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Category Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21

GIFtS
-

TOP1 Gene

protein-coding GIFtS: 68
GCID: GC20P039657

topoisomerase (DNA) I

Explore 131 diseases affiliated with
TOP1 via

MalaCards

our new
Human Malady Compendium

(According to ¹HGNC, ²Entrez Gene,
³UniProtKB/Swiss-Prot, ⁴UniProtKB/TrEMBL, ⁵OMIM, ⁶GeneLoc, ⁷Ensembl, ⁸DME, ⁹miRBase, and/or ¹⁰fRNAdb)
About This Section

Aliases
Topoisomerase (DNA) I¹ ²
EC 5.99.1.2³ ⁸
TOPI²
DNA Topoisomerase 1²
Type I DNA Topoisomerase²
DNA Topoisomerase I³

External Ids:	HGNC: 11986¹	Entrez Gene: 7150²	Ensembl: ENSG00000198900⁷	OMIM: 126420⁵	UniProtKB: P11387³

Export aliases for TOP1 gene to outside databases

Previous GC identifers: GC20P039385 GC20P040295 GC20P040342 GC20P039090 GC20P036395

(According to Entrez Gene, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
About This Section

Entrez Gene summary for TOP1:

This gene encodes a DNA topoisomerase, an enzyme that controls and alters the topologic states of DNA during

transcription. This enzyme catalyzes the transient breaking and rejoining of a single strand of DNA which allows the

strands to pass through one another, thus altering the topology of DNA. This gene is localized to chromosome 20 and

has pseudogenes which reside on chromosomes 1 and 22. (provided by RefSeq, Jul 2008)

UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387

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 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 (By similarity). Regulates the alternative splicing of tissue factor (F3)

pre-mRNA in endothelial cells

summary for TOP1:

Topoisomerases are ubiquitously expressed enzymes that overcome topological problems in genomic DNA, which

can result from DNA replication, transcription and repair. Common problems such as overwinding (positive

supercoiling), knots and tangles are resolved by topoisomerases by catalysing the breaking of one or two

strands of DNA. Topoisomerase type I enzymes cut just one strand of the DNA double helix, and hence relax

supercoiling of the DNA. Four genes encode Type I topoisomerases, which include nuclear topoisomerase I

(TOP1) and mitochondrial topoisomerase I (TOP1MT). Type I enzymes can also be sub-divided into Types A and B

based on their different catalytic mechanism for generating single DNA strand breaks. TOP1 and TOP1MT are

both type 1B since they form 3'-phosphotyrosyl bonds. Camptothecin is a natural product inhibitor of TOP1

that has led to the discovery of derivatives that are clinically used anti-cancer drugs. Such inhibitors

trap the enzyme in a cleavage complex with DNA. Type II topoisomerases (IIA and IIB) are particular

important for the disentanglement of DNA, which is overcome by generating double stranded DNA breaks.

Dysregulation of type II enzymes can therefore have a potentially significant genotoxic effect. There is a

broad range of topoisomerase II inhibitors that are used clinically as anticancer agents.

Gene Wiki entry for TOP1

(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section

RefSeq DNA sequence:

NC_000020.10 NC_018931.1 NT_011362.10

Regulatory elements:

SABiosciences Regulatory transcription factor binding sites in the TOP1 gene promoter:
CREB c-Fos Sp1 AP-1 ATF-2 c-Jun
Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): TOP1 promoter sequence

Search SABiosciences Chromatin IP Primers for TOP1

Epigenetics:

QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays in human, mouse, rat TOP1

Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 20q12-q13.1 Ensembl cytogenetic band: 20q12 HGNC cytogenetic band: 20q12-q13.1

TOP1 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
TOP1 gene location

GeneLoc information about chromosome 20 GeneLoc Exon Structure

GeneLoc location for GC20P039657: view genomic region (about GC identifiers)

Start:	39,657,458 bp from pter	End:	39,753,127 bp from pter
Size:	95,670 bases	Orientation:	plus strand

(According to ¹UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to ²PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section

UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387 (See protein sequence)

