PRSS8 (protease, serine, 8)

2012-04-01   Li-Mei Chen , Karl X Chai 

Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL 32816, USA

Identity

HGNC
LOCATION
16p11.2
LOCUSID
ALIAS
CAP1,PROSTASIN
FUSION GENES

DNA/RNA

Description

The human prostasin/PRSS8 gene consists of six (6) exons and five (5) introns. A 7-Kb (kilobase) genomic region containing the human prostasin/PRSS8 gene was fully sequenced in the original cloning report (Yu et al., 1996), with a 1.4-kb 5-flanking region and a 1.2-kb 3-flanking region. A single chromosomal location at 16p11.2 was reported to harbor the human prostasin/PRSS8 gene.
The mouse orthologue of the prostasin/prss8 gene, located on Chromosome 7, is highly homologous to the human prostasin/PRSS8 gene, with a six-exon organization (Verghese et al., 2004). The mouse prostasin/prss8 genes 3-untranslated region (UTR) overlaps with the 3-UTR of the Myst1 histone acetyltransferase gene. Genetic mapping evidence provided support for the rat fuzzy and hairless mutations to be orthologues of the mouse frizzy mutation (Ahearn et al., 2002). A T/A transversion missense mutation, changing a Val to an Asp at amino acid (AA) residue 170 of the mouse prostasin, was shown to be causative to the mutant frizzy phenotype (Spacek et al., 2010). The hairless rat has a 12-bp (base pair) deletion in the third exon of the prss8 genes coding region, whereas the fuzzy rat does not have any prss8 coding sequence changes.

Transcription

Description: The full-length human prostasin mRNA, as deduced from a cloned cDNA, contains a 1032-nucleotide (nt) open-reading frame that can be translated into 343 AA, a 138-nt 5-UTR, and a 572-nt 3-UTR (Yu et al., 1995).
Expression: In humans, prostasin mRNA expression was detected by reverse-transcription coupled polymerase chain reaction (RT-PCR) in the total RNA of the prostate, liver, salivary gland, kidney, lung, pancreas, colon, bronchus, and renal proximal tubular cells (Yu et al., 1995). In the human prostate, the prostasin mRNA was localized to the epithelial cells. The urinary bladder epithelial (urothelial) cells of the human and the mouse express the prostasin mRNA and the translated protein (Chen et al., 2009b; Chen et al., 2006a). Human breast epithelial cells also express the prostasin mRNA and the translated protein (Chen and Chai, 2002; Bergum et al., 2012). Prostasin mRNA is expressed in the rhesus monkey endometrial glandular epithelium on Day 12 and Day 18 of pregnancy, and in the placental villi, trophoblastic column, trophoblastic shell, and the fetal-maternal border on Day 18 and Day 26 (Lin et al., 2006). The endometrial prostasin expression subsides but the placental expression increases further along the gestational course.
Expression regulation: In the mouse renal cortical collecting duct M-1 cells prostasin mRNA expression can be up-regulated by aldosterone treatment, which is also a mechanism of increasing urinary prostasin excretion in rats following whole-animal infusion (Narikiyo et al., 2002). Aldosterone infusion was shown to induce prostasin mRNA expression in the left colon of the rat as well (Fukushima et al., 2004). Prostasin mRNA (and protein) expression in the M-1 cells can be repressed by transforming growth factor beta-1 (TGF-b1), via down-regulating the NF-kB signalling (Tuyen et al., 2005). In the mouse urinary bladder, prostasin mRNA expression is down-regulated in association with inflammation caused by intraperitoneal injection of bacterial lipopolysaccharides (LPS) (Chen et al., 2006a).
Promoter DNA hypermethylation and histone deacetylation are epigenetic mechanisms that down-regulate prostasin mRNA transcription in human breast and prostate cancer cell lines (Chen and Chai, 2002; Chen et al., 2004). Nerve growth factor (NGF) induces prostasin mRNA expression in human prostate cancer cell lines (DU-145 and PC-3) with epigenetically repressed prostasin expression (Chen et al., 2004). The sterol regulatory element-binding proteins (SREBPs) SREBP-1c and SREBP-2 are positive transcriptional regulators of prostasin expression in human epithelial cell lines (Chen et al., 2006b), and the binding sites of SREBP-2 in the human prostasin/PRSS8 gene promoter region have been determined (Chen et al., 2006c). The SNAIL family zinc-finger transcription factors SNAIL and SLUG are negative regulators of prostasin transcription in human epithelial cell lines (Chen et al., 2006b). The SREBPs and SLUG are responsive to dihydrotestosterone (DHT) with up-regulation of expression and thus making the prostasin/PRSS8 gene indirectly responsive to androgen regulation (Chen et al., 2006b).

