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P11387 (TOP1_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 165. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Interactions·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
DNA topoisomerase 1

EC=5.99.1.2
Alternative name(s):
DNA topoisomerase I
Gene names
Name:TOP1
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length765 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 the DNA replication and transcription 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. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. Ref.1 Ref.18 Ref.30 Ref.33

Catalytic activity

ATP-independent breakage of single-stranded DNA, followed by passage and rejoining. Ref.1 Ref.30 Ref.33

Enzyme regulation

Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.

Subunit structure

Monomer. Interacts with SV40 Large T antigen; this interactions allows viral DNA replication. Ref.15

Subcellular location

Nucleusnucleolus. Nucleusnucleoplasm. Note: Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumolyated forms found in both nucleoplasm and nucleoli. Ref.13

Tissue specificity

Endothelial cells. Ref.18

Post-translational modification

Sumoylated. Lys-117 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment. Ref.13

Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin.

Involvement in disease

A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.

Miscellaneous

Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.

Sequence similarities

Belongs to the type IB topoisomerase family.

Sequence caution

The sequence CAA36834.1 differs from that shown. Reason: Erroneous gene model prediction.

Ontologies

Keywords
   Biological processHost-virus interaction
   Cellular componentNucleus
   Coding sequence diversityChromosomal rearrangement
Polymorphism
   DiseaseProto-oncogene
   LigandATP-binding
DNA-binding
Nucleotide-binding
   Molecular functionIsomerase
Topoisomerase
   PTMAcetylation
Isopeptide bond
Phosphoprotein
Ubl conjugation
   Technical term3D-structure
Complete proteome
Direct protein sequencing
Reference proteome
Gene Ontology (GO)
   Biological_processDNA replication

Inferred from Biological aspect of Ancestor. Source: RefGenome

DNA topological change

Inferred from direct assay Ref.30. Source: UniProtKB

chromatin remodeling

Inferred from Biological aspect of Ancestor. Source: RefGenome

chromosome segregation

Inferred from Biological aspect of Ancestor. Source: RefGenome

embryonic cleavage

Inferred from electronic annotation. Source: Ensembl

phosphorylation

Non-traceable author statement PubMed 17481653. Source: UniProtKB

programmed cell death

Non-traceable author statement PubMed 17172417. Source: UniProtKB

response to drug

Inferred from expression pattern PubMed 16127745. Source: UniProtKB

viral process

Inferred from electronic annotation. Source: UniProtKB-KW

   Cellular_componentcytoplasmic mRNA processing body

Inferred from direct assay PubMed 12878161. Source: UniProtKB

nucleolus

Inferred from direct assay PubMed 9049244. Source: UniProtKB

nucleoplasm

Inferred from direct assay PubMed 9049244. Source: UniProtKB

nucleus

Inferred from direct assay PubMed 9049244. Source: UniProtKB

perikaryon

Inferred from electronic annotation. Source: Ensembl

replication fork protection complex

Inferred from Biological aspect of Ancestor. Source: RefGenome

   Molecular_functionATP binding

Inferred from electronic annotation. Source: UniProtKB-KW

DNA binding

Inferred from direct assay PubMed 17355975. Source: UniProtKB

DNA topoisomerase type I activity

Inferred from direct assay Ref.30. Source: UniProtKB

DNA topoisomerase type II (ATP-hydrolyzing) activity

Inferred from electronic annotation. Source: InterPro

chromatin binding

Inferred from direct assay PubMed 9049244. Source: UniProtKB

poly(A) RNA binding

Inferred from direct assay PubMed 22658674PubMed 22681889. Source: UniProtKB

Complete GO annotation...