Recommended Name: DNA topoisomerase 1

Size: 765 amino acids; 90726 Da

Subunit: Monomer. Interacts with SV40 Large T antigen; this interactions allows viral DNA replication

Subcellular location: Nucleus, nucleolus. Nucleus, nucleoplasm. Note=Diffuse nuclear localization with some enrichment

in nucleoli. On CPT treatment, cleared from nucleoli into nucleoplasm. Sumolyated forms found in both nucleoplasm and

nucleoli

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

enzymes relax only negative supercoils

Sequence caution: Sequence=CAA36834.1; Type=Erroneous gene model prediction;

6/15 PDB 3D structures from and Proteopedia for TOP1 (see all 15):

1A31 (3D)

1A35 (3D)

1A36 (3D)

1EJ9 (3D)

1K4S (3D)

1K4T (3D)

Secondary accessions: A8KA78 E1P5W3 O43256 Q12855 Q12856 Q15610 Q5TFY3 Q9UJN0

Explore the universe of human proteins at neXtProt for TOP1: NX_P11387

Post-translational modifications:

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) treatment¹

Phosphorylation at Ser-506 by CK2 increases binding to supercoiled DNA and sensitivity to camptothecin¹

View modification sites using PhosphoSitePlus²

View neXtProt modification sites for NX_P11387

4/27 DME Specific Peptides for TOP1 (P11387) (see all 27)

DFLGKDS

VKFYYDG

KHKDKHK

LRAGNEK

TOP1 Protein expression data from MOPED and PaxDb: About this image

REFSEQ proteins: NP_003277.1

ENSEMBL proteins:

ENSP00000354522

Human Recombinant Protein Products:

	Browse Purified and Recombinant Proteins at EMD Millipore
	Browse R&D Systems for human recombinant proteins
	Browse recombinant and purified proteins available from Enzo Life Sciences
	Browse OriGene full length recombinant human proteins expressed in human HEK293 cells OriGene Protein Over-expression Lysate: TOP1 OriGene Custom Protein Services for TOP1
	GenScript Custom Purified and Recombinant Proteins Services for TOP1
	Novus Biologicals TOP1 Protein Novus Biologicals TOP1 Lysate
	Browse Sino Biological Recombinant Proteins
	ProSpec Recombinant Protein for TOP1
	Uscn Proteins for TOP1

Gene Ontology (GO): 5/8 cellular component terms (GO ID links to tree view) (see all 8): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0000228	colocalizes with nuclear chromosome	IDA	9049244
GO:0000932	cytoplasmic mRNA processing body	IDA	12878161
GO:0005634	nucleus	IDA	--
GO:0005654	nucleoplasm	IDA	9049244
GO:0005730	nucleolus	IDA	--

TOP1 for ontologies About GeneDecksing

TOP1 Antibody Products:

	Browse EMD Millipore's Extensive Line of Mono- and Polyclonal Antibodies
	Browse R&D Systems for Antibodies
	OriGene Antibodies: TOP1 OriGene Custom Antibody Services for TOP1
	GenScript Custom Superior Antibodies Services for TOP1
	Novus Biologicals TOP1 Antibodies
	Abcam antibodies for TOP1
	Uscn Antibodies for TOP1
	ThermoFisher Antibodies for TOP1

Assay Products for TOP1:

	Browse Kits and Assays available from EMD Millipore
	OriGene Custom Immunoassay Development Browse OriGene Fluorogenic Cell Assay Kits
	Browse R&D Systems for biochemical assays
	GenScript Custom Assay Services for TOP1
	Browse Enzo Life Sciences for kits & assays
	Uscn ELISAs and CLIAs for TOP1

(According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
About This Section

TOP1 for domains About GeneDecksing

5/12 InterPro domains/families (see all 12):

IPR013030 TopoI_DNA-bd_mixed-a/b_euk

IPR008336 TopoI_DNA-bd_euk

IPR001631 TopoI

IPR018521 TopoI_AS

IPR014727 TopoI_cat_a/b-sub_euk

Graphical View of Domain Structure for InterPro Entry P11387

ProtoNet protein and cluster: P11387

2 Blocks protein families:

IPB001631 Eukaryotic-like DNA topoisomerase I

IPB008336 Eukaryotic DNA topoisomerase I

UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387

Similarity: Belongs to the type IB topoisomerase family

(According to ¹UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or ²DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
About This Section

