TISIDB

Summary
Symbol	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
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	Cytoplasm, cytoskeleton Note=Associates with F-actin stress fibers.
Domain	PF00261 Tropomyosin
Function	Binds to actin filaments in muscle and non-muscle cells. Plays a central role, in association with the troponin complex, in the calcium dependent regulation of vertebrate striated muscle contraction. Smooth muscle contraction is regulated by interaction with caldesmon. In non-muscle cells is implicated in stabilizing cytoskeleton actin filaments (By similarity). Binds calcium (PubMed:1836432).

> Gene Ontology [ TOP ]
Biological Process	GO:0001503 ossification GO:0001649 osteoblast differentiation GO:0003012 muscle system process GO:0006936 muscle contraction GO:0030048 actin filament-based movement GO:0030049 muscle filament sliding GO:0033275 actin-myosin filament sliding GO:0070252 actin-mediated cell contraction
Molecular Function	GO:0003779 actin binding GO:0008307 structural constituent of muscle
Cellular Component	GO:0001725 stress fiber GO:0002102 podosome GO:0005862 muscle thin filament tropomyosin GO:0005865 striated muscle thin filament GO:0005884 actin filament GO:0005924 cell-substrate adherens junction GO:0005925 focal adhesion GO:0005938 cell cortex GO:0015629 actin cytoskeleton GO:0030016 myofibril GO:0030017 sarcomere GO:0030055 cell-substrate junction GO:0030863 cortical cytoskeleton GO:0031941 filamentous actin GO:0032432 actin filament bundle GO:0036379 myofilament GO:0042641 actomyosin GO:0043292 contractile fiber GO:0044448 cell cortex part GO:0044449 contractile fiber part GO:0097517 contractile actin filament bundle GO:0099568 cytoplasmic region

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04260 Cardiac muscle contraction hsa04261 Adrenergic signaling in cardiomyocytes
Reactome	R-HSA-397014: Muscle contraction R-HSA-445355: Smooth Muscle Contraction R-HSA-390522: Striated Muscle Contraction

Summary
Symbol	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between TPM4 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 ]
There is no record.

Summary
Symbol	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
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 TPM4 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	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
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

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Points in the above scatter plot represent the expression difference of TPM4 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	-0.611	0.0388
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.696	0.844
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.542	0.826
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.689	0.0868
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.487	0.874
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.942	0.812
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	-0.199	0.741
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.415	0.868
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.06	0.983
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.361	0.865
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	1.463	0.653
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.127	0.168

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of TPM4 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	5.9	-5.9	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	7.1	-7.1	1
4	26359337	Melanoma	all	Anti-CTLA-4 (ipilimumab)	27	73	3.7	0	3.7	0.27
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	3.7	0	3.7	0.314
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	0	0	0	1
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	0	0	1
10	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0	0	0	1
11	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0	0	0	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	0	0	1
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	0	0	1
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	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of TPM4. 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	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of TPM4. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by TPM4. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of TPM4. 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	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of TPM4 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between TPM4 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	TPM4
Name	tropomyosin 4
Aliases	HEL-S-108; TM30p1; epididymis secretory protein Li 108; tropomyosin-4; Tropomyosin alpha-4 chain
Chromosomal Location	19p13.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting TPM4 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting TPM4.

ID	Name	Drug Type	Targets	#Targets
DB12695	Phenethyl Isothiocyanate	Small Molecule	ACTA2, ACTB, ATP5B, ATP5I, ATP5L, CYB5B, DIABLO, FBXO41, HNRNPF, H ......	45

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