Tclin TOP1 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

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

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: 5017.08   (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: 5017.08   (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: 181

Tclin

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

Active Drugs: 6

Expression Data (0 Tissues)

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No expression data found

Protein Sequence and Structure

Residue Counts

Protein Sequence

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Related Tools (4)

Target Illumination GWAS Analytics (TIGA)

TIGA scores and ranks GWAS discovered associations according to the quantity and quality of the evidence supporting the association.

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GENEVA

GENEVA (GENe Expression Variance Analysis) allows you to identify RNA-sequencing datasets from the Gene Expression Omnibus (GEO) that contain conditions modulating a gene or a gene signature.

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GlyGen

GlyGen is a data integration and dissemination project for carbohydrate and glycoconjugate related data.

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ARCHS4

ARCHS4 provides access to gene-function predictions based on RNA-seq co-expression, and gene expression levels across cell and tissues.

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Approved Drugs (6)

Explore Approved Drugs

1 – 6 of 6

aclarubicin

TOP1Tclin Enzyme

INHIBITOR :

irinotecan

TOP1Tclin Enzyme

INHIBITOR :

topotecan

TOP1Tclin Enzyme

INHIBITOR :

trastuzumab deruxtecan

TOP1Tclin Enzyme

INHIBITOR pIC50 : 7.51

sacituzumab govitecan

TOP1Tclin Enzyme

ANTIBODY BINDING pKd : 9.58

belotecan

TOP1Tclin Enzyme

INHIBITOR pIC50 : 6.56

Active Ligands (181)

Explore Active Ligands

1 – 10 of 181

Camptothecin

TOP1Tclin Enzyme

pKd : 7.08

SN-38

TOP1Tclin Enzyme

pEC50 : 7.16

5,10,15,20-Tetrakis(4-carboxyphenyl)porphyrin

TOP1Tclin Enzyme

pKd : 6.02

camptothecin-7-methylene-O-tolylamine

TOP1Tclin Enzyme

pKd : 9.53

camptothecin-7-carbaldehyde-O-3-hydroxypropyloxime

TOP1Tclin Enzyme

pKd : 8.58

CHEMBL474561

TOP1Tclin Enzyme

pEC50 : 8.48

NB-506 Analogue

TOP1Tclin Enzyme

pEC50 : 8.1

CHEMBL338843

TOP1Tclin Enzyme

pIC50 : 7.96

CHEMBL507686

TOP1Tclin Enzyme

pEC50 : 7.92

CHEMBL335455

TOP1Tclin Enzyme

pIC50 : 7.82

Protein-Protein Interactions (286)

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1 – 10 of 286

• See Interactions on String-DB

EAF1

Tbio

Novelty:  0.81120425

p_int:  0.99560056

p_ni:  0.00439944

Data Source:  BioPlex

ZRANB2

Tbio

Novelty:  0.06105086

p_int:  0.992838763

p_ni:  0.007161237

Score:  0.556

Data Source:  BioPlex,STRINGDB

ESAM

Tbio

Novelty:  0.00462452

p_int:  0.952336066

p_ni:  0.047663934

Score:  0.19

Data Source:  BioPlex,STRINGDB

CIDEC

Tbio

Novelty:  0.01081754

p_int:  0.910968099

p_ni:  0.089031901

Score:  0.252

Data Source:  BioPlex,STRINGDB

HDGFL2

Tbio

Family:  Epigenetic

Novelty:  0.11846257

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

Tbio

Novelty:  0.26347141

p_int:  0.882610129

p_ni:  0.117389871

Data Source:  BioPlex

DUS4L

Tbio

Family:  Enzyme

Novelty:  0.05943255

p_int:  0.860040648

p_ni:  0.139959352

Score:  0.209

Data Source:  BioPlex,STRINGDB

GTF2E2

Tbio

Novelty:  0.18033153

p_int:  0.809584398

p_ni:  0.190415602

Score:  0.219

Data Source:  BioPlex,STRINGDB

TOP2A

Tclin

Family:  Enzyme

Novelty:  0.00122788

Score:  0.997

Data Source:  STRINGDB

Nearest Tclin Targets

Nearest Tclin calculations are only available for targets with KEGG Pathway annotations.

Pathways (10)

Reactome (5)

PathwayCommons (3)

WikiPathways (2)

Metabolism of proteins (R-HSA-392499)

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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

Viral Interactions (0)

No viral interactions found

Gene Ontology Terms (32)

Functions (11)

Components (9)

Processes (12)

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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

Disease Associations (null)

No disease associations found

GWAS Traits (31)

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1 – 5 of 31

GWAS Trait	EFO ID	Study Count	SNP Count	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
low density lipoprotein cholesterol measurement	EFO_0004611	6	8	12		96.5
total cholesterol measurement	EFO_0004574	5	7	10		94.9
apolipoprotein B measurement	EFO_0004615	2	4	4		90.8
balding measurement	EFO_0007825	2	2	2		85.7
heel bone mineral density	EFO_0009270	2	2	3		83.7

• Explore on Target Illumination GWAS Analytics (TIGA)

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1 – 5 of 31

GWAS Trait	EFO ID	Beta Count	Odds Ratio	Evidence (Mean Rank Score)	Provenance
low density lipoprotein cholesterol measurement	EFO_0004611	12		96.5
total cholesterol measurement	EFO_0004574	10		94.9
apolipoprotein B measurement	EFO_0004615	4		90.8
balding measurement	EFO_0007825	2		85.7
heel bone mineral density	EFO_0009270	3		83.7

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UniProt Keyword Find Similar Targets

No Header	No Header
3D-structure
Acetylation
Biological rhythms
Chromosomal rearrangement
Complete proteome
Direct protein sequencing
DNA-binding
Host-virus interaction
Isomerase
Isopeptide bond

GWAS Trait Find Similar Targets

No Header	No Header
Alopecia
apolipoprotein B measurement
balding measurement
bilirubin measurement
birth weight
BMI-adjusted hip circumference
BMI-adjusted waist-hip ratio
body height
C-reactive protein measurement
coronary artery disease

MGI Phenotype Find Similar Targets

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mortality/aging

IDG Resources

No IDG generated resources found

Orthologs (16)

1 – 5 of 16

Species	Name	Source ID	Gene ID	OMA	EggNOG	Inparanoid
Chimp	DNA topoisomerase I	VGNC:10014	458252
Macaque	DNA topoisomerase I		697300
Mouse	topoisomerase (DNA) I	MGI:98788	21969
Rat	DNA topoisomerase I	RGD:621246	64550
Dog	DNA topoisomerase I	VGNC:49631	477229

Species	Name	OMA	EggNOG	Inparanoid
Chimp	DNA topoisomerase I
Macaque	DNA topoisomerase I
Mouse	topoisomerase (DNA) I
Rat	DNA topoisomerase I
Dog	DNA topoisomerase I

Publication Statistics

PubMed Score 5017.08

PubMed score by year

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PubTator Score 69.41

PubTator score by year

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Related Publications

Text Mined References (245)

GeneRif Annotations (180)

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PMID	Year	Title