UniProt functional annotation for P11387



	UniProt functional annotation for P11387

UniProt code: P11387.

Organism: Homo sapiens (Human).

Taxonomy: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.

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 ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter. {ECO:0000250|UniProtKB:Q13472, ECO:0000269|PubMed:14594810, ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:19168442, ECO:0000269|PubMed:22904072, ECO:0000269|PubMed:2833744}.

Catalytic activity: Reaction=ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.; EC=5.6.2.1; Evidence={ECO:0000255|PROSITE- ProRule:PRU10130, ECO:0000269|PubMed:14594810, ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:2833744};

Activity regulation: Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.

Subunit: Monomer. Interacts with ERCC6 (PubMed:26030138). {ECO:0000269|PubMed:10841763, ECO:0000269|PubMed:12209008, ECO:0000269|PubMed:12533542, ECO:0000269|PubMed:15165849, ECO:0000269|PubMed:16033260, ECO:0000269|PubMed:26030138, ECO:0000269|PubMed:9488644, ECO:0000269|PubMed:9488652}.

Subunit: (Microbial infection) Interacts with SV40 Large T antigen; this interactions allows viral DNA replication. {ECO:0000269|PubMed:18003733}.

Subcellular location: Nucleus, nucleolus {ECO:0000269|PubMed:12149243}. Nucleus, nucleoplasm {ECO:0000269|PubMed:12149243}. Note=Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumoylated forms found in both nucleoplasm and nucleoli.

Tissue specificity: Endothelial cells. {ECO:0000269|PubMed:19168442}.

Ptm: Sumoylated. Lys-117 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment. {ECO:0000269|PubMed:12149243}.

Ptm: Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin. {ECO:0000269|PubMed:23185622}.

Disease: Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98. {ECO:0000269|PubMed:10556215}.

Miscellaneous: Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.

Similarity: Belongs to the type IB topoisomerase family. {ECO:0000305}.

Sequence caution: Sequence=CAA36834.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};

Annotations taken from UniProtKB at the EBI.


Organism:		Homo sapiens (Human).
Taxonomy:		Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo.



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 ARNTL/BMAL1 by altering the chromatin structure around the ROR response elements (ROREs) on the ARNTL/BMAL1 promoter. {ECO:0000250\|UniProtKB:Q13472, ECO:0000269\|PubMed:14594810, ECO:0000269\|PubMed:16033260, ECO:0000269\|PubMed:19168442, ECO:0000269\|PubMed:22904072, ECO:0000269\|PubMed:2833744}.


Catalytic activity:		Reaction=ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.; EC=5.6.2.1; Evidence={ECO:0000255\|PROSITE- ProRule:PRU10130, ECO:0000269\|PubMed:14594810, ECO:0000269\|PubMed:16033260, ECO:0000269\|PubMed:2833744};
Activity regulation:		Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.
Subunit:		Monomer. Interacts with ERCC6 (PubMed:26030138). {ECO:0000269\|PubMed:10841763, ECO:0000269\|PubMed:12209008, ECO:0000269\|PubMed:12533542, ECO:0000269\|PubMed:15165849, ECO:0000269\|PubMed:16033260, ECO:0000269\|PubMed:26030138, ECO:0000269\|PubMed:9488644, ECO:0000269\|PubMed:9488652}.
Subunit:		(Microbial infection) Interacts with SV40 Large T antigen; this interactions allows viral DNA replication. {ECO:0000269\|PubMed:18003733}.
Subcellular location:		Nucleus, nucleolus {ECO:0000269\|PubMed:12149243}. Nucleus, nucleoplasm {ECO:0000269\|PubMed:12149243}. Note=Diffuse nuclear localization with some enrichment in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumoylated forms found in both nucleoplasm and nucleoli.
Tissue specificity:		Endothelial cells. {ECO:0000269\|PubMed:19168442}.
Ptm:		Sumoylated. Lys-117 is the main site of sumoylation. Sumoylation plays a role in partitioning TOP1 between nucleoli and nucleoplasm. Levels are dramatically increased on camptothecin (CPT) treatment. {ECO:0000269\|PubMed:12149243}.
Ptm:		Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin. {ECO:0000269\|PubMed:23185622}.
Disease:		Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98. {ECO:0000269\|PubMed:10556215}.
Miscellaneous:		Eukaryotic topoisomerase I and II can relax both negative and positive supercoils, whereas prokaryotic enzymes relax only negative supercoils.
Similarity:		Belongs to the type IB topoisomerase family. {ECO:0000305}.
Sequence caution:		Sequence=CAA36834.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};