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: 5839.97   (req: < 5)

Gene RIFs: 206   (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: 5839.97   (req: >= 5)

Gene RIFs: 206   (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: 182

Tclin

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

Active Drugs: 6