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FLASH GENE

Symbol

KLK6

contributors: mct/pgu - updated : 16-04-2020

HGNC name	kallikrein-related peptidase 6
HGNC id	6367

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Location	19q13.41      Physical location : 51.461.887 - 51.472.929
Synonym name	neurosin, zyme, protease serine 9
	kallikrein 6 (neurosin, zyme)
	protease, serine, 18
	protease M
Synonym symbol(s)	PRSS9, KLK9, ZYME, Bssp, Klk7, MGC9355, NEUROSIN, PRSS18, SP59
EC.number	3.4.21.-

DNA

TYPE	functioning gene
SPECIAL FEATURE	component of a cluster
text	tightly clustered multigene family on chromosome 19q13.4
STRUCTURE	10.97 kb     7 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

status

confirmed

Map	cen - D19S412 - D19S596 - D19S907 - KLK1 - KLK3 - KLK2 - KLK4 - KLK5 - KLK6 - KLK12 - KLK13 - KLK14 - KLK6 - KLK7 - KLK8 - KLK9 - KLK10 - KLK11 - D19S571- D19S927 - D19S418 - qter

regionally located

clustered with kallikrein gene family

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001012964 6 - 1527 NP_001012982 - 244 - 2011 22047144 multiple transcriptional start sites exist for variant B NM_001012965 5 - 1495 NP_001012983 - 137 - 2011 22047144 NM_002774 7 - 1527 NP_002765 - 244 - 2011 22047144 has a distinct C-terminus when it is compared to isoform A NM_001319949 5 - 1567 NP_001306878 - 137 - 2011 22047144 NM_001319948 6 - 1272 NP_001306877 - 137 - 2011 22047144

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 Nervous brain hindbrain cerebellum     Homo sapiens   spinal cord         Reproductive female system breast mammary gland     Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous oligodendrocyte Homo sapiens

cell lineage
cell lines	primary mammary carcinoma lines, prostate, ovarian
fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	trypsin domain
	a peptidase S1 domain

HOMOLOGY

interspecies

homolog to murine Klk29

Homologene

FAMILY	peptidase S1 family
	Kallikrein subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,organelle,mitochondria
	intracellular,cytoplasm,organelle,endoplasmic reticulum
	intracellular,cytoplasm,cytosolic,microsome
	intracellular,nucleus,nucleolus

basic FUNCTION	might play a role in tissue remodeling and/or tumor invasion and metastasis
	involved in desquamation cascade of the skin
	as other KLKs may participate in desquamation through cleavage of desmoglein 1 and regulation by LEKTI
	may play a crucial role in promoting cancer-cell invasion in bladder tumor
	trypsin-like serine peptidase, having oncogenic role of KLK6 in colorectal cancer
	exhibit trypsin-like specificity, with a strong preference for Arg at the P1 position of substrates
	oncogenic role of KLK6 in colorectal cancer
	regulatory activities for KLK6 in the development and progression of central nervous system (CNS) inflammation and demyelination
	is positioned to serve as a molecular trigger of select physiological processes involved in the development of astrogliosis and this is likely to occur at least in part by activation of the G-protein-coupled receptor, F2R
	plays a functional role in oligodendrocyte development and the expression of myelin proteins
	KLK6 can influence astrocyte plasticity through receptor-dependent mechanisms
	KLK6 is an important molecular link in the development of skin inflammation and in tumor-promoting inflammatory processes
	important role for KLK6 in human gastric cancer progression
	KLK6 is implicated in skin inflammation
	critical function of the KLK6 enzyme in colon cancer progression and its contribution to the signaling network in colon cancer

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

KLK6-signaling axis in CNS neurons that is mediated by F2R and F2RL1 and is positioned to contribute to neurodegeneration

a component

INTERACTION

DNA

RNA

small molecule

protein	activity of KLK6 on peptides containing clusters of basic amino acids
	kinin B1 receptor agonist induces secretion of KLK1, KLK6, KLK10, KLK13 and KLK14 into the medium nof neutrophils
	KLK6-F2R-mediated inflammation in the skin alone is sufficient to drive inflammatory joint disease

cell & other

REGULATION

Other

regulated by steroid hormones

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in cerebrospinal fluid and plasma in Alzheimer diseases tumoral     --over   in gastric cancer tumoral     --low   in breast and ovarian cancer, metastatic tumoral     --over   significantly increased in invasive cancers relative to normal ovaries tumoral     --over   in papillary renal cell carcinoma tumoral     --over   of KLK6 and KLK13 in ovarian cancer compared to normal ovarian tissues constitutional     --over   in multiple inflammatory and autoimmune conditions constitutional     --over   in demyelinating disease (pMID: 28254587) constitutional     --low   in Aneurysmal subarachnoid hemorrhage (aSAH), with the lowest levels in patients who died

Susceptibility

to aggressive PCa (prostate cancer)

Variant & Polymorphism SNP	SNP in the KLK 6 region strongly associated with aggressive PCa

Candidate gene	potential biomarkers that can significantly predict prognosis in terms of recurrence-free survival and overall survival in ovarian cancer
	high concentration of KLK6 is an indicator of tumor proliferation and an independent predictive factor in non-small cell lung cancer
Marker	potential biomarkers in ovarian cancer
	potential ability of KLK6 as a prognostic marker for gastric cancer
	elevations in glioblastoma KLK6 protein have utility as prognostic markers of patient survival
	KLK6 and KLK10 may be useful markers in gastroesophageal junction tumors
	detection of low KLK6 expression in primary tumors represents a promising tool to stratify head and neck squamous cell carcinoma (HNSCC) patients with high risk for treatment failure
	potential biomarker in colon adenocarcinoma
	KLK6 is a potential biomarker of Tau pathology in Alzheimer disease
Therapy target
	System Type Disorder Pubmed cancer reproductive ovary potential therapeutic targets for treatment of ovarian cancer (PMID: 19707197) dermatology skin   potential target for the treatment of skin disorders in which KLK activity is elevated cancer reproductive ovary may be therapeutic targets for treatment of ovarian cancer cancer digestive oesophagus potential therapeutic targets in gastroesophageal junction tumors dermatology skin   may represent a novel druggable target for Netherton syndrome and other inflammatory conditions e.g. atopic dermatitis cancer brain   could be used as target for therapeutic intervention in intracranial tumors

ANIMAL & CELL MODELS