DNA topoisomerase I, mitochondrial

Details

Name
DNA topoisomerase I, mitochondrial
Synonyms
  • 5.99.1.2
  • TOP1mt
Gene Name
TOP1MT
Organism
Humans
Amino acid sequence
>lcl|BSEQ0000182|DNA topoisomerase I, mitochondrial
MRVVRLLRLRAALTLLGEVPRRPASRGVPGSRRTQKGSGARWEKEKHEDGVKWRQLEHKG
PYFAPPYEPLPDGVRFFYEGRPVRLSVAAEEVATFYGRMLDHEYTTKEVFRKNFFNDWRK
EMAVEEREVIKSLDKCDFTEIHRYFVDKAAARKVLSREEKQKLKEEAEKLQQEFGYCILD
GHQEKIGNFKIEPPGLFRGRGDHPKMGMLKRRITPEDVVINCSRDSKIPEPPAGHQWKEV
RSDNTVTWLAAWTESVQNSIKYIMLNPCSKLKGETAWQKFETARRLRGFVDEIRSQYRAD
WKSREMKTRQRAVALYFIDKLALRAGNEKEDGEAADTVGCCSLRVEHVQLHPEADGCQHV
VEFDFLGKDCIRYYNRVPVEKPVYKNLQLFMENKDPRDDLFDRLTTTSLNKHLQELMDGL
TAKVFRTYNASITLQEQLRALTRAEDSIAAKILSYNRANRVVAILCNHQRATPSTFEKSM
QNLQTKIQAKKEQVAEARAELRRARAEHKAQGDGKSRSVLEKKRRLLEKLQEQLAQLSVQ
ATDKEENKQVALGTSKLNYLDPRISIAWCKRFRVPVEKIYSKTQRERFAWALAMAGEDFE
F
Number of residues
601
Molecular Weight
69871.39
Theoretical pI
9.94
GO Classification
Functions
DNA binding / DNA topoisomerase type I activity / DNA topoisomerase type II (ATP-hydrolyzing) activity
Processes
DNA replication / DNA topological change
Components
chromosome / mitochondrial nucleoid / mitochondrion / nucleus
General Function
Dna topoisomerase type ii (atp-hydrolyzing) activity
Specific 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).
Pfam Domain Function
Transmembrane Regions
Not Available
Cellular Location
Mitochondrion
Gene sequence
>lcl|BSEQ0010158|DNA topoisomerase I, mitochondrial (TOP1MT)
ATGTTAGATCATGAATACACAACAAAGGAGGTTTTCCGGAAGAACTTCTTCAATGACTGG
CGAAAGGAAATGGCGGTGGAAGAGAGGGAAGTCATCAAGAGCCTGGACAAGTGTGACTTC
ACGGAGATCCACAGATACTTTGTGGACAAGGCCGCAGCCCGGAAAGTCCTGAGCAGGGAG
GAGAAGCAGAAGCTAAAAGAAGAGGCAGAAAAACTTCAGCAAGAGTTCGGCTACTGTATT
TTAGATGGTCACCAAGAAAAAATAGGCAACTTCAAGATTGAGCCGCCTGGCTTGTTCCGT
GGCCGTGGCGACCATCCCAAGATGGGGATGCTGAAGAGAAGGATCACGCCAGAGGATGTG
GTTATCAACTGCAGCAGGGACTCGAAGATCCCCGAGCCGCCGGCGGGGCACCAGTGGAAG
GAGGTGCGCTCCGATAACACCGTCACGTGGCTGGCAGCTTGGACCGAGAGCGTTCAGAAC
TCCATCAAGTACATCATGCTGAACCCTTGCTCGAAGCTGAAGGGGGAGACAGCTTGGCAG
AAGTTTGAAACAGCTCGACGCCTGCGGGGATTTGTGGACGAGATCCGCTCCCAGTACCGG
GCTGACTGGAAGTCTCGGGAAATGAAGACGAGACAGCGGGCGGTGGCCCTGTATTTCATC
GATAAGCTGGCACTGAGAGCAGGAAATGAGAAGGAGGACGGTGAGGCGGCCGACACCGTG
GGCTGCTGTTCCCTCCGCGTGGAGCACGTCCAGCTGCACCCGGAGGCCGATGGCTGCCAA
CACGTGGTGGAATTTGACTTCCTGGGGAAGGACTGCATCCGCTACTACAACAGAGTGCCG
GTGGAGAAGCCGGTGTACAAGAACTTACAGCTCTTTATGGAGAACAAGGACCCCCGGGAC
GACCTCTTCGACAGGCTGACCACGACCAGCCTGAACAAGCACCTCCAGGAGCTGATGGAC
GGGCTGACGGCCAAGGTGTTCCGGACCTACAACGCCTCCATCACTCTGCAGGAGCAGCTG
CGGGCCCTGACGCGCGCCGAGGACAGCATAGCAGCTAAGATCTTATCCTACAACCGAGCC
AACCGAGTCGTGGCCATTCTCTGCAACCATCAGCGAGCAACCCCCAGTACGTTCGAGAAG
TCGATGCAGAATCTCCAGACGAAGATCCAGGCAAAGAAGGAGCAGGTGGCTGAGGCCAGG
GCAGAGCTGAGGAGGGCGAGGGCTGAGCACAAAGCCCAAGGGGATGGCAAGTCCAGGAGT
GTCCTGGAGAAGAAGAGGCGGCTCCTGGAGAAGCTGCAGGAGCAGCTGGCGCAGCTGAGT
GTGCAGGCCACGGACAAGGAGGAGAACAAGCAGGTGGCCCTGGGCACGTCCAAGCTCAAC
TACCTGGACCCCAGGATCAGCATTGCCTGGTGCAAGCGGTTCAGGGTGCCAGTGGAGAAG
ATCTACAGCAAAACACAGCGGGAGAGGTTCGCCTGGGCTCTCGCCATGGCAGGAGAAGAC
TTTGAATTCTAA
Chromosome Location
8
Locus
8q24.3
External Identifiers
ResourceLink
UniProtKB IDQ969P6