Binary interactions

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Initiator methionine11Removed Ref.7
Chain2 – 765764DNA topoisomerase 1
PRO_0000145201

Regions

Region425 – 4262Interaction with DNA
Region488 – 4936Interaction with DNA
Region585 – 5873Interaction with DNA
Compositional bias23 – 204182Lys-rich

Sites

Active site7231O-(3'-phospho-DNA)-tyrosine intermediate Ref.24 Ref.26 Ref.28 Ref.29 Ref.31 Ref.32 Ref.33
Site3161Interaction with DNA
Site3641Interaction with DNA
Site4121Interaction with DNA
Site4431Interaction with DNA
Site5011Interaction with DNA
Site5321Interaction with DNA
Site5741Interaction with DNA
Site6321Interaction with DNA
Site6501Interaction with DNA

Amino acid modifications

Modified residue21N-acetylserine Ref.7 Ref.20 Ref.22
Modified residue101Phosphoserine Ref.20 Ref.22
Modified residue571Phosphoserine Ref.20
Modified residue1121Phosphoserine Ref.20
Modified residue1721N6-acetyllysine By similarity
Modified residue2801N6-acetyllysine Ref.19
Modified residue5061Phosphoserine; by CK2 Ref.23
Cross-link103Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable
Cross-link117Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Ref.13
Cross-link153Glycyl lysine isopeptide (Lys-Gly) (interchain with G-Cter in SUMO) Probable

Natural variations

Natural variant2141G → S.
Corresponds to variant rs6029542 [ dbSNP | Ensembl ].
VAR_052592
Natural variant3261K → R in breast cancer; somatic mutation. Ref.36
VAR_036555
Natural variant3701M → T in CPT-resistant leukemia. Ref.8
VAR_010666
Natural variant5331D → G in CPT-resistant leukemia. Ref.34
VAR_007530
Natural variant7221N → S in CPT-resistant leukemia. Ref.8
VAR_010667
Natural variant7291T → A in CPT-resistant lung cancer. Ref.35
VAR_007531

Experimental info

Mutagenesis1031K → R: Localizes in both nucleoplasm and nucleoli; when associated with R-117 or R-153. Almost complete loss of sumoylation, concentrates in nucleoli and no clearing from nucleoli on CPT treatment; when associated with R-117 and R-153. Ref.13
Mutagenesis1171K → R: 5-fold decrease in sumoylation. Localizes in both nucleoplasm and nucleoli; when associated with or without R-103 or R-153. Almost complete loss of sumoylation, concentrates in nucleoli and no clearing from nucleoli on CPT treatment; when associated with R-103 and R-153. Ref.13
Mutagenesis1531K → R: Localizes in both nucleoplasm and nucleoli; when associated with R-103 or R-117. Almost complete loss of sumoylation, concentrates in nucleoli and no clearing from nucleoli on CPT treatment; when associated with R-103 and R-117. Ref.13
Mutagenesis5321K → A: Almost abolishes enzyme activity. Ref.30
Mutagenesis5321K → R: Strongly reduced enzyme activity. Ref.30
Mutagenesis7231Y → F: No change in CPT-induced clearing from nuclei. Ref.13
Sequence conflict1451A → V in AAA61207. Ref.1

Secondary structure

.................................................................................................... 765
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P11387 [UniParc].

Last modified December 1, 2000. Version 2.
Checksum: 6FBED540BCF7BE28

FASTA76590,726
        10         20         30         40         50         60 
MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK EKDREKSKHS NSEHKDSEKK 

        70         80         90        100        110        120 
HKEKEKTKHK DGSSEKHKDK HKDRDKEKRK EEKVRASGDA KIKKEKENGF SSPPQIKDEP 

       130        140        150        160        170        180 
EDDGYFVPPK EDIKPLKRPR DEDDADYKPK KIKTEDTKKE KKRKLEEEED GKLKKPKNKD 

       190        200        210        220        230        240 
KDKKVPEPDN KKKKPKKEEE QKWKWWEEER YPEGIKWKFL EHKGPVFAPP YEPLPENVKF 

       250        260        270        280        290        300 
YYDGKVMKLS PKAEEVATFF AKMLDHEYTT KEIFRKNFFK DWRKEMTNEE KNIITNLSKC 

