TOP1M_HUMAN
ID TOP1M_HUMAN Reviewed; 601 AA.
AC Q969P6; B7ZAR5; E7ES89; Q86ST4; Q86V82;
DT 31-JAN-2002, integrated into UniProtKB/Swiss-Prot.
DT 01-DEC-2001, sequence version 1.
DT 03-AUG-2022, entry version 182.
DE RecName: Full=DNA topoisomerase I, mitochondrial;
DE Short=TOP1mt;
DE EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10130};
DE Flags: Precursor;
GN Name=TOP1MT;
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 [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, COFACTOR,
RP SUBCELLULAR LOCATION, TRANSIT PEPTIDE CLEAVAGE SITE, AND TISSUE
RP SPECIFICITY.
RX PubMed=11526219; DOI=10.1073/pnas.191321998;
RA Zhang H., Barcelo J.M., Lee B., Kohlhagen G., Zimonjic D.B., Popescu N.C.,
RA Pommier Y.;
RT "Human mitochondrial topoisomerase I.";
RL Proc. Natl. Acad. Sci. U.S.A. 98:10608-10613(2001).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), AND VARIANT TRP-525.
RC TISSUE=Testis;
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 [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX PubMed=16421571; DOI=10.1038/nature04406;
RA Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M.,
RA Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L.,
RA Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S.,
RA Asakawa T., Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A.,
RA Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III,
RA Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K.,
RA Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P.,
RA Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H.,
RA Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B.,
RA O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K.,
RA Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L.,
RA Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G.,
RA Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W.,
RA Platzer M., Shimizu N., Lander E.S.;
RT "DNA sequence and analysis of human chromosome 8.";
RL Nature 439:331-335(2006).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), AND VARIANT ILE-256.
RC TISSUE=Brain, and Lung;
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 duplication of mitochondrial DNA 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-(3'-phosphotyrosyl)-
CC enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free
CC DNA strand then rotates around the intact phosphodiester bond on the
CC opposing strand, thus removing DNA supercoils. Finally, in the
CC religation step, the DNA 5'-OH attacks the covalent intermediate to
CC expel the active-site tyrosine and restore the DNA phosphodiester
CC backbone (By similarity). {ECO:0000250, ECO:0000269|PubMed:11526219}.
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:PRU10130};
CC -!- COFACTOR:
CC Name=Ca(2+); Xref=ChEBI:CHEBI:29108;
CC Evidence={ECO:0000269|PubMed:11526219};
CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420;
CC Evidence={ECO:0000269|PubMed:11526219};
CC Note=Divalent metal ions (calcium or magnesium).
CC {ECO:0000269|PubMed:11526219};
CC -!- SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:11526219}.
CC -!- ALTERNATIVE PRODUCTS:
CC Event=Alternative splicing; Named isoforms=2;
CC Name=1;
CC IsoId=Q969P6-1; Sequence=Displayed;
CC Name=2;
CC IsoId=Q969P6-2; Sequence=VSP_044783;
CC -!- TISSUE SPECIFICITY: Ubiquitous; highest in skeletal muscle, heart,
CC brain and fetal liver. {ECO:0000269|PubMed:11526219}.
CC -!- SIMILARITY: Belongs to the type IB topoisomerase family. {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAH44646.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; AF349031; AAL10791.1; -; Genomic_DNA.
DR EMBL; AF349018; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349019; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349020; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349021; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349022; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349023; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349024; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349025; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349026; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349027; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349028; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349029; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349030; AAL10791.1; JOINED; Genomic_DNA.
DR EMBL; AF349017; AAL05624.1; -; mRNA.
DR EMBL; AK316380; BAH14751.1; -; mRNA.
DR EMBL; AC087793; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR EMBL; BC044646; AAH44646.1; ALT_INIT; mRNA.
DR EMBL; BC052285; AAH52285.1; -; mRNA.
DR EMBL; BC071914; AAH71914.1; -; mRNA.
DR CCDS; CCDS59115.1; -. [Q969P6-2]
DR CCDS; CCDS6400.1; -. [Q969P6-1]
DR RefSeq; NP_001245375.1; NM_001258446.1. [Q969P6-2]
DR RefSeq; NP_001245376.1; NM_001258447.1. [Q969P6-2]
DR RefSeq; NP_443195.1; NM_052963.2. [Q969P6-1]
DR AlphaFoldDB; Q969P6; -.
DR SMR; Q969P6; -.
DR BioGRID; 125510; 30.
DR IntAct; Q969P6; 11.
