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Database: UniProt
Entry: P11387
LinkDB: P11387
Original site: P11387 
ID   TOP1_HUMAN              Reviewed;         765 AA.
AC   P11387; A8KA78; E1P5W3; O43256; Q12855; Q12856; Q15610; Q5TFY3; Q9UJN0;
DT   01-JUL-1989, integrated into UniProtKB/Swiss-Prot.
DT   01-DEC-2000, sequence version 2.
DT   07-APR-2021, entry version 232.
DE   RecName: Full=DNA topoisomerase 1;
DE            EC=5.6.2.1 {ECO:0000255|PROSITE-ProRule:PRU10130, ECO:0000269|PubMed:14594810, ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:2833744};
DE   AltName: Full=DNA topoisomerase I;
GN   Name=TOP1;
OS   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae;
OC   Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], FUNCTION, AND CATALYTIC ACTIVITY.
RX   PubMed=2833744; DOI=10.1073/pnas.85.8.2543;
RA   D'Arpa P., Machlin P.S., Ratrie H. III, Rothfield N.F., Cleveland D.W.,
RA   Earnshaw W.C.;
RT   "cDNA cloning of human DNA topoisomerase I: catalytic activity of a 67.7-
RT   kDa carboxyl-terminal fragment.";
RL   Proc. Natl. Acad. Sci. U.S.A. 85:2543-2547(1988).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX   PubMed=1851751;
RA   Kunze N., Yang G., Dolberg M., Sundarp R., Knippers R., Richter A.;
RT   "Structure of the human type I DNA topoisomerase gene.";
RL   J. Biol. Chem. 266:9610-9616(1991).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Trachea;
RX   PubMed=14702039; DOI=10.1038/ng1285;
RA   Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R.,
RA   Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H.,
RA   Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.,
RA   Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K.,
RA   Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H.,
RA   Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M.,
RA   Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K.,
RA   Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T.,
RA   Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M.,
RA   Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S.,
RA   Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H.,
RA   Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K.,
RA   Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N.,
RA   Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S.,
RA   Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O.,
RA   Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H.,
RA   Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B.,
RA   Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y.,
RA   Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K.,
RA   Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T.,
RA   Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T.,
RA   Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y.,
RA   Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H.,
RA   Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y.,
RA   Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H.,
RA   Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O.,
RA   Isogai T., Sugano S.;
RT   "Complete sequencing and characterization of 21,243 full-length human
RT   cDNAs.";
RL   Nat. Genet. 36:40-45(2004).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RX   PubMed=11780052; DOI=10.1038/414865a;
RA   Deloukas P., Matthews L.H., Ashurst J.L., Burton J., Gilbert J.G.R.,
RA   Jones M., Stavrides G., Almeida J.P., Babbage A.K., Bagguley C.L.,
RA   Bailey J., Barlow K.F., Bates K.N., Beard L.M., Beare D.M., Beasley O.P.,
RA   Bird C.P., Blakey S.E., Bridgeman A.M., Brown A.J., Buck D., Burrill W.D.,
RA   Butler A.P., Carder C., Carter N.P., Chapman J.C., Clamp M., Clark G.,
RA   Clark L.N., Clark S.Y., Clee C.M., Clegg S., Cobley V.E., Collier R.E.,
RA   Connor R.E., Corby N.R., Coulson A., Coville G.J., Deadman R., Dhami P.D.,
RA   Dunn M., Ellington A.G., Frankland J.A., Fraser A., French L., Garner P.,
RA   Grafham D.V., Griffiths C., Griffiths M.N.D., Gwilliam R., Hall R.E.,
RA   Hammond S., Harley J.L., Heath P.D., Ho S., Holden J.L., Howden P.J.,
RA   Huckle E., Hunt A.R., Hunt S.E., Jekosch K., Johnson C.M., Johnson D.,
RA   Kay M.P., Kimberley A.M., King A., Knights A., Laird G.K., Lawlor S.,
RA   Lehvaeslaiho M.H., Leversha M.A., Lloyd C., Lloyd D.M., Lovell J.D.,
RA   Marsh V.L., Martin S.L., McConnachie L.J., McLay K., McMurray A.A.,
RA   Milne S.A., Mistry D., Moore M.J.F., Mullikin J.C., Nickerson T.,
RA   Oliver K., Parker A., Patel R., Pearce T.A.V., Peck A.I.,
RA   Phillimore B.J.C.T., Prathalingam S.R., Plumb R.W., Ramsay H., Rice C.M.,
RA   Ross M.T., Scott C.E., Sehra H.K., Shownkeen R., Sims S., Skuce C.D.,
RA   Smith M.L., Soderlund C., Steward C.A., Sulston J.E., Swann R.M.,
RA   Sycamore N., Taylor R., Tee L., Thomas D.W., Thorpe A., Tracey A.,
RA   Tromans A.C., Vaudin M., Wall M., Wallis J.M., Whitehead S.L.,
RA   Whittaker P., Willey D.L., Williams L., Williams S.A., Wilming L.,
RA   Wray P.W., Hubbard T., Durbin R.M., Bentley D.R., Beck S., Rogers J.;
RT   "The DNA sequence and comparative analysis of human chromosome 20.";
RL   Nature 414:865-871(2001).
RN   [5]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RA   Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M.,
RA   Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J.,
RA   Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S.,
RA   Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H.,
RA   Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K.,
RA   Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D.,
RA   Hunkapiller M.W., Myers E.W., Venter J.C.;
RL   Submitted (SEP-2005) to the EMBL/GenBank/DDBJ databases.
RN   [6]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-14.
RX   PubMed=2176592; DOI=10.1111/j.1432-1033.1990.tb15620.x;
RA   Kunze N., Klein M., Richter A., Knippers R.;
RT   "Structural characterisation of the human DNA topoisomerase I gene
RT   promoter.";
RL   Eur. J. Biochem. 194:323-330(1990).
RN   [7]
RP   PROTEIN SEQUENCE OF 2-17; 107-117; 224-239; 253-262; 292-299; 355-362;
RP   426-434; 476-484; 509-532; 550-587; 591-615; 625-634; 656-663; 694-712;
RP   721-734 AND 736-742, CLEAVAGE OF INITIATOR METHIONINE, ACETYLATION AT
RP   SER-2, AND IDENTIFICATION BY MASS SPECTROMETRY.
RC   TISSUE=Ovarian carcinoma;
RA   Bienvenut W.V., Lilla S., von Kriegsheim A., Lempens A., Kolch W.;
RL   Submitted (DEC-2008) to UniProtKB.
RN   [8]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 5-765, AND VARIANTS CPT-RESISTANT LEUKEMIA
RP   THR-370 AND SER-722.
RC   TISSUE=Peripheral blood;
RX   PubMed=7882333;
RA   Fujimori A., Harker W.G., Kohlhagen G., Hoki Y., Pommier Y.;
RT   "Mutation at the catalytic site of topoisomerase I in CEM/C2, a human
RT   leukemia cell line resistant to camptothecin.";
RL   Cancer Res. 55:1339-1346(1995).
