lmmol · Proteins

DNA topoisomerase 1

UniProt P11387 Organism Homo sapiens Gene TOP1 EC 5.6.2.1

Also known as: TOP1

Function

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.

Classification

Family (Pfam)
PF14370 Topo_C_assoc, PF01028 Topoisom_I, PF02919 Topoisom_I_N
InterPro
DNA_brk_join_enz, DNA_topo_DNA_db_N_dom1, DNA_topo_DNA_db_N_dom2, TopoI, TopoI_C_dom, TopoI_cat_a-hlx-sub_euk, TopoI_cat_a/b-sub_euk, TopoI_cat_euk, TopoI_DNA-bd_euk, TopoI_DNA-bd_euk_N_sf, TopoI_euk, TopoIB_AS, Topoisomer_I_DNA-bd, Topoisomerase_IB
Functional cluster
DEAD-Box RNA Helicases & Biogenesis Factors

Experimental structures · PDB · 15

A predicted model is available from AlphaFold.

Gene Ontology · 38

Drugs targeting this protein · 17

Related proteins · sequence + function similarity

Co-cited proteins · studied together in the literature

Literature · 44 cited papers

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