TISIDB

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Basic function annotation. > Subcellular Location, Domain and Function > Gene Ontology > KEGG and Reactome Pathway

> Subcellular Location, Domain and Function [ TOP ]
Subcellular Location	Nucleus, nucleolus Nucleus, nucleoplasm 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.
Domain	PF14370 C-terminal topoisomerase domain PF01028 Eukaryotic DNA topoisomerase I PF02919 Eukaryotic DNA topoisomerase I
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.

> Gene Ontology [ TOP ]
Biological Process	GO:0006260 DNA replication GO:0006265 DNA topological change GO:0006338 chromatin remodeling GO:0007059 chromosome segregation GO:0007623 circadian rhythm GO:0016925 protein sumoylation GO:0018205 peptidyl-lysine modification GO:0032922 circadian regulation of gene expression GO:0040016 embryonic cleavage GO:0042493 response to drug GO:0048511 rhythmic process GO:0071103 DNA conformation change
Molecular Function	GO:0001046 core promoter sequence-specific DNA binding GO:0001047 core promoter binding GO:0003682 chromatin binding GO:0003916 DNA topoisomerase activity GO:0003917 DNA topoisomerase type I activity GO:0016853 isomerase activity
Cellular Component	GO:0000932 cytoplasmic mRNA processing body GO:0005657 replication fork GO:0031298 replication fork protection complex GO:0035770 ribonucleoprotein granule GO:0036464 cytoplasmic ribonucleoprotein granule GO:0043025 neuronal cell body GO:0043204 perikaryon GO:0043596 nuclear replication fork GO:0044297 cell body GO:0044454 nuclear chromosome part

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-3108232: SUMO E3 ligases SUMOylate target proteins R-HSA-2990846: SUMOylation R-HSA-4615885: SUMOylation of DNA replication proteins

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TOP1 and anti-tumor immunity. The specific mechanism were also collected if the literature reports that a gene specifically promotes or inhibits the infiltration or function of T/NK cells.

> Text Mining

[ TOP ]

Literatures describing the relation between TOP1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29267866	Melanoma	Inhibit immunity (T cell function); immunotherapy target	We found that Top1 inhibitors increased the sensitivity of patient-derived melanoma cell lines (n?=?7) to T-cell-mediated cytotoxicity (P < .001, Dunnett's test).
27875523	Non-Small Cell Lung Carcinoma; Gastric Carcinoma; Colorectal Carcinoma; Esophageal Squamous Cell Carcinoma	Promote immunity	The production of autoantibodies against tumour-associated antigens (TAAs) is believed to reflect greater immunologic reactivity in cancer patients and enhanced immune surveillance for cancer cells. Here we describe a novel TAA that was a fragment derived from human DNA-topoiomerase I and an autoantibody against the novel TAA with relatively high positive frequency in the sera of early-stage non-small-cell lung cancer (NSCLC), gastric cancer (GC), colorectal cancer (CRC) and oesophageal squamous cell carcinoma (ESCC). We identified the novel TAA as a fragment derived from human DNA-topoiomerase I (TOP1). We observed that the immune response against the novel TAA was associated with early stage ESCC, GC, CRC and NSCLC.

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	High-throughput screening data (e.g. CRISPR-Cas9, shRNA and RNAi) for T cell-mediated killing. Genetic screen techniques can identify mechanisms of tumor cell resistance (e.g., PTPN2) and sensitivity (e.g., APLNR) to killing by cytotoxic T cells, the central effectors of anti-tumor immunity. After comprehensively searching, eight groups of screening data sets were collected in the current database. In this tab, users can check whether their selected genes cause resistance or increase sensitivity to T cell-mediated killing in various data sets.

> High-throughput Screening

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Statistical results of TOP1 in screening data sets for detecting immune reponses.

PMID	Screening System	Cancer Type	Cell Line	Data Set	Statistical Results	Relation to immunity
29301958	CRISPR-Cas9	melanoma	B16F10	Pmel-1 T cell	NA/NS	NA/NS
29301958	CRISPR-Cas9	melanoma	B16F10	OT-1 T cell	NA/NS	NA/NS
28783722	CRISPR-Cas9	melanoma	Mel624	2CT-CRISPR	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX+Anti-PD1	NA/NS	NA/NS
28723893	CRISPR-Cas9	melanoma	B16	GVAX	NA/NS	NA/NS
25691366	RNAi	Breast cancer	MCF7	Luc-CTL assay	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Primary screen	NA/NS	NA/NS
24476824	shRNA	melanoma	B16	Secondary screen	NA/NS	NA/NS