RN   [9]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 344-765.
RX   PubMed=2461859; DOI=10.1111/j.1432-1033.1988.tb14404.x;
RA   Oddou P., Schmidt U., Knippers R., Richter A.;
RT   "Monoclonal antibodies neutralizing mammalian DNA topoisomerase I
RT   activity.";
RL   Eur. J. Biochem. 177:523-529(1988).
RN   [10]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 541-765.
RX   PubMed=2544263;
RA   Zhou B.S., Bastow K.F., Cheng Y.C.;
RT   "Characterization of the 3' region of the human DNA topoisomerase I gene.";
RL   Cancer Res. 49:3922-3927(1989).
RN   [11]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 657-765.
RX   PubMed=2479024; DOI=10.1073/pnas.86.21.8492;
RA   Maul G.G., Jimenez S.A., Riggs E., Ziemnicka-Kotula D.;
RT   "Determination of an epitope of the diffuse systemic sclerosis marker
RT   antigen DNA topoisomerase I: sequence similarity with retroviral p30gag
RT   protein suggests a possible cause for autoimmunity in systemic sclerosis.";
RL   Proc. Natl. Acad. Sci. U.S.A. 86:8492-8496(1989).
RN   [12]
RP   CHROMOSOMAL TRANSLOCATION WITH NUP98.
RX   PubMed=10556215;
RA   Ahuja H.G., Felix C.A., Aplan P.D.;
RT   "The t(11;20)(p15;q11) chromosomal translocation associated with therapy-
RT   related myelodysplastic syndrome results in an NUP98-TOP1 fusion.";
RL   Blood 94:3258-3261(1999).
RN   [13]
RP   SUMOYLATION AT LYS-117, SUBCELLULAR LOCATION, AND MUTAGENESIS OF LYS-103;
RP   LYS-117; LYS-153 AND TYR-723.
RX   PubMed=12149243; DOI=10.1074/jbc.m200388200;
RA   Rallabhandi P., Hashimoto K., Mo Y.-Y., Beck W.T., Moitra P.K., D'Arpa P.;
RT   "Sumoylation of topoisomerase I is involved in its partitioning between
RT   nucleoli and nucleoplasm and its clearing from nucleoli in response to
RT   camptothecin.";
RL   J. Biol. Chem. 277:40020-40026(2002).
RN   [14]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=17081983; DOI=10.1016/j.cell.2006.09.026;
RA   Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.;
RT   "Global, in vivo, and site-specific phosphorylation dynamics in signaling
RT   networks.";
RL   Cell 127:635-648(2006).
RN   [15]
RP   INTERACTION WITH SV40 LARGE T ANTIGEN (MICROBIAL INFECTION).
RX   PubMed=18003733; DOI=10.1128/jvi.01314-07;
RA   Khopde S., Simmons D.T.;
RT   "Simian virus 40 DNA replication is dependent on an interaction between
RT   topoisomerase I and the C-terminal end of T antigen.";
RL   J. Virol. 82:1136-1145(2008).
RN   [16]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=18669648; DOI=10.1073/pnas.0805139105;
RA   Dephoure N., Zhou C., Villen J., Beausoleil S.A., Bakalarski C.E.,
RA   Elledge S.J., Gygi S.P.;
RT   "A quantitative atlas of mitotic phosphorylation.";
RL   Proc. Natl. Acad. Sci. U.S.A. 105:10762-10767(2008).
RN   [17]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19413330; DOI=10.1021/ac9004309;
RA   Gauci S., Helbig A.O., Slijper M., Krijgsveld J., Heck A.J., Mohammed S.;
RT   "Lys-N and trypsin cover complementary parts of the phosphoproteome in a
RT   refined SCX-based approach.";
RL   Anal. Chem. 81:4493-4501(2009).
RN   [18]
RP   FUNCTION, AND TISSUE SPECIFICITY.
RX   PubMed=19168442; DOI=10.1161/circresaha.108.183905;
RA   Eisenreich A., Bogdanov V.Y., Zakrzewicz A., Pries A., Antoniak S.,
RA   Poller W., Schultheiss H.P., Rauch U.;
RT   "Cdc2-like kinases and DNA topoisomerase I regulate alternative splicing of
RT   tissue factor in human endothelial cells.";
RL   Circ. Res. 104:589-599(2009).
RN   [19]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT LYS-280, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=19608861; DOI=10.1126/science.1175371;
RA   Choudhary C., Kumar C., Gnad F., Nielsen M.L., Rehman M., Walther T.C.,
RA   Olsen J.V., Mann M.;
RT   "Lysine acetylation targets protein complexes and co-regulates major
RT   cellular functions.";
RL   Science 325:834-840(2009).
RN   [20]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP   ANALYSIS] AT SER-10; SER-57 AND SER-112, CLEAVAGE OF INITIATOR METHIONINE
RP   [LARGE SCALE ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE
RP   SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma;
RX   PubMed=20068231; DOI=10.1126/scisignal.2000475;
RA   Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L.,
RA   Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.;
RT   "Quantitative phosphoproteomics reveals widespread full phosphorylation
RT   site occupancy during mitosis.";
RL   Sci. Signal. 3:RA3-RA3(2010).
RN   [21]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21269460; DOI=10.1186/1752-0509-5-17;
RA   Burkard T.R., Planyavsky M., Kaupe I., Breitwieser F.P., Buerckstuemmer T.,
RA   Bennett K.L., Superti-Furga G., Colinge J.;
RT   "Initial characterization of the human central proteome.";
RL   BMC Syst. Biol. 5:17-17(2011).
RN   [22]
RP   ACETYLATION [LARGE SCALE ANALYSIS] AT SER-2, PHOSPHORYLATION [LARGE SCALE
RP   ANALYSIS] AT SER-10, CLEAVAGE OF INITIATOR METHIONINE [LARGE SCALE
RP   ANALYSIS], AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=21406692; DOI=10.1126/scisignal.2001570;
RA   Rigbolt K.T., Prokhorova T.A., Akimov V., Henningsen J., Johansen P.T.,
RA   Kratchmarova I., Kassem M., Mann M., Olsen J.V., Blagoev B.;
RT   "System-wide temporal characterization of the proteome and phosphoproteome
RT   of human embryonic stem cell differentiation.";
RL   Sci. Signal. 4:RS3-RS3(2011).
RN   [23]
RP   FUNCTION.
RX   PubMed=22904072; DOI=10.1093/nar/gks779;
RA   Onishi Y., Kawano Y.;
RT   "Rhythmic binding of Topoisomerase I impacts on the transcription of Bmal1
RT   and circadian period.";
RL   Nucleic Acids Res. 40:9482-9492(2012).
