TOP3A_HUMAN
ID TOP3A_HUMAN Reviewed; 1001 AA.
AC Q13472; A8KA61; B4DK80; D3DXC7; Q13473;
DT 01-NOV-1997, integrated into UniProtKB/Swiss-Prot.
DT 01-NOV-1997, sequence version 1.
DT 03-AUG-2022, entry version 190.
DE RecName: Full=DNA topoisomerase 3-alpha;
DE EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10131, ECO:0000269|PubMed:20445207, ECO:0000269|PubMed:8622991};
DE AltName: Full=DNA topoisomerase III alpha;
GN Name=TOP3A; Synonyms=TOP3;
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] (ISOFORMS LONG AND SHORT), FUNCTION, AND
RP CATALYTIC ACTIVITY.
RX 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 [GENOMIC DNA].
RX PubMed=20843780; DOI=10.1093/nar/gkq750;
RA Wang W., Shen P., Thiyagarajan S., Lin S., Palm C., Horvath R.,
RA Klopstock T., Cutler D., Pique L., Schrijver I., Davis R.W., Mindrinos M.,
RA Speed T.P., Scharfe C.;
RT "Identification of rare DNA variants in mitochondrial disorders with
RT improved array-based sequencing.";
RL Nucleic Acids Res. 39:44-58(2011).
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS LONG AND 3).
RC TISSUE=Thalamus, and Trachea;
RX PubMed=14702039; DOI=10.1038/ng1285;
RA Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA Isogai T., Sugano S.;
RT "Complete sequencing and characterization of 21,243 full-length human
RT cDNAs.";
RL Nat. Genet. 36:40-45(2004).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16625196; DOI=10.1038/nature04689;
RA Zody M.C., Garber M., Adams D.J., Sharpe T., Harrow J., Lupski J.R.,
RA Nicholson C., Searle S.M., Wilming L., Young S.K., Abouelleil A.,
RA Allen N.R., Bi W., Bloom T., Borowsky M.L., Bugalter B.E., Butler J.,
RA Chang J.L., Chen C.-K., Cook A., Corum B., Cuomo C.A., de Jong P.J.,
RA DeCaprio D., Dewar K., FitzGerald M., Gilbert J., Gibson R., Gnerre S.,
RA Goldstein S., Grafham D.V., Grocock R., Hafez N., Hagopian D.S., Hart E.,
RA Norman C.H., Humphray S., Jaffe D.B., Jones M., Kamal M., Khodiyar V.K.,
RA LaButti K., Laird G., Lehoczky J., Liu X., Lokyitsang T., Loveland J.,
RA Lui A., Macdonald P., Major J.E., Matthews L., Mauceli E., McCarroll S.A.,
RA Mihalev A.H., Mudge J., Nguyen C., Nicol R., O'Leary S.B., Osoegawa K.,
RA Schwartz D.C., Shaw-Smith C., Stankiewicz P., Steward C., Swarbreck D.,
RA Venkataraman V., Whittaker C.A., Yang X., Zimmer A.R., Bradley A.,
RA Hubbard T., Birren B.W., Rogers J., Lander E.S., Nusbaum C.;
RT "DNA sequence of human chromosome 17 and analysis of rearrangement in the
RT human lineage.";
RL Nature 440:1045-1049(2006).
RN [5]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA Hunkapiller M.W., Myers E.W., Venter J.C.;
RL Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN [6]
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 project:
RT the Mammalian Gene Collection (MGC).";
RL Genome Res. 14:2121-2127(2004).
RN [7]
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 that
RT maintain genome integrity.";
RL EMBO J. 24:1465-1476(2005).
RN [8]
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., Brown G.W.,
RA 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 [9]
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 component
RT of the Bloom helicase-double Holliday junction dissolvasome.";
RL Genes Dev. 22:2856-2868(2008).
RN [10]
RP IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC TISSUE=Cervix carcinoma;
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).
RN [11]
RP FUNCTION, CATALYTIC ACTIVITY, SUBUNIT, COFACTOR, AND INTERACTION WITH RMI1.
