TOP1_HUMAN
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 03-AUG-2022, entry version 237.
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; DOI=10.1016/s0021-9258(18)92864-4;
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 P11387; P42768: WAS; NbExp=3; IntAct=EBI-876302, EBI-346375;
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";
CC ---------------------------------------------------------------------------
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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 AlphaFoldDB; P11387; -.
DR SMR; P11387; -.
DR BioGRID; 113003; 348.
DR CORUM; P11387; -.
DR DIP; DIP-36356N; -.
DR ELM; P11387; -.
DR IntAct; P11387; 121.
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 GlyGen; P11387; 1 site, 1 O-linked glycan (1 site).
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; 453 antibodies from 42 providers.
DR CPTC; P11387; 4 antibodies.
DR DNASU; 7150; -.
DR Ensembl; ENST00000361337.3; ENSP00000354522.2; ENSG00000198900.7.
DR GeneID; 7150; -.
DR KEGG; hsa:7150; -.
DR MANE-Select; ENST00000361337.3; ENSP00000354522.2; NM_003286.4; NP_003277.1.
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; -.
DR eggNOG; KOG0981; Eukaryota.
DR GeneTree; ENSGT00940000155006; -.
DR HOGENOM; CLU_009193_0_1_1; -.
DR InParanoid; P11387; -.
DR OMA; GLRYQKW; -.
DR OrthoDB; 303947at2759; -.
DR PhylomeDB; P11387; -.
DR TreeFam; TF105281; -.
DR BRENDA; 5.6.2.1; 2681.
DR BRENDA; 5.99.1.2; 2681.
DR PathwayCommons; P11387; -.
DR Reactome; R-HSA-4615885; SUMOylation of DNA replication proteins.
DR SignaLink; P11387; -.
DR SIGNOR; P11387; -.
DR BioGRID-ORCS; 7150; 680 hits in 1087 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 oocyte and 187 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:0001673; C:male germ cell nucleus; IEA:Ensembl.
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:0009410; P:response to xenobiotic stimulus; IEP:UniProtKB.
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 1..199
FT /note="Disordered"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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 1..26
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
FT COMPBIAS 36..199
FT /note="Basic and acidic residues"
FT /evidence="ECO:0000256|SAM:MobiDB-lite"
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:0007829|PDB:1K4T"
FT STRAND 220..222
FT /evidence="ECO:0007829|PDB:1A35"
FT STRAND 236..238
FT /evidence="ECO:0007829|PDB:1A35"
FT STRAND 240..242
FT /evidence="ECO:0007829|PDB:1A36"
FT STRAND 245..247
FT /evidence="ECO:0007829|PDB:1A36"
FT HELIX 251..261
FT /evidence="ECO:0007829|PDB:1A31"
FT TURN 262..265
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 267..270
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 272..285
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 288..293
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 297..299
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 303..317
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 321..338
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 339..343
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 346..351
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 358..360
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 364..366
FT /evidence="ECO:0007829|PDB:1A31"
FT TURN 368..371
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 379..381
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 383..385
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 396..398
FT /evidence="ECO:0007829|PDB:1SEU"
FT STRAND 402..405
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 413..417
FT /evidence="ECO:0007829|PDB:1A31"
FT TURN 419..421
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 424..427
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 431..433
FT /evidence="ECO:0007829|PDB:1K4S"
FT HELIX 434..464
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 470..485
FT /evidence="ECO:0007829|PDB:1A31"
FT TURN 495..497
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 504..506
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 509..511
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 514..518
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 521..530
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 532..534
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 536..542
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 545..553
FT /evidence="ECO:0007829|PDB:1A31"
FT TURN 554..557
FT /evidence="ECO:0007829|PDB:1A31"
FT TURN 564..567
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 570..580
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 581..583
FT /evidence="ECO:0007829|PDB:1NH3"
FT HELIX 586..605
FT /evidence="ECO:0007829|PDB:1A31"
FT STRAND 608..610
FT /evidence="ECO:0007829|PDB:1T8I"
FT HELIX 612..625
FT /evidence="ECO:0007829|PDB:1A31"
FT TURN 626..631
FT /evidence="ECO:0007829|PDB:1SC7"
FT HELIX 640..643
FT /evidence="ECO:0007829|PDB:1K4T"
FT HELIX 644..673
FT /evidence="ECO:0007829|PDB:1K4T"
FT HELIX 678..710
FT /evidence="ECO:0007829|PDB:1K4T"
FT STRAND 712..714
FT /evidence="ECO:0007829|PDB:1K4T"
FT TURN 721..723
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 726..735
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 740..742
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 746..751
FT /evidence="ECO:0007829|PDB:1A31"
FT HELIX 753..758
FT /evidence="ECO:0007829|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
