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FLASH GENE

Symbol

KLK3

contributors: mct - updated : 16-04-2020

HGNC name	kallikrein-related peptidase 3
HGNC id	6364

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	restricted

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 Reproductive female system breast mammary gland       male system prostate     highly

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Blood / hematopoietic bone marrow       Connective bone

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a peptidase S1 domain

HOMOLOGY

intraspecies

homolog to KLK2

Homologene

FAMILY	peptidase s1 family
	kallikrein subfamily

CATEGORY

enzyme , antigen

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic,granule
	intracellular,nucleus

basic FUNCTION	serine protease hydrolyzing the high molecular mass seminal vesicle protein
	androgen-mediated expression by binding of the GAGATA binding factor and AR to GAGATA and AREs, respectively, of enhancer core
	serine protease functioning in the liquefaction of seminal coagulum
	direct transcriptional target
	inhibit angiogenesis
	activates TRPM8 current by inducing the accumulation of functional channels in the plasma membrane and reduces cell migration
	by increasing TRPM8 activity by the bradykin/protein kinase C pathway, KLK3 is implicated in the inhibition of prostate cell carcinoma motility
	exerts chymotrypsin-like proteolytic activity
	KLK2 is a key serine protease in semen liquefaction and prostate cancer together with KLK3/prostate-specific antigen
	chief executor of the fragmentation of semenogelins, dissolution of semen coagulum, thereby releasing sperm for active motility
	KLK3, KLK4, KLK11, and KLK2, belong to the prostatic group of the KLKs, whose major physiological function is semen liquefaction during the fertilization process
	significant association between the polycystic ovary syndrome and KLK3

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component

part of KLK proteolytic cascade with KLK11 and KLK1, activated by KLK14

INTERACTION

DNA

RNA

small molecule

protein	hydrolyzes semenogelin-1 (SEMG1) thus leading to the liquefaction of the seminal coagulum
	physiological and natural TRPM8 agonist in the prostate
	degrades semenogelins I and II much more efficiently than other previously identified protein substrates, e.g., fibronectin, galectin3 and IGFBP3
	KLK2 most likely activates and complements chymotryptic KLK3 (prostate-specific antigen) in cleaving seminal clotting proteins, resulting in sperm liquefaction
	overexpression of CRISP3 in prostate tumor may maintain higher KLK3 expression and lower ANXA1 expression
	crucial role of ESR1 for the mammalian female in regulating semen coagulation and liquefaction with KLK3
	KLK3 activated VEGFC specifically and efficiently through cleavage at a novel N-terminal site

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   lower in malignant than in normal prostatic epithelium and it is further reduced in poorly differentiated tumors constitutional germinal mutation     loss of function could lead to false-negative KLK3 findings used for screening, diagnosis, or monitoring of Prostate carcinoma

Susceptibility

to prostate cancer (minor role) (PCa) to infertility

Variant & Polymorphism SNP , other	two A-alleles have increased risk for prostate cancer onset under the age of 67
	SNP increasing the risk of prostate cancer
	rs17632542, introduces a non-synonymous amino acid change in the KLK3 protein with a predicted benign or neutral functional impact, and could influence the diagnosis of nonaggressive prostate cancer
	five SNPs, rs266881, rs174776, rs266875, rs35192866 and rs1810020 correlated with an increased risk of infertility

Candidate gene	early marker for the presence of prostate cancer, prostate-specific antigen, being the current serum biomarker for prostate cancer
	biomarker potential for chromophobe renal cell carcinoma
	polymorphism T>C of rs1058205 was associated with decreased risk of PCa
Marker	only independent predictor of extensive lymph node invasion (LNI) in prostate cancer and could be an important preoperative factor for stratifying high-risk patients
	OPSAD (the ratio of KLK3 to the outer gland volume of prostate) may be used as a new indicator for the diagnosis and prognosis of prostate cancer, and it can reduce the use of unnecessary puncture biopsy of the prostate
	KLK3 is a marker of Testosterone concentrations and it may represent a new tool in confirming hypogonadism
Therapy target
	System Type Disorder Pubmed cancer reproductive prostate potential target for tumor imaging and treatment in prostate cancer cells

ANIMAL & CELL MODELS