RX PubMed=20445207; DOI=10.1074/jbc.m110.123216;
RA Yang J., Bachrati C.Z., Ou J., Hickson I.D., Brown G.W.;
RT "Human topoisomerase IIIalpha is a single-stranded DNA decatenase that is
RT stimulated by BLM and RMI1.";
RL J. Biol. Chem. 285:21426-21436(2010).
RN [12]
RP INTERACTION WITH BLM.
RX PubMed=23509288; DOI=10.1073/pnas.1220921110;
RA Wan L., Han J., Liu T., Dong S., Xie F., Chen H., Huang J.;
RT "Scaffolding protein SPIDR/KIAA0146 connects the Bloom syndrome helicase
RT with homologous recombination repair.";
RL Proc. Natl. Acad. Sci. U.S.A. 110:10646-10651(2013).
RN [13]
RP FUNCTION, INVOLVEMENT IN MGRISCE2, AND VARIANT MGRISCE2 VAL-176.
RX PubMed=30057030; DOI=10.1016/j.ajhg.2018.07.001;
RG GOSgene;
RA Martin C.A., Sarlos K., Logan C.V., Thakur R.S., Parry D.A., Bizard A.H.,
RA Leitch A., Cleal L., Ali N.S., Al-Owain M.A., Allen W., Altmueller J.,
RA Aza-Carmona M., Barakat B.A.Y., Barraza-Garcia J., Begtrup A., Bogliolo M.,
RA Cho M.T., Cruz-Rojo J., Dhahrabi H.A.M., Elcioglu N.H., Gorman G.S.,
RA Jobling R., Kesterton I., Kishita Y., Kohda M., Le Quesne Stabej P.,
RA Malallah A.J., Nuernberg P., Ohtake A., Okazaki Y., Pujol R., Ramirez M.J.,
RA Revah-Politi A., Shimura M., Stevens P., Taylor R.W., Turner L.,
RA Williams H., Wilson C., Yigit G., Zahavich L., Alkuraya F.S., Surralles J.,
RA Iglesias A., Murayama K., Wollnik B., Dattani M., Heath K.E., Hickson I.D.,
RA Jackson A.P.;
RT "Mutations in TOP3A cause a Bloom syndrome-like disorder.";
RL Am. J. Hum. Genet. 103:221-231(2018).
RN [14]
RP FUNCTION, SUBUNIT, SUBCELLULAR LOCATION, INVOLVEMENT IN PEOB5, VARIANTS
RP PEOB5 VAL-100 AND 135-ARG--ARG-1001 DEL, CHARACTERIZATION OF VARIANT PEOB5
RP VAL-100, AND MUTAGENESIS OF TYR-362.
RX PubMed=29290614; DOI=10.1016/j.molcel.2017.11.033;
RA Nicholls T.J., Nadalutti C.A., Motori E., Sommerville E.W., Gorman G.S.,
RA Basu S., Hoberg E., Turnbull D.M., Chinnery P.F., Larsson N.G., Larsson E.,
RA Falkenberg M., Taylor R.W., Griffith J.D., Gustafsson C.M.;
RT "Topoisomerase 3alpha is required for decatenation and segregation of human
RT mtDNA.";
RL Mol. Cell 69:9-23(2018).
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
CC (PubMed:30057030). It is required for mtDNA decatenation and
CC segregation after completion of replication, in a process that does not
CC require BLM, RMI1 and RMI2 (PubMed:29290614).
CC {ECO:0000269|PubMed:20445207, ECO:0000269|PubMed:29290614,
CC ECO:0000269|PubMed:30057030, ECO:0000269|PubMed:8622991}.
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, ECO:0000269|PubMed:20445207,
CC ECO:0000269|PubMed:8622991};
CC -!- COFACTOR:
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:20445207};
CC -!- SUBUNIT: Binds ssDNA (PubMed:29290614). Interacts (via N-terminal
CC region) with BLM; the interaction is direct. Directly interacts with
CC RMI1. Component of the RMI complex, containing at least TOP3A, RMI1 and
CC RMI2. The RMI complex interacts with BLM. {ECO:0000269|PubMed:15775963,
CC ECO:0000269|PubMed:18923082, ECO:0000269|PubMed:18923083,
CC ECO:0000269|PubMed:20445207, ECO:0000269|PubMed:23509288,
CC ECO:0000269|PubMed:29290614}.