Pseudogene

No prostasin/PRSS8 pseudogene has been identified to date.

Proteins

Description

The mature form of the human prostasin is 40 kDa in size as determined by SDS-PAGE, and has a pI in the range of 4.5-4.8 (Yu et al., 1994). The pro-peptide of the human prostasin is 311 AA in length (Yu et al., 1995), and it is cleaved at Arg12 in the sequence of Gln-Ala-Arg-Ile by matriptase, hepsin, or plasmin (Chen et al., 2010a; Svenningsen et al., 2009) to produce a two-chain (12 AA and 277 AA) disulphide-linked mature protein (Yu et al., 1995).

Expression

In humans the prostasin protein could be detected by radioimmunoassay (RIA) in tissue extracts of the prostate, colon, lung, kidney, pancreas, salivary gland, liver, and bronchi, as well as in seminal fluid and urine; but not in tissue extracts of the brain, muscle, testis, ventricle, atrium, or aorta (Yu et al., 1994). By immunohistochemistry (IHC), human prostasin has been detected in the epithelial cells of the prostate (Yu et al., 1994; Chen et al., 2001a), the urinary bladder (Chen et al., 2009b), and the breast (Bergum et al., 2012); and the placenta trophoblasts during early pregnancy (Ma et al., 2009).

Localisation

A glycosylphosphatidylinositol (GPI) anchor tethers the mature prostasin protein to the plasma membrane (Chen et al., 2001b). The mature prostasin protein can be released from the membrane by phosphatidylinositol-specific phospholipase C (Chen et al., 2001b), or GPI-specific phospholipase D1 (Gpld1) (Verghese et al., 2006). But in the kidney shedding of prostasin from the cell membrane may be peptidase-dependent (Verghese et al., 2006). In the epithelium proteolytic cleavage of the pro-prostasin by matriptase must occur at the basolateral membrane but transcytosis brings the GPI-anchored prostasin to its major cellular location, the apical membrane (Friis et al., 2011).

