Reactome | UniProt:P11387 TOP1

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UniProt:P11387 TOP1 Show undefined attributes

chain	initiator methionine:1 chain:2-765
checksum	6FBED540BCF7BE28
comment	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.CATALYTIC ACTIVITY ATP-independent breakage of single-stranded DNA, followed by passage and rejoining.ACTIVITY REGULATION Specifically inhibited by camptothecin (CPT), a plant alkaloid with antitumor activity.SUBUNIT 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).SUBUNIT (Microbial infection) Interacts with SV40 Large T antigen; this interactions allows viral DNA replication.INTERACTION 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.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.PTM Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin.DISEASE A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome. Translocation t(11;20)(p15;q11) with NUP98.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.
crossReference	[DatabaseIdentifier:11631074] ENSEMBL:ENSP00000354522 [DatabaseIdentifier:12818426] ZINC - World Drugs:TOP1_HUMAN [DatabaseIdentifier:12816538] ZINC target:P11387 [DatabaseIdentifier:12813140] ZINC - Substances:TOP1_HUMAN [DatabaseIdentifier:12808949] ZINC - Predictions - Purchasable:TOP1_HUMAN [DatabaseIdentifier:12806905] ZINC - Investigational:TOP1_HUMAN [DatabaseIdentifier:12805819] ZINC - FDA approved:TOP1_HUMAN [DatabaseIdentifier:12804712] ZINC - Biogenic:TOP1_HUMAN [DatabaseIdentifier:12457912] RefSeq:NP_003277.1 [DatabaseIdentifier:12285958] Pharos - Targets:P11387 [DatabaseIdentifier:12265519] PRO:P11387 [DatabaseIdentifier:12182082] PDB:1TL8 [DatabaseIdentifier:12182077] PDB:1K4S [DatabaseIdentifier:12182083] PDB:1A31 [DatabaseIdentifier:12182081] PDB:1EJ9 [DatabaseIdentifier:12182084] PDB:1NH3 [DatabaseIdentifier:12182080] PDB:1R49 [DatabaseIdentifier:12182079] PDB:1RR8 [DatabaseIdentifier:12182078] PDB:1RRJ [DatabaseIdentifier:12182073] PDB:1A35 [DatabaseIdentifier:12182074] PDB:1SEU [DatabaseIdentifier:12182070] PDB:1SC7 [DatabaseIdentifier:12182075] PDB:1LPQ [DatabaseIdentifier:12182076] PDB:1K4T [DatabaseIdentifier:12182072] PDB:1A36 [DatabaseIdentifier:12182071] PDB:1T8I [DatabaseIdentifier:12125681] OpenTargets:ENSG00000198900 [DatabaseIdentifier:11841128] HPA:ENSG00000198900-TOP1 [DatabaseIdentifier:11803607] GlyGen:P11387 [DatabaseIdentifier:11788065] GeneCards:TOP1 [DatabaseIdentifier:11779451] Guide to Pharmacology - Targets:2636 [DatabaseIdentifier:11753773] ENSEMBL:ENST00000361337 [DatabaseIdentifier:11514641] ENSEMBL:ENSG00000198900
databaseName	UniProt
dbId	69718
description	recommendedName: DNA topoisomerase 1 ecNumber evidence="4 13 16 25"5.6.2.1 alternativeName: DNA topoisomerase I
displayName	UniProt:P11387 TOP1
geneName	TOP1
