LOCUS       NP_082680                593 aa            linear   ROD 27-APR-2025
DEFINITION  DNA topoisomerase I, mitochondrial isoform 1 [Mus musculus].
ACCESSION   NP_082680 XP_128145
VERSION     NP_082680.1
DBSOURCE    REFSEQ: accession NM_028404.3
KEYWORDS    RefSeq; RefSeq Select.
SOURCE      Mus musculus (house mouse)
  ORGANISM  Mus musculus
            Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
            Mammalia; Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha;
            Muroidea; Muridae; Murinae; Mus; Mus.
REFERENCE   1  (residues 1 to 593)
  AUTHORS   Al Khatib,I., Deng,J., Lei,Y., Torres-Odio,S., Rojas,G.R.,
            Newman,L.E., Chung,B.K., Symes,A., Zhang,H., Huang,S.N.,
            Pommier,Y., Khan,A., Shadel,G.S., West,A.P., Gibson,W.T. and
            Shutt,T.E.
  TITLE     Activation of the cGAS-STING innate immune response in cells with
            deficient mitochondrial topoisomerase TOP1MT
  JOURNAL   Hum Mol Genet 32 (15), 2422-2440 (2023)
   PUBMED   37129502
  REMARK    GeneRIF: Activation of the cGAS-STING innate immune response in
            cells with deficient mitochondrial topoisomerase TOP1MT.
REFERENCE   2  (residues 1 to 593)
  AUTHORS   Baechler,S.A., Factor,V.M., Dalla Rosa,I., Ravji,A., Becker,D.,
            Khiati,S., Miller Jenkins,L.M., Lang,M., Sourbier,C.,
            Michaels,S.A., Neckers,L.M., Zhang,H.L., Spinazzola,A., Huang,S.N.,
            Marquardt,J.U. and Pommier,Y.
  TITLE     The mitochondrial type IB topoisomerase drives mitochondrial
            translation and carcinogenesis
  JOURNAL   Nat Commun 10 (1), 83 (2019)
   PUBMED   30622257
  REMARK    GeneRIF: Study demonstrated that lack of TOP1MT results in delayed
            and decreased tumor growth due to impaired mitochondrial
            translation. The TOP1MT genomic signature profile, based on mouse
            model for Top1mt-KO liver cancers, is correlated with enhanced
            survival of hepatocellular carcinoma patients.
            Publication Status: Online-Only
REFERENCE   3  (residues 1 to 593)
  AUTHORS   Dalla Rosa,I., Zhang,H., Khiati,S., Wu,X. and Pommier,Y.
  TITLE     Transcription profiling suggests that mitochondrial topoisomerase
            IB acts as a topological barrier and regulator of mitochondrial DNA
            transcription
  JOURNAL   J Biol Chem 292 (49), 20162-20172 (2017)
   PUBMED   29021209
  REMARK    GeneRIF: TOP1MT acts as a topological barrier and regulator for
            mtDNA transcription and D-loop formation
REFERENCE   4  (residues 1 to 593)
  AUTHORS   Khiati,S., Baechler,S.A., Factor,V.M., Zhang,H., Huang,S.Y., Dalla
            Rosa,I., Sourbier,C., Neckers,L., Thorgeirsson,S.S. and Pommier,Y.
  TITLE     Lack of mitochondrial topoisomerase I (TOP1mt) impairs liver
            regeneration
  JOURNAL   Proc Natl Acad Sci U S A 112 (36), 11282-11287 (2015)
   PUBMED   26305952
REFERENCE   5  (residues 1 to 593)
  AUTHORS   Lefebvre,J., Clarkson,M., Massa,F., Bradford,S.T., Charlet,A.,
            Buske,F., Lacas-Gervais,S., Schulz,H., Gimpel,C., Hata,Y.,
            Schaefer,F. and Schedl,A.
  TITLE     Alternatively spliced isoforms of WT1 control podocyte-specific
            gene expression
  JOURNAL   Kidney Int 88 (2), 321-331 (2015)
   PUBMED   25993318
REFERENCE   6  (residues 1 to 593)
  AUTHORS   Zhang,H., Zhang,Y.W., Yasukawa,T., Dalla Rosa,I., Khiati,S. and
            Pommier,Y.
  TITLE     Increased negative supercoiling of mtDNA in TOP1mt knockout mice
            and presence of topoisomerases IIalpha and IIbeta in vertebrate
            mitochondria
  JOURNAL   Nucleic Acids Res 42 (11), 7259-7267 (2014)
   PUBMED   24803675
REFERENCE   7  (residues 1 to 593)
  AUTHORS   Sobek,S., Dalla Rosa,I., Pommier,Y., Bornholz,B., Kalfalah,F.,
            Zhang,H., Wiesner,R.J., von Kleist-Retzow,J.C., Hillebrand,F.,
            Schaal,H., Mielke,C., Christensen,M.O. and Boege,F.
  TITLE     Negative regulation of mitochondrial transcription by mitochondrial
            topoisomerase I
  JOURNAL   Nucleic Acids Res 41 (21), 9848-9857 (2013)
   PUBMED   23982517
REFERENCE   8  (residues 1 to 593)
  AUTHORS   Douarre,C., Sourbier,C., Dalla Rosa,I., Brata Das,B., Redon,C.E.,
            Zhang,H., Neckers,L. and Pommier,Y.
  TITLE     Mitochondrial topoisomerase I is critical for mitochondrial
            integrity and cellular energy metabolism
  JOURNAL   PLoS One 7 (7), e41094 (2012)
   PUBMED   22911747
REFERENCE   9  (residues 1 to 593)
  AUTHORS   Zhang,H. and Pommier,Y.
  TITLE     Mitochondrial topoisomerase I sites in the regulatory D-loop region
            of mitochondrial DNA
  JOURNAL   Biochemistry 47 (43), 11196-11203 (2008)
   PUBMED   18826252
REFERENCE   10 (residues 1 to 593)
  AUTHORS   Zhang,H., Meng,L.H., Zimonjic,D.B., Popescu,N.C. and Pommier,Y.
  TITLE     Thirteen-exon-motif signature for vertebrate nuclear and
            mitochondrial type IB topoisomerases
  JOURNAL   Nucleic Acids Res 32 (7), 2087-2092 (2004)
   PUBMED   15096574
  REMARK    Publication Status: Online-Only
COMMENT     VALIDATED REFSEQ: This record has undergone validation or
            preliminary review. The reference sequence was derived from
            AC116393.10.
            