CC -!- INTERACTION:
CC Q13472; P54132: BLM; NbExp=9; IntAct=EBI-621345, EBI-621372;
CC Q13472; Q9H9A7: RMI1; NbExp=10; IntAct=EBI-621345, EBI-621339;
CC -!- SUBCELLULAR LOCATION: Mitochondrion matrix
CC {ECO:0000269|PubMed:29290614}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=3;
CC Name=Long;
CC IsoId=Q13472-1; Sequence=Displayed;
CC Name=Short;
CC IsoId=Q13472-2; Sequence=VSP_006524;
CC Name=3;
CC IsoId=Q13472-3; Sequence=VSP_054189;
CC -!- TISSUE SPECIFICITY: High expression is found in testis, heart, skeletal
CC muscle and pancreas.
CC -!- DISEASE: Microcephaly, growth restriction, and increased sister
CC chromatid exchange 2 (MGRISCE2) [MIM:618097]: An autosomal recessive
CC disorder characterized by intrauterine growth restriction, poor
CC postnatal growth with short stature and microcephaly, and increased
CC sister chromatid exchange on cell studies.
CC {ECO:0000269|PubMed:30057030}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- DISEASE: Progressive external ophthalmoplegia with mitochondrial DNA
CC deletions, autosomal recessive 5 (PEOB5) [MIM:618098]: A form of
CC progressive external ophthalmoplegia, a mitochondrial myopathy
CC characterized by progressive paralysis of the levator palpebrae,
CC orbicularis oculi, and extraocular muscles. PEOB5 features include
CC slowly progressive ptosis, intermittent double vision, cardiac
CC arrhythmias, exercise intolerance, proximal limb and neck muscle
CC weakness, and cerebellar ataxia. Patients skeletal muscle biopsy show
CC numerous COX-deficient ragged-red fibers, increased mtDNA deletions,
CC and extensive variable mtDNA rearrangements.
CC {ECO:0000269|PubMed:29290614}. Note=The disease is caused by variants
CC affecting the gene represented in this entry.
CC -!- SIMILARITY: Belongs to the type IA topoisomerase family. {ECO:0000305}.
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DR EMBL; U43431; AAB03694.1; -; mRNA.
DR EMBL; U43431; AAB03695.1; -; mRNA.
DR EMBL; HQ205026; ADP90454.1; -; Genomic_DNA.
DR EMBL; HQ205027; ADP90455.1; -; Genomic_DNA.
DR EMBL; HQ205028; ADP90456.1; -; Genomic_DNA.
DR EMBL; HQ205029; ADP90457.1; -; Genomic_DNA.
DR EMBL; HQ205030; ADP90458.1; -; Genomic_DNA.
DR EMBL; HQ205031; ADP90459.1; -; Genomic_DNA.
DR EMBL; HQ205032; ADP90460.1; -; Genomic_DNA.
DR EMBL; HQ205033; ADP90461.1; -; Genomic_DNA.
DR EMBL; HQ205034; ADP90462.1; -; Genomic_DNA.
DR EMBL; HQ205035; ADP90463.1; -; Genomic_DNA.
DR EMBL; HQ205036; ADP90464.1; -; Genomic_DNA.
DR EMBL; HQ205037; ADP90465.1; -; Genomic_DNA.
DR EMBL; HQ205038; ADP90466.1; -; Genomic_DNA.
DR EMBL; HQ205039; ADP90467.1; -; Genomic_DNA.
DR EMBL; HQ205040; ADP90468.1; -; Genomic_DNA.
DR EMBL; HQ205041; ADP90469.1; -; Genomic_DNA.
DR EMBL; HQ205042; ADP90470.1; -; Genomic_DNA.
DR EMBL; HQ205043; ADP90471.1; -; Genomic_DNA.
DR EMBL; HQ205044; ADP90472.1; -; Genomic_DNA.
DR EMBL; HQ205045; ADP90473.1; -; Genomic_DNA.
DR EMBL; HQ205046; ADP90474.1; -; Genomic_DNA.
