TISIDB

Summary
Symbol	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
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	Cytoplasmic granule Secreted Cell membrane Peripheral membrane protein Extracellular side Membrane raft Peripheral membrane protein Extracellular side Note=Localizes predominantly to azurophil granules (primary secretory granules) in neutrophils (PubMed:2033050, PubMed:3198760, PubMed:7897245, PubMed:18462208). Secreted upon neutrophil stimulation by TNF-alpha, lipopolysaccharide (LPS), fMLP and CXCL8/IL8 or during neutrophil transmigration (PubMed:22266279, PubMed:28240246). Following secretion tethered to the cell membrane by CD177 (PubMed:18462208, PubMed:22266279).
Domain	PF00089 Trypsin
Function	Serine protease that degrades elastin, fibronectin, laminin, vitronectin, and collagen types I, III, and IV (in vitro) (PubMed:3198760, PubMed:2033050, PubMed:28240246). By cleaving and activating receptor F2RL1/PAR-2, enhances endothelial cell barrier function and thus vascular integrity during neutrophil transendothelial migration (PubMed:23202369). May play a role in neutrophil transendothelial migration, probably when associated with CD177 (PubMed:22266279).

> Gene Ontology [ TOP ]
Biological Process	GO:0002521 leukocyte differentiation GO:0002573 myeloid leukocyte differentiation GO:0006909 phagocytosis GO:0007596 blood coagulation GO:0007599 hemostasis GO:0030099 myeloid cell differentiation GO:0030100 regulation of endocytosis GO:0030574 collagen catabolic process GO:0032963 collagen metabolic process GO:0044236 multicellular organism metabolic process GO:0044243 multicellular organism catabolic process GO:0044259 multicellular organismal macromolecule metabolic process GO:0045806 negative regulation of endocytosis GO:0050764 regulation of phagocytosis GO:0050765 negative regulation of phagocytosis GO:0050817 coagulation GO:0050878 regulation of body fluid levels GO:0051051 negative regulation of transport GO:0060627 regulation of vesicle-mediated transport GO:0097028 dendritic cell differentiation GO:0097029 mature conventional dendritic cell differentiation
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	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-6803157: Antimicrobial peptides R-HSA-140875: Common Pathway of Fibrin Clot Formation R-HSA-1280215: Cytokine Signaling in Immune system R-HSA-140877: Formation of Fibrin Clot (Clotting Cascade) R-HSA-109582: Hemostasis R-HSA-168256: Immune System R-HSA-168249: Innate Immune System R-HSA-6798695: Neutrophil degranulation R-HSA-449147: Signaling by Interleukins

Summary
Symbol	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between PRTN3 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	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
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 PRTN3 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	Second most enriched score: 0.5	Sensitive to T cell-mediated killing
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	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
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 PRTN3 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	1
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	0	1
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0	1
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	0.632	0.519
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	0.334	0.836
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	1.012	0.581
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0	1
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	0	1
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0	1
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	0.228	0.613
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	1
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.306	0.0655

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of PRTN3 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	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	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	11.1	0	11.1	0.36
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	25	0	25	0.364
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	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of PRTN3. 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	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of PRTN3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by PRTN3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of PRTN3. 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	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of PRTN3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between PRTN3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	PRTN3
Name	proteinase 3
Aliases	PR-3; ACPA; C-ANCA; AGP7; MBT; myeloblastin; serine proteinase, neutrophil; Wegener granulomatosis autoantig ......
Chromosomal Location	19p13.3
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting PRTN3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting PRTN3.

ID	Name	Drug Type	Targets	#Targets
DB05161	Elafin	Small Molecule	ELANE, PRTN3	2

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