Tclin TOP1 DNA topoisomerase 1

Protein Classes

PANTHER Classes

Protein / Nucleic Acid Binding / Dna Binding Protein / Dna Topoisomerase / Dna Topoisomerase 1

DTO Classes

Protein / Enzyme / Isomerase / Dna Topoisomerase / Dna Topoisomerase 1

Protein Summary

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. This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the strands to pass through one another, thus altering the topology of DNA. This gene is localized to chromosome 20 and has pseudogenes which reside on chromosomes 1 and 22. [provided by RefSeq, Jul 2008]

Uniprot Accession IDs

• P11387
• A8KA78
• E1P5W3
• O43256
• Q12855
• Q12856
• Q15610
• Q5TFY3
• Q9UJN0

Gene Name

• TOP1

Ensembl ID

• ENST00000361337
• ENSP00000354522
• ENSG00000198900

Symbol

• TOPI

Knowledge Table

Most Knowledge About	Knowledge Value (0 to 1 scale)
hub protein	1
interacting protein	1
protein domain	1
transcription factor perturbation	0.96
molecular function	0.95

IDG Development Level Summary

Tdark

These are targets about which virtually nothing is known. They do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4256.55   (req: < 5)

Gene RIFs: 180   (req: <= 3)

Antibodies: 382   (req: <= 50)

Tbio

These targets do not have known drug or small molecule activities
- AND - satisfy two or more of the following criteria:

Pubmed score: 4256.55   (req: >= 5)

Gene RIFs: 180   (req: > 3)

Antibodies: 382   (req: > 50)

- OR - satisfy the following criterion:

Gene Ontology Terms: 23

Tchem

Target has at least one ChEMBL compound with an activity cutoff of < 30 nM - AND - satisfies the preceding conditions

Active Ligands: 139

Tclin

Target has at least one approved drug - AND - satisfies the preceding conditions

Active Drugs: 4

Approved Drugs (4)

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1 – 4 of 4

topotecan

TOP1Tclin Enzyme

Kd: 7.58

trastuzumab deruxtecan

TOP1Tclin Enzyme

INHIBITOR IC50: 7.51

irinotecan

TOP1Tclin Enzyme

INHIBITOR :

belotecan

TOP1Tclin Enzyme

INHIBITOR IC50: 6.5614419

Active Ligands (139)

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1 – 10 of 139

CHEMBL65

TOP1Tclin Enzyme

IC50: 6.52

CHEMBL307794

TOP1Tclin Enzyme

IC50: 7.57

CHEMBL837

TOP1Tclin Enzyme

EC50: 7.16

CHEMBL47027

TOP1Tclin Enzyme

Ki: 6.4

CHEMBL13998

TOP1Tclin Enzyme

IC50: 6.84

CHEMBL13935

TOP1Tclin Enzyme

IC50: 7.55

CHEMBL52057

TOP1Tclin Enzyme

IC50: 7.42

CHEMBL315269

TOP1Tclin Enzyme

IC50: 6.36

CHEMBL525240

TOP1Tclin Enzyme

IC50: 7.3

CHEMBL90761

TOP1Tclin Enzyme

IC50: 7.16

Protein Data Bank (15)

1 – 5 of 15

PDB Structure Id	Ligand	Method	Resolution (Å)	M.W. (kDa)	Pub Year	Title

PDB Structure Id	M.W.	Resolution	Pub Year

Pathways (10)

Reactome (5)

PathwayCommons (3)

WikiPathways (2)

Metabolism of proteins (R-HSA-392499)

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Items per page:

5

1 – 5 of 5

Data Source	Name	Explore in Pharos	Explore in Source
Reactome	Metabolism of proteins	2050 targets	R-HSA-392499
Reactome	Post-translational protein modification	1450 targets	R-HSA-597592
Reactome	SUMO E3 ligases SUMOylate target proteins	170 targets	R-HSA-3108232
Reactome	SUMOylation	176 targets	R-HSA-2990846
Reactome	SUMOylation of DNA replication proteins	46 targets	R-HSA-4615885

Name	Explore in Pharos	Explore in Source
Metabolism of proteins	2050 targets	R-HSA-392499
Post-translational protein modification	1450 targets	R-HSA-597592
SUMO E3 ligases SUMOylate target proteins	170 targets	R-HSA-3108232
SUMOylation	176 targets	R-HSA-2990846
SUMOylation of DNA replication proteins	46 targets	R-HSA-4615885

Gene Ontology Terms (32)

Functions (11)

Components (9)

Processes (12)

Items per page:

10

1 – 10 of 11

GO Term	Evidence	Assigned by
chromatin binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
DNA topoisomerase type I activity	Inferred from Direct Assay (IDA)	UniProtKB
RNA polymerase II proximal promoter sequence-specific DNA binding	Inferred from Direct Assay (IDA)	UniProtKB
protein domain specific binding	Inferred from Physical Interaction (IPI)	CAFA
ATP binding	Inferred from Mutant Phenotype (IMP)	CAFA
double-stranded DNA binding	Inferred from Mutant Phenotype (IMP)	CAFA
protein serine/threonine kinase activity	Inferred from Mutant Phenotype (IMP)	CAFA
single-stranded DNA binding	Inferred from Mutant Phenotype (IMP)	CAFA
supercoiled DNA binding	Inferred from Mutant Phenotype (IMP)	CAFA