RN   [24]
RP   PHOSPHORYLATION AT SER-506.
RX   PubMed=23185622; DOI=10.1371/journal.pone.0050427;
RA   Bandyopadhyay K., Li P., Gjerset R.A.;
RT   "CK2-mediated hyperphosphorylation of topoisomerase I targets serine 506,
RT   enhances topoisomerase I-DNA Binding, and increases cellular camptothecin
RT   sensitivity.";
RL   PLoS ONE 7:E50427-E50427(2012).
RN   [25]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-2 AND SER-10, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Cervix carcinoma, and Erythroleukemia;
RX   PubMed=23186163; DOI=10.1021/pr300630k;
RA   Zhou H., Di Palma S., Preisinger C., Peng M., Polat A.N., Heck A.J.,
RA   Mohammed S.;
RT   "Toward a comprehensive characterization of a human cancer cell
RT   phosphoproteome.";
RL   J. Proteome Res. 12:260-271(2013).
RN   [26]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Liver;
RX   PubMed=24275569; DOI=10.1016/j.jprot.2013.11.014;
RA   Bian Y., Song C., Cheng K., Dong M., Wang F., Huang J., Sun D., Wang L.,
RA   Ye M., Zou H.;
RT   "An enzyme assisted RP-RPLC approach for in-depth analysis of human liver
RT   phosphoproteome.";
RL   J. Proteomics 96:253-262(2014).
RN   [27]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-117; LYS-134; LYS-153; LYS-158
RP   AND LYS-164, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE
RP   ANALYSIS].
RX   PubMed=25218447; DOI=10.1038/nsmb.2890;
RA   Hendriks I.A., D'Souza R.C., Yang B., Verlaan-de Vries M., Mann M.,
RA   Vertegaal A.C.;
RT   "Uncovering global SUMOylation signaling networks in a site-specific
RT   manner.";
RL   Nat. Struct. Mol. Biol. 21:927-936(2014).
RN   [28]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-117, AND IDENTIFICATION BY MASS
RP   SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25114211; DOI=10.1073/pnas.1413825111;
RA   Impens F., Radoshevich L., Cossart P., Ribet D.;
RT   "Mapping of SUMO sites and analysis of SUMOylation changes induced by
RT   external stimuli.";
RL   Proc. Natl. Acad. Sci. U.S.A. 111:12432-12437(2014).
RN   [29]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-117; LYS-148; LYS-153 AND
RP   LYS-164, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25772364; DOI=10.1016/j.celrep.2015.02.033;
RA   Hendriks I.A., Treffers L.W., Verlaan-de Vries M., Olsen J.V.,
RA   Vertegaal A.C.;
RT   "SUMO-2 orchestrates chromatin modifiers in response to DNA damage.";
RL   Cell Rep. 10:1778-1791(2015).
RN   [30]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-148; LYS-153; LYS-164 AND
RP   LYS-336, AND IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=25755297; DOI=10.1074/mcp.o114.044792;
RA   Xiao Z., Chang J.G., Hendriks I.A., Sigurdsson J.O., Olsen J.V.,
RA   Vertegaal A.C.;
RT   "System-wide analysis of SUMOylation dynamics in response to replication
RT   stress reveals novel small ubiquitin-like modified target proteins and
RT   acceptor lysines relevant for genome stability.";
RL   Mol. Cell. Proteomics 14:1419-1434(2015).
RN   [31]
RP   INTERACTION WITH ERCC6.
RX   PubMed=26030138; DOI=10.1371/journal.pone.0128558;
RA   Nicolai S., Filippi S., Caputo M., Cipak L., Gregan J., Ammerer G.,
RA   Frontini M., Willems D., Prantera G., Balajee A.S., Proietti-De-Santis L.;
RT   "Identification of Novel Proteins Co-Purifying with Cockayne Syndrome Group
RT   B (CSB) Reveals Potential Roles for CSB in RNA Metabolism and Chromatin
RT   Dynamics.";
RL   PLoS ONE 10:E0128558-E0128558(2015).
RN   [32]
RP   SUMOYLATION [LARGE SCALE ANALYSIS] AT LYS-101; LYS-103; LYS-117; LYS-134;
RP   LYS-148; LYS-153; LYS-158; LYS-164; LYS-172; LYS-204; LYS-336; LYS-549;
RP   LYS-642; LYS-700 AND LYS-712, AND IDENTIFICATION BY MASS SPECTROMETRY
RP   [LARGE SCALE ANALYSIS].
RX   PubMed=28112733; DOI=10.1038/nsmb.3366;
RA   Hendriks I.A., Lyon D., Young C., Jensen L.J., Vertegaal A.C.,
RA   Nielsen M.L.;
RT   "Site-specific mapping of the human SUMO proteome reveals co-modification
RT   with phosphorylation.";
RL   Nat. Struct. Mol. Biol. 24:325-336(2017).
RN   [33]
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 175-765 IN COMPLEX WITH DNA, AND
RP   ACTIVE SITE.
RX   PubMed=9488644; DOI=10.1126/science.279.5356.1504;
RA   Redinbo M.R., Stewart L., Kuhn P., Champoux J.J., Hol W.G.J.;
RT   "Crystal structures of human topoisomerase I in covalent and noncovalent
RT   complexes with DNA.";
RL   Science 279:1504-1513(1998).
RN   [34]
RP   X-RAY CRYSTALLOGRAPHY (2.8 ANGSTROMS) OF 215-765 OF MUTANT PHE-723 IN
RP   COMPLEX WITH DNA.
RX   PubMed=9488652; DOI=10.1126/science.279.5356.1534;
RA   Stewart L., Redinbo M.R., Qiu X., Hol W.G.J., Champoux J.J.;
RT   "A model for the mechanism of human topoisomerase I.";
RL   Science 279:1534-1541(1998).
RN   [35]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 203-765 IN COMPLEX WITH DNA, AND
RP   ACTIVE SITE.
RX   PubMed=10841763; DOI=10.1021/bi992690t;
RA   Redinbo M.R., Champoux J.J., Hol W.G.J.;
RT   "Novel insights into catalytic mechanism from a crystal structure of human
RT   topoisomerase I in complex with DNA.";
RL   Biochemistry 39:6832-6840(2000).
RN   [36]
RP   X-RAY CRYSTALLOGRAPHY (3.14 ANGSTROMS) OF 202-765 IN COMPLEX WITH DNA.
RX   PubMed=12209008; DOI=10.1073/pnas.192282699;
RA   Lesher D.T., Pommier Y., Stewart L., Redinbo M.R.;
RT   "8-Oxoguanine rearranges the active site of human topoisomerase I.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:12102-12107(2002).
RN   [37]
RP   X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 174-765 IN COMPLEXES WITH DNA AND
RP   TOPOTECAN, AND ACTIVE SITE.