Function Summary:

UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387

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 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 (By similarity). Regulates the alternative splicing of tissue factor (F3)

pre-mRNA in endothelial cells

Catalytic activity: ATP-independent breakage of single-stranded DNA, followed by passage and rejoining

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

Genatlas biochemistry entry for TOP1:

DNA topoisomerase I,ubiquitous,catalyzing the ATP independent breakage and rejoining of single strand of DNA,relaxing

negatively supercoiled DNA,involved in DNA repair

Enzyme Number (IUBMB): EC 5.99.1.2¹ ²

miRNA Products:		OriGene 3'-UTR Clone: TOP1 Browse MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TOP1
		8/52 QIAGEN miScript miRNA Assays for microRNAs that regulate TOP1 (see all 52):
		hsa-miR-549 hsa-miR-4307 hsa-miR-3607-3p hsa-miR-1197 hsa-miR-139-5p hsa-miR-25 hsa-miR-485-3p hsa-miR-374a

		SwitchGear 3'UTR luciferase reporter plasmid: TOP1 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TOP1 (see all 7) OriGene shRNA RFP: TOP1 OriGene siRNA: TOP1
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TOP1

Gene Editing
Products:

DNA2.0 Custom Protein Engineering Service for TOP1

Clone Products:		Browse Clones for the Expression of Recombinant Proteins Available from EMD Millipore
		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TOP1 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TOP1 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TOP1 (NM_003286)
		Browse Sino Biological Human cDNA Clones
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TOP1
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TOP1

Cell Line Products:		GenScript Custom overexpressing Cell Line Services for TOP1
		Search LifeMap BioReagents cell lines for TOP1

In Situ Assay
Products:

Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for TOP1

Gene Ontology (GO): 5/6 molecular function terms (GO ID links to tree view) (see all 6): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0003677	DNA binding	IDA	17355975
GO:0003682	chromatin binding	IDA	9049244
GO:0003917	DNA topoisomerase type I activity	IMP	17355975
GO:0003918	DNA topoisomerase type II (ATP-hydrolyzing) activity	IEA	--
GO:0005515	protein binding	IPI	--

TOP1 for ontologies           About GeneDecksing

Animal Models:
     Mouse knock-out Top1^tm1Unc for TOP1
     1 MGI mutant phenotype (inferred from 1 allele) (MGI details for Top1):

mortality/aging

TOP1 for phenotypes About GeneDecksing

(Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, and/or STRING, Interactions according to ¹UniProtKB, ²MINT, ³I2D, and/or ⁴STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene).
About This Section

Unified GeneCards pathways About this table

See pathways by source

Super-pathway

contained gene-specific pathways

Cell cycle Chromosome condensation in prometaphase

Cell cycle Chromosome condensation in prometaphase

1.00

Cell cycle_Chromosome condensation in prometaphase

1.00

Cell cycle Transition and termination of DNA replacation

Cell cycle Transition and termination of DNA replacation

1.00

Cell cycle_Transition and termination of DNA replication

0.95

Integrated Pancreatic Cancer Pathway

Integrated Pancreatic Cancer Pathway

1.00

Integrated Pancreatic Cancer Pathway

0.99

Irinotecan Pathway, Pharmacokinetics

Irinotecan Pathway, Pharmacodynamics

0.50

Apoptosis and survival_Caspase cascade

Caspase cascade in apoptosis

0.42

Pathway sources
See GeneCards unified pathways
Show all pathways

2 EMD Millipore Pathways for TOP1

	Cell cycle Transition and termination of DNA replacation
	Cell cycle Chromosome condensation in prometaphase

2 GeneGo (Thomson Reuters) Pathways for TOP1

	Cell cycle Chromosome condensation in prometaphase
	Cell cycle Transition and termination of DNA replication

3 BioSystems Pathways for TOP1

	Integrated Pancreatic Cancer Pathway
	Integrated Pancreatic Cancer Pathway
	Caspase cascade in apoptosis

