CPLM 1.0 - Compendium of Protein Lysine Modification
TagContent
CPLM ID CPLM-003915
UniProt Accession
Genbank Protein ID
Genbank Nucleotide ID
Protein Name
 DNA topoisomerase 1 
Protein Synonyms/Alias
 DNA topoisomerase I 
Gene Name
 TOP1 
Gene Synonyms/Alias
  
Created Date
 July 27, 2013 
Organism
 Homo sapiens (Human) 
NCBI Taxa ID
 9606 
Lysine Modification
Position
Peptide
Type
References
103ASGDAKIKKEKENGFsumoylation[1]
117FSSPPQIKDEPEDDGsumoylation[1, 2, 3]
134VPPKEDIKPLKRPRDacetylation[4]
148DEDDADYKPKKIKTEacetylation[4, 5, 6]
148DEDDADYKPKKIKTEubiquitination[6, 7]
150DDADYKPKKIKTEDTacetylation[6]
153DYKPKKIKTEDTKKEsumoylation[1, 2]
164TKKEKKRKLEEEEDGacetylation[5]
172LEEEEDGKLKKPKNKacetylation[4, 6, 8, 9]
218YPEGIKWKFLEHKGPubiquitination[10]
223KWKFLEHKGPVFAPPubiquitination[6, 10, 11, 12]
239EPLPENVKFYYDGKVubiquitination[7]
245VKFYYDGKVMKLSPKacetylation[4]
245VKFYYDGKVMKLSPKubiquitination[7, 10, 11, 12, 13]
252KVMKLSPKAEEVATFubiquitination[6, 10, 13, 14]
262EVATFFAKMLDHEYTubiquitination[6, 10, 15]
280IFRKNFFKDWRKEMTacetylation[4, 8]
280IFRKNFFKDWRKEMTubiquitination[10, 11, 12]
291KEMTNEEKNIITNLSacetylation[9]
326MSKEEKLKIKEENEKubiquitination[11, 12]
328KEEKLKIKEENEKLLsumoylation[1]
347FCIMDNHKERIANFKubiquitination[10]
354KERIANFKIEPPGLFubiquitination[6, 11, 12]
391INCSKDAKVPSPPPGubiquitination[10]
400PSPPPGHKWKEVRHDubiquitination[7]
436LNPSSRIKGEKDWQKsumoylation[1]
493ALRAGNEKEEGETADubiquitination[10]
545YNKVPVEKRVFKNLQacetylation[6]
549PVEKRVFKNLQLFMEubiquitination[11, 12, 13]
558LQLFMENKQPEDDLFubiquitination[7]
587LMEGLTAKVFRTYNAubiquitination[7, 10]
603ITLQQQLKELTAPDEubiquitination[7]
615PDENIPAKILSYNRAubiquitination[6, 7, 10]
642APPKTFEKSMMNLQTubiquitination[7, 10, 11, 12, 13]
712ATDREENKQIALGTSubiquitination[7, 10]
720QIALGTSKLNYLDPRubiquitination[7]
742KWGVPIEKIYNKTQRubiquitination[7, 10]
Reference
 [1] Nucleolar delocalization of human topoisomerase I in response to topotecan correlates with sumoylation of the protein.
 Mo YY, Yu Y, Shen Z, Beck WT.
 J Biol Chem. 2002 Jan 25;277(4):2958-64. [PMID: 11709553]
 [2] SUMO-1 conjugation to intact DNA topoisomerase I amplifies cleavable complex formation induced by camptothecin.
 Horie K, Tomida A, Sugimoto Y, Yasugi T, Yoshikawa H, Taketani Y, Tsuruo T.
 Oncogene. 2002 Nov 14;21(52):7913-22. [PMID: 12439742]
 [3] Site-specific identification of SUMO-2 targets in cells reveals an inverted SUMOylation motif and a hydrophobic cluster SUMOylation motif.
 Matic I, Schimmel J, Hendriks IA, van Santen MA, van de Rijke F, van Dam H, Gnad F, Mann M, Vertegaal AC.
 Mol Cell. 2010 Aug 27;39(4):641-52. [PMID: 20797634]
 [4] Proteomic investigations reveal a role for RNA processing factor THRAP3 in the DNA damage response.
 Beli P, Lukashchuk N, Wagner SA, Weinert BT, Olsen JV, Baskcomb L, Mann M, Jackson SP, Choudhary C.
 Mol Cell. 2012 Apr 27;46(2):212-25. [PMID: 22424773]
 [5] Spermidine and resveratrol induce autophagy by distinct pathways converging on the acetylproteome.
