UniProt Accession

 TOP1_MOUSE; Q04750; A2A4B7 

Genbank Protein ID

 D10061; L20632; AL590414; AL591673; AL591673; AL590414 

Genbank Nucleotide ID

 BAA00950.1; AAA40466.1; CAM20297.1; CAM20297.1; CAM25349.1; CAM25349.1 

Protein Name

 DNA topoisomerase 1 

Protein Synonyms/Alias

 DNA topoisomerase I 

Gene Name

 Top1 

Gene Synonyms/Alias

 Top-1 

Created Date

 July 27, 2013 

Organism

 Mus musculus (Mouse) 

NCBI Taxa ID

 10090 

Lysine Modification

Position	Peptide	Type	References
174	SEEEEDGKLKKPKNK	acetylation	[1]
206	KEEEQKWKWWEEERY	acetylation	[1]
254	KVMKLSPKAEEVATF	ubiquitination	[2]
356	RERIANFKIEPPGLF	acetylation	[3]
551	PVEKRVFKNLQLFME	acetylation	[3]
617	PDENVPAKILSYNRA	acetylation	[4]

Reference

 [1] SIRT5-Mediated Lysine Desuccinylation Impacts Diverse Metabolic Pathways.
 Park J, Chen Y, Tishkoff DX, Peng C, Tan M, Dai L, Xie Z, Zhang Y, Zwaans BM, Skinner ME, Lombard DB, Zhao Y.
 Mol Cell. 2013 Jun 27;50(6):919-30. [PMID: 23806337]
 [2] Proteomic analyses reveal divergent ubiquitylation site patterns in murine tissues.
 Wagner SA, Beli P, Weinert BT, Schölz C, Kelstrup CD, Young C, Nielsen ML, Olsen JV, Brakebusch C, Choudhary C.
 Mol Cell Proteomics. 2012 Dec;11(12):1578-85. [PMID: 22790023]
 [3] Quantitative acetylome analysis reveals the roles of SIRT1 in regulating diverse substrates and cellular pathways.
 Chen Y, Zhao W, Yang JS, Cheng Z, Luo H, Lu Z, Tan M, Gu W, Zhao Y.
 Mol Cell Proteomics. 2012 Oct;11(10):1048-62. [PMID: 22826441]
 [4] Proteomic investigations of lysine acetylation identify diverse substrates of mitochondrial deacetylase sirt3.
 Sol EM, Wagner SA, Weinert BT, Kumar A, Kim HS, Deng CX, Choudhary C.
 PLoS One. 2012;7(12):e50545. [PMID: 23236377] 

Functional 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 undergoes passage around the unbroken 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. Regulates the alternative splicing of tissue factor (F3) pre-mRNA in endothelial cells (By similarity). 

Sequence Annotation

 REGION 427 428 Interaction with DNA (By similarity).
 REGION 490 495 Interaction with DNA (By similarity).
 REGION 587 589 Interaction with DNA (By similarity).
 ACT_SITE 725 725 O-(3'-phospho-DNA)-tyrosine intermediate
 MOD_RES 2 2 N-acetylserine (By similarity).
 MOD_RES 10 10 Phosphoserine (By similarity).
 MOD_RES 59 59 Phosphoserine (By similarity).
 MOD_RES 114 114 Phosphoserine (By similarity).
 MOD_RES 282 282 N6-acetyllysine (By similarity).
 MOD_RES 508 508 Phosphoserine; by CK2 (By similarity).
 CROSSLNK 105 105 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 119 119 Glycyl lysine isopeptide (Lys-Gly)
 CROSSLNK 155 155 Glycyl lysine isopeptide (Lys-Gly)  

Keyword

 Acetylation; ATP-binding; Complete proteome; Direct protein sequencing; DNA-binding; Isomerase; Isopeptide bond; Nucleotide-binding; Nucleus; Phosphoprotein; Reference proteome; Topoisomerase; Ubl conjugation. 

Sequence Source

 UniProt (SWISSPROT/TrEMBL); GenBank; EMBL 

Protein Length

 767 AA 

Protein Sequence

Gene Ontology

 GO:0005737; C:cytoplasm; IDA:MGI.
 GO:0000932; C:cytoplasmic mRNA processing body; IEA:Compara.
 GO:0005730; C:nucleolus; IBA:RefGenome.
 GO:0005654; C:nucleoplasm; IEA:UniProtKB-SubCell.
 GO:0043204; C:perikaryon; IDA:MGI.
 GO:0031298; C:replication fork protection complex; IBA:RefGenome.
 GO:0005524; F:ATP binding; IEA:UniProtKB-KW.
 GO:0003682; F:chromatin binding; IEA:Compara.
 GO:0003917; F:DNA topoisomerase type I activity; IDA:MGI.
 GO:0003918; F:DNA topoisomerase type II (ATP-hydrolyzing) activity; IEA:InterPro.
 GO:0006338; P:chromatin remodeling; IBA:RefGenome.
 GO:0007059; P:chromosome segregation; IBA:RefGenome.
 GO:0006260; P:DNA replication; IMP:MGI.
 GO:0006265; P:DNA topological change; IDA:MGI.
 GO:0040016; P:embryonic cleavage; IMP:MGI.
 GO:0042493; P:response to drug; IEA:Compara. 

Interpro

 IPR011010; DNA_brk_join_enz.
 IPR013034; DNA_topo_domain1.
 IPR001631; TopoI.
 IPR018521; TopoI_AS.
 IPR025834; TopoI_C_dom.
 IPR014711; TopoI_cat_a-hlx-sub_euk.
 IPR014727; TopoI_cat_a/b-sub_euk.
 IPR013500; TopoI_cat_euk.
 IPR008336; TopoI_DNA-bd_euk.
 IPR013030; TopoI_DNA-bd_mixed-a/b_euk.
 IPR013499; TopoI_euk.
 IPR009054; TopoI_insert_euk. 

Pfam

 PF14370; Topo_C_assoc
 PF01028; Topoisom_I
 PF02919; Topoisom_I_N 

SMART

 SM00435; TOPEUc 

PROSITE

 PS00176; TOPOISOMERASE_I_EUK 

PRINTS

 PR00416; EUTPISMRASEI.