1 PharmGKB Pathway for TOP1

Irinotecan Pathway, Pharmacodynamics

TOP1 for pathways About GeneDecksing

Interactions:

SABiosciences Gene Network Central^TM Interacting Genes and Proteins Network for TOP1

STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

5/523 Interacting proteins for TOP1 (P11387^{1, 2, 3} ENSP00000354522⁴) via UniProtKB, MINT, STRING, and/or I2D (see all 523)

Interactant		Interaction Details
GeneCard	External ID(s)	Interaction Details
HIST1H4A	P62805³	I2D: score=1
HIST1H4B	P62805³	I2D: score=1
HIST1H4C	P62805³	I2D: score=1
HIST1H4D	P62805³	I2D: score=1
HIST1H4E	P62805³	I2D: score=1

About this table

Gene Ontology (GO): 5/10 biological process terms (GO ID links to tree view) (see all 10): About this table

GO ID	Qualified GO term	Evidence	PubMed IDs
GO:0006260	DNA replication	IBA	--
GO:0006265	DNA topological change	IDA	14594810
GO:0006338	chromatin remodeling	IBA	--
GO:0007059	chromosome segregation	IBA	--
GO:0012501	programmed cell death	NAS	17172417

TOP1 for ontologies About GeneDecksing

(Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
About This Section

TOP1 for compounds About GeneDecksing

EMD Millipore small molecules for TOP1:
Small Molecule - inhibitor

Enzo Life Sciences drugs & compounds for TOP1

Compounds for TOP1 available from Tocris Bioscience About this table

Compound	Action	CAS #
CPT 11	DNA topoisomerase I inhibitor; antitumor	[100286-90-6]
SN 38	DNA topoisomerase I inhibitor; antitumor	[86639-52-3]
Camptothecin	DNA topoisomerase inhibitor	[7689-03-4]
Banoxantrone dihydrochloride	Prodrug topoisomerase II inhibitor	[136470-65-0]
Topotecan hydrochloride	DNA topoisomerase I inhibitor. Camptothecin (Cat. No. 1100) analog	[119413-54-6]

7 DrugBank Compounds for TOP1 About this table

Compound	Synonyms	CAS #	Type	Actions	PubMed Ids
Topotecan	Topotecan Hcl (see all 5)	119413-54-6	target	inhibitor	9885371 11752352 12437383 12855624 8853931 11443926 12520736 9122737 11166732
Irinotecan	Irinotecan Hcl (see all 4)	100286-90-6	target	inhibitor	15975002 19852077 15170677 9342501 11752352 15255290 16309825 16454746
Camptothecin	(+)-camptothecin (see all 8)	7689-03-4	target	--	18056711 11752352 10592235 18061144
Sodium stibogluconate	Antimony sodium gluconate (see all 6)	16037-91-5	target	inhibitor	15562618 2835038 10592235
Lucanthone	1-((2-(Diethylamino)ethyl)amino)-4-methylthioxanthen-9-one (see all 7)	479-50-5	target	inhibitor	9169823 10487533
2,3-DIMETHOXY-12H-[1,3]DIOXOLO[5,6]INDENO[1,2-C]ISOQUINOLIN-6-IUM	--	--	target	--	10592235
4-(5,11-DIOXO-5H-INDENO[1,2-C]ISOQUINOLIN-6(11H)-YL)BUTANOATE	--	--	target	--	10592235

10/124 Novoseek chemical compound relationships for TOP1 gene (see all 124) About this table

Compound	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
camptothecin	98	1214	11479235 (8), 9305865 (7), 7538195 (7), 14729676 (6) (see all 99)
topotecan	96	364	9717830 (4), 8621255 (3), 15471886 (3), 14587067 (3) (see all 99)
irinotecan	92.1	270	18823053 (3), 2168285 (3), 15160997 (3), 8162152 (2) (see all 99)
9-aminocamptothecin	90.7	43	8892462 (2), 9815685 (2), 8634995 (1), 10912951 (1) (see all 24)
sn 38	88.5	30	15574786 (2), 9771954 (1), 9825730 (1), 11000580 (1) (see all 28)
lurtotecan	86.4	13	8611374 (1), 9328158 (1), 11870164 (1), 7834631 (1) (see all 11)
tdp-1	86.2	52	15494395 (6), 15920477 (3), 16793421 (2), 13679147 (2) (see all 23)
rebeccamycin	85.8	25	11032967 (3), 12901916 (2), 10322124 (2), 11733535 (1) (see all 19)
saintopin	82.8	29	9203632 (5), 1646001 (3), 7961822 (2), 7890748 (2) (see all 7)
9-nitrocamptothecin	82.5	27	11585748 (1), 18434109 (1), 11193897 (1), 9328159 (1) (see all 13)

