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Q969P6 (TOP1M_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified July 9, 2014. Version 124. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (5) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Alt products·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA topoisomerase I, mitochondrial

Short name=TOP1mt
EC=5.99.1.2
Gene names
Name:TOP1MT
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length601 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is further processed into a mature form.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

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. Ref.1

Catalytic activity

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

Cofactor

Divalent metal ions (calcium or magnesium). Ref.1

Subcellular location

Mitochondrion Ref.1.

Tissue specificity

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

Sequence similarities

Belongs to the type IB topoisomerase family.

Sequence caution

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

Alternative products

This entry describes 2 isoforms produced by alternative splicing. [Align] [Select]
Isoform 1 (identifier: Q969P6-1)

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.
Isoform 2 (identifier: Q969P6-2)

The sequence of this isoform differs from the canonical sequence as follows:
     1-98: Missing.
Note: No experimental confirmation available.

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Transit peptide1 – 5050Mitochondrion Probable
Chain51 – 601551DNA topoisomerase I, mitochondrial
PRO_0000034797

Regions

Region261 – 2622Interaction with DNA By similarity
Region324 – 3296Interaction with DNA By similarity
Region421 – 4233Interaction with DNA By similarity

Sites

Active site5591O-(3'-phospho-DNA)-tyrosine intermediate By similarity
Site1521Interaction with DNA By similarity
Site2001Interaction with DNA By similarity
Site2481Interaction with DNA By similarity
Site2791Interaction with DNA By similarity
Site3371Interaction with DNA By similarity
Site3681Interaction with DNA By similarity
Site4101Interaction with DNA By similarity
Site4681Interaction with DNA By similarity
Site4861Interaction with DNA By similarity

Natural variations

Alternative sequence1 – 9898Missing in isoform 2.
VSP_044783
Natural variant2561V → I. Ref.4
Corresponds to variant rs11544484 [ dbSNP | Ensembl ].
VAR_052593
Natural variant5251R → W. Ref.2
Corresponds to variant rs2293925 [ dbSNP | Ensembl ].
VAR_021863

Experimental info

Sequence conflict1161N → S in BAH14751. Ref.2

Sequences

Sequence LengthMass (Da)Tools
Isoform 1 [UniParc].

Last modified December 1, 2001. Version 1.
Checksum: A012248D4250C675

FASTA60169,872
        10         20         30         40         50         60 
MRVVRLLRLR AALTLLGEVP RRPASRGVPG SRRTQKGSGA RWEKEKHEDG VKWRQLEHKG 

        70         80         90        100        110        120 
PYFAPPYEPL PDGVRFFYEG RPVRLSVAAE EVATFYGRML DHEYTTKEVF RKNFFNDWRK 

       130        140        150        160        170        180 
EMAVEEREVI KSLDKCDFTE IHRYFVDKAA ARKVLSREEK QKLKEEAEKL QQEFGYCILD 

       190        200        210        220        230        240 
GHQEKIGNFK IEPPGLFRGR GDHPKMGMLK RRITPEDVVI NCSRDSKIPE PPAGHQWKEV 

       250        260        270        280        290        300 
RSDNTVTWLA AWTESVQNSI KYIMLNPCSK LKGETAWQKF ETARRLRGFV DEIRSQYRAD 

       310        320        330        340        350        360 
WKSREMKTRQ RAVALYFIDK LALRAGNEKE DGEAADTVGC CSLRVEHVQL HPEADGCQHV 

       370        380        390        400        410        420 
VEFDFLGKDC IRYYNRVPVE KPVYKNLQLF MENKDPRDDL FDRLTTTSLN KHLQELMDGL 

       430        440        450        460        470        480 
TAKVFRTYNA SITLQEQLRA LTRAEDSIAA KILSYNRANR VVAILCNHQR ATPSTFEKSM 

       490        500        510        520        530        540 
QNLQTKIQAK KEQVAEARAE LRRARAEHKA QGDGKSRSVL EKKRRLLEKL QEQLAQLSVQ 

       550        560        570        580        590        600 
ATDKEENKQV ALGTSKLNYL DPRISIAWCK RFRVPVEKIY SKTQRERFAW ALAMAGEDFE 


F 

« Hide

Isoform 2 [UniParc].