Protein-Protein Interactions (286)

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1 – 10 of 286

• See Interactions on String-DB

EAF1

Tbio

Novelty: 0.86956522

p_int: 0.99560056

p_ni: 0.00439944

Data Source: BioPlex

ZRANB2

Tbio

Novelty: 0.02084407

p_int: 0.992838763

p_ni: 0.007161237

Score: 0.556

Data Source: BioPlex,STRINGDB

ESAM

Tbio

Novelty: 0.00636783

p_int: 0.952336066

p_ni: 0.047663934

Score: 0.19

Data Source: BioPlex,STRINGDB

CIDEC

Tbio

Novelty: 0.01333028

p_int: 0.910968099

p_ni: 0.089031901

Score: 0.252

Data Source: BioPlex,STRINGDB

HDGFL2

Tbio

Family: Epigenetic

Novelty: 0.12835229

p_int: 0.901074525

p_ni: 0.098925475

Data Source: BioPlex

SNRPGP15

Tdark

p_int: 0.89344272

p_ni: 0.10655728

Data Source: BioPlex

PRICKLE3

Tdark

Novelty: 0.43613707

p_int: 0.882610129

p_ni: 0.117389871

Data Source: BioPlex

DUS4L

Tbio

Family: Enzyme

Novelty: 0.06032049

p_int: 0.860040648

p_ni: 0.139959352

Score: 0.209

Data Source: BioPlex,STRINGDB

GTF2E2

Tbio

Novelty: 0.16730745

p_int: 0.809584398

p_ni: 0.190415602

Score: 0.219

Data Source: BioPlex,STRINGDB

TOP2A

Tclin

Family: Enzyme

Novelty: 0.00121459

Score: 0.997

Data Source: STRINGDB

Publication Statistics

PubMed Score  4256.55

PubMed score by year

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PubTator Score  69.41

PubTator score by year

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Amino Acid Sequence

Residue Counts

Sequence

MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKKHKEKEKTKHK

1-70

DGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEPEDDGYFVPPKEDIKPLKRPR

70-140

DEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKDKDKKVPEPDNKKKKPKKEEEQKWKWWEEER

140-210

YPEGIKWKFLEHKGPVFAPPYEPLPENVKFYYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFK

210-280

DWRKEMTNEEKNIITNLSKCDFTQMSQYFKAQTEARKQMSKEEKLKIKEENEKLLKEYGFCIMDNHKERI

280-350

ANFKIEPPGLFRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENI

350-420

QGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALYFIDKLALRAG

420-490

NEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFLGKDSIRYYNKVPVEKRVFKNLQLFMENKQP

490-560

EDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQQLKELTAPDENIPAKILSYNRANRAVAILC

560-630

NHQRAPPKTFEKSMMNLQTKIDAKKEQLADARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMK

630-700

LEVQATDREENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMADEDYEF

700-765

MSGDHLHNDSQIEADFRLNDSHKHKDKHKDREHRHKEHKKEKDREKSKHSNSEHKDSEKKHKEKEKTKHKDGSSEKHKDKHKDRDKEKRKEEKVRASGDAKIKKEKENGFSSPPQIKDEPEDDGYFVPPKEDIKPLKRPRDEDDADYKPKKIKTEDTKKEKKRKLEEEEDGKLKKPKNKDKDKKVPEPDNKKKKPKKEEEQKWKWWEEERYPEGIKWKFLEHKGPVFAPPYEPLPENVKFYYDGKVMKLSPKAEEVATFFAKMLDHEYTTKEIFRKNFFKDWRKEMTNEEKNIITNLSKCDFTQMSQYFKAQTEARKQMSKEEKLKIKEENEKLLKEYGFCIMDNHKERIANFKIEPPGLFRGRGNHPKMGMLKRRIMPEDIIINCSKDAKVPSPPPGHKWKEVRHDNKVTWLVSWTENIQGSIKYIMLNPSSRIKGEKDWQKYETARRLKKCVDKIRNQYREDWKSKEMKVRQRAVALYFIDKLALRAGNEKEEGETADTVGCCSLRVEHINLHPELDGQEYVVEFDFLGKDSIRYYNKVPVEKRVFKNLQLFMENKQPEDDLFDRLNTGILNKHLQDLMEGLTAKVFRTYNASITLQQQLKELTAPDENIPAKILSYNRANRAVAILCNHQRAPPKTFEKSMMNLQTKIDAKKEQLADARRDLKSAKADAKVMKDAKTKKVVESKKKAVQRLEEQLMKLEVQATDREENKQIALGTSKLNYLDPRITVAWCKKWGVPIEKIYNKTQREKFAWAIDMADEDYEF

Find similar targets by:

Uniprot Keyword

3D-structure
Acetylation
Biological rhythms
Chromosomal rearrangement
Complete proteome
Direct protein sequencing
DNA-binding
Host-virus interaction
Isomerase
Isopeptide bond