Function

Prostasin was first identified as a serine protease in human seminal fluid, purified by the use of aprotinin-affinity chromatography (Yu et al., 1994). This native purified form of human prostasin displayed a trypsin-like proteolytic activity with a pH optimum of 9.0 on some synthetic substrates. The serine protease catalytic triad of the human prostasin was deduced after the cloning of its cDNA, as His53/Asp102/Ser206 (Yu et al., 1995). A Ser206Ala mutant of the human prostasin was used to confirm the serine active site (Chen et al., 2008). Using a recombinant human prostasin catalytic domain (i.e., lacking the GPI anchor and cellular context) produced in insect cells, the substrate specificity at the P1 position was determined to be either Arg or Lys (Shipway et al., 2004). The S1 substrate subsite loop of human prostasin was found to bind divalent ions such as Ca++ in a crystallized form with protease inhibitors, suggesting that divalent cations can regulate the protease activity (Spraggon et al., 2009).
Natural substrates: ENaC - The first candidate physiological substrate of prostasin was identified in a Xenopus kidney epithelial cell line (A6) in a functional cloning assay to find proteolytic activators of the epithelial sodium channel (ENaC), thus earning the nickname CAP1 (channel-activating protease 1) for prostasin (Vallet et al., 1997). The rat prostasin, when co-expressed with rat ENaC in Xenopus oocytes produces increased amiloride-sensitive sodium current, indicating ENaC activation by the co-expressed prostasin (Adachi et al., 2001). Activation of ENaC in the Xenopus oocyte requires the GPI-anchorage of the xCAP1 (Xenopus CAP1), indicating an extracellular location for the proteolytic activation of ENaC by xCAP1/prostasin (Vallet et al., 2002). Using a nasal epithelial cell line JMF/CF15 homozygous for the ΔF508 cystic fibrosis mutation, prostasin down-regulation by small-interfering RNA (siRNA) was shown to drop ENaC currents by >70% (Tong et al., 2004). The human prostasin cleaves the gamma subunit of ENaC at RKRK(186) (Carattino et al., 2008). In the mouse however, ENaC activation by mCAP1 (mouse CAP1) does not require its catalytic/proteolytic function, though the GPI anchorage is still required for mCAP1 in this role (Andreasen et al., 2006).
Natural substrates: Matriptase - While an activating protease for pro-prostasin, matriptase has also been shown to be a substrate of prostasin in mouse lung fibroblast cells and human keratinocytes with the use of soluble recombinant active human prostasin (Camerer et al., 2010). This mechanism explains the activation of protease-activated receptor 2 (PAR-2) upon addition of the soluble active prostasin, which accomplishes the PAR-2 activation via activating matriptase, a direct PAR-2 activating protease. This mechanism also helps explain the enhancement of matriptase cleavage of the extracellular domain (ECD) of the epidermal growth factor receptor (EGFR), which was first thought to be potentially cleaved by prostasin as well (Chen et al., 2008), but later proven not to be the case (Chen et al., 2010a). In human prostate epithelial cells however, prostasin also negatively regulate PAR-2 signalling, an action that requires prostasins serine active site but not its GPI anchor (Chen et al., 2009a).
Inhibitors: As a serine protease, the purified form of the human prostasin can be inhibited by aprotinin, antipain, leupeptin, and benzamidine (Yu et al., 1994). In the serpin-class serine protease inhibitors, protease nexin 1 (PN-1) is the cognate serpin for prostasin, forming a covalent complex with the latter to achieve inhibition of its serine protease activity (Chen et al., 2004). In the human PN-1 reactive site, the Leu-Ile-Ala-Arg residues at the P4-P1 positions of this suicide inhibitor should represent also the optimal substrate for prostasin. A Kunitz-type reversible serine protease inhibitor, hepatocyte growth factor activator inhibitor 1 (HAI-1) is a physiologically relevant inhibitor of prostasin (Fan et al., 2005; Chen et al., 2010b), whereas HAI-2 can inhibit the prostasin protease domain in vitro (Shipway et al., 2004). The synthetic serine protease inhibitor camostat mesilate and its active metabolite FOY-251 can inhibit prostasin serine protease activity in vitro (Maekawa et al., 2009), and possibly in vivo as well (Coote et al., 2009).

Homology

The human prostasin was shown to share sequence homology at the amino acid level with acrosin, plasma kallikrein, and hepsin upon sequencing of its full-length cDNA (Yu et al., 1995). Prostasin also shares amino acid sequence homology with testisin (Hooper et al., 1999) and gamma tryptase (Caughey et al., 2000).

Mutations

Germinal

In mice, homozygous loss of the prostasin/prss8 gene is embryonically lethal so conditional knockouts are needed for investigating prostasin/prss8 functions in vivo (Rubera et al., 2002). In humans, no Mendelian hereditary conditions on the basis of prostasin/PRSS8 gene mutations have been described to date. A transcribed single nucleotide polymorphism (tSNP) in the human prostasin/PRSS8 gene (rs12597511: C;T) shows genotype association with hypertension (Zhu et al., 2008). A missense SNP, E342K, of the human prostasin/PRSS8 gene has been reported (Li et al., 2011). Another human prostasin/PRSS8 gene SNP, 2827 G>A, was reported to show genotype association with body mass index (BMI), OGTT-2h glucose, IRT-3h insulin, and serum potassium (Li et al., 2011).

