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Protein

DNA topoisomerase I, mitochondrial

Gene

TOP1MT

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Releases the supercoiling and torsional tension of DNA introduced during duplication of mitochondrial DNA by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity).By similarity

Catalytic activityi

ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.PROSITE-ProRule annotation

Cofactori

Ca2+1 Publication, Mg2+1 PublicationNote: Divalent metal ions (calcium or magnesium).1 Publication

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei152 – 1521Interaction with DNABy similarity
Sitei200 – 2001Interaction with DNABy similarity
Sitei248 – 2481Interaction with DNABy similarity
Sitei279 – 2791Interaction with DNABy similarity
Sitei337 – 3371Interaction with DNABy similarity
Sitei368 – 3681Interaction with DNABy similarity
Sitei410 – 4101Interaction with DNABy similarity
Sitei468 – 4681Interaction with DNABy similarity
Sitei486 – 4861Interaction with DNABy similarity
Active sitei559 – 5591O-(3'-phospho-DNA)-tyrosine intermediatePROSITE-ProRule annotation

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

Isomerase, Topoisomerase

Keywords - Ligandi

DNA-binding

Enzyme and pathway databases

BRENDAi5.99.1.2. 2681.

Names & Taxonomyi

Protein namesi
Recommended name:
DNA topoisomerase I, mitochondrial (EC:5.99.1.2)
Short name:
TOP1mt
Gene namesi
Name:TOP1MT
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
ProteomesiUP000005640 Componenti: Chromosome 8

Organism-specific databases

HGNCiHGNC:29787. TOP1MT.

Subcellular locationi

GO - Cellular componenti

  • chromosome Source: InterPro
  • mitochondrial nucleoid Source: BHF-UCL
  • mitochondrion Source: HPA
  • nucleus Source: HPA
Complete GO annotation...

Keywords - Cellular componenti

Mitochondrion

Pathology & Biotechi

Organism-specific databases

PharmGKBiPA134922772.

Chemistry

DrugBankiDB00762. Irinotecan.
DB01030. Topotecan.

Polymorphism and mutation databases

BioMutaiTOP1MT.
DMDMi20140694.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Transit peptidei1 – 5050Mitochondrion1 PublicationAdd
BLAST
Chaini51 – 601551DNA topoisomerase I, mitochondrialPRO_0000034797Add
BLAST

Proteomic databases

MaxQBiQ969P6.
PaxDbiQ969P6.
PRIDEiQ969P6.

PTM databases

PhosphoSiteiQ969P6.

Expressioni

Tissue specificityi

Ubiquitous; highest in skeletal muscle, heart, brain and fetal liver.1 Publication

Gene expression databases

BgeeiQ969P6.
CleanExiHS_TOP1MT.
ExpressionAtlasiQ969P6. baseline and differential.
GenevisibleiQ969P6. HS.

Organism-specific databases

HPAiHPA001915.
HPA021542.

Interactioni

Protein-protein interaction databases

BioGridi125510. 2 interactions.
STRINGi9606.ENSP00000328835.

Structurei

3D structure databases

ProteinModelPortaliQ969P6.
SMRiQ969P6. Positions 42-601.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni261 – 2622Interaction with DNABy similarity
Regioni324 – 3296Interaction with DNABy similarity
Regioni421 – 4233Interaction with DNABy similarity

Sequence similaritiesi

Belongs to the type IB topoisomerase family.Curated

Keywords - Domaini

Transit peptide

Phylogenomic databases

eggNOGiCOG3569.
GeneTreeiENSGT00390000016347.
HOGENOMiHOG000105469.
HOVERGENiHBG007988.
InParanoidiQ969P6.
KOiK03163.
OMAiYNRANRV.
OrthoDBiEOG7CVPX5.
PhylomeDBiQ969P6.
TreeFamiTF105281.