Search CenterWatch for drugs/clinical trials and news about TOP1

(Secondary structures according to fRNAdb,
GenBank/EMBL/DDBJ Accessions according to
Unigene (Build 235 Homo sapiens; Mar 10 2013) or GenBank,
RefSeq according to Entrez Gene,
DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
RNAi Products from EMD Millipore,
siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
About This Section

REFSEQ mRNAs for TOP1 gene:

NM_003286.2

Unigene Cluster for TOP1:

Topoisomerase (DNA) I

Hs.472737 [show with all ESTs]

Unigene Representative Sequence: NM_003286

1 Ensembl transcript including schematic representation, and UCSC links where relevant:

ENST00000361337(uc010ggd.1 uc010gge.1 uc002xjl.3)

miRNA Products:		OriGene 3'-UTR Clone: TOP1 Browse OriGene MicroRNA Expression Plasmids
		QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat TOP1
		8/52 QIAGEN miScript miRNA Assays for microRNAs that regulate TOP1 (see all 52):
		hsa-miR-549 hsa-miR-4307 hsa-miR-3607-3p hsa-miR-1197 hsa-miR-139-5p hsa-miR-25 hsa-miR-485-3p hsa-miR-374a

		SwitchGear 3'UTR luciferase reporter plasmid: TOP1 3' UTR sequence

Inhib. RNA Products:		Browse for Gene Knock-down Tools from EMD Millipore
		OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for TOP1 (see all 7) OriGene shRNA RFP: TOP1 OriGene siRNA: TOP1
		QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat TOP1

Clone Products:		OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for TOP1 (see all 3) OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for TOP1 OriGene custom cloning services � gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
		GenScript: all cDNA clones in your preferred vector: TOP1 (NM_003286)
		DNA2.0 Custom Codon Optimized Gene Synthesis Service for TOP1
		Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat TOP1

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for TOP1 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat TOP1
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TOP1
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TOP1

Additional cDNA sequence:

AK225095.1 AK292943.1 AK310508.1 AK310516.1 BC000943.2 BC004475.2 BC039009.1 BC056681.1

BC067349.1 BC136297.1 J03250.1 M27913.1 U07804.1 U07806.1 X16479.2

14 DOTS entries:

DT.97780620 DT.425139 DT.99987653 DT.75183810 DT.99955016 DT.120819606 DT.40209313 DT.95191468

DT.120819634 DT.40261268 DT.86840413 DT.95194887 DT.95191472 DT.95210182

24/299 AceView cDNA sequences (see all 299):

BX391491 CF137671 R00391 AA830283 BM676885 F07589 BU686012 AW206091

CF127017 BC000943 BP871306 CB852622 BM541278 CR604483 BM722996 AI828741

BM786075 BM974259 BU632004 CA487823 BX393368 R76489 CA488073 T29529

GeneLoc Exon Structure

(RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
About This Section

TOP1 expression in normal human tissues (normalized intensities)
See probesets specificity/sensitivity at GeneAnnot
About this imageBioGPS
CGAP TAG: AATTCCCTTT

About this image

TOP1 expression in embryonic tissues and stem cells

Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine About this table

1 LifeMap In Vivo Development Anatomical Compartment/Cell

Tissue

Anatomical Compartment

Cell

Category (developmental path)

Heart

Endocardium

Endocardial Tube Cells

Endocardium

Expression:

Positive

Negative

Selective marker

Experimental details:

Curated

Microarrays

In-situ hybridization

See TOP1 Protein Expression from SPIRE MOPED and PaxDB
Genevestigator expression for TOP1

SOURCE GeneReport for Unigene cluster: Hs.472737

UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387

Tissue specificity: Endothelial cells

SABiosciences Expression via Pathway-Focused PCR Arrays including TOP1:

Multiple Sclerosis in human mouse rat

Cancer Drug Resistance in human mouse rat

Primer Products:		OriGene genome-wide validated SYBR primer pairs in human, mouse, rat for TOP1 Browse OriGene validated miRNA SYBR primer pairs
		SABiosciences RT² qPCR Primer Assay in human, mouse, rat TOP1
		QIAGEN QuantiTect SYBR Green Assays in human, mouse, rat TOP1
		QIAGEN QuantiFast Probe-based Assays in human, mouse, rat TOP1

In Situ
Assay Products:

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(Orthologs according to ^1,2HomoloGene (²older version, for species not in ¹newer version), ³euGenes, ⁴SGD , ⁵MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or ⁶Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
About This Section

This gene was present in the common ancestor of eukaryotes.

Orthologs for TOP1 gene from 9/39 species (see all 39) About this table

Organism	Taxonomic classification	Gene	Description	Human Similarity	Orthology Type	Details
chicken (Gallus gallus)	Aves	TOP1¹	topoisomerase (DNA) I	83.73(n) 92.91(a)		396004 NM_205110.1 NP_990441.1
lizard (Anolis carolinensis)	Reptilia	TOP1⁶	--	89(a)	1 ↔ 1	GL343291.1(783269-828779)
African clawed frog (Xenopus laevis)	Amphibia	Xl.62²	Xenopus laevis DNA topoisomerase I (TOP1) mRNA, complete more	78.4(n)		L07777.1
zebrafish (Danio rerio)	Actinopterygii	57064100²	--	75.23(n)		57064100
fruit fly (Drosophila melanogaster)	Insecta	Top1^{1 , 3}	embryonic morphogenesis DNA topoisomerase I³ Topoisomerase 1¹	67(a)³ 61.72(n)¹ 63.27(a)¹		1 13B6³ 32458¹ NM_001014742.1¹ NP_001014742.1¹
worm (Caenorhabditis elegans)	Secernentea	top-1¹	Protein TOP-1	59.05(n) 58.77(a)		266847 NM_060936.4 NP_493337.1
baker's yeast (Saccharomyces cerevisiae)	Saccharomycetes	TOP1¹	Top1p	52.39(n) 45.73(a)		854156 NP_014637.1
thale cress (Arabidopsis thaliana)	eudicotyledons	TOP1BETA¹	DNA topoisomerase 1 beta	51.8(n) 43.41(a)		835624 NM_124913.3 NP_200342.1
rice (Oryza sativa)	Liliopsida	Os08g0154600¹	hypothetical protein	50.87(n) 44.06(a)		4344685 NM_001067550.1 NP_001061015.1

ENSEMBL Gene Tree for TOP1 (if available)
TreeFam Gene Tree for TOP1 (if available)

(Paralogs according to ¹HomoloGene,
²Ensembl, and ³SIMAP, Pseudogenes according to ⁴Pseudogene.org Build 68)
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Paralogs for TOP1 gene