RX   PubMed=12426403; DOI=10.1073/pnas.242259599;
RA   Staker B.L., Hjerrild K., Feese M.D., Behnke C.A., Burgin A.B. Jr.,
RA   Stewart L.;
RT   "The mechanism of topoisomerase I poisoning by a camptothecin analog.";
RL   Proc. Natl. Acad. Sci. U.S.A. 99:15387-15392(2002).
RN   [38]
RP   X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 203-764 IN COMPLEX WITH DNA, AND
RP   ACTIVE SITE.
RX   PubMed=12533542; DOI=10.1074/jbc.m212930200;
RA   Chrencik J.E., Burgin A.B., Pommier Y., Stewart L., Redinbo M.R.;
RT   "Structural impact of the leukemia drug 1-beta-D-arabinofuranosylcytosine
RT   (Ara-C) on the covalent human topoisomerase I-DNA complex.";
RL   J. Biol. Chem. 278:12461-12466(2003).
RN   [39]
RP   X-RAY CRYSTALLOGRAPHY (3.13 ANGSTROMS) OF 174-765, MUTAGENESIS OF LYS-532,
RP   CATALYTIC ACTIVITY, AND FUNCTION.
RX   PubMed=14594810; DOI=10.1074/jbc.m309959200;
RA   Interthal H., Quigley P.M., Hol W.G., Champoux J.J.;
RT   "The role of lysine 532 in the catalytic mechanism of human topoisomerase
RT   I.";
RL   J. Biol. Chem. 279:2984-2992(2004).
RN   [40]
RP   X-RAY CRYSTALLOGRAPHY (2.30 ANGSTROMS) OF 201-765 IN COMPLEX WITH DNA AND
RP   TOPOTECAN, AND ACTIVE SITE.
RX   PubMed=15165849; DOI=10.1016/j.jmb.2004.03.077;
RA   Chrencik J.E., Staker B.L., Burgin A.B., Pourquier P., Pommier Y.,
RA   Stewart L., Redinbo M.R.;
RT   "Mechanisms of camptothecin resistance by human topoisomerase I
RT   mutations.";
RL   J. Mol. Biol. 339:773-784(2004).
RN   [41]
RP   X-RAY CRYSTALLOGRAPHY (3.00 ANGSTROMS) OF 174-765 IN COMPLEXES WITH DNA AND
RP   SYNTHETIC INHIBITORS, AND ACTIVE SITE.
RX   PubMed=15801827; DOI=10.1021/jm049146p;
RA   Staker B.L., Feese M.D., Cushman M., Pommier Y., Zembower D., Stewart L.,
RA   Burgin A.B.;
RT   "Structures of three classes of anticancer agents bound to the human
RT   topoisomerase I-DNA covalent complex.";
RL   J. Med. Chem. 48:2336-2345(2005).
RN   [42]
RP   X-RAY CRYSTALLOGRAPHY (3.10 ANGSTROMS) OF 174-765 IN COMPLEX WITH DNA AND
RP   SYNTHETIC INHIBITORS, CATALYTIC ACTIVITY, FUNCTION, AND ACTIVE SITE.
RX   PubMed=16033260; DOI=10.1021/jm050076b;
RA   Ioanoviciu A., Antony S., Pommier Y., Staker B.L., Stewart L., Cushman M.;
RT   "Synthesis and mechanism of action studies of a series of
RT   norindenoisoquinoline topoisomerase I poisons reveal an inhibitor with a
RT   flipped orientation in the ternary DNA-enzyme-inhibitor complex as
RT   determined by X-ray crystallographic analysis.";
RL   J. Med. Chem. 48:4803-4814(2005).
RN   [43]
RP   VARIANT CPT-RESISTANT LEUKEMIA GLY-533.
RX   PubMed=1849260; DOI=10.1093/nar/19.1.69;
RA   Tamura H., Kohchi C., Yamada R., Ikeda T., Koiwai O., Patterson E.,
RA   Keene J.D., Okada K., Kjeldsen E., Nishikawa K.;
RT   "Molecular cloning of a cDNA of a camptothecin-resistant human DNA
RT   topoisomerase I and identification of mutation sites.";
RL   Nucleic Acids Res. 19:69-75(1991).
RN   [44]
RP   VARIANT CPT-RESISTANT LUNG CANCER ALA-729.
RX   PubMed=1332703; DOI=10.1016/0006-291x(92)91094-7;
RA   Kubota N., Kanzawa F., Nishio K., Takeda Y., Ohmori T., Fujiwara Y.,
RA   Terashima Y., Saijo N.;
RT   "Detection of topoisomerase I gene point mutation in CPT-11 resistant lung
RT   cancer cell line.";
RL   Biochem. Biophys. Res. Commun. 188:571-577(1992).
RN   [45]
RP   VARIANT [LARGE SCALE ANALYSIS] BREAST CANCER ARG-326.
RX   PubMed=16959974; DOI=10.1126/science.1133427;
RA   Sjoeblom T., Jones S., Wood L.D., Parsons D.W., Lin J., Barber T.D.,
RA   Mandelker D., Leary R.J., Ptak J., Silliman N., Szabo S., Buckhaults P.,
RA   Farrell C., Meeh P., Markowitz S.D., Willis J., Dawson D., Willson J.K.V.,
RA   Gazdar A.F., Hartigan J., Wu L., Liu C., Parmigiani G., Park B.H.,
RA   Bachman K.E., Papadopoulos N., Vogelstein B., Kinzler K.W.,
RA   Velculescu V.E.;
RT   "The consensus coding sequences of human breast and colorectal cancers.";
RL   Science 314:268-274(2006).
CC   -!- FUNCTION: Releases the supercoiling and torsional tension of DNA
CC       introduced during the DNA replication and transcription by transiently
CC       cleaving and rejoining one strand of the DNA duplex. Introduces a
CC       single-strand break via transesterification at a target site in duplex
CC       DNA. The scissile phosphodiester is attacked by the catalytic tyrosine
CC       of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-
CC       enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free
CC       DNA strand then rotates around the intact phosphodiester bond on the
CC       opposing strand, thus removing DNA supercoils. Finally, in the
CC       religation step, the DNA 5'-OH attacks the covalent intermediate to
CC       expel the active-site tyrosine and restore the DNA phosphodiester
CC       backbone (By similarity). Regulates the alternative splicing of tissue
CC       factor (F3) pre-mRNA in endothelial cells. Involved in the circadian
CC       transcription of the core circadian clock component ARNTL/BMAL1 by
CC       altering the chromatin structure around the ROR response elements
CC       (ROREs) on the ARNTL/BMAL1 promoter. {ECO:0000250|UniProtKB:Q13472,
CC       ECO:0000269|PubMed:14594810, ECO:0000269|PubMed:16033260,
CC       ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:22904072,
CC       ECO:0000269|PubMed:2833744}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=ATP-independent breakage of single-stranded DNA, followed by
CC         passage and rejoining.; EC=5.6.2.1; Evidence={ECO:0000255|PROSITE-
CC         ProRule:PRU10130, ECO:0000269|PubMed:14594810,
CC         ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:2833744};
CC   -!- ACTIVITY REGULATION: Specifically inhibited by camptothecin (CPT), a
CC       plant alkaloid with antitumor activity.