Family and domain databases

Gene3Di1.10.10.41. 1 hit.
1.10.132.10. 1 hit.
2.170.11.10. 2 hits.
3.90.15.10. 1 hit.
InterProiIPR011010. DNA_brk_join_enz.
IPR013034. DNA_topo_domain1.
IPR001631. TopoI.
IPR018521. TopoI_AS.
IPR025834. TopoI_C_dom.
IPR014711. TopoI_cat_a-hlx-sub_euk.
IPR014727. TopoI_cat_a/b-sub_euk.
IPR013500. TopoI_cat_euk.
IPR008336. TopoI_DNA-bd_euk.
IPR013030. TopoI_DNA-bd_mixed-a/b_euk.
IPR013499. TopoI_euk.
[Graphical view]
PfamiPF14370. Topo_C_assoc. 1 hit.
PF01028. Topoisom_I. 1 hit.
PF02919. Topoisom_I_N. 1 hit.
[Graphical view]
PRINTSiPR00416. EUTPISMRASEI.
SMARTiSM00435. TOPEUc. 1 hit.
[Graphical view]
SUPFAMiSSF56349. SSF56349. 2 hits.
SSF56741. SSF56741. 1 hit.
PROSITEiPS00176. TOPOISOMERASE_I_EUK. 1 hit.
[Graphical view]

Sequences (2)i

Sequence statusi: Complete.

Sequence processingi: The displayed sequence is further processed into a mature form.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Isoform 1 (identifier: Q969P6-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MRVVRLLRLR AALTLLGEVP RRPASRGVPG SRRTQKGSGA RWEKEKHEDG
60 70 80 90 100
VKWRQLEHKG PYFAPPYEPL PDGVRFFYEG RPVRLSVAAE EVATFYGRML
110 120 130 140 150
DHEYTTKEVF RKNFFNDWRK EMAVEEREVI KSLDKCDFTE IHRYFVDKAA
160 170 180 190 200
ARKVLSREEK QKLKEEAEKL QQEFGYCILD GHQEKIGNFK IEPPGLFRGR
210 220 230 240 250
GDHPKMGMLK RRITPEDVVI NCSRDSKIPE PPAGHQWKEV RSDNTVTWLA
260 270 280 290 300
AWTESVQNSI KYIMLNPCSK LKGETAWQKF ETARRLRGFV DEIRSQYRAD
310 320 330 340 350
WKSREMKTRQ RAVALYFIDK LALRAGNEKE DGEAADTVGC CSLRVEHVQL
360 370 380 390 400
HPEADGCQHV VEFDFLGKDC IRYYNRVPVE KPVYKNLQLF MENKDPRDDL
410 420 430 440 450
FDRLTTTSLN KHLQELMDGL TAKVFRTYNA SITLQEQLRA LTRAEDSIAA
460 470 480 490 500
KILSYNRANR VVAILCNHQR ATPSTFEKSM QNLQTKIQAK KEQVAEARAE
510 520 530 540 550
LRRARAEHKA QGDGKSRSVL EKKRRLLEKL QEQLAQLSVQ ATDKEENKQV
560 570 580 590 600
ALGTSKLNYL DPRISIAWCK RFRVPVEKIY SKTQRERFAW ALAMAGEDFE

F
Length:601
Mass (Da):69,872
Last modified:December 1, 2001 - v1
Checksum:iA012248D4250C675
GO
Isoform 2 (identifier: Q969P6-2) [UniParc]FASTAAdd to basket

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: Missing.

Note: No experimental confirmation available.
Show »
Length:503
Mass (Da):58,645
Checksum:i7E0138EE2931B903
GO

Sequence cautioni

The sequence AAH44646.1 differs from that shown. Reason: Erroneous initiation. Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti116 – 1161N → S in BAH14751 (PubMed:14702039).Curated

Natural variant

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Natural varianti256 – 2561V → I.1 Publication
Corresponds to variant rs11544484 [ dbSNP | Ensembl ].
VAR_052593
Natural varianti525 – 5251R → W.1 Publication
Corresponds to variant rs2293925 [ dbSNP | Ensembl ].
VAR_021863

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 9898Missing in isoform 2. 1 PublicationVSP_044783Add
BLAST