 Morselli E, Mariño G, Bennetzen MV, Eisenberg T, Megalou E, Schroeder S, Cabrera S, Bénit P, Rustin P, Criollo A, Kepp O, Galluzzi L, Shen S, Malik SA, Maiuri MC, Horio Y, López-Otín C, Andersen JS, Tavernarakis N, Madeo F, Kroemer G.
 J Cell Biol. 2011 Feb 21;192(4):615-29. [PMID: 21339330]
 [6] Integrated proteomic analysis of post-translational modifications by serial enrichment.
 Mertins P, Qiao JW, Patel J, Udeshi ND, Clauser KR, Mani DR, Burgess MW, Gillette MA, Jaffe JD, Carr SA.
 Nat Methods. 2013 Jul;10(7):634-7. [PMID: 23749302]
 [7] Systematic and quantitative assessment of the ubiquitin-modified proteome.
 Kim W, Bennett EJ, Huttlin EL, Guo A, Li J, Possemato A, Sowa ME, Rad R, Rush J, Comb MJ, Harper JW, Gygi SP.
 Mol Cell. 2011 Oct 21;44(2):325-40. [PMID: 21906983]
 [8] Lysine acetylation targets protein complexes and co-regulates major cellular functions.
 Choudhary C, Kumar C, Gnad F, Nielsen ML, Rehman M, Walther TC, Olsen JV, Mann M.
 Science. 2009 Aug 14;325(5942):834-40. [PMID: 19608861]
 [9] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377]
 [10] Refined preparation and use of anti-diglycine remnant (K-ε-GG) antibody enables routine quantification of 10,000s of ubiquitination sites in single proteomics experiments.
 Udeshi ND, Svinkina T, Mertins P, Kuhn E, Mani DR, Qiao JW, Carr SA.
 Mol Cell Proteomics. 2013 Mar;12(3):825-31. [PMID: 23266961]
 [11] A proteome-wide, quantitative survey of in vivo ubiquitylation sites reveals widespread regulatory roles.
 Wagner SA, Beli P, Weinert BT, Nielsen ML, Cox J, Mann M, Choudhary C.
 Mol Cell Proteomics. 2011 Oct;10(10):M111.013284. [PMID: 21890473]
 [12] hCKSAAP_UbSite: improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.
 Chen Z, Zhou Y, Song J, Zhang Z.
 Biochim Biophys Acta. 2013 Aug;1834(8):1461-7. [PMID: 23603789]
 [13] Systems-wide analysis of ubiquitylation dynamics reveals a key role for PAF15 ubiquitylation in DNA-damage bypass.
 Povlsen LK, Beli P, Wagner SA, Poulsen SL, Sylvestersen KB, Poulsen JW, Nielsen ML, Bekker-Jensen S, Mailand N, Choudhary C.
 Nat Cell Biol. 2012 Oct;14(10):1089-98. [PMID: 23000965]
 [14] Global analysis of lysine ubiquitination by ubiquitin remnant immunoaffinity profiling.
 Xu G, Paige JS, Jaffrey SR.
 Nat Biotechnol. 2010 Aug;28(8):868-73. [PMID: 20639865]
 [15] Methods for quantification of in vivo changes in protein ubiquitination following proteasome and deubiquitinase inhibition.
 Udeshi ND, Mani DR, Eisenhaure T, Mertins P, Jaffe JD, Clauser KR, Hacohen N, Carr SA.
 Mol Cell Proteomics. 2012 May;11(5):148-59. [PMID: 22505724
Functional Description
 Releases the supercoiling and torsional tension of DNA introduced during the DNA replication and transcription by transiently cleaving and rejoining one strand of the DNA duplex. Introduces a single-strand break via transesterification at a target site in duplex DNA. The scissile phosphodiester is attacked by the catalytic tyrosine of the enzyme, resulting in the formation of a DNA-(3'-phosphotyrosyl)-enzyme intermediate and the expulsion of a 5'-OH DNA strand. The free DNA strand then undergoes passage around the unbroken strand thus removing DNA supercoils. Finally, in the religation step, the DNA 5'-OH attacks the covalent intermediate to expel the active-site tyrosine and restore the DNA phosphodiester backbone (By similarity). Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells. 
Sequence Annotation
 REGION 425 426 Interaction with DNA.
 REGION 488 493 Interaction with DNA.
 REGION 585 587 Interaction with DNA.
 ACT_SITE 723 723 O-(3'-phospho-DNA)-tyrosine intermediate.
 MOD_RES 2 2 N-acetylserine.
 MOD_RES 10 10 Phosphoserine.
 MOD_RES 57 57 Phosphoserine.
 MOD_RES 112 112 Phosphoserine.
 MOD_RES 280 280 N6-acetyllysine.
 MOD_RES 506 506 Phosphoserine; by CK2.