TOP1MT²

1 SIMAP similar gene for TOP1 using alignment to 4 protein entries: TOP1_HUMAN (see all proteins):

TOP1MT

TOP1 for paralogs About GeneDecksing

1 Pseudogenes.org Pseudogene for TOP1
PGOHUM00000245083

(SNPs/Variants according to the ¹NCBI SNP Database, ²Ensembl, ³PupaSUITE, UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
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SNP ID	Valid	Clinical significance	Chr 20 pos	Sequence	#	AA Chg	Type	More	#	Allele freq	Pop	Total sample	More
Genomic Data					Transcription Related Data				Allele Frequencies
				--	--	--		--	--
rs73909126^1,2	C,	--	36393970(+)	`CAATTG/ATTGGA`	1	--	us2k¹		2		WA	120
rs6072250^1,2	C,H	--	36394435(+)	`AATCAG/TCGGGA`	1	--	us2k¹		4		NS EA	416
rs59836397^1,2		--	36394610(+)	`GACCTC/TACAGA`	1	--	us2k¹		0	--	--	--	--
rs6102247^1,2	C,H	--	36395482(+)	`ACTTAG/AGCTGT`	1	--	ut5¹ ese³		7		NS EA NA	598
rs79866880^1,2	C,F,	--	36396825(+)	`AGTTCT/CCTGTG`	1	--	int¹		2		WA EA	238
rs79296143^1,2	C,	--	36397164(+)	`CTTTTC/TAGCCA`	1	--	int¹		4		CSA WA NA EA	360
rs117757029^1,2	C,F,	--	36397585(+)	`TAACCA/CTAACA`	1	--	int¹		1		NA	120
rs75253847^1,2	F,	--	36397770(+)	`GGCGCA/GGAGAA`	1	--	int¹		1		WA	118
rs73257891^1,2	C,	--	36398118(+)	`TATTGA/GTNNNN`	1	--	int¹		3		WA NA	240
rs75534547^1,2	C,	--	36398614(+)	`TGGAAG/TATGTG`	1	--	int¹		4		CSA WA NA EA	360

HapMap Linkage Disequilibrium report for TOP1 (39657458 - 39753127 bp)
Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
Database of Genomic Variants (DGV): 1 variation for TOP1
1 CNV: 5138
Human Gene Mutation Database (HGMD): TOP1

SABiosciences Cancer Mutation PCR Assays

QIAGEN SeqTarget long-range PCR primers in human, mouse, rat for resequencing TOP1

DNA2.0 Custom Variant and Variant Library Synthesis for TOP1

(in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
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TOP1 for disorders About GeneDecksing

OMIM gene information: 126420 OMIM disorders: --

UniProtKB/Swiss-Prot: TOP1_HUMAN, P11387

Note=A chromosomal aberration involving TOP1 is found in a form of therapy-related myelodysplastic syndrome.

Translocation t(11;20)(p15;q11) with NUP98

20/131 diseases for TOP1 (see all 131): About MalaCards

dna topoisomerase i, camptothecin-resistant dna topoisomerase i monoclonal gammopathy of undetermined significance xeroderma pigmentosum, group a

molluscum contagiosum spinal muscular atrophy xeroderma pigmentosum human t-cell leukemia virus type 1

dna topoisomerase ii central nervous system lymphoma connective tissue disease graft versus host disease

non-small cell lung carcinoma collecting duct carcinoma treacher collins syndrome pericardial effusion

uterine carcinosarcoma non-hodgkin lymphoma soft tissue sarcoma severe combined immunodeficiency

10 diseases from the University of Copenhagen DISEASES database for TOP1:

Neutropenia Colorectal cancer Systemic scleroderma Lung cancer

Diarrhea Ovarian cancer Thrombocytopenia Leukemia

Vaccinia Axonal neuropathy

10/93 Novoseek disease relationships for TOP1 gene (see all 93) About this table

Disease	-log (P-Val)	Hits	PubMed IDs for Articles with Shared Sentences (# sentences)
scan1	81.7	13	15920477 (2), 17600775 (1), 17707402 (1), 16935573 (1)
solid tumor	67.7	36	16807458 (2), 8835290 (1), 9058732 (1), 10021292 (1) (see all 32)
neutropenia	67.3	5	8611374 (1), 11081458 (1), 19604089 (1), 15470958 (1) (see all 5)
sclerosis systemic	66.6	45	7615831 (2), 11465716 (2), 19211583 (2), 1319697 (2) (see all 37)
colon carcinoma	66.3	16	11594758 (2), 1310066 (1), 9321666 (1), 18538108 (1) (see all 15)
cancer	64.2	186	19584232 (3), 15735043 (2), 11020283 (2), 12852757 (2) (see all 99)
ovarian cancer	61.8	29	16462890 (4), 18405948 (2), 9497914 (2), 10502731 (2) (see all 21)
small cell lung cancer	61.7	16	17645849 (2), 8853931 (1), 15735665 (1), 19996589 (1) (see all 15)
leukemia p388	61.6	7	9927631 (1), 11205907 (1), 9892183 (1), 11118036 (1) (see all 5)
leukemia	60.8	40	17418582 (2), 1997159 (1), 1848545 (1), 8914817 (1) (see all 36)