CC   -!- SUBUNIT: Monomer. Interacts with ERCC6 (PubMed:26030138).
CC       {ECO:0000269|PubMed:10841763, ECO:0000269|PubMed:12209008,
CC       ECO:0000269|PubMed:12533542, ECO:0000269|PubMed:15165849,
CC       ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:26030138,
CC       ECO:0000269|PubMed:9488644, ECO:0000269|PubMed:9488652}.
CC   -!- SUBUNIT: (Microbial infection) Interacts with SV40 Large T antigen;
CC       this interactions allows viral DNA replication.
CC       {ECO:0000269|PubMed:18003733}.
CC   -!- INTERACTION:
CC       P11387; P00519: ABL1; NbExp=7; IntAct=EBI-876302, EBI-375543;
CC       P11387; P01106: MYC; NbExp=2; IntAct=EBI-876302, EBI-447544;
CC       P11387; Q99801: NKX3-1; NbExp=6; IntAct=EBI-876302, EBI-1385894;
CC   -!- SUBCELLULAR LOCATION: Nucleus, nucleolus {ECO:0000269|PubMed:12149243}.
CC       Nucleus, nucleoplasm {ECO:0000269|PubMed:12149243}. Note=Diffuse
CC       nuclear localization with some enrichment in nucleoli. On CPT
CC       treatment, cleared from nucleoli into nucleoplasm. Sumoylated forms
CC       found in both nucleoplasm and nucleoli.
CC   -!- TISSUE SPECIFICITY: Endothelial cells. {ECO:0000269|PubMed:19168442}.
CC   -!- PTM: Sumoylated. Lys-117 is the main site of sumoylation. Sumoylation
CC       plays a role in partitioning TOP1 between nucleoli and nucleoplasm.
CC       Levels are dramatically increased on camptothecin (CPT) treatment.
CC       {ECO:0000269|PubMed:12149243}.
CC   -!- PTM: Phosphorylation at Ser-506 by CK2 increases binding to supercoiled
CC       DNA and sensitivity to camptothecin. {ECO:0000269|PubMed:23185622}.
CC   -!- DISEASE: Note=A chromosomal aberration involving TOP1 is found in a
CC       form of therapy-related myelodysplastic syndrome. Translocation
CC       t(11;20)(p15;q11) with NUP98. {ECO:0000269|PubMed:10556215}.
CC   -!- MISCELLANEOUS: Eukaryotic topoisomerase I and II can relax both
CC       negative and positive supercoils, whereas prokaryotic enzymes relax
CC       only negative supercoils.
CC   -!- SIMILARITY: Belongs to the type IB topoisomerase family. {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA36834.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and
CC       Haematology;
CC       URL="http://atlasgeneticsoncology.org/Genes/TOP1ID320ch20q11.html";
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DR   EMBL; J03250; AAA61207.1; -; mRNA.
DR   EMBL; M60706; AAA61206.1; -; Genomic_DNA.
DR   EMBL; M60688; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60689; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60690; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60691; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60692; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60693; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60694; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60695; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60696; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60697; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60698; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60699; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60700; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60701; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60702; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60703; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60704; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; M60705; AAA61206.1; JOINED; Genomic_DNA.
DR   EMBL; AK292943; BAF85632.1; -; mRNA.
DR   EMBL; AL035652; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; AL022394; -; NOT_ANNOTATED_CDS; Genomic_DNA.
DR   EMBL; CH471077; EAW75994.1; -; Genomic_DNA.
DR   EMBL; CH471077; EAW75995.1; -; Genomic_DNA.
DR   EMBL; X52601; CAA36834.1; ALT_SEQ; Genomic_DNA.
DR   EMBL; U07804; AAB60379.1; -; mRNA.
DR   EMBL; U07806; AAB60380.1; -; mRNA.
DR   EMBL; X16479; CAA34500.2; -; mRNA.
DR   EMBL; M27913; AAA61208.1; -; mRNA.
DR   CCDS; CCDS13312.1; -.
DR   PIR; A30887; ISHUT1.
DR   RefSeq; NP_003277.1; NM_003286.3.
DR   PDB; 1A31; X-ray; 2.10 A; A=175-765.
DR   PDB; 1A35; X-ray; 2.50 A; A=175-765.
DR   PDB; 1A36; X-ray; 2.80 A; A=175-765.
DR   PDB; 1EJ9; X-ray; 2.60 A; A=203-765.
DR   PDB; 1K4S; X-ray; 3.20 A; A=174-765.
DR   PDB; 1K4T; X-ray; 2.10 A; A=174-765.
DR   PDB; 1LPQ; X-ray; 3.14 A; A=202-765.
DR   PDB; 1NH3; X-ray; 3.10 A; A=203-765.
DR   PDB; 1R49; X-ray; 3.13 A; A=174-765.
DR   PDB; 1RR8; X-ray; 2.60 A; C=203-765.
DR   PDB; 1RRJ; X-ray; 2.30 A; A=201-765.
DR   PDB; 1SC7; X-ray; 3.00 A; A=174-765.
DR   PDB; 1SEU; X-ray; 3.00 A; A=174-765.
DR   PDB; 1T8I; X-ray; 3.00 A; A=174-765.
DR   PDB; 1TL8; X-ray; 3.10 A; A=174-765.
DR   PDBsum; 1A31; -.
DR   PDBsum; 1A35; -.
DR   PDBsum; 1A36; -.
DR   PDBsum; 1EJ9; -.
DR   PDBsum; 1K4S; -.
DR   PDBsum; 1K4T; -.
DR   PDBsum; 1LPQ; -.
DR   PDBsum; 1NH3; -.
DR   PDBsum; 1R49; -.
DR   PDBsum; 1RR8; -.
DR   PDBsum; 1RRJ; -.
DR   PDBsum; 1SC7; -.
DR   PDBsum; 1SEU; -.
DR   PDBsum; 1T8I; -.
DR   PDBsum; 1TL8; -.
DR   SMR; P11387; -.
DR   BioGRID; 113003; 261.
DR   CORUM; P11387; -.
DR   DIP; DIP-36356N; -.
DR   ELM; P11387; -.
DR   IntAct; P11387; 108.
DR   MINT; P11387; -.
DR   STRING; 9606.ENSP00000354522; -.
DR   BindingDB; P11387; -.
