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FLASH GENE

Symbol

KLK14

contributors: mct - updated : 22-04-2020

HGNC name	kallikrein-related peptidase 14
HGNC id	6362

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Nervous brain hindbrain cerebellum     Homo sapiens   spinal cord         Homo sapiens Reproductive female system breast     highly Homo sapiens   male system prostate     highly Homo sapiens Respiratory lung         Homo sapiens Urinary kidney tubule     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow     highly Nervous central       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Respiratory epithelial cell Homo sapiens

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

fetal

Text	liver, spleen

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	trypsin-like substrate specificity
	signal sequence and catalytic domains

HOMOLOGY

Homologene

FAMILY	kallikrein family
	peptidase S1 family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic,granule
text	localized in the cytoplasm of epithelial cells of normal bronchus

basic FUNCTION	involved in carcinogenesis
	may participate in desquamation through cleavage of desmoglein 1 and regulation by LEKTI
	may be a major contributor to trypsin-like proteolytic activity in stratum corneum, and key trypsin-like proteases involved in skin desquamation
	playing a potential role in seminal plasma
	exerting a significant and dose-dependent effect in the process of semen liquefaction
	might function as a key factor in the proteolytic cascade in seminal plasma, regulating major seminal KLKs, including KLK1, KLK3, and KLK11
	as other KLKs may participate in desquamation through cleavage of desmoglein 1 and regulation by LEKTI
	activating KLK proteolytic cascade, including KLK3, KLK11 and KLK1
	estrogen-sensitive kallikreins with KLK11, and KLK10, all synergistically enhanced and upregulated by androgens in breast cancer cells via a membrane bound androgen receptor
	KLK14 promotes tumourigenesis by activating proteinase-activated receptors
	is a serine protease linked to several pathologies including prostate cancer
	HPN and TMPRSS2 colocalize on the cell surface with the secreted serine proteases KLK4 and KLK14, only in membrane protrusions, suggesting that reciprocal proteolytic interactions occur in defined cellular structures that are important during cancer dissemination for cell migration, invasion and survival
	KLK5, KLK7 and KLK14 are important proteases in skin desquamation

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	cleaving semenogelins (SEMG1 and SEMG2 were able to reverse KLK14 inhibition by Zn2+, providing a novel regulatory mechanism for KLK14 activity)
	KLK14, acting via F2RL1, represents an autocrine/paracrine regulator of colon tumorigenesis
	KLK14 is a second KLK protease to be inhibited by SERPINA12
	in contrast with HPN, TMPRSS2 degrades KLK14 and TMPRSS2 cleavage is mediated by KLK14
	kinin B1 receptor agonist induces secretion of KLK1, KLK6, KLK10, KLK13 and KLK14 into the medium nof neutrophils

cell & other

REGULATION

activated by

citrate

inhibited by	by autolytic cleavage
	zinc ions

Other	regulated by the inhibitory serpins alpha1-antitrypsin, alpha2-antiplasmin, antithrombin III, alpha1-antichymotrypsin and plasminogen activator inhibitor-1
	regulated by androgens and progestins

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in testicular and ovarian cancer tumoral     --over   in invasive breast carcinomas compared to normal breast tissues, associated with higher tumour grade and size constitutional     --other   differentially expressed in asthenospermic cases tumoral     --over   during Prostate carcinoma development, and in advanced PCa, and particularly in metastasis

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	its expression could be evaluated as a putative independent diagnostic biomarker in breast tumour biopsies
	may be a promising new biomarker in salivary gland tumors
	KLK7 and KLK14 gene expression can be regarded as markers of poor prognosis for Colon cancer (CC) patients with discriminating power between CC and adenoma patients
Therapy target	therapeutic induction of the seminal proteolytic cascade can be utilized to supplement the current clinical treatment of male subfertility and conversely, targeted inhibition of key components of the cascade may have potential pharmaceutical utility as a novel topical contraceptive strategy
	potential target for the treatment of skin disorders in which KLK activity is elevated

ANIMAL & CELL MODELS