Human Genome Epidemiology (HuGE) Navigator: TOP1 (3 documents)

Export disorders for TOP1 gene to outside databases

(in PubMed. Associations of this gene to articles via ¹Entrez Gene, ²UniProtKB/Swiss-Prot, ³HGNC, ⁴GAD, ⁵PharmGKB, ⁶HMDB, ⁷DrugBank, ⁸UniProtKB/TrEMBL, ⁹ Novoseek, and/or ¹⁰fRNAdb)
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PubMed articles for TOP1 gene, integrated from 9 sources (see all 1434):
(articles sorted by number of sources associating them with TOP1)

Utopia: connect your pdf to the dynamic
world of online information

Sumoylation of topoisomerase I is involved in its partitioning between nucleoli and nucleoplasm and its clearing from nucleoli in response to camptothecin. (PubMed id 12149243)^{1, 2, 9} Rallabhandi P....D'Arpa P. (2002)
8-Oxoguanine rearranges the active site of human topoisomerase I. (PubMed id 12209008)^{1, 2, 9} Lesher D.T....Redinbo M.R. (2002)
Mutation at the catalytic site of topoisomerase I in CEM/C2, a human leukemia cell line resistant to camptothecin. (PubMed id 7882333)^{1, 2, 9} Fujimori A.... Pommier Y. (1995)
The mechanism of topoisomerase I poisoning by a camptothecin analog. (PubMed id 12426403)^{1, 2, 9} Staker B.L....Stewart L. (2002)
Molecular cloning of a cDNA of a camptothecin-resistant human DNA topoisomerase I and identification of mutation sites. (PubMed id 1849260)^{1, 2, 9} Tamura H.... Nishikawa K. (1991)
Simian virus 40 DNA replication is dependent on an interaction between topoisomerase I and the C-terminal end of T antigen. (PubMed id 18003733)^{1, 2} Khopde S. and Simmons D.T. (2008)
The role of lysine 532 in the catalytic mechanism of human topoisomerase I. (PubMed id 14594810)^{1, 2} Interthal H....Champoux J.J. (2004)
The DNA sequence and comparative analysis of human chromosome 20. (PubMed id 11780052)^{1, 2} Deloukas P....Rogers J. (2001)
Novel insights into catalytic mechanism from a crystal structure of human topoisomerase I in complex with DNA. (PubMed id 10841763)^{1, 2} Redinbo M.R.... Hol W.G.J. (2000)
The t(11;20)(p15;q11) chromosomal translocation associated with therapy-related myelodysplastic syndrome results in an NUP98-TOP1 fusion. (PubMed id 10556215)^{1, 2} Ahuja H.G.... Aplan P.D. (1999)

(in PubMed, OMIM, and NCBI Bookshelf)
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		AND	OR
Aliases
Disorders
Free Text

Query String		PubMed OMIM NCBI Bookshelf
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(According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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Entrez Gene: 7150	HGNC: 11986	AceView: TOP1	Ensembl:ENSG00000198900	euGenes: HUgn7150
ECgene: TOP1	H-InvDB: TOP1

(According to HUGE)
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(According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL,
Wikipedia and/or GeneReviews via UniProtKB/Swiss-Prot)
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Name	Description
PharmGKB entry for TOP1	Pharmacogenomics, SNPs, Pathways
ATLAS Chromosomes in Cancer entry for TOP1	Genetics and Cytogenetics in Oncology and Haematology

Intellectual Property for TOP1 gene
(Patent information from GeneIP, Licensable technologies from WIS Yeda, Salk, Tufts, IP news from LifeMap Sciences, Inc.)

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Patent Information for TOP1 gene:
Search GeneIP for patents involving TOP1

GeneCards and IP:
Japan Patent Office Licenses GeneCards European Patent Office Licenses GeneCards Improving the IP Search

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topoisomerase (DNA) I

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TOP1 Gene

topoisomerase (DNA) I

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