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Transcriptomic and genomic profiling of pre-treated tumor biopsies from responders and non-responders to immunotherapy. These data were used to identify signatures and mechanisms of response to checkpoint blockade (e.g., anti-PDL1 and anti-PD1). One example is that mutations in the gene PBRM1 benefit clinical survival of patients with clear cell renal cell carcinoma. After comprehensively searching, we collected 5 and 6 of transcriptomic and genomic data sets, respectively. In this tab, users can check whether their selected genes have significant difference of expression or mutation between responders and non-responders in various data sets. > Expression difference between responders and non-responders > Mutation difference between responders and non-responders

> Expression difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the expression difference of TOP1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	Log2 (Fold Change)	P value
1	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	14	12	-0.229	0.394
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.03	0.99
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.38	0.834
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.022	0.929
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.07	0.975
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.141	0.962
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.026	0.954
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.185	0.927
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.221	0.918
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.292	0.841
11	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	2	0	0	1
12	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	2	8	0.6	0.79
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	0.099	0.0492

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of TOP1 in various data sets.

No	PMID	Cancer type	Group	Drug	# Res	# NRes	% Mut/Res	% Mut/NRes	% Diff (R vs NR)	Pval
1	25765070	Non-small cell lung cancer (NSCLC)	all	Anti-PD-1 (pembrolizumab)	14	17	0	0	0	1
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	0	0	0	1
3	25765070	Non-small cell lung cancer (NSCLC)	non-smoking	Anti-PD-1 (pembrolizumab)	4	14	0	0	0	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	7.4	2.7	4.7	0.294
5	26359337	Melanoma	BRAFi	Anti-CTLA-4 (ipilimumab)	0	14	0	0	0	1
6	26359337	Melanoma	non-BRAFi	Anti-CTLA-4 (ipilimumab)	27	59	7.4	3.4	4	0.587
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	5.9	-5.9	0.447
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	0	0	0	1
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	0	9.1	-9.1	0.458
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	6.2	-6.2	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	11.1	-11.1	1
12	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0	0	0	1
13	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	38	27	0	3.7	-3.7	0.415
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	0	0	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	0	7.1	-7.1	0.467
16	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	11	13	0	0	0	1
17	29301960	Clear cell renal cell carcinoma (ccRCC)	VEGFRi	Anti-PD-1 (nivolumab)	6	1	0	0	0	1
18	29301960	Clear cell renal cell carcinoma (ccRCC)	non-VEGFRi	Anti-PD-1 (nivolumab)	5	12	0	0	0	1

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TOP1. The immune-related signatures of 28 TIL types from Charoentong's study, which can be viewed in the download page. For each cancer type, the relative abundance of TILs were inferred by using gene set variation analysis (GSVA) based on gene expression profile. In this tab, users can examine which kinds of TILs might be regulated by the current gene.

> Lymphocyte [ TOP ]

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TOP1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TOP1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TOP1. In this tab, users can examine which chemokines (or receptors) might be regulated by the current gene. > Chemokine > Receptor

> Chemokine [ TOP ]

> Receptor [ TOP ]

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TOP1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TOP1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TOP1
Name	topoisomerase (DNA) I
Aliases	TOPI; type I DNA topoisomerase; DNA topoisomerase I; DNA topoisomerase 1
Chromosomal Location	20q12-q13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TOP1 collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting TOP1.

ID	Name	Drug Type	Targets	#Targets
DB00762	Irinotecan	Small Molecule	TOP1, TOP1MT	2
DB01030	Topotecan	Small Molecule	TOP1, TOP1MT	2
DB04690	Camptothecin	Small Molecule	TOP1	1
DB04882	Edotecarin	Small Molecule	TOP1	1
DB04967	Lucanthone	Small Molecule	APEX1, TOP1, TOP2A	3
DB05129	Elsamitrucin	Small Molecule	TOP1, TOP2A	2
DB05482	7-ethyl-10-hydroxycamptothecin	Small Molecule	TOP1	1
DB05630	Sodium stibogluconate	Small Molecule	TOP1	1
DB05806	Cositecan	Small Molecule	TOP1	1
DB06069	XMT-1001	Small Molecule	TOP1	1
DB06159	Rubitecan	Small Molecule	TOP1	1
DB07354	2,3-DIMETHOXY-12H-[1,3]DIOXOLO[5,6]INDENO[1,2-C]ISOQUINOLIN-6-IUM	Small Molecule	TOP1	1
DB08159	4-(5,11-DIOXO-5H-INDENO[1,2-C]ISOQUINOLIN-6(11H)-YL)BUTANOATE	Small Molecule	TOP1	1

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