DR EMBL; HQ205047; ADP90475.1; -; Genomic_DNA.
DR EMBL; HQ205048; ADP90476.1; -; Genomic_DNA.
DR EMBL; HQ205049; ADP90477.1; -; Genomic_DNA.
DR EMBL; HQ205050; ADP90478.1; -; Genomic_DNA.
DR EMBL; HQ205051; ADP90479.1; -; Genomic_DNA.
DR EMBL; HQ205052; ADP90480.1; -; Genomic_DNA.
DR EMBL; HQ205053; ADP90481.1; -; Genomic_DNA.
DR EMBL; HQ205054; ADP90482.1; -; Genomic_DNA.
DR EMBL; HQ205055; ADP90483.1; -; Genomic_DNA.
DR EMBL; HQ205056; ADP90484.1; -; Genomic_DNA.
DR EMBL; HQ205057; ADP90485.1; -; Genomic_DNA.
DR EMBL; HQ205058; ADP90486.1; -; Genomic_DNA.
DR EMBL; HQ205059; ADP90487.1; -; Genomic_DNA.
DR EMBL; HQ205060; ADP90488.1; -; Genomic_DNA.
DR EMBL; HQ205061; ADP90489.1; -; Genomic_DNA.
DR EMBL; HQ205062; ADP90490.1; -; Genomic_DNA.
DR EMBL; HQ205063; ADP90491.1; -; Genomic_DNA.
DR EMBL; HQ205064; ADP90492.1; -; Genomic_DNA.
DR EMBL; HQ205065; ADP90493.1; -; Genomic_DNA.
DR EMBL; AK292926; BAF85615.1; -; mRNA.
DR EMBL; AK296437; BAG59092.1; -; mRNA.
DR EMBL; AC127537; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; CH471196; EAW55646.1; -; Genomic_DNA.
DR EMBL; CH471196; EAW55648.1; -; Genomic_DNA.
DR EMBL; CH471196; EAW55649.1; -; Genomic_DNA.
DR EMBL; BC051748; AAH51748.1; -; mRNA.
DR CCDS; CCDS11194.1; -. [Q13472-1]
DR RefSeq; NP_001307688.1; NM_001320759.1. [Q13472-3]
DR RefSeq; NP_004609.1; NM_004618.4. [Q13472-1]
DR PDB; 4CGY; X-ray; 2.85 A; A=2-753.
DR PDB; 4CHT; X-ray; 3.25 A; A=2-753.
DR PDBsum; 4CGY; -.
DR PDBsum; 4CHT; -.
DR AlphaFoldDB; Q13472; -.
DR SMR; Q13472; -.
DR BioGRID; 113009; 97.
DR ComplexPortal; CPX-3301; BTR double Holliday Junction dissolution complex.
DR CORUM; Q13472; -.
DR DIP; DIP-33323N; -.
DR IntAct; Q13472; 38.
DR MINT; Q13472; -.
DR STRING; 9606.ENSP00000442336; -.
DR iPTMnet; Q13472; -.
DR PhosphoSitePlus; Q13472; -.
DR BioMuta; TOP3A; -.
DR DMDM; 2501242; -.
DR EPD; Q13472; -.
DR jPOST; Q13472; -.
DR MassIVE; Q13472; -.
DR MaxQB; Q13472; -.
DR PaxDb; Q13472; -.
DR PeptideAtlas; Q13472; -.
DR PRIDE; Q13472; -.
DR ProteomicsDB; 4437; -.
DR ProteomicsDB; 59469; -. [Q13472-1]
DR ProteomicsDB; 59470; -. [Q13472-2]
DR Antibodypedia; 43348; 83 antibodies from 19 providers.
DR DNASU; 7156; -.
DR Ensembl; ENST00000321105.10; ENSP00000321636.5; ENSG00000177302.15. [Q13472-1]
DR Ensembl; ENST00000542570.5; ENSP00000442336.2; ENSG00000177302.15. [Q13472-1]
DR Ensembl; ENST00000580095.5; ENSP00000462790.1; ENSG00000177302.15. [Q13472-2]
DR Ensembl; ENST00000638894.1; ENSP00000492229.1; ENSG00000284238.2. [Q13472-1]
DR Ensembl; ENST00000639065.1; ENSP00000491260.1; ENSG00000284238.2. [Q13472-2]
DR Ensembl; ENST00000640743.2; ENSP00000491689.1; ENSG00000284238.2. [Q13472-1]
DR GeneID; 7156; -.
