TISIDB

Summary
Symbol	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
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	Cell membrane; Multi-pass membrane protein.
Domain	PF00001 7 transmembrane receptor (rhodopsin family)
Function	Receptor for activated thrombin or trypsin coupled to G proteins that stimulate phosphoinositide hydrolysis. May play a role in platelets activation.

> Gene Ontology [ TOP ]
Biological Process	GO:0006816 calcium ion transport GO:0006874 cellular calcium ion homeostasis GO:0006875 cellular metal ion homeostasis GO:0007200 phospholipase C-activating G-protein coupled receptor signaling pathway GO:0007204 positive regulation of cytosolic calcium ion concentration GO:0007596 blood coagulation GO:0007599 hemostasis GO:0010522 regulation of calcium ion transport into cytosol GO:0010524 positive regulation of calcium ion transport into cytosol GO:0010959 regulation of metal ion transport GO:0016050 vesicle organization GO:0030168 platelet activation GO:0032844 regulation of homeostatic process GO:0032845 negative regulation of homeostatic process GO:0032846 positive regulation of homeostatic process GO:0033363 secretory granule organization GO:0034762 regulation of transmembrane transport GO:0034764 positive regulation of transmembrane transport GO:0034765 regulation of ion transmembrane transport GO:0034767 positive regulation of ion transmembrane transport GO:0043270 positive regulation of ion transport GO:0050817 coagulation GO:0050878 regulation of body fluid levels GO:0051208 sequestering of calcium ion GO:0051209 release of sequestered calcium ion into cytosol GO:0051235 maintenance of location GO:0051238 sequestering of metal ion GO:0051279 regulation of release of sequestered calcium ion into cytosol GO:0051281 positive regulation of release of sequestered calcium ion into cytosol GO:0051282 regulation of sequestering of calcium ion GO:0051283 negative regulation of sequestering of calcium ion GO:0051480 regulation of cytosolic calcium ion concentration GO:0051924 regulation of calcium ion transport GO:0051928 positive regulation of calcium ion transport GO:0055074 calcium ion homeostasis GO:0060155 platelet dense granule organization GO:0060401 cytosolic calcium ion transport GO:0060402 calcium ion transport into cytosol GO:0070493 thrombin receptor signaling pathway GO:0070509 calcium ion import GO:0070588 calcium ion transmembrane transport GO:0070838 divalent metal ion transport GO:0072503 cellular divalent inorganic cation homeostasis GO:0072507 divalent inorganic cation homeostasis GO:0072511 divalent inorganic cation transport GO:0090279 regulation of calcium ion import GO:0090280 positive regulation of calcium ion import GO:0097553 calcium ion transmembrane import into cytosol GO:1902656 calcium ion import into cytosol GO:1903169 regulation of calcium ion transmembrane transport GO:1904062 regulation of cation transmembrane transport GO:1904064 positive regulation of cation transmembrane transport GO:1904427 positive regulation of calcium ion transmembrane transport GO:2000021 regulation of ion homeostasis
Molecular Function	GO:0001653 peptide receptor activity GO:0008528 G-protein coupled peptide receptor activity GO:0015057 thrombin receptor activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04015 Rap1 signaling pathway hsa04080 Neuroactive ligand-receptor interaction hsa04610 Complement and coagulation cascades hsa04611 Platelet activation
Reactome	R-HSA-373076: Class A/1 (Rhodopsin-like receptors) R-HSA-416476: G alpha (q) signalling events R-HSA-388396: GPCR downstream signaling R-HSA-500792: GPCR ligand binding R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK R-HSA-109582: Hemostasis R-HSA-375276: Peptide ligand-binding receptors R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-162582: Signal Transduction R-HSA-372790: Signaling by GPCR R-HSA-456926: Thrombin signalling through proteinase activated receptors (PARs)

> KEGG and Reactome Pathway

[ TOP ]

KEGG

hsa04015 Rap1 signaling pathway
hsa04080 Neuroactive ligand-receptor interaction
hsa04610 Complement and coagulation cascades
hsa04611 Platelet activation

Reactome

R-HSA-373076: Class A/1 (Rhodopsin-like receptors)
R-HSA-416476: G alpha (q) signalling events
R-HSA-388396: GPCR downstream signaling
R-HSA-500792: GPCR ligand binding
R-HSA-881907: Gastrin-CREB signalling pathway via PKC and MAPK
R-HSA-109582: Hemostasis
R-HSA-375276: Peptide ligand-binding receptors
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-162582: Signal Transduction
R-HSA-372790: Signaling by GPCR
R-HSA-456926: Thrombin signalling through proteinase activated receptors (PARs)

Summary
Symbol	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between F2RL3 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	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
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 F2RL3 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	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
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 F2RL3 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	-0.883	0.0196
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-1.382	0.0268
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	-0.528	0.368
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.215	0.621
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-0.346	0.797
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-0.046	0.979
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.377	0.424
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.283	0.701
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	1.063	0.161
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.894	0.185
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	1.51	0.0886
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.329	0.0789

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of F2RL3 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	33.3	-33.3	0.231
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	0	0	0	1
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	0	0	0	1
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	0	4.8	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	12.5	0	12.5	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	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of F2RL3. 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	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of F2RL3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by F2RL3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of F2RL3. 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	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of F2RL3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between F2RL3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	F2RL3
Name	coagulation factor II (thrombin) receptor-like 3
Aliases	proteinase-activated receptor-4; protease-activated receptor-4; thrombin receptor-like 3; Coagulation factor ......
Chromosomal Location	19p12
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting F2RL3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting F2RL3.

ID	Name	Drug Type	Targets	#Targets
DB11300	Thrombin	Small Molecule	F2R, F2RL3	2

Browse F2RL3