TISIDB

Summary
Symbol	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
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 Golgi apparatus Endoplasmic reticulum
Domain	PF00008 EGF-like domain PF00594 Vitamin K-dependent carboxylation/gamma-carboxyglutamic (GLA) domain PF00089 Trypsin
Function	Protein C is a vitamin K-dependent serine protease that regulates blood coagulation by inactivating factors Va and VIIIa in the presence of calcium ions and phospholipids (PubMed:25618265). Exerts a protective effect on the endothelial cell barrier function (PubMed:25651845).

> Gene Ontology [ TOP ]
Biological Process	GO:0001885 endothelial cell development GO:0002064 epithelial cell development GO:0003158 endothelium development GO:0006465 signal peptide processing GO:0006888 ER to Golgi vesicle-mediated transport GO:0007596 blood coagulation GO:0007599 hemostasis GO:0010720 positive regulation of cell development 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:0030856 regulation of epithelial cell differentiation GO:0030858 positive regulation of epithelial cell differentiation GO:0031348 negative regulation of defense response GO:0032102 negative regulation of response to external stimulus GO:0045446 endothelial cell differentiation GO:0045601 regulation of endothelial cell differentiation GO:0045603 positive regulation of endothelial cell differentiation GO:0048193 Golgi vesicle transport GO:0050727 regulation of inflammatory response GO:0050728 negative 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:0051604 protein maturation GO:0061028 establishment of endothelial barrier GO:0061041 regulation of wound healing GO:0061045 negative regulation of wound healing GO:1900046 regulation of hemostasis GO:1900047 negative regulation of hemostasis GO:1901550 regulation of endothelial cell development GO:1901552 positive regulation of endothelial cell development GO:1903034 regulation of response to wounding GO:1903035 negative regulation of response to wounding GO:1903140 regulation of establishment of endothelial barrier GO:1903142 positive regulation of establishment of endothelial barrier
Molecular Function	GO:0004175 endopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0008236 serine-type peptidase activity GO:0017171 serine hydrolase activity
Cellular Component	GO:0005788 endoplasmic reticulum lumen GO:0005796 Golgi lumen

> 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-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-140837: Intrinsic Pathway of Fibrin Clot Formation R-HSA-392499: Metabolism of proteins R-HSA-597592: Post-translational protein modification R-HSA-159782: Removal of aminoterminal propeptides from gamma-carboxylated proteins 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-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-140837: Intrinsic Pathway of Fibrin Clot Formation
R-HSA-392499: Metabolism of proteins
R-HSA-597592: Post-translational protein modification
R-HSA-159782: Removal of aminoterminal propeptides from gamma-carboxylated proteins
R-HSA-159763: Transport of gamma-carboxylated protein precursors from the endoplasmic reticulum to the Golgi apparatus

Summary
Symbol	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PROC 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	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
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 PROC 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	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
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 PROC 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	0.583	0.243
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.06	0.942
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	1.06	0.135
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.314	0.458
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.259	0.82
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.39	0.799
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	1.222	0.0984
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	1.304	0.323
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.811	0.489
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.018	0.992
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	1.566	0.471
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.696	0.00875

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PROC 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	3.7	1.4	2.3	0.469
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	1.7	2	0.532
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	9.5	0	9.5	0.492
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	7.7	0	7.7	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	2.6	7.4	-4.8	0.565
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	7.7	-3.2	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	7.7	-7.7	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	8.3	-8.3	1

Summary
Symbol	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PROC. 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	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PROC. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PROC. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PROC. 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	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PROC expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PROC and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PROC
Name	protein C (inactivator of coagulation factors Va and VIIIa)
Aliases	prepro-protein C; THPH3; THPH4; anticoagulant protein C; autoprothrombin IIA; blood coagulation factor XIV; ......
Chromosomal Location	2q13-q14
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PROC collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PROC.

ID	Name	Drug Type	Targets	#Targets
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
DB09131	Cupric Chloride	Small Molecule	CSTB, PROC	2
DB09332	Kappadione	Small Molecule	F10, F2, F7, F9, GGCX, PROC, PROS1	7
DB13149	Protein S human	Biotech	F10, F5, PROC	3

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