DR KEGG; hsa:7156; -.
DR MANE-Select; ENST00000321105.10; ENSP00000321636.5; NM_004618.5; NP_004609.1.
DR UCSC; uc002gsx.1; human. [Q13472-1]
DR CTD; 7156; -.
DR DisGeNET; 7156; -.
DR GeneCards; TOP3A; -.
DR HGNC; HGNC:11992; TOP3A.
DR HPA; ENSG00000177302; Low tissue specificity.
DR MalaCards; TOP3A; -.
DR MIM; 601243; gene.
DR MIM; 618097; phenotype.
DR MIM; 618098; phenotype.
DR neXtProt; NX_Q13472; -.
DR OpenTargets; ENSG00000177302; -.
DR Orphanet; 508512; Intrauterine growth restriction-congenital multiple cafe-au-lait macules-increased sister chromatid exchange syndrome.
DR PharmGKB; PA36673; -.
DR VEuPathDB; HostDB:ENSG00000177302; -.
DR eggNOG; KOG1956; Eukaryota.
DR GeneTree; ENSGT00940000156701; -.
DR HOGENOM; CLU_002929_1_2_1; -.
DR InParanoid; Q13472; -.
DR OMA; EHICFEV; -.
DR OrthoDB; 373433at2759; -.
DR PhylomeDB; Q13472; -.
DR TreeFam; TF105287; -.
DR PathwayCommons; Q13472; -.
DR Reactome; R-HSA-5685938; HDR through Single Strand Annealing (SSA).
DR Reactome; R-HSA-5685942; HDR through Homologous Recombination (HRR).
DR Reactome; R-HSA-5693554; Resolution of D-loop Structures through Synthesis-Dependent Strand Annealing (SDSA).
DR Reactome; R-HSA-5693568; Resolution of D-loop Structures through Holliday Junction Intermediates.
DR Reactome; R-HSA-5693579; Homologous DNA Pairing and Strand Exchange.
DR Reactome; R-HSA-5693607; Processing of DNA double-strand break ends.
DR Reactome; R-HSA-5693616; Presynaptic phase of homologous DNA pairing and strand exchange.
DR Reactome; R-HSA-6804756; Regulation of TP53 Activity through Phosphorylation.
DR Reactome; R-HSA-69473; G2/M DNA damage checkpoint.
DR Reactome; R-HSA-912446; Meiotic recombination.
DR Reactome; R-HSA-9701192; Defective HDR through Homologous Recombination (HRR) due to BRCA1 loss-of-function.
DR Reactome; R-HSA-9704331; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA1 binding function.
DR Reactome; R-HSA-9704646; Defective HDR through Homologous Recombination Repair (HRR) due to PALB2 loss of BRCA2/RAD51/RAD51C binding function.
DR Reactome; R-HSA-9709570; Impaired BRCA2 binding to RAD51.
DR Reactome; R-HSA-9709603; Impaired BRCA2 binding to PALB2.
DR SignaLink; Q13472; -.
DR BioGRID-ORCS; 7156; 726 hits in 1090 CRISPR screens.
DR ChiTaRS; TOP3A; human.
DR GeneWiki; TOP3A; -.
DR GenomeRNAi; 7156; -.
DR Pharos; Q13472; Tbio.
DR PRO; PR:Q13472; -.
DR Proteomes; UP000005640; Chromosome 17.
DR RNAct; Q13472; protein.
DR Bgee; ENSG00000177302; Expressed in blood and 107 other tissues.
DR ExpressionAtlas; Q13472; baseline and differential.
DR Genevisible; Q13472; HS.
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; IDA:UniProtKB.
DR GO; GO:0031422; C:RecQ family helicase-topoisomerase III complex; IPI: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; IDA:UniProtKB.