DR STRING; 9606.ENSP00000328835; -.
DR ChEMBL; CHEMBL2362989; -.
DR DrugBank; DB00762; Irinotecan.
DR DrugBank; DB01030; Topotecan.
DR DrugCentral; Q969P6; -.
DR iPTMnet; Q969P6; -.
DR PhosphoSitePlus; Q969P6; -.
DR SwissPalm; Q969P6; -.
DR BioMuta; TOP1MT; -.
DR DMDM; 20140694; -.
DR EPD; Q969P6; -.
DR jPOST; Q969P6; -.
DR MassIVE; Q969P6; -.
DR MaxQB; Q969P6; -.
DR PaxDb; Q969P6; -.
DR PeptideAtlas; Q969P6; -.
DR PRIDE; Q969P6; -.
DR ProteomicsDB; 17936; -.
DR ProteomicsDB; 75812; -. [Q969P6-1]
DR Antibodypedia; 958; 256 antibodies from 27 providers.
DR CPTC; Q969P6; 3 antibodies.
DR DNASU; 116447; -.
DR Ensembl; ENST00000329245.9; ENSP00000328835.3; ENSG00000184428.13. [Q969P6-1]
DR Ensembl; ENST00000519148.5; ENSP00000429169.1; ENSG00000184428.13. [Q969P6-2]
DR Ensembl; ENST00000521193.5; ENSP00000428369.1; ENSG00000184428.13. [Q969P6-2]
DR Ensembl; ENST00000523676.5; ENSP00000429181.1; ENSG00000184428.13. [Q969P6-2]
DR GeneID; 116447; -.
DR KEGG; hsa:116447; -.
DR MANE-Select; ENST00000329245.9; ENSP00000328835.3; NM_052963.3; NP_443195.1.
DR UCSC; uc003yxz.6; human. [Q969P6-1]
DR CTD; 116447; -.
DR DisGeNET; 116447; -.
DR GeneCards; TOP1MT; -.
DR HGNC; HGNC:29787; TOP1MT.
DR HPA; ENSG00000184428; Low tissue specificity.
DR MIM; 606387; gene.
DR neXtProt; NX_Q969P6; -.
DR OpenTargets; ENSG00000184428; -.
DR PharmGKB; PA134922772; -.
DR VEuPathDB; HostDB:ENSG00000184428; -.
DR eggNOG; KOG0981; Eukaryota.
DR GeneTree; ENSGT00940000162943; -.
DR HOGENOM; CLU_009193_2_0_1; -.
DR InParanoid; Q969P6; -.
DR OMA; RNYIDPR; -.
DR OrthoDB; 303947at2759; -.
DR PhylomeDB; Q969P6; -.
DR TreeFam; TF105281; -.
DR BRENDA; 5.6.2.1; 2681.
DR PathwayCommons; Q969P6; -.
DR SignaLink; Q969P6; -.
DR SIGNOR; Q969P6; -.
DR BioGRID-ORCS; 116447; 63 hits in 1079 CRISPR screens.
DR ChiTaRS; TOP1MT; human.
DR GenomeRNAi; 116447; -.
DR Pharos; Q969P6; Tclin.
DR PRO; PR:Q969P6; -.
DR Proteomes; UP000005640; Chromosome 8.
DR RNAct; Q969P6; protein.
DR Bgee; ENSG00000184428; Expressed in right lobe of liver and 137 other tissues.
DR ExpressionAtlas; Q969P6; baseline and differential.
DR Genevisible; Q969P6; HS.
DR GO; GO:0005694; C:chromosome; IEA:InterPro.
DR GO; GO:0042645; C:mitochondrial nucleoid; IDA:BHF-UCL.
DR GO; GO:0005739; C:mitochondrion; IDA:HPA.
DR GO; GO:0005654; C:nucleoplasm; IDA:HPA.
DR GO; GO:0003677; F:DNA binding; IEA:UniProtKB-KW.
DR GO; GO:0003917; F:DNA topoisomerase type I (single strand cut, ATP-independent) activity; IBA:GO_Central.
DR GO; GO:0006260; P:DNA replication; IBA:GO_Central.
DR GO; GO:0006265; P:DNA topological change; IBA:GO_Central.
DR CDD; cd00659; Topo_IB_C; 1.
DR Gene3D; 1.10.10.41; -; 1.
DR Gene3D; 1.10.132.10; -; 1.
DR Gene3D; 2.170.11.10; -; 1.
DR Gene3D; 3.90.15.10; -; 1.