Implicated in

Entity name
Prostate cancer
Note
Prostasin expression is down-regulated in high-grade prostate cancers, and correspondingly in highly invasive human and mouse prostate cancer cell lines (Chen et al., 2001a). Re-expression of prostasin in highly invasive human prostate cancer cell lines (DU-145 and PC-3) reduced their in vitro invasion. Down-regulated prostasin expression was associated with metastatic and hormone-refractory prostate cancers in a small study involving 54 cases (Takahashi et al., 2003). This study confirmed the inverse correlation of prostasin expression with histological differentiation but failed to find correlations with clinical staging. Another small study (96 cases and 86 controls) suggested that RT-PCR amplification of the prostasin mRNA from circulating tumor cells may be applicable as a method for early diagnosis of prostate cancer cell dissemination (Laribi et al., 2001).
Entity name
Breast cancer
Note
A coordinated co-expression pattern in human breast cancers has been reported for prostasin and its activating enzyme/substrate matriptase (Bergum et al., 2012). Prostasin expression is down-regulated in highly invasive human breast cancer cells whereas re-expression of prostasin in these cells reduced their in vitro invasion (Chen and Chai, 2002).
Entity name
Ovarian cancer
Note
Prostasin is detected by IHC more intensely in the epithelial and stromal cells of cancerous ovarian tissues than those of normal ovarian tissues (Mok et al., 2001). Serum prostasin levels may be applicable as a highly sensitive and specific marker for detecting ovarian cancer. Another study also revealed serum prostasin as a potentially informative marker for ovarian cancer (Yip et al., 2011).
Entity name
Colon cancer
Note
Prostasin mRNA expression was found to be correlated to prolonged survival after surgery in colon cancer patients in a small study (Cavalieri et al., 2007). In tissues from the same colon cancer patients, prostasin mRNA expression was found to be slightly increased in the cancerous sections whereas membrane localization of the prostasin protein in colon cancer tissues appears to be disturbed as well (Selzer-Plon et al., 2009).
Entity name
Other cancers
Note
Prostasin is among five (5) genes that can be used for separating the chromophobe renal cell carcinoma (RCC) from oncocytoma based on their differential mRNA expression in these two tumor types (Rohan et al., 2006). In the human hepatoma cell line HepG2 prostasin mRNA expression can be reduced by poly unsaturated fatty acids (Fujiwara et al., 2003).
Entity name
Inflammation
Disease
Prostasin expression in the urinary bladder is down-regulated by LPS-induced inflammation marked by the characteristic up-regulation of the inducible nitric oxide synthase (iNOS) expression (Chen et al., 2006a). Forced expression of prostasin in the bladder urothelial cells attenuated the iNOS induction. Silencing prostasin expression in the human benign prostatic hyperplasia cell line BPH-1 is associated with up-regulation of iNOS expression as well as that of interleukins 6 and 8 (IL-6 and IL-8) (Chen et al., 2009a). In the mouse kidney cortical collecting duct M-1 cells, treatment with IL-6 was shown to increase prostasin protein expression (Li et al., 2010). Transgenic mice over-expressing prostasin in the skin show skin inflammation and ichthyosis, phenotypes that are not manifested in PAR-2 null mice, indicating a PAR-2 mediated mechanism for prostasins role in skin inflammation (Frateschi et al., 2011).
Entity name
Aldosteronism and hypertension
Note
ENaC function related condition.
Disease
Consistent with aldosterones transcriptional activator role on prostasin expression, urinary excretion of prostasin in primary aldosteronism patients is significantly increased (Narikiyo et al., 2002). Rats receiving tail-vein injection of adenoviruses carrying a human prostasin transgene expressed the transgene ubiquitously and showed elevated plasma aldosterone and hypertension along with reduced urinary potassium excretion and increased urinary sodium and kallikrein excretion (Wang et al., 2003). Prostasin regulates aldosterone production in human adrenocortical H295R cells by a protease-independent but calcium- and protein kinase C (PKC) dependent mechanism (Ko et al., 2010).
Entity name
Urinary prostasin
Note
Urinary prostasin level may be applicable as a marker for upstream ENaC activation and this marker is increased in primary aldosteronism patients after volume expansion (Olivieri et al., 2005). Another study also indicated a strong correlation between urinary prostasin levels and urinary or plasma aldosterone levels in hypertensive patients (Koda et al., 2009).
Entity name
Cystic fibrosis (CF)
Note
ENaC function related condition.
Disease
Prostasin was found to be a major regulator of ENaC-mediated sodium current in a human epithelial cell line carrying the ΔF508 CF mutation (Tong et al., 2004). In this context, prostasin expression in human airway epithelial cells can be regulated by the airway surface liquid (ASL) volume and CF patients express >50% more prostasin in their airway epithelial cells than non-CF subjects (Myerburg et al., 2008).
Entity name
Epidermal/Epithelial terminal differentiation
Disease
Mice born with a prostasin/prss8 knockout in the skin die within 60 hours, presenting a phenotype of severely malformed stratum corneum (SC) (Leyvraz et al., 2005). This defect results in impaired skin barrier function manifested as increased skin permeability and dehydration. At the molecular level, occludin is absent among the tight junction (TJ) proteins thus preventing the proper formation of the tight junctions and terminal differentiation of the epidermis. Along the same line of reasoning, the renal collecting duct epithelium requires apically expressed, GPI-anchored, and lipid-raft-associated active prostasin serine protease for establishment of high transepithelial resistance (TER), an indicator of epithelial terminal differentiation (Steensgaard et al., 2010).