identifier	P11387
isSequenceChanged	false
keyword	3D-structure Acetylation Biological rhythms Chromosomal rearrangement Direct protein sequencing DNA-binding Host-virus interaction Isomerase Isopeptide bond Nucleus Phosphoprotein Proteomics identification Proto-oncogene Reference proteome Topoisomerase Ubl conjugation
modified	[InstanceEdit:9963647] Weiser, Joel, 2025-08-15
moleculeType	Protein
name	TOP1
otherIdentifier	1030_s_at 11717437_x_at 11717438_x_at 11717439_s_at 16913737 1710_s_at 208900_PM_s_at 208900_s_at 208901_PM_s_at 208901_s_at 2367108 2367109 2367112 2367113 31680_at 3885463 3885465 3885466 3885467 3885468 3885469 3885490 3885491 3885496 3885497 3885498 3885499 3885500 3885502 3885507 3885508 3885509 3885511 3885512 3885513 3885515 3885517 3885518 3885520 3885521 3885522 3885525 3885526 3885527 3885528 3885538 7150 8062603 A_23_P305507 A_33_P3371493 GE57478 GE60513 GO:0000228 GO:0000932 GO:0000978 GO:0001650 GO:0001651 GO:0001673 GO:0003677 GO:0003682 GO:0003690 GO:0003697 GO:0003723 GO:0003824 GO:0003916 GO:0003917 GO:0004674 GO:0005515 GO:0005524 GO:0005634 GO:0005654 GO:0005694 GO:0005730 GO:0005737 GO:0006260 GO:0006265 GO:0006325 GO:0006338 GO:0006351 GO:0007059 GO:0007623 GO:0008301 GO:0009266 GO:0009303 GO:0009410 GO:0010332 GO:0012501 GO:0016740 GO:0016853 GO:0018105 GO:0019904 GO:0031100 GO:0031490 GO:0032922 GO:0032993 GO:0040016 GO:0043204 GO:0043226 GO:0044877 GO:0048511 GO:0048856 GO:0051591 GO:0071373 GO:0097100 GO:0140096 GO:0140097 HMNXSV003009439 Hs.317.0.S1_3p_a_at ILMN_1763419 ILMN_2192316 PH_hs_0040753 TC20000302.hg TC20001221.hg U07804_s_at U07806_s_at g339805_3p_a_at
physicalEntity	[EntityWithAccessionedSequence:R-HSA-4641363] TOP1 [nucleoplasm] - Homo sapiens [EntityWithAccessionedSequence:R-HSA-4641364] monoSUMO1-K117-TOP1 [nucleoplasm] - Homo sapiens
referenceDatabase	[ReferenceDatabase:2] UniProt
referenceGene	[ReferenceDNASequence:ensembl:ENSG00000198900] ENSEMBL:ENSG00000198900 TOP1 [ReferenceDNASequence:12711646] UCSC:P11387 TOP1 [ReferenceDNASequence:12110924] OMIM:126420 TOP1 [ReferenceDNASequence:12092889] NCBI Gene:7150 TOP1 [ReferenceDNASequence:12008796] Monarch:7150 TOP1 [ReferenceDNASequence:11916204] KEGG:hsa:7150 TOP1 [ReferenceDNASequence:11819714] HGNC:11986 TOP1 [ReferenceDNASequence:11379007] BioGPS Gene:7150 TOP1 [ReferenceDNASequence:11395610] COSMIC - genes:TOP1 TOP1 [ReferenceDNASequence:11414151] CTD Gene:7150 TOP1 [ReferenceDNASequence:11431863] dbSNP Gene:7150 TOP1
referenceTranscript	[ReferenceRNASequence:12639381] RefSeq:NM_003286.4 TOP1
schemaClass	ReferenceGeneProduct
secondaryIdentifier	TOP1_HUMAN A8KA78 E1P5W3 O43256 Q12855 Q12856 Q15610 Q5TFY3 Q9UJN0
sequenceLength	765
species	[Species:48887] Homo sapiens
stId	uniprot:P11387
url	http://purl.uniprot.org/uniprot/P11387

