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FLASH GENE

Symbol

KLK8

contributors: mct - updated : 16-04-2020

HGNC name	kallikrein-related peptidase 8
HGNC id	6369

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_007196 6 - 1013 NP_009127 - 260 brain 2007 17487847 neuropsin type 1 NM_144505 6 initiation site 1148 NP_653088 - 305 hippocampus, fetal brain, placenta; abundantly expressed in embryonic stem cells and in embryo brain samples, suggesting a potential role in embryogenesis 2007 17487847 neuropsin type 2 insert of 45 AA at the N terminus of leader sequence important role in the normal function of the cognition only in the humans NM_144506 4 - 590 NP_653089 - 119 - 2007 17487847 NM_144507 3 - 456 NP_653090 - 32 - 2007 17487847 NM_001281431 5 - 863 NP_001268360 - 139 - 2007 17487847

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 Cardiovascular heart         Homo sapiens Digestive esophagus         Homo sapiens   salivary gland         Homo sapiens Lymphoid/Immune tonsils         Homo sapiens Nervous brain diencephalon amygdala   highly Homo sapiens   brain limbic system hippocampus     Homo sapiens Reproductive female system breast     highly Homo sapiens Skin/Tegument skin appendages skin gland sweat gland   highly Homo sapiens Urinary kidney         Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining epidermis stratum corneum   Homo sapiens Muscular striatum cardiac myocardium   Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Skin/Tegument keratinocyte Homo sapiens

cell lineage
cell lines
fluid/secretion	breast milk, amniotic fluid, seminal fluid and serum

at STAGE

physiological period

fetal, pregnancy

Text	placenta, brain

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

Homologene

FAMILY	peptidase S1 family
	kallikrein subfamily

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytosolic,granule

basic FUNCTION	having a trypsin-like activity
	involved in the pathogenesis of inflammatory skin diseases
	involved in desquamation cascade of the skin
	involved in proliferation of keratinocytes and desquamation possibly through other kallikreins
	may play a crucial role in promoting cancer-cell invasion in bladder tumor
	might be involved in desquamation through the degradation of adhesive molecules that connect layers of the epidermis and in tissue development and rearrangement
	keratinocyte-specific protease, having an active role for in upper epidermis
	active serine protease in stratum corneum and sweat, with potential regulators and targets that augment its involvement in a skin barrier proteolytic cascade
	key regulator of the FKBP5 gene and protein expression
	is involved in synaptic tagging and cross-tagging during long-term potentiation (LTP) at apical dendritic inputs via ITGB1 and calcium/calmodulin-dependent protein kinase II signalling
	is believed to be involved in the maintenance of skin homeostasis and pathogenesis of inflammatory skin diseases
	may promote cardiomyocyte hypertrophy through EGF signaling- and PARs-dependent but a kinin receptor-independent pathway
	sex-specific difference in Alzheimer disease (AD) may be meditated by estrogen-induced KLK8 overproduction long before AD pathology emerges
	emerges as a regulator of regulators in memory

CELLULAR PROCESS

protein, degradation

PHYSIOLOGICAL PROCESS

development

text	both types necessary for brain development type 2, also important in brain plasticity

PATHWAY

metabolism

signaling

a component

INTERACTION

DNA

RNA

small molecule

protein	cleaves the extracellular portion of EPHB2 and facilitates the dynamic interaction of EPHB2 with the NR1 subunit of the NMDA receptor
	KLK8 is likely involved in the proliferation and migration of keratinocytes through the upregulation and activation of KLK6 in the early stages of wound healing, and possibly in keratinocyte differentiation associated with the upregulation and activation of F2RL1 in the late stages of wound healing
	KLK5 and KLK8 remove the N-terminal eight AAs from the proform thereby converting CCL14 to its active state

cell & other

REGULATION

induced by

estradiol but not testosterone (estradiol induces KLK8 synthesis in neuronal and microglial cells)

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function constitutional     --over   in skin diseases, such as psoriasis vulgaris, lichen planus, and atopic dermatitis tumoral     --over   confers a favorable clinical outcome in non-small cell lung cancer by suppressing tumor cell invasiveness tumoral     --over   in oral squamous cell carcinoma and may be implicated in malignant progression tumoral     --over   in most salivary gland tumors constitutional     --over   in skin inflammation increased expression in the stratum spinosum constitutional     --over   higher levels of KLK8 in female brain may increase the risk for Alzheimer disease tumoral     --over   was correlated with the progression of Colorectal cancer

Susceptibility

Variant & Polymorphism

Candidate gene
Marker	KLK8-T4 alternative splice variant, alone or in combination, may be a new independent marker of unfavorable prognosis in lung cancer
	can serve as a novel independent biomarker of unfavorable prognosis for Breast cancer patients
	potential independent prognostic indicator for Colorectal cancer
	potential biomarker in colon adenocarcinoma
	potential clinical utility of blood and CSF KLK8 as a biomarker for incipient Alzheimer disease
Therapy target
	System Type Disorder Pubmed neurology neurodegenerative alzheimer therapeutic potential of KLK8 inhibition by counteracting plasticity deficits in AD-affected brain

ANIMAL & CELL MODELS

on stress, neuropsin-deficient mice do not show EphB2 cleavage and its dissociation from NR1 resulting in a static EphB2–NR1 interaction, attenuated induction of the Fkbp5 gene and low anxiety