            On Sep 3, 2004 this sequence version replaced XP_128145.3.
            
            Sequence Note: The RefSeq transcript and protein were derived from
            genomic sequence to make the sequence consistent with the reference
            genome assembly. The genomic coordinates used for the transcript
            record were based on alignments.
            
            ##Evidence-Data-START##
            Transcript exon combination :: AF362952.1, AK147119.1 [ECO:0000332]
            RNAseq introns              :: single sample supports all introns
                                           SAMN01164135, SAMN01164139
                                           [ECO:0000348]
            ##Evidence-Data-END##
            
            ##RefSeq-Attributes-START##
            gene product(s) localized to mito. :: reported by MitoCarta
            RefSeq Select criteria             :: based on conservation,
                                                  expression, longest protein
            ##RefSeq-Attributes-END##
FEATURES             Location/Qualifiers
     source          1..593
                     /organism="Mus musculus"
                     /strain="C57BL/6"
                     /db_xref="taxon:10090"
                     /chromosome="15"
                     /map="15 34.69 cM"
     Protein         1..593
                     /product="DNA topoisomerase I, mitochondrial isoform 1"
                     /EC_number="5.6.2.1"
                     /note="DNA topoisomerase I, mitochondrial; mitochondrial
                     topoisomerase I"
                     /calculated_mol_wt=64050
     transit_peptide 1..43
                     /note="Mitochondrion. /evidence=ECO:0000250; propagated
                     from UniProtKB/Swiss-Prot (Q8R4U6.1)"
                     /calculated_mol_wt=4972
     mat_peptide     44..593
                     /product="DNA topoisomerase I, mitochondrial.
                     /id=PRO_0000384393"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
                     /calculated_mol_wt=64050
     Region          44..258
                     /region_name="Topoisom_I_N"
                     /note="Eukaryotic DNA topoisomerase I, DNA binding
                     fragment; pfam02919"
                     /db_xref="CDD:460746"
     Site            145
                     /site_type="other"
                     /note="Interaction with DNA. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Region          189..565
                     /region_name="TOPEUc"
                     /note="DNA Topoisomerase I (eukaryota); smart00435"
                     /db_xref="CDD:214661"
     Site            193
                     /site_type="other"
                     /note="Interaction with DNA. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Site            241
                     /site_type="other"
                     /note="Interaction with DNA. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Region          254..255
                     /region_name="Interaction with DNA. /evidence=ECO:0000250"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Site            272
                     /site_type="other"
                     /note="Interaction with DNA. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Region          317..322
                     /region_name="Interaction with DNA. /evidence=ECO:0000250"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Site            330
                     /site_type="other"
                     /note="Interaction with DNA. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Site            361
                     /site_type="other"
                     /note="Interaction with DNA. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Site            403
                     /site_type="other"
                     /note="Interaction with DNA. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Region          414..416
                     /region_name="Interaction with DNA. /evidence=ECO:0000250"
                     /note="propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Site            461
                     /site_type="other"
                     /note="Interaction with DNA. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     Site            479
                     /site_type="other"
                     /note="Interaction with DNA. /evidence=ECO:0000250;
                     propagated from UniProtKB/Swiss-Prot (Q8R4U6.1)"
     CDS             1..593
                     /gene="Top1mt"
                     /gene_synonym="2900052H09Rik"
                     /coded_by="NM_028404.3:45..1826"
                     /note="isoform 1 is encoded by transcript variant 1"
                     /db_xref="CCDS:CCDS27547.1"
                     /db_xref="GeneID:72960"
                     /db_xref="MGI:MGI:1920210"
ORIGIN      
        1 mlllwlralc rrfqhvpcrv pscqvsrvak anragweets kssvkwrqle hkgpyftpay
       61 eplpdgvhfl ydgkplklsl aaeevatfyg kmlhlectsk evfrrnffsd wrkemtpeer
      121 rlithldkcd fteihkhfle raearrtlpr eqkqklkeea eklqqefgyc vldghrekig
      181 nfkteppglf rgrgdhpkmg mlkrrvmped vvincsrdsk ipeppaghqw kevrsdntvm
      241 wlaawvehiq nsfkyvilnp sskpkgemdw qkyevarrlk gvvdkiraqy qadwkspemk
      301 krqlavalyf idklalrtgn ekeegetadt vgccslrveh irlhapaggq ehvveldflg
      361 kdsiryknhv tveklvfqnl qhfmedkdpr ddlfdaltts slnkhlqdlm egltakvfrt
      421 ynasvtlqeq lrvltraeds vtckvlaynr anravavlcn hqravpktfe ksmqtlqkki
      481 etkkaqvaea qvelqkaetd lrmrgdskpk sflqkqrrll kleeqlarlc akatdkeenk
      541 qvalgtakln yldprisiaw ckrfgvpvek iynktqrerf awafnqaged fef
//