DR   ChEMBL; CHEMBL1781; -.
DR   DrugBank; DB07354; 2,3-DIMETHOXY-12H-[1,3]DIOXOLO[5,6]INDENO[1,2-C]ISOQUINOLIN-6-IUM.
DR   DrugBank; DB08159; 4-(5,11-DIOXO-5H-INDENO[1,2-C]ISOQUINOLIN-6(11H)-YL)BUTANOATE.
DR   DrugBank; DB05482; 7-ethyl-10-hydroxycamptothecin.
DR   DrugBank; DB04690; Camptothecin.
DR   DrugBank; DB05806; Cositecan.
DR   DrugBank; DB04882; Edotecarin.
DR   DrugBank; DB05129; Elsamitrucin.
DR   DrugBank; DB11254; Hexylresorcinol.
DR   DrugBank; DB00762; Irinotecan.
DR   DrugBank; DB04967; Lucanthone.
DR   DrugBank; DB06159; Rubitecan.
DR   DrugBank; DB12893; Sacituzumab govitecan.
DR   DrugBank; DB05630; Sodium stibogluconate.
DR   DrugBank; DB01030; Topotecan.
DR   DrugBank; DB14962; Trastuzumab deruxtecan.
DR   DrugBank; DB06069; XMT-1001.
DR   DrugCentral; P11387; -.
DR   iPTMnet; P11387; -.
DR   MetOSite; P11387; -.
DR   PhosphoSitePlus; P11387; -.
DR   SwissPalm; P11387; -.
DR   BioMuta; TOP1; -.
DR   DMDM; 12644118; -.
DR   SWISS-2DPAGE; P11387; -.
DR   EPD; P11387; -.
DR   jPOST; P11387; -.
DR   MassIVE; P11387; -.
DR   MaxQB; P11387; -.
DR   PaxDb; P11387; -.
DR   PeptideAtlas; P11387; -.
DR   PRIDE; P11387; -.
DR   ProteomicsDB; 52766; -.
DR   Antibodypedia; 3962; 433 antibodies.
DR   CPTC; P11387; 3 antibodies.
DR   Ensembl; ENST00000361337; ENSP00000354522; ENSG00000198900.
DR   GeneID; 7150; -.
DR   KEGG; hsa:7150; -.
DR   UCSC; uc002xjl.4; human.
DR   CTD; 7150; -.
DR   DisGeNET; 7150; -.
DR   GeneCards; TOP1; -.
DR   HGNC; HGNC:11986; TOP1.
DR   HPA; ENSG00000198900; Low tissue specificity.
DR   MIM; 126420; gene.
DR   neXtProt; NX_P11387; -.
DR   OpenTargets; ENSG00000198900; -.
DR   PharmGKB; PA353; -.
DR   VEuPathDB; HostDB:ENSG00000198900.5; -.
DR   eggNOG; KOG0981; Eukaryota.
DR   GeneTree; ENSGT00940000155006; -.
DR   HOGENOM; CLU_009193_0_1_1; -.
DR   InParanoid; P11387; -.
DR   OMA; CSLKYEH; -.
DR   OrthoDB; 303947at2759; -.
DR   PhylomeDB; P11387; -.
DR   TreeFam; TF105281; -.
DR   BRENDA; 5.99.1.2; 2681.
DR   PathwayCommons; P11387; -.
DR   Reactome; R-HSA-4615885; SUMOylation of DNA replication proteins.
DR   SIGNOR; P11387; -.
DR   BioGRID-ORCS; 7150; 665 hits in 1002 CRISPR screens.
DR   ChiTaRS; TOP1; human.
DR   EvolutionaryTrace; P11387; -.
DR   GeneWiki; TOP1; -.
DR   GenomeRNAi; 7150; -.
DR   Pharos; P11387; Tclin.
DR   PRO; PR:P11387; -.
DR   Proteomes; UP000005640; Chromosome 20.
DR   RNAct; P11387; protein.
DR   Bgee; ENSG00000198900; Expressed in trabecular bone tissue and 241 other tissues.
DR   Genevisible; P11387; HS.
DR   GO; GO:0005694; C:chromosome; IEA:InterPro.
DR   GO; GO:0001650; C:fibrillar center; IDA:HPA.
DR   GO; GO:0005730; C:nucleolus; IDA:UniProtKB.
DR   GO; GO:0005654; C:nucleoplasm; IDA:UniProtKB.
DR   GO; GO:0005634; C:nucleus; IDA:UniProtKB.
DR   GO; GO:0000932; C:P-body; IDA:UniProtKB.
DR   GO; GO:0043204; C:perikaryon; IEA:Ensembl.
DR   GO; GO:0032993; C:protein-DNA complex; IMP:CAFA.
DR   GO; GO:0005524; F:ATP binding; IMP:CAFA.
DR   GO; GO:0003682; F:chromatin binding; IDA:UniProtKB.
DR   GO; GO:0003677; F:DNA binding; IDA:UniProtKB.
DR   GO; GO:0003917; F:DNA topoisomerase type I (single strand cut, ATP-independent) activity; IDA:UniProtKB.
DR   GO; GO:0003690; F:double-stranded DNA binding; IMP:CAFA.
DR   GO; GO:0019904; F:protein domain specific binding; IPI:CAFA.
DR   GO; GO:0004674; F:protein serine/threonine kinase activity; IMP:CAFA.
DR   GO; GO:0003723; F:RNA binding; HDA:UniProtKB.
DR   GO; GO:0000978; F:RNA polymerase II cis-regulatory region sequence-specific DNA binding; IDA:UniProtKB.
DR   GO; GO:0003697; F:single-stranded DNA binding; IMP:CAFA.
DR   GO; GO:0097100; F:supercoiled DNA binding; IMP:CAFA.
DR   GO; GO:0006338; P:chromatin remodeling; IMP:UniProtKB.
DR   GO; GO:0007059; P:chromosome segregation; IBA:GO_Central.
DR   GO; GO:0032922; P:circadian regulation of gene expression; IMP:UniProtKB.
DR   GO; GO:0007623; P:circadian rhythm; IEP:UniProtKB.
DR   GO; GO:0006260; P:DNA replication; IBA:GO_Central.
DR   GO; GO:0006265; P:DNA topological change; IDA:UniProtKB.
DR   GO; GO:0040016; P:embryonic cleavage; IEA:Ensembl.
DR   GO; GO:0018105; P:peptidyl-serine phosphorylation; IMP:CAFA.
DR   GO; GO:0016310; P:phosphorylation; NAS:UniProtKB.
DR   GO; GO:0012501; P:programmed cell death; NAS:UniProtKB.
DR   GO; GO:0042493; P:response to drug; IEP:UniProtKB.
DR   GO; GO:0016032; P:viral process; IEA:UniProtKB-KW.