 CROSSLNK 103 103 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 117 117 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 153 153 Glycyl lysine isopeptide (Lys-Gly)  
Keyword
 3D-structure; Acetylation; ATP-binding; Chromosomal rearrangement; Complete proteome; Direct protein sequencing; DNA-binding; Host-virus interaction; Isomerase; Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein; Polymorphism; Proto-oncogene; Reference proteome; Topoisomerase; Ubl conjugation. 
Sequence Source
 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 
Protein Length
 765 AA 
Protein Sequence
MSGDHLHNDS QIEADFRLND SHKHKDKHKD REHRHKEHKK EKDREKSKHS NSEHKDSEKK 60
HKEKEKTKHK DGSSEKHKDK HKDRDKEKRK EEKVRASGDA KIKKEKENGF SSPPQIKDEP 120
EDDGYFVPPK EDIKPLKRPR DEDDADYKPK KIKTEDTKKE KKRKLEEEED GKLKKPKNKD 180
KDKKVPEPDN KKKKPKKEEE QKWKWWEEER YPEGIKWKFL EHKGPVFAPP YEPLPENVKF 240
YYDGKVMKLS PKAEEVATFF AKMLDHEYTT KEIFRKNFFK DWRKEMTNEE KNIITNLSKC 300
DFTQMSQYFK AQTEARKQMS KEEKLKIKEE NEKLLKEYGF CIMDNHKERI ANFKIEPPGL 360
FRGRGNHPKM GMLKRRIMPE DIIINCSKDA KVPSPPPGHK WKEVRHDNKV TWLVSWTENI 420
QGSIKYIMLN PSSRIKGEKD WQKYETARRL KKCVDKIRNQ YREDWKSKEM KVRQRAVALY 480
FIDKLALRAG NEKEEGETAD TVGCCSLRVE HINLHPELDG QEYVVEFDFL GKDSIRYYNK 540
VPVEKRVFKN LQLFMENKQP EDDLFDRLNT GILNKHLQDL MEGLTAKVFR TYNASITLQQ 600
QLKELTAPDE NIPAKILSYN RANRAVAILC NHQRAPPKTF EKSMMNLQTK IDAKKEQLAD 660
ARRDLKSAKA DAKVMKDAKT KKVVESKKKA VQRLEEQLMK LEVQATDREE NKQIALGTSK 720
LNYLDPRITV AWCKKWGVPI EKIYNKTQRE KFAWAIDMAD EDYEF 765 
Gene Ontology
 GO:0000932; C:cytoplasmic mRNA processing body; IDA:UniProtKB.
 GO:0005730; C:nucleolus; IDA:UniProtKB.
 GO:0005654; C:nucleoplasm; IDA:UniProtKB.
 GO:0043204; C:perikaryon; IEA:Compara.
 GO:0031298; C:replication fork protection complex; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003682; F:chromatin binding; IDA:UniProtKB.
 GO:0003917; F:DNA topoisomerase type I activity; IDA:UniProtKB.
 GO:0003918; F:DNA topoisomerase type II (ATP-hydrolyzing) activity; IEA:InterPro.
 GO:0006338; P:chromatin remodeling; IBA:RefGenome.
 GO:0007059; P:chromosome segregation; IBA:RefGenome.
 GO:0006260; P:DNA replication; IBA:RefGenome.
 GO:0006265; P:DNA topological change; IDA:UniProtKB.
 GO:0040016; P:embryonic cleavage; IEA:Compara.
 GO:0016310; P:phosphorylation; NAS:UniProtKB.
 GO:0012501; P:programmed cell death; NAS:UniProtKB.
 GO:0042493; P:response to drug; IEP:UniProtKB.
 GO:0019048; P:virus-host interaction; IEA:UniProtKB-KW. 
Interpro
 IPR011010; DNA_brk_join_enz.
 IPR013034; DNA_topo_domain1.
 IPR001631; TopoI.
 IPR018521; TopoI_AS.
 IPR025834; TopoI_C_dom.
 IPR014711; TopoI_cat_a-hlx-sub_euk.
 IPR014727; TopoI_cat_a/b-sub_euk.
 IPR013500; TopoI_cat_euk.
 IPR008336; TopoI_DNA-bd_euk.
 IPR013030; TopoI_DNA-bd_mixed-a/b_euk.
 IPR013499; TopoI_euk.
 IPR009054; TopoI_insert_euk. 
Pfam
 PF14370; Topo_C_assoc
 PF01028; Topoisom_I
 PF02919; Topoisom_I_N 
SMART
 SM00435; TOPEUc 
PROSITE
 PS00176; TOPOISOMERASE_I_EUK 
PRINTS
 PR00416; EUTPISMRASEI.