       310        320        330        340        350        360 
DFTQMSQYFK AQTEARKQMS KEEKLKIKEE NEKLLKEYGF CIMDNHKERI ANFKIEPPGL 

       370        380        390        400        410        420 
FRGRGNHPKM GMLKRRIMPE DIIINCSKDA KVPSPPPGHK WKEVRHDNKV TWLVSWTENI 

       430        440        450        460        470        480 
QGSIKYIMLN PSSRIKGEKD WQKYETARRL KKCVDKIRNQ YREDWKSKEM KVRQRAVALY 

       490        500        510        520        530        540 
FIDKLALRAG NEKEEGETAD TVGCCSLRVE HINLHPELDG QEYVVEFDFL GKDSIRYYNK 

       550        560        570        580        590        600 
VPVEKRVFKN LQLFMENKQP EDDLFDRLNT GILNKHLQDL MEGLTAKVFR TYNASITLQQ 

       610        620        630        640        650        660 
QLKELTAPDE NIPAKILSYN RANRAVAILC NHQRAPPKTF EKSMMNLQTK IDAKKEQLAD 

       670        680        690        700        710        720 
ARRDLKSAKA DAKVMKDAKT KKVVESKKKA VQRLEEQLMK LEVQATDREE NKQIALGTSK 

       730        740        750        760 
LNYLDPRITV AWCKKWGVPI EKIYNKTQRE KFAWAIDMAD EDYEF 

« Hide

References

« Hide 'large scale' references
[1]"cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-kDa carboxyl-terminal fragment."
D'Arpa P., Machlin P.S., Ratrie H. III, Rothfield N.F., Cleveland D.W., Earnshaw W.C.
Proc. Natl. Acad. Sci. U.S.A. 85:2543-2547(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, CATALYTIC ACTIVITY.
[2]"Structure of the human type I DNA topoisomerase gene."
Kunze N., Yang G., Dolberg M., Sundarp R., Knippers R., Richter A.
J. Biol. Chem. 266:9610-9616(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
[3]"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].
Tissue: Trachea.
[4]"The DNA sequence and comparative analysis of human chromosome 20."
Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R., Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L., Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P., Bird C.P., Blakey S.E. expand/collapse author list , Bridgeman A.M., Brown A.J., Buck D., Burrill W.D., Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G., Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E., Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D., Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P., Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E., Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J., Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D., Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S., Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D., Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A., Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T., Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I., Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M., Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D., Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M., Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A., Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L., Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L., Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.
Nature 414:865-871(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[5]Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., Turner R. expand/collapse author list , Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., Hunkapiller M.W., Myers E.W., Venter J.C.
Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
[6]"Structural characterisation of the human DNA topoisomerase I gene promoter."
Kunze N., Klein M., Richter A., Knippers R.
Eur. J. Biochem. 194:323-330(1990) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
[7]Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.
Submitted (DEC-2008) to UniProtKB
Cited for: PROTEIN SEQUENCE OF 2-17; 107-117; 224-239; 253-262; 292-299; 355-362; 426-434; 476-484; 509-532; 550-587; 591-615; 625-634; 656-663; 694-712; 721-734 AND 736-742, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT SER-2, IDENTIFICATION BY MASS SPECTROMETRY.
Tissue: Ovarian carcinoma.
[8]"Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin."
Fujimori A., Harker W.G., Kohlhagen G., Hoki Y., Pommier Y.
Cancer Res. 55:1339-1346(1995) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 5-765, VARIANTS CPT-RESISTANT LEUKEMIA THR-370 AND SER-722.
Tissue: Peripheral blood.
[9]"Monoclonal antibodies neutralizing mammalian DNA topoisomerase I activity."
Oddou P., Schmidt U., Knippers R., Richter A.
Eur. J. Biochem. 177:523-529(1988) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE OF 344-765.
[10]"Characterization of the 3' region of the human DNA topoisomerase I gene."