Bibliography

Pubmed IDLast YearTitleAuthors
113733342001Activation of epithelial sodium channels by prostasin in Xenopus oocytes.Adachi M et al
121950392002The Charles River "hairless" rat mutation maps to chromosome 1: allelic with fuzzy and a likely orthologue of mouse frizzy.Ahearn K et al
165249502006Activation of epithelial sodium channels by mouse channel activating proteases (mCAP) expressed in Xenopus oocytes requires catalytic activity of mCAP3 and mCAP2 but not mCAP1.Andreasen D et al
216784122012Strong expression association between matriptase and its substrate prostasin in breast cancer.Bergum C et al
201521752010Local protease signaling contributes to neural tube closure in the mouse embryo.Camerer E et al
186504382008Proteolytic processing of the epithelial sodium channel gamma subunit has a dominant role in channel activation.Carattino MD et al
108437162000Characterization of human gamma-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families.Caughey GH et al
183069332007Analysis of gene expression profiles reveals novel correlations with the clinical course of colorectal cancer.Cavalieri D et al
117742832002Prostasin serine protease inhibits breast cancer invasiveness and is transcriptionally regulated by promoter DNA methylation.Chen LM et al
196702492009Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells.Chen LM et al
114334192001Down-regulation of prostasin serine protease: a potential invasion suppressor in prostate cancer.Chen LM et al
112741752001Prostasin is a glycosylphosphatidylinositol-anchored active serine protease.Chen LM et al
198498472009Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT).Chen LM et al
166389132006Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation.Chen LM et al
149918612004Regulation of prostasin expression and function in the prostate.Chen LM et al
199112552010Hepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor.Chen M et al
206967672010Regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 during epidermal differentiation.Chen YW et al
191902332009Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease.Coote K et al
161031262005Identification of hepatocyte growth factor activator inhibitor-1B as a potential physiological inhibitor of prostasin.Fan B et al
212458422011PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin.Frateschi S et al
211485582011Transport via the transcytotic pathway makes prostasin available as a substrate for matriptase.Friis S et al
128871592003Analysis of the comprehensive effects of polyunsaturated fatty acid on mRNA expression using a gene chip.Fujiwara Y et al
155494462004In vivo induction of prostasin mRNA in colonic epithelial cells by dietary sodium depletion and aldosterone infusion in rats.Fukushima K et al
103972661999Testisin, a new human serine proteinase expressed by premeiotic testicular germ cells and lost in testicular germ cell tumors.Hooper JD et al
202041332010Regulation of adrenal aldosterone production by serine protease prostasin.Ko T et al
192624972009Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity.Koda A et al
111739412001Blood-borne RT-PCR assay for prostasin- specific transcripts to identify circulating prostate cells in cancer patients.Laribi A et al
160616972005The epidermal barrier function is dependent on the serine protease CAP1/Prss8.Leyvraz C et al
205049032010Interleukin-6 stimulates epithelial sodium channels in mouse cortical collecting duct cells.Li K et al
219336102011Association of genetic variations of the prostasin gene with essential hypertension in the Xinjiang Kazakh population.Li NF et al
168015252006Expression of prostasin and protease nexin-1 in rhesus monkey (Macaca mulatta) endometrium and placenta during early pregnancy.Lin HY et al
198474582009Prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells.Ma XJ et al
191457832009Camostat mesilate inhibits prostasin activity and reduces blood pressure and renal injury in salt-sensitive hypertension.Maekawa A et al
115840612001Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology.Mok SC et al
183102262008Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis.Myerburg MM et al
118280002002Regulation of prostasin by aldosterone in the kidney.Narikiyo T et al
161724302005Urinary prostasin: a candidate marker of epithelial sodium channel activation in humans.Olivieri O et al
171458112006Gene expression profiling separates chromophobe renal cell carcinoma from oncocytoma and identifies vesicular transport and cell junction proteins as differentially expressed genes.Rohan S et al
118578122002A conditional allele at the mouse channel activating protease 1 (Prss8) gene locus.Rubera I et al
195554702009Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis.Selzer-Plon J et al
154745202004Biochemical characterization of prostasin, a channel activating protease.Shipway A et al
202019582010The mouse frizzy (fr) and rat 'hairless' (frCR) mutations are natural variants of protease serine S1 family member 8 (Prss8).Spacek DV et al
193880542009Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations.Spraggon G et al
206459292010Apical serine protease activity is necessary for assembly of a high-resistance renal collecting duct epithelium.Steensgaard M et al
197939562009Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations.Svenningsen P et al
125183232003Down-regulated expression of prostasin in high-grade or hormone-refractory human prostate cancers.Takahashi S et al
152469752004Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line.Tong Z et al
156102432005Inhibition of prostasin expression by TGF-beta1 in renal epithelial cells.Tuyen DG et al
93355011997An epithelial serine protease activates the amiloride-sensitive sodium channel.Vallet V et al
118567612002Cell-surface expression of the channel activating protease xCAP-1 is required for activation of ENaC in the Xenopus oocyte.Vallet V et al
168229392006Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor.Verghese GM et al
126263642003Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats.Wang C et al
222163062011Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers.Yip P et al
88387961996Structure and chromosomal localization of the human prostasin (PRSS8) gene.Yu JX et al
185839842008Prostasin: a possible candidate gene for human hypertension.Zhu H et al