DR   CDD; cd00659; Topo_IB_C; 1.
DR   DisProt; DP00075; -.
DR   Gene3D; 1.10.10.41; -; 1.
DR   Gene3D; 1.10.132.10; -; 1.
DR   Gene3D; 2.170.11.10; -; 1.
DR   Gene3D; 3.90.15.10; -; 1.
DR   InterPro; IPR011010; DNA_brk_join_enz.
DR   InterPro; IPR013034; DNA_topo_DNA_db_N_dom1.
DR   InterPro; IPR013030; DNA_topo_DNA_db_N_dom2.
DR   InterPro; IPR001631; TopoI.
DR   InterPro; IPR018521; TopoI_AS.
DR   InterPro; IPR025834; TopoI_C_dom.
DR   InterPro; IPR014711; TopoI_cat_a-hlx-sub_euk.
DR   InterPro; IPR014727; TopoI_cat_a/b-sub_euk.
DR   InterPro; IPR013500; TopoI_cat_euk.
DR   InterPro; IPR008336; TopoI_DNA-bd_euk.
DR   InterPro; IPR036202; TopoI_DNA-bd_euk_N_sf.
DR   InterPro; IPR013499; TopoI_euk.
DR   Pfam; PF14370; Topo_C_assoc; 1.
DR   Pfam; PF01028; Topoisom_I; 1.
DR   Pfam; PF02919; Topoisom_I_N; 1.
DR   PRINTS; PR00416; EUTPISMRASEI.
DR   SMART; SM00435; TOPEUc; 1.
DR   SUPFAM; SSF56349; SSF56349; 1.
DR   SUPFAM; SSF56741; SSF56741; 1.
DR   PROSITE; PS00176; TOPOISOMERASE_I_EUK; 1.
PE   1: Evidence at protein level;
KW   3D-structure; Acetylation; Biological rhythms; Chromosomal rearrangement;
KW   Direct protein sequencing; DNA-binding; Host-virus interaction; Isomerase;
KW   Isopeptide bond; Nucleus; Phosphoprotein; Proto-oncogene;
KW   Reference proteome; Topoisomerase; Ubl conjugation.
FT   INIT_MET        1
FT                   /note="Removed"
FT                   /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:20068231,
FT                   ECO:0007744|PubMed:21406692"
FT   CHAIN           2..765
FT                   /note="DNA topoisomerase 1"
FT                   /id="PRO_0000145201"
FT   REGION          425..426
FT                   /note="Interaction with DNA"
FT   REGION          488..493
FT                   /note="Interaction with DNA"
FT   REGION          585..587
FT                   /note="Interaction with DNA"
FT   COMPBIAS        23..204
FT                   /note="Lys-rich"
FT   ACT_SITE        723
FT                   /note="O-(3'-phospho-DNA)-tyrosine intermediate"
FT                   /evidence="ECO:0000255|PROSITE-ProRule:PRU10130,
FT                   ECO:0000269|PubMed:10841763, ECO:0000269|PubMed:12426403,
FT                   ECO:0000269|PubMed:12533542, ECO:0000269|PubMed:15165849,
FT                   ECO:0000269|PubMed:15801827, ECO:0000269|PubMed:16033260,
FT                   ECO:0000269|PubMed:9488644"
FT   SITE            316
FT                   /note="Interaction with DNA"
FT   SITE            364
FT                   /note="Interaction with DNA"
FT   SITE            412
FT                   /note="Interaction with DNA"
FT   SITE            443
FT                   /note="Interaction with DNA"
FT   SITE            501
FT                   /note="Interaction with DNA"
FT   SITE            532
FT                   /note="Interaction with DNA"
FT   SITE            574
FT                   /note="Interaction with DNA"
FT   SITE            632
FT                   /note="Interaction with DNA"
FT   SITE            650
FT                   /note="Interaction with DNA"
FT   MOD_RES         2
FT                   /note="N-acetylserine"
FT                   /evidence="ECO:0000269|Ref.7, ECO:0007744|PubMed:20068231,
FT                   ECO:0007744|PubMed:21406692"
FT   MOD_RES         2
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:23186163"
FT   MOD_RES         10
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:20068231,
FT                   ECO:0007744|PubMed:21406692, ECO:0007744|PubMed:23186163"
FT   MOD_RES         57
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:20068231"
FT   MOD_RES         112
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0007744|PubMed:20068231"
FT   MOD_RES         172
FT                   /note="N6-acetyllysine; alternate"
FT                   /evidence="ECO:0000250|UniProtKB:Q04750"
FT   MOD_RES         280
FT                   /note="N6-acetyllysine"
FT                   /evidence="ECO:0007744|PubMed:19608861"
FT   MOD_RES         506
FT                   /note="Phosphoserine; by CK2"
FT                   /evidence="ECO:0000269|PubMed:23185622"
FT   CROSSLNK        101
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        103
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT                   /evidence="ECO:0000305"
FT   CROSSLNK        103
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        117
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT   CROSSLNK        117
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO1); alternate"
FT                   /evidence="ECO:0007744|PubMed:25114211"
FT   CROSSLNK        117
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0007744|PubMed:25114211,
FT                   ECO:0007744|PubMed:25218447, ECO:0007744|PubMed:25772364,
FT                   ECO:0007744|PubMed:28112733"
FT   CROSSLNK        134
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:25218447,
FT                   ECO:0007744|PubMed:28112733"
FT   CROSSLNK        148
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:25755297,
FT                   ECO:0007744|PubMed:25772364, ECO:0007744|PubMed:28112733"
FT   CROSSLNK        153
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO); alternate"
FT                   /evidence="ECO:0000305"
FT   CROSSLNK        153
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0007744|PubMed:25218447,
FT                   ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT                   ECO:0007744|PubMed:28112733"
FT   CROSSLNK        158
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:25218447,
FT                   ECO:0007744|PubMed:28112733"
FT   CROSSLNK        164
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:25218447,
FT                   ECO:0007744|PubMed:25755297, ECO:0007744|PubMed:25772364,
FT                   ECO:0007744|PubMed:28112733"
FT   CROSSLNK        172
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2); alternate"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        204
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        336
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:25755297,
FT                   ECO:0007744|PubMed:28112733"
FT   CROSSLNK        549
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        642
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        700
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   CROSSLNK        712
FT                   /note="Glycyl lysine isopeptide (Lys-Gly) (interchain with
FT                   G-Cter in SUMO2)"
FT                   /evidence="ECO:0007744|PubMed:28112733"
FT   VARIANT         214
FT                   /note="G -> S (in dbSNP:rs6029542)"
FT                   /id="VAR_052592"
FT   VARIANT         326
FT                   /note="K -> R (in breast cancer; somatic mutation)"
FT                   /evidence="ECO:0000269|PubMed:16959974"
FT                   /id="VAR_036555"
FT   VARIANT         370
FT                   /note="M -> T (in CPT-resistant leukemia)"
FT                   /evidence="ECO:0000269|PubMed:7882333"
FT                   /id="VAR_010666"
FT   VARIANT         533
FT                   /note="D -> G (in CPT-resistant leukemia;
FT                   dbSNP:rs267607131)"
FT                   /evidence="ECO:0000269|PubMed:1849260"
FT                   /id="VAR_007530"
FT   VARIANT         722
FT                   /note="N -> S (in CPT-resistant leukemia)"
FT                   /evidence="ECO:0000269|PubMed:7882333"
FT                   /id="VAR_010667"
FT   VARIANT         729
FT                   /note="T -> A (in CPT-resistant lung cancer)"
FT                   /evidence="ECO:0000269|PubMed:1332703"
FT                   /id="VAR_007531"
FT   MUTAGEN         103
FT                   /note="K->R: Localizes in both nucleoplasm and nucleoli;
FT                   when associated with R-117 or R-153. Almost complete loss
FT                   of sumoylation, concentrates in nucleoli and no clearing
FT                   from nucleoli on CPT treatment; when associated with R-117
FT                   and R-153."