Zhou B.S., Bastow K.F., Cheng Y.C.
Cancer Res. 49:3922-3927(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 541-765.
[11]"Determination of an epitope of the diffuse systemic sclerosis marker antigen DNA topoisomerase I: sequence similarity with retroviral p30gag protein suggests a possible cause for autoimmunity in systemic sclerosis."
Maul G.G., Jimenez S.A., Riggs E., Ziemnicka-Kotula D.
Proc. Natl. Acad. Sci. U.S.A. 86:8492-8496(1989) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 657-765.
[12]"The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion."
Ahuja H.G., Felix C.A., Aplan P.D.
Blood 94:3258-3261(1999) [PubMed] [Europe PMC] [Abstract]
Cited for: CHROMOSOMAL TRANSLOCATION WITH NUP98.
[13]"Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecin."
Rallabhandi P., Hashimoto K., Mo Y.-Y., Beck W.T., Moitra P.K., D'Arpa P.
J. Biol. Chem. 277:40020-40026(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUMOYLATION AT LYS-117, SUBCELLULAR LOCATION, MUTAGENESIS OF LYS-103; LYS-117; LYS-153 AND TYR-723.
[14]"Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[15]"Simian virus 40 DNA replication is dependent on an interaction between topoisomerase I and the C-terminal end of T antigen."
Khopde S., Simmons D.T.
J. Virol. 82:1136-1145(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH SV40 LARGE T ANTIGEN.
[16]"A quantitative atlas of mitotic phosphorylation."
Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E., Elledge S.J., Gygi S.P.
Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[17]"Lys-N and trypsin cover complementary parts of the phosphoproteome in a refined SCX-based approach."
Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.
Anal. Chem. 81:4493-4501(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[18]"Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of tissue factor in human endothelial cells."
Eisenreich A., Bogdanov V.Y., Zakrzewicz A., Pries A., Antoniak S., Poller W., Schultheiss H.P., Rauch U.
Circ. Res. 104:589-599(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION, TISSUE SPECIFICITY.
[19]"Lysine acetylation targets protein complexes and co-regulates major cellular functions."
Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C., Olsen J.V., Mann M.
Science 325:834-840(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-280, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[20]"Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10; SER-57 AND SER-112, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
Tissue: Cervix carcinoma.
[21]"Initial characterization of the human central proteome."
Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T., Bennett K.L., Superti-Furga G., Colinge J.
BMC Syst. Biol. 5:17-17(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[22]"System-wide temporal characterization of the proteome and phosphoproteome of human embryonic stem cell differentiation."
Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T., Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.
Sci. Signal. 4:RS3-RS3(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-10, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
[23]"CK2-mediated hyperphosphorylation of topoisomerase I targets serine 506, enhances topoisomerase I-DNA Binding, and increases cellular camptothecin sensitivity."
Bandyopadhyay K., Li P., Gjerset R.A.
PLoS ONE 7:E50427-E50427(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: PHOSPHORYLATION AT SER-506.
[24]"Crystal structures of human topoisomerase I in covalent and noncovalent complexes with DNA."
Redinbo M.R., Stewart L., Kuhn P., Champoux J.J., Hol W.G.J.
Science 279:1504-1513(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 175-765 IN COMPLEX WITH DNA, ACTIVE SITE.
[25]"A model for the mechanism of human topoisomerase I."
Stewart L., Redinbo M.R., Qiu X., Hol W.G.J., Champoux J.J.
Science 279:1534-1541(1998) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 215-765 OF MUTANT PHE-723 IN COMPLEX WITH DNA.
[26]"Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA."
Redinbo M.R., Champoux J.J., Hol W.G.J.
Biochemistry 39:6832-6840(2000) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 203-765 IN COMPLEX WITH DNA, ACTIVE SITE.
[27]"8-Oxoguanine rearranges the active site of human topoisomerase I."
Lesher D.T., Pommier Y., Stewart L., Redinbo M.R.
Proc. Natl. Acad. Sci. U.S.A. 99:12102-12107(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.14 ANGSTROMS) OF 202-765 IN COMPLEX WITH DNA.
[28]"The mechanism of topoisomerase I poisoning by a camptothecin analog."
Staker B.L., Hjerrild K., Feese M.D., Behnke C.A., Burgin A.B. Jr., Stewart L.
