.20.10; Topoisomerase I, domain 3; 1.
DR   Gene3D; 1.10.290.10; Topoisomerase I, domain 4; 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; IPR006171; TOPRIM_domain.
DR   InterPro; IPR034144; TOPRIM_TopoIII.
DR   PANTHER; PTHR11390:SF20; DNA TOPOISOMERASE 3-BETA-1; 1.
DR   PANTHER; PTHR11390; PROKARYOTIC DNA TOPOISOMERASE; 1.
DR   Pfam; PF01131; Topoisom_bac; 1.
DR   Pfam; PF01751; Toprim; 1.
DR   PRINTS; PR00417; PRTPISMRASEI.
DR   SMART; SM00437; TOP1Ac; 1.
DR   SMART; SM00436; TOP1Bc; 1.
DR   SMART; SM00493; TOPRIM; 1.
DR   SUPFAM; SSF56712; Prokaryotic type I DNA topoisomerase; 1.
DR   PROSITE; PS00396; TOPO_IA_1; 1.
DR   PROSITE; PS52039; TOPO_IA_2; 1.
DR   PROSITE; PS50880; TOPRIM; 1.
DR   Genevisible; O95985; HS.
PE   1: Evidence at protein level;
KW   3D-structure; Alternative splicing; DNA-binding; Isomerase;
KW   Reference proteome; Topoisomerase.
FT   CHAIN           1..862
FT                   /note="DNA topoisomerase 3-beta-1"
FT                   /id="PRO_0000145192"
FT   DOMAIN          3..153
FT                   /note="Toprim"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU00995"
FT   DOMAIN          171..593
FT                   /note="Topo IA-type catalytic"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01383"
FT   REGION          821..854
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   COMPBIAS        826..844
FT                   /note="Basic residues"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   ACT_SITE        336
FT                   /note="O-(5'-phospho-DNA)-tyrosine intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU01383"
FT   VAR_SEQ         703..730
FT                   /note="GMGCNECTHPSCQHSLSMLGIGQCVECE -> GECSHSLLSTGSCSLFSVPT
FT                   PALHQAGL (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_006525"
FT   VAR_SEQ         703..707
FT                   /note="GMGCN -> VVPCV (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_006527"
FT   VAR_SEQ         708..862
FT                   /note="Missing (in isoform 3)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_006528"
FT   VAR_SEQ         731..862
FT                   /note="Missing (in isoform 2)"
FT                   /evidence="ECO:0000305"
FT                   /id="VSP_006526"
FT   VARIANT         365
FT                   /note="D -> N (in dbSNP:rs9610728)"
FT                   /evidence="ECO:0000269|PubMed:15489334"
FT                   /id="VAR_052591"
FT   STRAND          3..10
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           11..21
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   TURN            22..24
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          27..30
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          37..56
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          61..66
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           78..81
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   TURN            82..84
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          87..92
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           94..96
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           98..106
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          110..115
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           120..133
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           134..136
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   TURN            140..143
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          147..149
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          153..156
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           157..165
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           172..199
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   TURN            200..203
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           209..211
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           218..233
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          239..248
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          254..259
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           267..275
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   TURN            276..279
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          282..295
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           303..312
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           318..330
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          333..335
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           350..355
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   TURN            356..359
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   TURN            361..363
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           364..373
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           398..401
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           403..419
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          424..435
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          438..449
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           451..454
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           457..459
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          475..487
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           496..505
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   TURN            510..513
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           514..523
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          526..530
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   TURN            531..533
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   STRAND          534..537
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           539..551
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           553..555
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           559..572
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           578..598
FT                   /evidence="ECO:0007829|PDB:5GVC"
FT   HELIX           601..610
FT                   /evidence="ECO:0007829|PDB:5GVC"
SQ   SEQUENCE   862 AA;  96662 MW;  75532827856CFF8F CRC64;
     MKTVLMVAEK PSLAQSIAKI LSRGSLSSHK GLNGACSVHE YTGTFAGQPV RFKMTSVCGH
     VMTLDFLGKY NKWDKVDPAE LFSQAPTEKK EANPKLNMVK FLQVEGRGCD YIVLWLDCDK
     EGENICFEVL DAVLPVMNKA HGGEKTVFRA RFSSITDTDI CNAMACLGEP DHNEALSVDA
     RQELDLRIGC AFTRFQTKYF QGKYGDLDSS LISFGPCQTP TLGFCVERHD KIQSFKPETY
     WVLQAKVNTD KDRSLLLDWD RVRVFDREIA QMFLNMTKLE KEAQVEATSR KEKAKQRPLA
     LNTVEMLRVA SSSLGMGPQH AMQTAERLYT QGYISYPRTE TTHYPENFDL KGSLRQQANH
     PYWADTVKRL LAEGINRPRK GHDAGDHPPI TPMKSATEAE LGGDAWRLYE YITRHFIATV
     SHDCKYLQST ISFRIGPELF TCSGKTVLSP GFTEVMPWQS VPLEESLPTC QRGDAFPVGE
     VKMLEKQTNP PDYLTEAELI TLMEKHGIGT DASIPVHINN ICQRNYVTVE SGRRLKPTNL
     GIVLVHGYYK IDAELVLPTI RSAVEKQLNL IAQGKADYRQ VLGHTLDVFK RKFHYFVDSI
     AGMDELMEVS FSPLAATGKP LSRCGKCHRF MKYIQAKPSR LHCSHCDETY TLPQNGTIKL
     YKELRCPLDD FELVLWSSGS RGKSYPLCPY CYNHPPFRDM KKGMGCNECT HPSCQHSLSM
     LGIGQCVECE SGVLVLDPTS GPKWKVACNK CNVVAHCFEN AHRVRVSADT CSVCEAALLD
     VDFNKAKSPL PGDETQHMGC VFCDPVFQEL VELKHAASCH PMHRGGPGRR QGRGRGRARR
     PPGKPNPRRP KDKMSALAAY FV
//