P11387

PTMD Annotation Information

※ Protein Information

Tag	Content
UniProt Accession	TOP1_HUMAN; P11387;
Entrez ID	7150
GenBank Protein ID
GenBank Nucleotide ID
Protein Name	DNA topoisomerase 1 (EC 5.99.1.2) (DNA topoisomerase I)
Gene Name	TOP1
Organism	Homo sapiens
NCBI Taxa ID	9606
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 rotates around the intact phosphodiester bond on the opposing 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. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter. 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 rotates around the intact phosphodiester bond on the opposing 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. Involved in the circadian transcription of the core circadian clock component ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter.
Sequence (Fasta)	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 766 Fasta Sequence >P11387\|TOP1\|Homo sapiens (Human) MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKKHKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEPEDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKDKDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPENVKFYYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNEEKNIITNLSKCDFTQMSQYFKAQTEARKQMSKEEKLKIKEENEKLLKEYGFCIMDNHKERIANFKIEPPGLFRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENIQGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALYFIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFLGKDSIRYYNKVPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQQLKELTAPDENIPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLADARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMADEDYEF

※ PTM-Disease Association

Num	PTM	Disease	Cell Type	Type	PTM Site	PMID
1	Serine Phosphorylation	Colon cancer/carcinoma	cell line	U	S506	26248194
1	[Reference]: Our results suggest that elevated PS506 expression may correlate with clinical chemosensitivity to these agents in ovarian, colon, and NSCLC. PS506 may therefore serve as a biomarker for diagnosis or therapy selection.
2	Serine Phosphorylation	Non-small cell lung cancer/carcinoma	cell line	U	S506	26248194
2	[Reference]: Our results suggest that elevated PS506 expression may correlate with clinical chemosensitivity to these agents in ovarian, colon, and NSCLC. PS506 may therefore serve as a biomarker for diagnosis or therapy selection.
3	Serine Phosphorylation	Ovarian cancer/carcinoma	cell line	U	S506	26248194
3	[Reference]: Our results suggest that elevated PS506 expression may correlate with clinical chemosensitivity to these agents in ovarian, colon, and NSCLC. PS506 may therefore serve as a biomarker for diagnosis or therapy selection.

※ Disease Cross-ref Annotation

Database	Annotation
Cancer Gene Census	AML*
CTD (Curated) (count: 2)	MESH:D064420 ; Drug-Related Side Effects and Adverse Reactions MESH:D009369 ; Neoplasms
GWASdb (count: 9) (view all)	rs117756447; Carotid intima media thickness; atherosclerosis rs6029526; Cholesterol, total; coronary artery disease\|lipid metabolism disorder\|arteriosclerosis rs6029526; LDL cholesterol; atherosclerosis\|coronary artery disease rs6029526; Prostate cancer; prostate cancer rs8122094; Coronary heart disease; coronary artery disease rs1997833; Taste perception; sensory system disease rs2076574; Prostate cancer; prostate cancer rs6072275; Fasting blood glucose; type 2 diabetes mellitus rs6129760; Prostate cancer; prostate cancer