DR InterPro; IPR011010; DNA_brk_join_enz.
DR InterPro; IPR013034; DNA_topo_DNA_db_N_dom1.
DR InterPro; IPR013030; DNA_topo_DNA_db_N_dom2.
DR InterPro; IPR001631; TopoI.
DR InterPro; IPR018521; TopoI_AS.
DR InterPro; IPR025834; TopoI_C_dom.
DR InterPro; IPR014711; TopoI_cat_a-hlx-sub_euk.
DR InterPro; IPR014727; TopoI_cat_a/b-sub_euk.
DR InterPro; IPR013500; TopoI_cat_euk.
DR InterPro; IPR008336; TopoI_DNA-bd_euk.
DR InterPro; IPR036202; TopoI_DNA-bd_euk_N_sf.
DR InterPro; IPR013499; TopoI_euk.
DR Pfam; PF14370; Topo_C_assoc; 1.
DR Pfam; PF01028; Topoisom_I; 1.
DR Pfam; PF02919; Topoisom_I_N; 1.
DR PRINTS; PR00416; EUTPISMRASEI.
DR SMART; SM00435; TOPEUc; 1.
DR SUPFAM; SSF56349; SSF56349; 1.
DR SUPFAM; SSF56741; SSF56741; 1.
DR PROSITE; PS00176; TOPOISOMERASE_I_EUK; 1.
PE 1: Evidence at protein level;
KW Alternative splicing; DNA-binding; Isomerase; Mitochondrion;
KW Reference proteome; Topoisomerase; Transit peptide.
FT TRANSIT 1..50
FT /note="Mitochondrion"
FT /evidence="ECO:0000305|PubMed:11526219"
FT CHAIN 51..601
FT /note="DNA topoisomerase I, mitochondrial"
FT /id="PRO_0000034797"
FT REGION 22..48
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT REGION 261..262
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 324..329
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT REGION 421..423
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT ACT_SITE 559
FT /note="O-(3'-phospho-DNA)-tyrosine intermediate"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10130"
FT SITE 152
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 200
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 248
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 279
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 337
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 368
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 410
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 468
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT SITE 486
FT /note="Interaction with DNA"
FT /evidence="ECO:0000250"
FT VAR_SEQ 1..98
FT /note="Missing (in isoform 2)"
FT /evidence="ECO:0000303|PubMed:14702039"
FT /id="VSP_044783"
FT VARIANT 256
FT /note="V -> I (in dbSNP:rs11544484)"
FT /evidence="ECO:0000269|PubMed:15489334"
FT /id="VAR_052593"
FT VARIANT 525
FT /note="R -> W (in dbSNP:rs2293925)"
FT /evidence="ECO:0000269|PubMed:14702039"
FT /id="VAR_021863"
FT CONFLICT 116
FT /note="N -> S (in Ref. 2; BAH14751)"
FT /evidence="ECO:0000305"
SQ SEQUENCE 601 AA; 69872 MW; A012248D4250C675 CRC64;
MRVVRLLRLR AALTLLGEVP RRPASRGVPG SRRTQKGSGA RWEKEKHEDG VKWRQLEHKG
PYFAPPYEPL PDGVRFFYEG RPVRLSVAAE EVATFYGRML DHEYTTKEVF RKNFFNDWRK
EMAVEEREVI KSLDKCDFTE IHRYFVDKAA ARKVLSREEK QKLKEEAEKL QQEFGYCILD
GHQEKIGNFK IEPPGLFRGR GDHPKMGMLK RRITPEDVVI NCSRDSKIPE PPAGHQWKEV
RSDNTVTWLA AWTESVQNSI KYIMLNPCSK LKGETAWQKF ETARRLRGFV DEIRSQYRAD
WKSREMKTRQ RAVALYFIDK LALRAGNEKE DGEAADTVGC CSLRVEHVQL HPEADGCQHV
VEFDFLGKDC IRYYNRVPVE KPVYKNLQLF MENKDPRDDL FDRLTTTSLN KHLQELMDGL
TAKVFRTYNA SITLQEQLRA LTRAEDSIAA KILSYNRANR VVAILCNHQR ATPSTFEKSM
QNLQTKIQAK KEQVAEARAE LRRARAEHKA QGDGKSRSVL EKKRRLLEKL QEQLAQLSVQ
ATDKEENKQV ALGTSKLNYL DPRISIAWCK RFRVPVEKIY SKTQRERFAW ALAMAGEDFE
F