Checksum: 7E0138EE2931B903
Show »

FASTA50358,645

References

« Hide 'large scale' references
[1]"Human mitochondrial topoisomerase I."
Zhang H., Barcelo J.M., Lee B., Kohlhagen G., Zimonjic D.B., Popescu N.C., Pommier Y.
Proc. Natl. Acad. Sci. U.S.A. 98:10608-10613(2001) [PubMed] [Europe PMC] [Abstract]
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. expand/collapse author list , 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. expand/collapse author list , 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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF349031 expand/collapse EMBL AC list , 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.
CCDSCCDS59115.1. [Q969P6-2]
CCDS6400.1. [Q969P6-1]
RefSeqNP_001245375.1. NM_001258446.1. [Q969P6-2]
NP_001245376.1. NM_001258447.1. [Q969P6-2]
NP_443195.1. NM_052963.2. [Q969P6-1]
UniGeneHs.528574.

3D structure databases

ProteinModelPortalQ969P6.
SMRQ969P6. Positions 42-601.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid125510. 3 interactions.
STRING9606.ENSP00000328835.

Chemistry

ChEMBLCHEMBL2362989.
DrugBankDB00762. Irinotecan.
DB01030. Topotecan.

PTM databases

PhosphoSiteQ969P6.

Polymorphism databases

DMDM20140694.

Proteomic databases

MaxQBQ969P6.
PaxDbQ969P6.
PRIDEQ969P6.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000329245; ENSP00000328835; ENSG00000184428. [Q969P6-1]
ENST00000519148; ENSP00000429169; ENSG00000184428. [Q969P6-2]
ENST00000521193; ENSP00000428369; ENSG00000184428. [Q969P6-2]
ENST00000523676; ENSP00000429181; ENSG00000184428. [Q969P6-2]
GeneID116447.
KEGGhsa:116447.
UCSCuc003yxz.4. human. [Q969P6-1]

Organism-specific databases

CTD116447.
GeneCardsGC08M144391.
HGNCHGNC:29787. TOP1MT.
HPAHPA001915.
HPA021542.
MIM606387. gene.
neXtProtNX_Q969P6.
PharmGKBPA134922772.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3569.
HOGENOMHOG000105469.
HOVERGENHBG007988.
InParanoidQ969P6.
KOK03163.
OMAVINCSRD.
OrthoDBEOG7CVPX5.
PhylomeDBQ969P6.
TreeFamTF105281.

Gene expression databases

ArrayExpressQ969P6.
BgeeQ969P6.
CleanExHS_TOP1MT.
GenevestigatorQ969P6.

Family and domain databases

Gene3D1.10.10.41. 1 hit.
1.10.132.10. 1 hit.
2.170.11.10. 2 hits.
3.90.15.10. 1 hit.
InterProIPR011010. 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]
PfamPF14370. Topo_C_assoc. 1 hit.
PF01028. Topoisom_I. 1 hit.
PF02919. Topoisom_I_N. 1 hit.
[Graphical view]
PRINTSPR00416. EUTPISMRASEI.
SMARTSM00435. TOPEUc. 1 hit.
[Graphical view]
SUPFAMSSF56349. SSF56349. 2 hits.
SSF56741. SSF56741. 1 hit.
PROSITEPS00176. TOPOISOMERASE_I_EUK. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

GenomeRNAi116447.
NextBio79927.
PROQ969P6.
SOURCESearch...

Entry information

Entry nameTOP1M_HUMAN
AccessionPrimary (citable) accession number: Q969P6
Secondary accession number(s): B7ZAR5 expand/collapse secondary AC list , E7ES89, Q86ST4, Q86V82
Entry history
Integrated into UniProtKB/Swiss-Prot: January 31, 2002
Last sequence update: December 1, 2001
Last modified: July 9, 2014
This is version 124 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 8

Human chromosome 8: entries, gene names and cross-references to MIM