※ PTM Sites

PTM	Modification Sites
Phosphorylation (count: 26) (view all)	10 GDHLHNDSQIEADFR dbPAF 111 KEKENGFSSPPQIKD dbPAF 112 EKENGFSSPPQIKDE dbPAF 125 DEPEDDGYFVPPKED dbPAF 147 RDEDDADYKPKKIKT dbPAF 2 ******MSGDHLHND dbPAF 21 ADFRLNDSHKHKDKH dbPAF 268 AKMLDHEYTTKEIFR dbPAF 295 NEEKNIITNLSKCDF dbPAF 298 KNIITNLSKCDFTQM dbPAF 303 NLSKCDFTQMSQYFK dbPAF 394 SKDAKVPSPPPGHKW dbPAF 423 WTENIQGSIKYIMLN dbPAF 426 NIQGSIKYIMLNPSS dbPAF 432 KYIMLNPSSRIKGEK dbPAF 433 YIMLNPSSRIKGEKD dbPAF 444 GEKDWQKYETARRLK dbPAF 506 ADTVGCCSLRVEHIN dbPAF 57 SNSEHKDSEKKHKEK dbPAF 591 LTAKVFRTYNASITL dbPAF 592 TAKVFRTYNASITLQ dbPAF 649 KSMMNLQTKIDAKKE dbPAF 686 KTKKVVESKKKAVQR dbPAF 723 LGTSKLNYLDPRITV dbPAF 73 KTKHKDGSSEKHKDK dbPAF 74 TKHKDGSSEKHKDKH dbPAF
Acetylation (count: 39) (view all)	117 FSSPPQIKDEPEDDG PLMD 134 VPPKEDIKPLKRPRD PLMD 148 DEDDADYKPKKIKTE PLMD 150 DDADYKPKKIKTEDT PLMD 164 TKKEKKRKLEEEEDG PLMD 172 LEEEEDGKLKKPKNK PLMD 223 KWKFLEHKGPVFAPP PLMD 239 EPLPENVKFYYDGKV PLMD 245 VKFYYDGKVMKLSPK PLMD 248 YYDGKVMKLSPKAEE PLMD 252 KVMKLSPKAEEVATF PLMD 262 EVATFFAKMLDHEYT PLMD 271 LDHEYTTKEIFRKNF PLMD 280 IFRKNFFKDWRKEMT PLMD 284 NFFKDWRKEMTNEEK PLMD 291 KEMTNEEKNIITNLS PLMD 299 NIITNLSKCDFTQMS PLMD 336 EENEKLLKEYGFCIM PLMD 347 FCIMDNHKERIANFK PLMD 354 KERIANFKIEPPGLF PLMD 388 DIIINCSKDAKVPSP PLMD 436 LNPSSRIKGEKDWQK PLMD 443 KGEKDWQKYETARRL PLMD 456 RLKKCVDKIRNQYRE PLMD 484 VALYFIDKLALRAGN PLMD 493 ALRAGNEKEEGETAD PLMD 540 DSIRYYNKVPVEKRV PLMD 545 YNKVPVEKRVFKNLQ PLMD 549 PVEKRVFKNLQLFME PLMD 575 LNTGILNKHLQDLME PLMD 587 LMEGLTAKVFRTYNA PLMD 615 PDENIPAKILSYNRA PLMD 642 APPKTFEKSMMNLQT PLMD 650 SMMNLQTKIDAKKEQ PLMD 673 KSAKADAKVMKDAKT PLMD 712 ATDREENKQIALGTS PLMD 720 QIALGTSKLNYLDPR PLMD 735 ITVAWCKKWGVPIEK PLMD 742 KWGVPIEKIYNKTQR PLMD
Ubiquitination (count: 31) (view all)	148 DEDDADYKPKKIKTE PLMD 218 YPEGIKWKFLEHKGP PLMD 223 KWKFLEHKGPVFAPP PLMD 239 EPLPENVKFYYDGKV PLMD 245 VKFYYDGKVMKLSPK PLMD 252 KVMKLSPKAEEVATF PLMD 262 EVATFFAKMLDHEYT PLMD 280 IFRKNFFKDWRKEMT PLMD 326 MSKEEKLKIKEENEK PLMD 347 FCIMDNHKERIANFK PLMD 354 KERIANFKIEPPGLF PLMD 388 DIIINCSKDAKVPSP PLMD 391 INCSKDAKVPSPPPG PLMD 400 PSPPPGHKWKEVRHD PLMD 456 RLKKCVDKIRNQYRE PLMD 484 VALYFIDKLALRAGN PLMD 493 ALRAGNEKEEGETAD PLMD 532 VEFDFLGKDSIRYYN PLMD 545 YNKVPVEKRVFKNLQ PLMD 549 PVEKRVFKNLQLFME PLMD 558 LQLFMENKQPEDDLF PLMD 575 LNTGILNKHLQDLME PLMD 587 LMEGLTAKVFRTYNA PLMD 603 ITLQQQLKELTAPDE PLMD 615 PDENIPAKILSYNRA PLMD 642 APPKTFEKSMMNLQT PLMD 655 QTKIDAKKEQLADAR PLMD 712 ATDREENKQIALGTS PLMD 720 QIALGTSKLNYLDPR PLMD 734 RITVAWCKKWGVPIE PLMD 742 KWGVPIEKIYNKTQR PLMD
Sumoylation (count: 18) (view all)	103 ASGDAKIKKEKENGF PLMD 117 FSSPPQIKDEPEDDG PLMD 134 VPPKEDIKPLKRPRD PLMD 148 DEDDADYKPKKIKTE PLMD 153 DYKPKKIKTEDTKKE PLMD 158 KIKTEDTKKEKKRKL PLMD 164 TKKEKKRKLEEEEDG PLMD 172 LEEEEDGKLKKPKNK PLMD 174 EEEDGKLKKPKNKDK PLMD 204 KEEEQKWKWWEEERY PLMD 27 DSHKHKDKHKDREHR PLMD 328 KEEKLKIKEENEKLL PLMD 336 EENEKLLKEYGFCIM PLMD 354 KERIANFKIEPPGLF PLMD 391 INCSKDAKVPSPPPG PLMD 436 LNPSSRIKGEKDWQK PLMD 484 VALYFIDKLALRAGN PLMD 712 ATDREENKQIALGTS PLMD
Glycation (count: 1)	223 KWKFLEHKGPVFAPP PLMD
Methylation (count: 2)	466 NQYREDWKSKEMKVR PLMD 471 DWKSKEMKVRQRAVA PLMD

※ Protein-Protein Interaction

Network

Interaction

A

B

Source

P03372	P11387	IntAct
P04637	P11387	HPRD
P05412	P11387	HPRD
P09874	P11387	IntAct
P11387	P16403	IntAct
P11387	P17844	IntAct
P11387	P22626	IntAct
P11387	P63279	HPRD
P11387	Q15796	IntAct