DR GO; GO:0003697; F:single-stranded DNA binding; IDA:UniProtKB.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0051304; P:chromosome separation; IMP:UniProtKB.
DR GO; GO:0006265; P:DNA topological change; IDA:UniProtKB.
DR GO; GO:0000724; P:double-strand break repair via homologous recombination; IDA:ComplexPortal.
DR GO; GO:0051321; P:meiotic cell cycle; TAS:ProtInc.
DR GO; GO:0032042; P:mitochondrial DNA metabolic process; IMP:UniProtKB.
DR GO; GO:0071139; P:resolution of recombination intermediates; IDA:ComplexPortal.
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 1: Evidence at protein level;
KW 3D-structure; Alternative splicing; Disease variant; DNA-binding; Dwarfism;
KW Isomerase; Magnesium; Metal-binding; Mitochondrion;
KW Primary mitochondrial disease; Progressive external ophthalmoplegia;
KW Reference proteome; Repeat; Topoisomerase; Zinc; Zinc-finger.
FT CHAIN 1..1001
FT /note="DNA topoisomerase 3-alpha"
FT /id="PRO_0000145190"
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 811..851
FT /note="GRF-type 1"
FT ZN_FING 896..939
FT /note="GRF-type 2"
FT REGION 400..424
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 774..810
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 937..1001
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 937..951
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"
FT VAR_SEQ 1..105
FT /note="MIFPVARYALRWLRRPEDRAFSRAAMEMALRGVRKVLCVAEKNDAAKGIADL
FT LSNGRMRRREGLSKFNKIYEFDYHLYGQNVTMVMTSVSGHLLAHDFQMQFRKW -> MN
FT LIIICMAR (in isoform 3)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_054189"
FT VAR_SEQ 1..25
FT /note="Missing (in isoform Short)"
FT /evidence="ECO:0000303|PubMed:8622991"
FT /id="VSP_006524"
FT VARIANT 100
FT /note="M -> V (in PEOB5; results in decreased DNA
FT decatenation; dbSNP:rs376902371)"
FT /evidence="ECO:0000269|PubMed:29290614"
FT /id="VAR_081105"
FT VARIANT 135..1001
FT /note="Missing (in PEOB5)"
FT /evidence="ECO:0000269|PubMed:29290614"
FT /id="VAR_081106"
FT VARIANT 176
FT /note="A -> V (in MGRISCE2)"
FT /evidence="ECO:0000269|PubMed:30057030"
FT /id="VAR_081107"
FT VARIANT 459
FT /note="D -> N (in dbSNP:rs28671051)"
FT /id="VAR_052588"
FT VARIANT 596
FT /note="C -> Y"
FT /id="VAR_007529"
FT VARIANT 742
FT /note="D -> N (in dbSNP:rs9909732)"
FT /id="VAR_052589"
FT VARIANT 773
FT /note="N -> D (in dbSNP:rs9911283)"
FT /id="VAR_052590"
FT MUTAGEN 362
FT /note="Y->F: Decreased DNA decatenation."
FT /evidence="ECO:0000269|PubMed:29290614"
FT HELIX 23..30
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 35..42
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 43..54
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 59..61
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 70..77
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 80..88
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 95..98
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 100..103
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 105..107
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 110..114
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 118..121
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 124..126
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 127..139
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 141..147
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 151..165
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 172..175
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 183..191
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 198..229
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 231..234
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 245..261
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 266..276
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 279..285
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 293..304
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 309..321
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 329..338
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 344..356
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 376..381
FT /evidence="ECO:0007829|PDB:4CGY"
FT TURN 382..385
FT /evidence="ECO:0007829|PDB:4CGY"
FT TURN 387..389
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 390..398
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 428..444
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 449..460
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 463..474
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 476..479
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 503..511
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 520..530
FT /evidence="ECO:0007829|PDB:4CGY"
FT TURN 534..537
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 538..547
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 550..553
FT /evidence="ECO:0007829|PDB:4CGY"
FT STRAND 559..561
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 563..573
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 583..596
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 602..622
FT /evidence="ECO:0007829|PDB:4CGY"
FT HELIX 625..635
FT /evidence="ECO:0007829|PDB:4CGY"
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