Referrals

(referenceEntity)	[EntityWithAccessionedSequence:R-HSA-4641363] TOP1 [nucleoplasm] [EntityWithAccessionedSequence:R-HSA-4641364] monoSUMO1-K117-TOP1 [nucleoplasm]
(referenceSequence)	[GroupModifiedResidue:4641305] sumoylated lysine (monoSUMO1 [nucleoplasm]) at 117
(interactor)	[UndirectedInteraction:11134873] UniProt:P23246 <-> UniProt:P11387 (IntAct) [UndirectedInteraction:11144259] UniProt:Q92841 <-> UniProt:P11387 (IntAct) [UndirectedInteraction:11160461] UniProt:P48431 <-> UniProt:P11387 (IntAct) [UndirectedInteraction:11165567] UniProt:P09874 <-> UniProt:P11387 (IntAct) [UndirectedInteraction:11180317] UniProt:P11387 <-> UniProt:P03070 (IntAct) [UndirectedInteraction:11180319] UniProt:P11387 <-> UniProt:P01106 (IntAct) [UndirectedInteraction:11180323] UniProt:P11387 <-> UniProt:Q99801 (IntAct) [UndirectedInteraction:11180325] UniProt:P11387 <-> UniProt:P00519 (IntAct) [UndirectedInteraction:11180327] UniProt:P11387 <-> UniProt:P07910 (IntAct) [UndirectedInteraction:11180329] UniProt:P11387 <-> UniProt:Q00839 (IntAct) [UndirectedInteraction:11180331] UniProt:P11387 <-> UniProt:Q9NR30 (IntAct) [UndirectedInteraction:11180333] UniProt:P11387 <-> UniProt:O75643 (IntAct) [UndirectedInteraction:11180335] UniProt:P11387 <-> UniProt:O43390 (IntAct) [UndirectedInteraction:11180337] UniProt:P11387 <-> UniProt:P11388 (IntAct) [UndirectedInteraction:11180339] UniProt:P11387 <-> UniProt:P22626 (IntAct) [UndirectedInteraction:11180341] UniProt:P11387 <-> UniProt:Q6P2Q9 (IntAct) [UndirectedInteraction:11180343] UniProt:P11387 <-> UniProt:Q15233 (IntAct) [UndirectedInteraction:11180345] UniProt:P11387 <-> UniProt:P61978 (IntAct) [UndirectedInteraction:11180347] UniProt:P11387 <-> UniProt:Q08211 (IntAct) [UndirectedInteraction:11180349] UniProt:P11387 <-> UniProt:P78527 (IntAct) [UndirectedInteraction:11180351] UniProt:P11387 <-> UniProt:Q15717 (IntAct) [UndirectedInteraction:11180353] UniProt:P11387 <-> UniProt:P09651 (IntAct) [UndirectedInteraction:11180355] UniProt:P11387 <-> UniProt:P19338 (IntAct) [UndirectedInteraction:11180357] UniProt:P11387 <-> UniProt:P13010 (IntAct) [UndirectedInteraction:11180359] UniProt:P11387 <-> UniProt:P42768 (IntAct) [UndirectedInteraction:11180361] UniProt:P11387 <-> UniProt:Q15029 (IntAct) [UndirectedInteraction:11180363] UniProt:P11387 <-> UniProt:Q96JC9 (IntAct) [UndirectedInteraction:11180365] UniProt:P11387 <-> UniProt:Q9BUQ8 (IntAct) [UndirectedInteraction:11180367] UniProt:P11387 <-> UniProt:P51991 (IntAct) [UndirectedInteraction:11180369] UniProt:P11387 <-> UniProt:P17844 (IntAct) [UndirectedInteraction:11180371] UniProt:P11387 <-> UniProt:Q96SB4 (IntAct) [UndirectedInteraction:11180373] UniProt:P11387 <-> UniProt:P19320 (IntAct) [UndirectedInteraction:11180375] UniProt:P11387 <-> UniProt:P14866 (IntAct) [UndirectedInteraction:11180377] UniProt:P11387 <-> UniProt:P06748 (IntAct) [UndirectedInteraction:11180379] UniProt:P11387 <-> UniProt:P09661 (IntAct) [UndirectedInteraction:11180381] UniProt:P11387 <-> UniProt:Q07955 (IntAct) [UndirectedInteraction:11180383] UniProt:P11387 <-> UniProt:P03372 (IntAct) [UndirectedInteraction:11180385] UniProt:P11387 <-> UniProt:P16403 (IntAct)

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