TISIDB

Summary
Symbol	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
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	Secreted.
Domain	PF00008 EGF-like domain PF07645 Calcium-binding EGF domain PF00594 Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain PF00054 Laminin G domain PF02210 Laminin G domain
Function	Anticoagulant plasma protein; it is a cofactor to activated protein C in the degradation of coagulation factors Va and VIIIa. It helps to prevent coagulation and stimulating fibrinolysis.

> Gene Ontology [ TOP ]
Biological Process	GO:0002526 acute inflammatory response GO:0002576 platelet degranulation GO:0002673 regulation of acute inflammatory response GO:0002697 regulation of immune effector process GO:0002920 regulation of humoral immune response GO:0006465 signal peptide processing GO:0006887 exocytosis GO:0006888 ER to Golgi vesicle-mediated transport GO:0006956 complement activation GO:0006959 humoral immune response GO:0007596 blood coagulation GO:0007599 hemostasis GO:0010466 negative regulation of peptidase activity GO:0010951 negative regulation of endopeptidase activity GO:0016485 protein processing GO:0017187 peptidyl-glutamic acid carboxylation GO:0018200 peptidyl-glutamic acid modification GO:0018214 protein carboxylation GO:0030193 regulation of blood coagulation GO:0030195 negative regulation of blood coagulation GO:0030449 regulation of complement activation GO:0032102 negative regulation of response to external stimulus GO:0042730 fibrinolysis GO:0045055 regulated exocytosis GO:0045861 negative regulation of proteolysis GO:0048193 Golgi vesicle transport GO:0050727 regulation of inflammatory response GO:0050817 coagulation GO:0050818 regulation of coagulation GO:0050819 negative regulation of coagulation GO:0050878 regulation of body fluid levels GO:0050900 leukocyte migration GO:0051346 negative regulation of hydrolase activity GO:0051604 protein maturation GO:0052547 regulation of peptidase activity GO:0052548 regulation of endopeptidase activity GO:0061041 regulation of wound healing GO:0061045 negative regulation of wound healing GO:0070613 regulation of protein processing GO:0072376 protein activation cascade GO:1900046 regulation of hemostasis GO:1900047 negative regulation of hemostasis GO:1903034 regulation of response to wounding GO:1903035 negative regulation of response to wounding GO:1903317 regulation of protein maturation GO:2000257 regulation of protein activation cascade
Molecular Function	GO:0004857 enzyme inhibitor activity GO:0004866 endopeptidase inhibitor activity GO:0030414 peptidase inhibitor activity GO:0061134 peptidase regulator activity GO:0061135 endopeptidase regulator activity
Cellular Component	GO:0005796 Golgi lumen GO:0030141 secretory granule GO:0031091 platelet alpha granule GO:0031093 platelet alpha granule lumen GO:0031983 vesicle lumen GO:0034774 secretory granule lumen GO:0060205 cytoplasmic membrane-bounded vesicle lumen GO:0072562 blood microparticle GO:0099503 secretory vesicle

> KEGG and Reactome Pathway [ TOP ]
KEGG	hsa04610 Complement and coagulation cascades
Reactome	R-HSA-202733: Cell surface interactions at the vascular wall R-HSA-140875: Common Pathway of Fibrin Clot Formation R-HSA-166658: Complement cascade R-HSA-140877: Formation of Fibrin Clot (Clotting Cascade) R-HSA-163841: Gamma carboxylation, hypusine formation and arylsulfatase activation R-HSA-159740: Gamma-carboxylation of protein precursors R-HSA-159854: Gamma-carboxylation, transport, and amino-terminal cleavage of proteins R-HSA-109582: Hemostasis R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-392499: Metabolism of proteins R-HSA-76002: Platelet activation, signaling and aggregation R-HSA-114608: Platelet degranulation R-HSA-597592: Post-translational protein modification R-HSA-977606: Regulation of Complement cascade R-HSA-159782: Removal of aminoterminal propeptides from gamma-carboxylated proteins R-HSA-76005: Response to elevated platelet cytosolic Ca2+ R-HSA-159763: Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus

> KEGG and Reactome Pathway

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KEGG

hsa04610 Complement and coagulation cascades

Reactome

R-HSA-202733: Cell surface interactions at the vascular wall
R-HSA-140875: Common Pathway of Fibrin Clot Formation
R-HSA-166658: Complement cascade
R-HSA-140877: Formation of Fibrin Clot (Clotting Cascade)
R-HSA-163841: Gamma carboxylation, hypusine formation and arylsulfatase activation
R-HSA-159740: Gamma-carboxylation of protein precursors
R-HSA-159854: Gamma-carboxylation, transport, and amino-terminal cleavage of proteins
R-HSA-109582: Hemostasis
R-HSA-168256: Immune System
R-HSA-168249: Innate Immune System
R-HSA-392499: Metabolism of proteins
R-HSA-76002: Platelet activation, signaling and aggregation
R-HSA-114608: Platelet degranulation
R-HSA-597592: Post-translational protein modification
R-HSA-977606: Regulation of Complement cascade
R-HSA-159782: Removal of aminoterminal propeptides from gamma-carboxylated proteins
R-HSA-76005: Response to elevated platelet cytosolic Ca2+
R-HSA-159763: Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus

Summary
Symbol	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PROS1 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

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Literatures describing the relation between PROS1 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
29708510	Melanoma	Inhibit immunity	Tumor-secreted Pros1 inhibits macrophage M1 polarization to reduce antitumor immune response. We demonstrate that tumor-secreted protein S (Pros1), a Mer/Tyro3 ligand, decreased macrophage M1 cytokine expression in vitro and in vivo. Mice bearing Pros1-deficient tumors showed increased innate and adaptive immune infiltration, as well as increased median survival.

Summary
Symbol	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
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 PROS1 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	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
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 PROS1 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	0.098	0.824
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.517	0.834
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.561	0.727
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.284	0.485
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.336	0.821
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.218	0.907
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.047	0.936
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0.245	0.896
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	-0.262	0.905
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.056	0.976
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	0.038	0.99
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.442	0.00306

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PROS1 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	7.1	0	7.1	0.452
2	25765070	Non-small cell lung cancer (NSCLC)	smoking	Anti-PD-1 (pembrolizumab)	10	3	10	0	10	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	9.6	-2.2	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	7.4	11.9	-4.5	0.713
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	4.8	5.9	-1.1	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	9.1	-9.1	0.458
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	2.6	7.4	-4.8	0.565
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	0	15.4	-15.4	0.131
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	0	6.2	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	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PROS1. 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	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PROS1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PROS1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PROS1. 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	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PROS1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PROS1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PROS1
Name	protein S (alpha)
Aliases	PROS; PS21; PS22; PS23; PS24; PS25; THPH5; THPH6; protein Sa; vitamin K-dependent plasma protein S; Vitamin ......
Chromosomal Location	3q11.1
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PROS1 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PROS1.

ID	Name	Drug Type	Targets	#Targets
DB00055	Drotrecogin alfa	Biotech	CP, F2, F5, F8, GGCX, PF4, PROCR, PROS1, SERPINA5, SERPINB6, SERPI ......	12
DB00170	Menadione	Small Molecule	BGLAP, F10, F2, F7, F9, GGCX, NQO1, NQO2, PROC, PROS1, PROZ, VKORC ......	13
DB00464	Sodium Tetradecyl Sulfate	Small Molecule	PROC, PROS1	2
DB09332	Kappadione	Small Molecule	F10, F2, F7, F9, GGCX, PROC, PROS1	7

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