TISIDB

Summary
Symbol	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
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	PF00089 Trypsin
Function	Hydrolyzes semenogelin-1 thus leading to the liquefaction of the seminal coagulum.

> Gene Ontology [ TOP ]
Biological Process	GO:0001525 angiogenesis GO:0002440 production of molecular mediator of immune response GO:0002775 antimicrobial peptide production GO:0002778 antibacterial peptide production GO:0006959 humoral immune response GO:0016525 negative regulation of angiogenesis GO:0019730 antimicrobial humoral response GO:0019731 antibacterial humoral response GO:0042742 defense response to bacterium GO:0045765 regulation of angiogenesis GO:0048514 blood vessel morphogenesis GO:0098542 defense response to other organism GO:1901342 regulation of vasculature development GO:1901343 negative regulation of vasculature development GO:2000181 negative regulation of blood vessel morphogenesis
Molecular Function	GO:0004175 endopeptidase activity GO:0004252 serine-type endopeptidase activity GO:0008236 serine-type peptidase activity GO:0016810 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds GO:0016811 hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in linear amides GO:0017171 serine hydrolase activity
Cellular Component	-

> KEGG and Reactome Pathway [ TOP ]
KEGG	-
Reactome	R-HSA-5625886: Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3 R-HSA-392499: Metabolism of proteins R-HSA-195258: RHO GTPase Effectors R-HSA-5625740: RHO GTPases activate PKNs R-HSA-381426: Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs) R-HSA-162582: Signal Transduction R-HSA-194315: Signaling by Rho GTPases

> KEGG and Reactome Pathway

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KEGG

Reactome

R-HSA-5625886: Activated PKN1 stimulates transcription of AR (androgen receptor) regulated genes KLK2 and KLK3
R-HSA-392499: Metabolism of proteins
R-HSA-195258: RHO GTPase Effectors
R-HSA-5625740: RHO GTPases activate PKNs
R-HSA-381426: Regulation of Insulin-like Growth Factor (IGF) transport and uptake by Insulin-like Growth Factor Binding Proteins (IGFBPs)
R-HSA-162582: Signal Transduction
R-HSA-194315: Signaling by Rho GTPases

Summary
Symbol	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KLK3 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 KLK3 and anti-tumor immunity in human cancer.

PMID	Cancer type	Relation to immunity	Evidence sentences
20100959	Intermediate Atypical Prostate Carcinoma	Promote immunity	Overall survival analysis of a phase II randomized controlled trial of a Poxviral-based PSA-targeted immunotherapy in metastatic castration-resistant prostate cancer. Therapeutic prostate-specific antigen (PSA) -targeted poxviral vaccines for prostate cancer have been well tolerated.

Summary
Symbol	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
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 KLK3 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	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
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 KLK3 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	-1.695	0.0581
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-2.122	0.0993
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	-1.173	0.43
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	1
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	0.128	0.595

> Mutation difference between responders and non-responders

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Points in the above scatter plot represent the mutation difference of KLK3 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	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	2.6	0	2.6	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	4.5	0	4.5	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	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KLK3. 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	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KLK3. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KLK3. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KLK3. 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	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KLK3 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KLK3 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KLK3
Name	kallikrein-related peptidase 3
Aliases	kallikrein 3, (prostate specific antigen); KLK2A1; P-30 antigen; gamma-seminoprotein; kallikrein-3; prostate ......
Chromosomal Location	19q13.41
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KLK3 collected from DrugBank database.

> Drugs from DrugBank database

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Details on drugs targeting KLK3.

ID	Name	Drug Type	Targets	#Targets
DB00834	Mifepristone	Small Molecule	KLK3, NR1I2, NR3C1, PGR	4
DB04839	Cyproterone acetate	Small Molecule	AR, KLK3	2

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