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 27-MAR-2024, entry version 246. 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 BMAL1 by altering CC the chromatin structure around the ROR response elements (ROREs) on the CC 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=3; 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="https://atlasgeneticsoncology.org/gene/320/TOP1"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- 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; 653. DR CORUM; P11387; -. DR DIP; DIP-36356N; -. DR ELM; P11387; -. DR IntAct; P11387; 129. 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; DB00970; Dactinomycin. DR DrugBank; DB00997; Doxorubicin. 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 EPD; P11387; -. DR jPOST; P11387; -. DR MassIVE; P11387; -. DR MaxQB; P11387; -. DR PaxDb; 9606-ENSP00000354522; -. DR PeptideAtlas; P11387; -. DR ProteomicsDB; 52766; -. DR Pumba; P11387; -. DR Antibodypedia; 3962; 527 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 AGR; HGNC:11986; -. 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; HRWKEVK; -. DR OrthoDB; 10940at2759; -. 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; 709 hits in 1173 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 189 other cell types or tissues. 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:0008301; F:DNA binding, bending; EXP:DisProt. 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 CDD; cd03488; Topoisomer_IB_N_htopoI_like; 1. DR DisProt; DP00075; -. DR Gene3D; 1.10.132.10; -; 1. DR Gene3D; 2.170.11.10; DNA Topoisomerase I, domain 2; 1. DR Gene3D; 1.10.10.41; Yeast DNA topoisomerase - domain 1; 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 InterPro; IPR048045; Topoisomer_I_DNA-bd. DR PANTHER; PTHR10290:SF5; DNA TOPOISOMERASE 1; 1. DR PANTHER; PTHR10290; DNA TOPOISOMERASE I; 1. 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; DNA breaking-rejoining enzymes; 1. DR SUPFAM; SSF46596; Eukaryotic DNA topoisomerase I, dispensable insert domain; 1. DR SUPFAM; SSF56741; Eukaryotic DNA topoisomerase I, N-terminal DNA-binding fragment; 1. DR PROSITE; PS00176; TOPO_IB_1; 1. DR PROSITE; PS52038; TOPO_IB_2; 1. DR SWISS-2DPAGE; P11387; -. DR Genevisible; P11387; HS. 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 DOMAIN 432..765 FT /note="Topo IB-type catalytic" FT /evidence="ECO:0000255|PROSITE-ProRule:PRU01382" 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:PRU01382, FT 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 //