UniProtKB Entry NameTOP1M_HUMAN
GenBank Protein ID15919359
GenBank Gene IDAF349031
GenAtlas IDTOP1MT
HGNC IDHGNC:29787
General References
  1. Zhang H, Barcelo JM, Lee B, Kohlhagen G, Zimonjic DB, Popescu NC, Pommier Y: Human mitochondrial topoisomerase I. Proc Natl Acad Sci U S A. 2001 Sep 11;98(19):10608-13. Epub 2001 Aug 28. [Article]
  2. 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 TO, 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: Complete sequencing and characterization of 21,243 full-length human cDNAs. Nat Genet. 2004 Jan;36(1):40-5. Epub 2003 Dec 21. [Article]
  3. Nusbaum C, Mikkelsen TS, Zody MC, Asakawa S, Taudien S, Garber M, Kodira CD, Schueler MG, Shimizu A, Whittaker CA, Chang JL, Cuomo CA, Dewar K, FitzGerald MG, Yang X, Allen NR, Anderson S, Asakawa T, Blechschmidt K, Bloom T, Borowsky ML, Butler J, Cook A, Corum B, DeArellano K, DeCaprio D, Dooley KT, Dorris L 3rd, Engels R, Glockner G, Hafez N, Hagopian DS, Hall JL, Ishikawa SK, Jaffe DB, Kamat A, Kudoh J, Lehmann R, Lokitsang T, Macdonald P, Major JE, Matthews CD, Mauceli E, Menzel U, Mihalev AH, Minoshima S, Murayama Y, Naylor JW, Nicol R, Nguyen C, O'Leary SB, O'Neill K, Parker SC, Polley A, Raymond CK, Reichwald K, Rodriguez J, Sasaki T, Schilhabel M, Siddiqui R, Smith CL, Sneddon TP, Talamas JA, Tenzin P, Topham K, Venkataraman V, Wen G, Yamazaki S, Young SK, Zeng Q, Zimmer AR, Rosenthal A, Birren BW, Platzer M, Shimizu N, Lander ES: DNA sequence and analysis of human chromosome 8. Nature. 2006 Jan 19;439(7074):331-5. [Article]
  4. Gerhard DS, Wagner L, Feingold EA, Shenmen CM, Grouse LH, Schuler G, Klein SL, Old S, Rasooly R, Good P, Guyer M, Peck AM, Derge JG, Lipman D, Collins FS, Jang W, Sherry S, Feolo M, Misquitta L, Lee E, Rotmistrovsky K, Greenhut SF, Schaefer CF, Buetow K, Bonner TI, Haussler D, Kent J, Kiekhaus M, Furey T, Brent M, Prange C, Schreiber K, Shapiro N, Bhat NK, Hopkins RF, Hsie F, Driscoll T, Soares MB, Casavant TL, Scheetz TE, Brown-stein MJ, Usdin TB, Toshiyuki S, Carninci P, Piao Y, Dudekula DB, Ko MS, Kawakami K, Suzuki Y, Sugano S, Gruber CE, Smith MR, Simmons B, Moore T, Waterman R, Johnson SL, Ruan Y, Wei CL, Mathavan S, Gunaratne PH, Wu J, Garcia AM, Hulyk SW, Fuh E, Yuan Y, Sneed A, Kowis C, Hodgson A, Muzny DM, McPherson J, Gibbs RA, Fahey J, Helton E, Ketteman M, Madan A, Rodrigues S, Sanchez A, Whiting M, Madari A, Young AC, Wetherby KD, Granite SJ, Kwong PN, Brinkley CP, Pearson RL, Bouffard GG, Blakesly RW, Green ED, Dickson MC, Rodriguez AC, Grimwood J, Schmutz J, Myers RM, Butterfield YS, Griffith M, Griffith OL, Krzywinski MI, Liao N, Morin R, Palmquist D, Petrescu AS, Skalska U, Smailus DE, Stott JM, Schnerch A, Schein JE, Jones SJ, Holt RA, Baross A, Marra MA, Clifton S, Makowski KA, Bosak S, Malek J: The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. 2004 Oct;14(10B):2121-7. [Article]

Drug Relations

Drug Relations
DrugBank IDNameDrug groupPharmacological action?ActionsDetails
DB00762Irinotecanapproved, investigationalyesinhibitorDetails
DB01030Topotecanapproved, investigationalunknowninhibitorDetails