FT                   /evidence="ECO:0000269|PubMed:12149243"
FT   MUTAGEN         117
FT                   /note="K->R: 5-fold decrease in sumoylation. Localizes in
FT                   both nucleoplasm and nucleoli; when associated with or
FT                   without R-103 or R-153. Almost complete loss of
FT                   sumoylation, concentrates in nucleoli and no clearing from
FT                   nucleoli on CPT treatment; when associated with R-103 and
FT                   R-153."
FT                   /evidence="ECO:0000269|PubMed:12149243"
FT   MUTAGEN         153
FT                   /note="K->R: Localizes in both nucleoplasm and nucleoli;
FT                   when associated with R-103 or R-117. Almost complete loss
FT                   of sumoylation, concentrates in nucleoli and no clearing
FT                   from nucleoli on CPT treatment; when associated with R-103
FT                   and R-117."
FT                   /evidence="ECO:0000269|PubMed:12149243"
FT   MUTAGEN         532
FT                   /note="K->A: Almost abolishes enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:14594810"
FT   MUTAGEN         532
FT                   /note="K->R: Strongly reduced enzyme activity."
FT                   /evidence="ECO:0000269|PubMed:14594810"
FT   MUTAGEN         723
FT                   /note="Y->F: No change in CPT-induced clearing from
FT                   nuclei."
FT                   /evidence="ECO:0000269|PubMed:12149243"
FT   CONFLICT        145
FT                   /note="A -> V (in Ref. 1; AAA61207)"
FT                   /evidence="ECO:0000305"
FT   HELIX           205..207
FT                   /evidence="ECO:0007744|PDB:1K4T"
FT   STRAND          220..222
FT                   /evidence="ECO:0007744|PDB:1A35"
FT   STRAND          236..238
FT                   /evidence="ECO:0007744|PDB:1A35"
FT   STRAND          240..242
FT                   /evidence="ECO:0007744|PDB:1A36"
FT   STRAND          245..247
FT                   /evidence="ECO:0007744|PDB:1A36"
FT   HELIX           251..261
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   TURN            262..265
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           267..270
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           272..285
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           288..293
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           297..299
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           303..317
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           321..338
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          339..343
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          346..351
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          358..360
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          364..366
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   TURN            368..371
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           379..381
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          383..385
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          396..398
FT                   /evidence="ECO:0007744|PDB:1SEU"
FT   STRAND          402..405
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          413..417
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   TURN            419..421
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          424..427
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          431..433
FT                   /evidence="ECO:0007744|PDB:1K4S"
FT   HELIX           434..464
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           470..485
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   TURN            495..497
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           504..506
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           509..511
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          514..518
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          521..530
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           532..534
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          536..542
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           545..553
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   TURN            554..557
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   TURN            564..567
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           570..580
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          581..583
FT                   /evidence="ECO:0007744|PDB:1NH3"
FT   HELIX           586..605
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   STRAND          608..610
FT                   /evidence="ECO:0007744|PDB:1T8I"
FT   HELIX           612..625
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   TURN            626..631
FT                   /evidence="ECO:0007744|PDB:1SC7"
FT   HELIX           640..643
FT                   /evidence="ECO:0007744|PDB:1K4T"
FT   HELIX           644..673
FT                   /evidence="ECO:0007744|PDB:1K4T"
FT   HELIX           678..710
FT                   /evidence="ECO:0007744|PDB:1K4T"
FT   STRAND          712..714
FT                   /evidence="ECO:0007744|PDB:1K4T"
FT   TURN            721..723
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           726..735
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           740..742
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           746..751
FT                   /evidence="ECO:0007744|PDB:1A31"
FT   HELIX           753..758
FT                   /evidence="ECO:0007744|PDB:1A31"
SQ   SEQUENCE   765 AA;  90726 MW;  6FBED540BCF7BE28 CRC64;
     MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK EKDREKSKHS NSEHKDSEKK
     HKEKEKTKHK DGSSEKHKDK HKDRDKEKRK EEKVRASGDA KIKKEKENGF SSPPQIKDEP
     EDDGYFVPPK EDIKPLKRPR DEDDADYKPK KIKTEDTKKE KKRKLEEEED GKLKKPKNKD
     KDKKVPEPDN KKKKPKKEEE QKWKWWEEER YPEGIKWKFL EHKGPVFAPP YEPLPENVKF
     YYDGKVMKLS PKAEEVATFF AKMLDHEYTT KEIFRKNFFK DWRKEMTNEE KNIITNLSKC
     DFTQMSQYFK AQTEARKQMS KEEKLKIKEE NEKLLKEYGF CIMDNHKERI ANFKIEPPGL
     FRGRGNHPKM GMLKRRIMPE DIIINCSKDA KVPSPPPGHK WKEVRHDNKV TWLVSWTENI
     QGSIKYIMLN PSSRIKGEKD WQKYETARRL KKCVDKIRNQ YREDWKSKEM KVRQRAVALY
     FIDKLALRAG NEKEEGETAD TVGCCSLRVE HINLHPELDG QEYVVEFDFL GKDSIRYYNK
     VPVEKRVFKN LQLFMENKQP EDDLFDRLNT GILNKHLQDL MEGLTAKVFR TYNASITLQQ
     QLKELTAPDE NIPAKILSYN RANRAVAILC NHQRAPPKTF EKSMMNLQTK IDAKKEQLAD
     ARRDLKSAKA DAKVMKDAKT KKVVESKKKA VQRLEEQLMK LEVQATDREE NKQIALGTSK
     LNYLDPRITV AWCKKWGVPI EKIYNKTQRE KFAWAIDMAD EDYEF
//
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