Other Information

Locus ID:

NCBI: 5652
MIM: 600823
HGNC: 9491
Ensembl: ENSG00000052344

Variants:

dbSNP: 5652
ClinVar: 5652
TCGA: ENSG00000052344
COSMIC: PRSS8

RNA/Proteins

Gene IDTranscript IDUniprot
ENSG00000052344ENST00000317508Q16651
ENSG00000052344ENST00000567531H3BUJ8
ENSG00000052344ENST00000567797H3BVC8
ENSG00000052344ENST00000568261Q16651

Expression (GTEx)

0
50
100
150
200
250

Pathways

PathwaySourceExternal ID
Developmental BiologyREACTOMER-HSA-1266738
KeratinizationREACTOMER-HSA-6805567
Formation of the cornified envelopeREACTOMER-HSA-6809371

Protein levels (Protein atlas)

Not detected
Low
Medium
High

References

Pubmed IDYearTitleCitations
117564322002Regulation of the epithelial sodium channel by serine proteases in human airways.90
179402832007Autosomal ichthyosis with hypotrichosis syndrome displays low matriptase proteolytic activity and is phenocopied in ST14 hypomorphic mice.45
236736612013A matriptase-prostasin reciprocal zymogen activation complex with unique features: prostasin as a non-enzymatic co-factor for matriptase activation.36
161031262005Identification of hepatocyte growth factor activator inhibitor-1B as a potential physiological inhibitor of prostasin.33
152469752004Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line.32
154745202004Biochemical characterization of prostasin, a channel activating protease.30
206967672010Regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 during epidermal differentiation.29
183102262008Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis.28
234436622013Prostasin is required for matriptase activation in intestinal epithelial cells to regulate closure of the paracellular pathway.26
171458112006Gene expression profiling separates chromophobe renal cell carcinoma from oncocytoma and identifies vesicular transport and cell junction proteins as differentially expressed genes.22

Citation

Li-Mei Chen ; Karl X Chai

PRSS8 (protease, serine, 8)

Atlas Genet Cytogenet Oncol Haematol. 2012-04-01

Online version: http://atlasgeneticsoncology.org/gene/41880/prss8