Proc. Natl. Acad. Sci. U.S.A. 99:15387-15392(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 174-765 IN COMPLEXES WITH DNA AND TOPOTECAN, ACTIVE SITE.
[29]"Structural impact of the leukemia drug 1-beta-D-arabinofuranosylcytosine (Ara-C) on the covalent human topoisomerase I-DNA complex."
Chrencik J.E., Burgin A.B., Pommier Y., Stewart L., Redinbo M.R.
J. Biol. Chem. 278:12461-12466(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 203-764 IN COMPLEX WITH DNA, ACTIVE SITE.
[30]"The role of lysine 532 in the catalytic mechanism of human topoisomerase I."
Interthal H., Quigley P.M., Hol W.G., Champoux J.J.
J. Biol. Chem. 279:2984-2992(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.13 ANGSTROMS) OF 174-765, MUTAGENESIS OF LYS-532, CATALYTIC ACTIVITY, FUNCTION.
[31]"Mechanisms of camptothecin resistance by human topoisomerase I mutations."
Chrencik J.E., Staker B.L., Burgin A.B., Pourquier P., Pommier Y., Stewart L., Redinbo M.R.
J. Mol. Biol. 339:773-784(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 201-765 IN COMPLEX WITH DNA AND TOPOTECAN, ACTIVE SITE.
[32]"Structures of three classes of anticancer agents bound to the human topoisomerase I-DNA covalent complex."
Staker B.L., Feese M.D., Cushman M., Pommier Y., Zembower D., Stewart L., Burgin A.B.
J. Med. Chem. 48:2336-2345(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 174-765 IN COMPLEXES WITH DNA AND SYNTHETIC INHIBITORS, ACTIVE SITE.
[33]"Synthesis and mechanism of action studies of a series of norindenoisoquinoline topoisomerase I poisons reveal an inhibitor with a flipped orientation in the ternary DNA-enzyme-inhibitor complex as determined by X-ray crystallographic analysis."
Ioanoviciu A., Antony S., Pommier Y., Staker B.L., Stewart L., Cushman M.
J. Med. Chem. 48:4803-4814(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 174-765 IN COMPLEX WITH DNA AND SYNTHETIC INHIBITORS, CATALYTIC ACTIVITY, FUNCTION, ACTIVE SITE.
[34]"Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites."
Tamura H., Kohchi C., Yamada R., Ikeda T., Koiwai O., Patterson E., Keene J.D., Okada K., Kjeldsen E., Nishikawa K.
Nucleic Acids Res. 19:69-75(1991) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPT-RESISTANT LEUKEMIA GLY-533.
[35]"Detection of topoisomerase I gene point mutation in CPT-11 resistant lung cancer cell line."
Kubota N., Kanzawa F., Nishio K., Takeda Y., Ohmori T., Fujiwara Y., Terashima Y., Saijo N.
Biochem. Biophys. Res. Commun. 188:571-577(1992) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT CPT-RESISTANT LUNG CANCER ALA-729.
[36]"The consensus coding sequences of human breast and colorectal cancers."
Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D., Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P., Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V. expand/collapse author list , Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H., Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W., Velculescu V.E.
Science 314:268-274(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: VARIANT [LARGE SCALE ANALYSIS] BREAST CANCER ARG-326.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
J03250 mRNA. Translation: AAA61207.1.
M60706 expand/collapse EMBL AC list , M60688, M60689, M60690, M60691, M60692, M60693, M60694, M60695, M60696, M60697, M60698, M60699, M60700, M60701, M60702, M60703, M60704, M60705 Genomic DNA. Translation: AAA61206.1.
AK292943 mRNA. Translation: BAF85632.1.
AL035652, AL022394 Genomic DNA. Translation: CAI19767.1.
AL022394, AL035652 Genomic DNA. Translation: CAI42886.1.
CH471077 Genomic DNA. Translation: EAW75994.1.
CH471077 Genomic DNA. Translation: EAW75995.1.
X52601 Genomic DNA. Translation: CAA36834.1. Sequence problems.
U07804 mRNA. Translation: AAB60379.1.
U07806 mRNA. Translation: AAB60380.1.
X16479 mRNA. Translation: CAA34500.2.
M27913 mRNA. Translation: AAA61208.1.
PIRISHUT1. A30887.
RefSeqNP_003277.1. NM_003286.2.
UniGeneHs.472737.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1A31X-ray2.10A175-765[»]
1A35X-ray2.50A175-765[»]
1A36X-ray2.80A175-765[»]
1EJ9X-ray2.60A203-765[»]
1K4SX-ray3.20A174-765[»]
1K4TX-ray2.10A174-765[»]
1LPQX-ray3.14A202-765[»]
1NH3X-ray3.10A203-764[»]
1R49X-ray3.13A174-765[»]
1RR8X-ray2.60C203-765[»]
1RRJX-ray2.30A201-765[»]
1SC7X-ray3.00A174-765[»]
1SEUX-ray3.00A174-765[»]
1T8IX-ray3.00A174-765[»]
1TL8X-ray3.10A174-765[»]
DisProtDP00075.
ProteinModelPortalP11387.
SMRP11387. Positions 201-765.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid113003. 126 interactions.
IntActP11387. 57 interactions.
MINTMINT-94018.
STRING9606.ENSP00000354522.