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF349031
, AF349018, AF349019, AF349020, AF349021, AF349022, AF349023, AF349024, AF349025, AF349026, AF349027, AF349028, AF349029, AF349030 Genomic DNA. Translation: AAL10791.1.
AF349017 mRNA. Translation: AAL05624.1.
AK316380 mRNA. Translation: BAH14751.1.
AC087793 Genomic DNA. No translation available.
BC044646 mRNA. Translation: AAH44646.1. Different initiation.
BC052285 mRNA. Translation: AAH52285.1.
BC071914 mRNA. Translation: AAH71914.1.
CCDSiCCDS59115.1. [Q969P6-2]
CCDS6400.1. [Q969P6-1]
RefSeqiNP_001245375.1. NM_001258446.1. [Q969P6-2]
NP_001245376.1. NM_001258447.1. [Q969P6-2]
NP_443195.1. NM_052963.2. [Q969P6-1]
UniGeneiHs.528574.

Genome annotation databases

EnsembliENST00000329245; ENSP00000328835; ENSG00000184428.
ENST00000519148; ENSP00000429169; ENSG00000184428. [Q969P6-2]
ENST00000521193; ENSP00000428369; ENSG00000184428. [Q969P6-2]
ENST00000523676; ENSP00000429181; ENSG00000184428. [Q969P6-2]
GeneIDi116447.
KEGGihsa:116447.
UCSCiuc003yxz.4. human. [Q969P6-1]

Keywords - Coding sequence diversityi

Alternative splicing, Polymorphism

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
AF349031
, AF349018, AF349019, AF349020, AF349021, AF349022, AF349023, AF349024, AF349025, AF349026, AF349027, AF349028, AF349029, AF349030 Genomic DNA. Translation: AAL10791.1.
AF349017 mRNA. Translation: AAL05624.1.
AK316380 mRNA. Translation: BAH14751.1.
AC087793 Genomic DNA. No translation available.
BC044646 mRNA. Translation: AAH44646.1. Different initiation.
BC052285 mRNA. Translation: AAH52285.1.
BC071914 mRNA. Translation: AAH71914.1.
CCDSiCCDS59115.1. [Q969P6-2]
CCDS6400.1. [Q969P6-1]
RefSeqiNP_001245375.1. NM_001258446.1. [Q969P6-2]
NP_001245376.1. NM_001258447.1. [Q969P6-2]
NP_443195.1. NM_052963.2. [Q969P6-1]
UniGeneiHs.528574.

3D structure databases

ProteinModelPortaliQ969P6.
SMRiQ969P6. Positions 42-601.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi125510. 2 interactions.
STRINGi9606.ENSP00000328835.

Chemistry

ChEMBLiCHEMBL2362989.
DrugBankiDB00762. Irinotecan.
DB01030. Topotecan.

PTM databases

PhosphoSiteiQ969P6.

Polymorphism and mutation databases

BioMutaiTOP1MT.
DMDMi20140694.

Proteomic databases

MaxQBiQ969P6.
PaxDbiQ969P6.
PRIDEiQ969P6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000329245; ENSP00000328835; ENSG00000184428.
ENST00000519148; ENSP00000429169; ENSG00000184428. [Q969P6-2]
ENST00000521193; ENSP00000428369; ENSG00000184428. [Q969P6-2]
ENST00000523676; ENSP00000429181; ENSG00000184428. [Q969P6-2]
GeneIDi116447.
KEGGihsa:116447.
UCSCiuc003yxz.4. human. [Q969P6-1]

Organism-specific databases

CTDi116447.
GeneCardsiGC08M144391.
HGNCiHGNC:29787. TOP1MT.
HPAiHPA001915.
HPA021542.
MIMi606387. gene.
neXtProtiNX_Q969P6.
PharmGKBiPA134922772.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiCOG3569.
GeneTreeiENSGT00390000016347.
HOGENOMiHOG000105469.
HOVERGENiHBG007988.
InParanoidiQ969P6.
KOiK03163.
OMAiYNRANRV.
OrthoDBiEOG7CVPX5.
PhylomeDBiQ969P6.
TreeFamiTF105281.

Enzyme and pathway databases

BRENDAi5.99.1.2. 2681.

Miscellaneous databases

ChiTaRSiTOP1MT. human.
GenomeRNAii116447.
NextBioi79927.
PROiQ969P6.
SOURCEiSearch...

