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FLASH GENE

Symbol

PRSS8

contributors: mct/npt - updated : 01-09-2016

HGNC name	protease, serine, 8
HGNC id	9491

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

EXPRESSION

Type	ubiquitous

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 Digestive esophagus       highly   intestine large intestine colon   highly   stomach       highly Reproductive male system prostate     predominantly Homo sapiens Respiratory lung       highly Homo sapiens Skin/Tegument skin       highly Homo sapiens Urinary kidney tubule convoluted tubule proximal tubule   Homo sapiens

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Epithelial barrier lining uroepithelium   highly Homo sapiens Epithelial barrier lining epidermis   highly Homo sapiens

cells

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

cell lineage
cell lines
fluid/secretion	prostasin from the seminal fluid

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

a peptidase S1 domain

mono polymer

heteromer , dimer

HOMOLOGY

intraspecies	homolog to acrosin,strongly
	homolog to plasma kallikrein
	homolog to hepsin

Homologene

FAMILY

peptidase S1 family

CATEGORY

enzyme

SUBCELLULAR LOCALIZATION	extracellular
	plasma membrane
text	membrane-bound
	secreted after cleavage of its C-terminus
	majority of prostasin is located on the apical plasma membrane albeit a minor fraction of prostasin is present on the basolateral plasma membrane

basic FUNCTION	active protease serine in its membrane bound form
	activates the epithelial sodium channel (SCNN1A) and suppresses invasion of prostate and breast cancer cells
	critical role for prostasin in regulating epithelial monolayer function
	glycosylphosphatidylinositol-anchored membrane serine protease believed to be critical for the regulation of epithelial sodium channel (SCNN1A) activity
	extracellular serine protease implicated in the modulation of fluid and electrolyte regulation via proteolysis of the epithelial sodium channel
	involved in the extracellular proteolytic modulation of the epidermal growth factor receptor (EGFR) and is an invasion suppressor
	may regulate trophoblast cell proliferation via modulating the EGFR-MAPK signaling pathway
	requirement of PRSS8 for conversion of the ST14 zymogen to active ST14, whereas PRSS8 zymogen activation was ST14-independent
	membrane-anchored serine proteases, PRSS8 and ST14, constitute a single proteolytic signaling cascade that is active at multiple stages of development
	is required for the activation of ST14 during development and placental differentiation
	PRSS8-ST14 cell surface protease cascade activity must be suppressed by SPINT1 and SPINT2 to enable early embryonic ectoderm formation, placental morphogenesis, and neural tube closure
	crucial role in placental development and function
	serves as a critical co-factor for matriptase activation
	potential regulator of epithelial sodium channel (ENaC) function
	is part of a cell surface proteolytic cascade that is essential for epithelial barrier formation and homeostasis
	essential functions of prostasin are executed by a non-enzymatic activity of this unique membrane-anchored serine protease

CELLULAR PROCESS

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

ST14/PRSS8 proteolytic cascade is essential for epidermal tight junction formation and terminal epidermal differentiation

a component

heterodimer of two chains, light and heavy, held by a disulfide bond

INTERACTION

DNA

RNA

small molecule

protein	interacting with SPINT1 (HAI-1B, potential physiological regulator of prostasin function)
	cell-specific GPLD1- or peptidase-dependent pathways for PRSS8 secretion may control PRSS8 functions in a tissue-specific manner
	displays a near-ubiquitous co-localization with its candidate activator matriptase (ST14) in a variety of normal epithelial tissues
	ST14 activates PRSS8 by cleaving in the N-terminal pro-peptide region of PRSS8, presumably at the Arg residue of position 44 (R44) of the full-length human PRSS8
	HPN activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor
	membrane-bound serine protease involved in the regulation of several different effectors, such as the epithelial sodium channel SCNN1A, the protease-activated receptor PAR2, the tight junction proteins, and the profilaggrin polypeptide
	PRSS8 activity eliminates SPINT1 and SPINT2 deficiency-associated developmental defects by preventing ST14 activation
	can proteolytically activate ST14 and is critical for the generation of active ST14 during placental development
	SPINT1 is critically required for the cell surface localization of ST14 in trophoblasts, and, in the absence of SPINT1, physiological activation of PRSS8 and other protease(s) initiated by cell surface matriptase may be impaired
	is a regulator of SCNN1A in colon
	inhibitory interaction between PRSS8 and nexin-1, opening the search for specific PRSS8 antagonists that are independent of its catalytic activity
	MSMB is a key upstream factor in mediating PRSS8 signaling that regulates PRSS8 expression and action in ovarian cancer cells

cell & other

REGULATION

Other

regulated by dihydrotestosterone in prostate cells via SREBF1 stimulation and SNAI2 repression of prostasin promoter

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --low   in hormone-refractory prostate cancers tumoral     --low   in bladder transitional cell carcinomas is associated with epithelial-mesenchymal transition (EMT), and may have functional implications in tumor invasion and resistance to chemotherapy

Susceptibility

Variant & Polymorphism

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Prss8(-/-) mice lack barrier formation and display fatal postnatal dehydration
	liver-specific PRSS8 knockout (LKO) mice develop insulin resistance associated with the increase in hepatic Tlr4
	Prss8-deficient newborns presented abnormal epidermis, and died soon after birth due to impaired skin function
	hypomorphic mutations in Prss8, restored placentation and normal development of Spint1-deficient embryos and prevented early embryonic lethality, mid-gestation lethality due to placental labyrinth failure, and neural tube defects in Spint2-deficient embryos