Chemistry

BindingDBP11387.
ChEMBLCHEMBL1781.
DrugBankDB00762. Irinotecan.
DB04967. Lucanthone.
DB01030. Topotecan.

PTM databases

PhosphoSiteP11387.

Polymorphism databases

DMDM12644118.

2D gel databases

SWISS-2DPAGEP11387.

Proteomic databases

PaxDbP11387.
PeptideAtlasP11387.
PRIDEP11387.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000361337; ENSP00000354522; ENSG00000198900.
GeneID7150.
KEGGhsa:7150.
UCSCuc002xjl.3. human.

Organism-specific databases

CTD7150.
GeneCardsGC20P039657.
H-InvDBHIX0015818.
HIX0040702.
HGNCHGNC:11986. TOP1.
HPACAB009058.
HPA019039.
MIM126420. gene.
neXtProtNX_P11387.
PharmGKBPA353.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG3569.
HOVERGENHBG007988.
InParanoidP11387.
KOK03163.
OMAEFDFPGK.
OrthoDBEOG7CVPX5.
PhylomeDBP11387.
TreeFamTF105281.

Gene expression databases

ArrayExpressP11387.
BgeeP11387.
CleanExHS_TOP1.
GenevestigatorP11387.

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

ChiTaRSTOP1. human.
EvolutionaryTraceP11387.
GeneWikiTOP1.
GenomeRNAi7150.
NextBio27982.
PMAP-CutDBP11387.
PROP11387.
SOURCESearch...

Entry information

Entry nameTOP1_HUMAN
AccessionPrimary (citable) accession number: P11387
Secondary accession number(s): A8KA78 expand/collapse secondary AC list , E1P5W3, O43256, Q12855, Q12856, Q15610, Q5TFY3, Q9UJN0
Entry history
Integrated into UniProtKB/Swiss-Prot: July 1, 1989
Last sequence update: December 1, 2000
Last modified: April 16, 2014
This is version 165 of the entry and version 2 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

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

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 20

Human chromosome 20: entries, gene names and cross-references to MIM