TISIDB

Summary
Symbol	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
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	PF00024 PAN domain PF00089 Trypsin
Function	The enzyme cleaves Lys-Arg and Arg-Ser bonds. It activates, in a reciprocal reaction, factor XII after its binding to a negatively charged surface. It also releases bradykinin from HMW kininogen and may also play a role in the renin-angiotensin system by converting prorenin into renin.

> Gene Ontology [ TOP ]
Biological Process	GO:0002254 kinin cascade GO:0002353 plasma kallikrein-kinin cascade GO:0002526 acute inflammatory response GO:0002541 activation of plasma proteins involved in acute inflammatory response GO:0002542 Factor XII activation GO:0002673 regulation of acute inflammatory response GO:0002675 positive regulation of acute inflammatory response GO:0007596 blood coagulation GO:0007597 blood coagulation, intrinsic pathway GO:0007599 hemostasis GO:0010954 positive regulation of protein processing GO:0016485 protein processing GO:0022617 extracellular matrix disassembly GO:0030193 regulation of blood coagulation GO:0030195 negative regulation of blood coagulation GO:0030198 extracellular matrix organization GO:0031349 positive regulation of defense response GO:0031638 zymogen activation GO:0031639 plasminogen activation GO:0032102 negative regulation of response to external stimulus GO:0032103 positive regulation of response to external stimulus GO:0042730 fibrinolysis GO:0043062 extracellular structure organization GO:0045862 positive regulation of proteolysis GO:0050727 regulation of inflammatory response GO:0050729 positive 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:0051604 protein maturation GO:0051917 regulation of fibrinolysis GO:0051919 positive regulation of fibrinolysis 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:0072378 blood coagulation, fibrin clot formation 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:1903319 positive regulation of protein maturation
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	hsa04610 Complement and coagulation cascades
Reactome	R-HSA-1592389: Activation of Matrix Metalloproteinases R-HSA-1474228: Degradation of the extracellular matrix R-HSA-1474244: Extracellular matrix organization R-HSA-140877: Formation of Fibrin Clot (Clotting Cascade) R-HSA-109582: Hemostasis R-HSA-140837: Intrinsic Pathway of Fibrin Clot Formation

Summary
Symbol	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Literatures that report relations between KLKB1 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	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
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

[ TOP ]

Statistical results of KLKB1 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	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
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

[ TOP ]

Points in the above scatter plot represent the expression difference of KLKB1 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	0.432	0.359
2	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	6	5	-0.336	0.664
3	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	7	0.997	0.124
4	28552987	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	9	16	-0.593	0.262
5	28552987	Urothelial cancer	smoking	Anti-PD-L1 (atezolizumab)	5	9	-1.383	0.182
6	28552987	Urothelial cancer	non-smoking	Anti-PD-L1 (atezolizumab)	4	7	0.389	0.71
7	29033130	Melanoma	all	Anti-PD-1 (nivolumab)	26	23	0.368	0.623
8	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	15	11	-0.204	0.851
9	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	11	12	0.739	0.504
10	29301960	Clear cell renal cell carcinoma (ccRCC)	all	Anti-PD-1 (nivolumab)	4	8	-0.041	0.975
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	1.008	0.543
13	29443960	Urothelial cancer	all	Anti-PD-L1 (atezolizumab)	68	230	-0.193	0.356

> Mutation difference between responders and non-responders

[ TOP ]

Points in the above scatter plot represent the mutation difference of KLKB1 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	14.8	2.7	12.1	0.0439
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	14.8	3.4	11.4	0.0746
7	26997480	Melanoma	all	Anti-PD-1 (pembrolizumab and nivolumab)	21	17	14.3	11.8	2.5	1
8	26997480	Melanoma	MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	8	6	25	0	25	0.473
9	26997480	Melanoma	non-MAPKi	Anti-PD-1 (pembrolizumab and nivolumab)	13	11	7.7	18.2	-10.5	0.576
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	10.5	7.4	3.1	1
14	29033130	Melanoma	NIV3-PROG	Anti-PD-1 (nivolumab)	22	13	13.6	7.7	5.9	1
15	29033130	Melanoma	NIV3-NAIVE	Anti-PD-1 (nivolumab)	16	14	6.2	7.1	-0.9	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	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between abundance of tumor-infiltrating lymphocytes (TILs) and expression, copy number, methylation, or mutation of KLKB1. 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	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between three kinds of immunomodulators and expression, copy number, methylation, or mutation of KLKB1. These immunomo-dulators were collected from Charoentong's study. In this tab, users can examine which immunomodulators might be regulated by KLKB1. > Immunoinhibitor > Immunostimulator > MHC molecule

> Immunoinhibitor [ TOP ]

> Immunostimulator [ TOP ]

> MHC molecule [ TOP ]

Summary
Symbol	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Relations between chemokines (or receptors) and expression, copy number, methylation, or mutation of KLKB1. 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	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Distribution of KLKB1 expression across immune and molecular subtypes. > Immune subtype > Molecular subtype

> Immune subtype [ TOP ]

> Molecular subtype [ TOP ]

Summary
Symbol	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Associations between KLKB1 and clinical features. > Overall survival analysis > Cancer stage > Tumor grade

> Overall survival [ TOP ]

> Stage [ TOP ]

> Grade [ TOP ]

Summary
Symbol	KLKB1
Name	kallikrein B, plasma (Fletcher factor) 1
Aliases	PKKD; Fletcher factor; kininogenin; plasma kallikrein heavy chain; plasma kallikrein light chain; plasma pre ......
Chromosomal Location	4q35
External Links	HGNC, NCBI, Ensembl, Uniprot, GeneCards
Content	Drugs targeting KLKB1 collected from DrugBank database.

> Drugs from DrugBank database

[ TOP ]

Details on drugs targeting KLKB1.

ID	Name	Drug Type	Targets	#Targets
DB01593	Zinc	Small Molecule	A1BG, A2M, AGT, AHSG, ALDOA, APCS, APLP1, APLP2, APOA1, APOA2, APO ......	119
DB05311	Ecallantide	Biotech	KLKB1	1
DB06404	Human C1-esterase inhibitor	Biotech	C1R, C1S, F11, F12, F2, KLKB1, PLAT	7
DB09228	Conestat alfa	Biotech	C1R, C1S, F11, F12, F2, KLKB1, PLAT	7
DB12831	Gabexate	Small Molecule	F2, KLKB1, PLG	3

Browse KLKB1