OTOP1

DNA topoisomerase 1 UniProt accession P11387

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 BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the BMAL1 promoter

Source: UniProt

Monomer. Interacts with ERCC6 (PubMed:26030138). Interacts with TPRN; TPRN interacts with a number of DNA damage response proteins, is recruited to sites of DNA damage and may play a role in DNA damage repair (PubMed:23213405)

(Microbial infection) Interacts with SV40 Large T antigen; this interactions allows viral DNA replication

Source: UniProt
Nucleus, nucleolus, Nucleus, nucleoplasm
Source: UniProt

Endothelial cells

Source: UniProt
  • Unknown disease
Source: UniProt
  • SUMOylation of DNA replication proteins
Source: Reactome via UniProt

Mutations

No mutation information available.

Synthetic Lethal Network

Genes with an experimentally identified or computationally predicted synthetic-lethal relationship to OTOP1, aggregated across our SSL data sources. Click any partner node to view that gene’s page.

Nodes and edges are coloured by the SSL data source. Partners appearing in more than one source are shown in grey.

BioGRID SLOrth SynLethDB MexDrugs Multi-source
Sources: BioGRID, SLOrth, SynLethDB, MexDrugs

Clinical Trials

Total Trials Found: 35

NCT ID Condition Brief Title Phase Status
NCT06797999 Metastatic Soft Tissue Sarcoma, Unresectable Soft Tissue Sarcoma First-in-Human Study of ADCE-D01 in Soft Tissue Sarcoma PHASE1, PHASE2 RECRUITING
NCT03030417 Solid Tumors, Lymphoma Indenoisoquinoline LMP744 in Adults With Relapsed Solid Tumors and Lymphomas PHASE1 COMPLETED
NCT06619236 Platinum-resistant Ovarian Cancer Study to Assess the Efficacy of Rina-S Compared to Treatment of Investigator's Choice in Participants With Platinum Resistant Ovarian Cancer PHASE3 ACTIVE_NOT_RECRUITING
NCT00358319 Malignant Melanoma Phase I/II Trial of Valproic Acid and Karenitecin for Melanoma PHASE1, PHASE2 TERMINATED
NCT07444814 Endometrial Cancer, Ovarian Cancer, Ovarian Cancer Metastatic, Ovarian Cancer Metastatic Recurrent, Non-squamous EGFR Wt NSCLC, Platinum Resistant Ovarian Cancer, PROC Study Evaluating the Safety and Efficacy of HWK-007, a PTK7-directed Antibody Drug Conjugate in Participants With Advanced Solid Tumors PHASE1 RECRUITING
NCT07360314 Advanced Solid Tumors Anti-Ly6E Exatecan ADC M7437 in Advanced Solid Tumors PHASE1 RECRUITING
NCT05579366 High Grade Epithelial Ovarian Cancer, High Grade Serous Ovarian Cancer, Primary Peritoneal Carcinoma, Fallopian Tube Cancer, Endometrial Cancer, Non-small Cell Lung Cancer, Epidermal Growth Factor Receptor (EGFR)-Mutated Non-Small Cell Lung Cancer (NSCLC), Mesothelioma, Breast Adenocarcinoma, Triple Negative Breast Cancer, Hormone Receptor-positive/Her2 Negative Breast Cancer, Platinum-resistant Ovarian Cancer (PROC), Platinum Sensitive Ovarian Cancer (PSOC), Primary Refractory Ovarian Cancer, Uterine Cancer Rinatabart Sesutecan (Rina-S, PRO1184, GEN1184) for Advanced Solid Tumors (GCT1184-01/ PRO1184-001) PHASE1, PHASE2 RECRUITING
NCT05178719 Osteoporosis Treatment of Osteoporosis - TOP 2-5 Clinical Studies (Pear Control) NA COMPLETED
NCT06721689 Refractory Solid Tumors, Relapsed Solid Tumors, Relapsed Neuroblastoma, Refractory Neuroblastoma, Relapsed Rhabdomyosarcoma, Refractory Rhabdomyosarcoma PEEL-224, Vincristine and Temozolomide in Pediatric Solid Tumors PHASE1, PHASE2 RECRUITING
NCT01550510 Stage IV Colorectal Cancer Research Study of IV Vitamin C in Combination With Irinotecan vs Irinotecan Alone for Advanced Colorectal CA PHASE1, PHASE2 TERMINATED