Gene expression databases

BgeeiQ969P6.
CleanExiHS_TOP1MT.
ExpressionAtlasiQ969P6. baseline and differential.
GenevisibleiQ969P6. HS.

Family and domain databases

Gene3Di1.10.10.41. 1 hit.
1.10.132.10. 1 hit.
2.170.11.10. 2 hits.
3.90.15.10. 1 hit.
InterProiIPR011010. DNA_brk_join_enz.
IPR013034. DNA_topo_domain1.
IPR001631. TopoI.
IPR018521. TopoI_AS.
IPR025834. TopoI_C_dom.
IPR014711. TopoI_cat_a-hlx-sub_euk.
IPR014727. TopoI_cat_a/b-sub_euk.
IPR013500. TopoI_cat_euk.
IPR008336. TopoI_DNA-bd_euk.
IPR013030. TopoI_DNA-bd_mixed-a/b_euk.
IPR013499. TopoI_euk.
[Graphical view]
PfamiPF14370. Topo_C_assoc. 1 hit.
PF01028. Topoisom_I. 1 hit.
PF02919. Topoisom_I_N. 1 hit.
[Graphical view]
PRINTSiPR00416. EUTPISMRASEI.
SMARTiSM00435. TOPEUc. 1 hit.
[Graphical view]
SUPFAMiSSF56349. SSF56349. 2 hits.
SSF56741. SSF56741. 1 hit.
PROSITEiPS00176. TOPOISOMERASE_I_EUK. 1 hit.
[Graphical view]
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA / MRNA] (ISOFORM 1), FUNCTION, COFACTOR, SUBCELLULAR LOCATION, TRANSIT PEPTIDE CLEAVAGE SITE, TISSUE SPECIFICITY.
  2. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
    Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
    , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
    Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 2), VARIANT TRP-525.
    Tissue: Testis.
  3. "DNA sequence and analysis of human chromosome 8."
    Nusbaum C., Mikkelsen T.S., Zody M.C., Asakawa S., Taudien S., Garber M., Kodira C.D., Schueler M.G., Shimizu A., Whittaker C.A., Chang J.L., Cuomo C.A., Dewar K., FitzGerald M.G., Yang X., Allen N.R., Anderson S., Asakawa T.
    , Blechschmidt K., Bloom T., Borowsky M.L., Butler J., Cook A., Corum B., DeArellano K., DeCaprio D., Dooley K.T., Dorris L. III, Engels R., Gloeckner G., Hafez N., Hagopian D.S., Hall J.L., Ishikawa S.K., Jaffe D.B., Kamat A., Kudoh J., Lehmann R., Lokitsang T., Macdonald P., Major J.E., Matthews C.D., Mauceli E., Menzel U., Mihalev A.H., Minoshima S., Murayama Y., Naylor J.W., Nicol R., Nguyen C., O'Leary S.B., O'Neill K., Parker S.C.J., Polley A., Raymond C.K., Reichwald K., Rodriguez J., Sasaki T., Schilhabel M., Siddiqui R., Smith C.L., Sneddon T.P., Talamas J.A., Tenzin P., Topham K., Venkataraman V., Wen G., Yamazaki S., Young S.K., Zeng Q., Zimmer A.R., Rosenthal A., Birren B.W., Platzer M., Shimizu N., Lander E.S.
    Nature 439:331-335(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
  4. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
    The MGC Project Team
    Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1), VARIANT ILE-256.
    Tissue: Brain and Lung.

Entry informationi

Entry nameiTOP1M_HUMAN
AccessioniPrimary (citable) accession number: Q969P6
Secondary accession number(s): B7ZAR5
, E7ES89, Q86ST4, Q86V82
Entry historyi
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: December 1, 2001
Last modified: July 22, 2015
This is version 134 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. Human chromosome 8
    Human chromosome 8: entries, gene names and cross-references to MIM
  2. Human entries with polymorphisms or disease mutations
    List of human entries with polymorphisms or disease mutations
  3. Human polymorphisms and disease mutations
    Index of human polymorphisms and disease mutations
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. SIMILARITY comments
    Index of protein domains and families

External Data

Dasty 3

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.