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PRSS8 (protease, serine, 8)

Written2012-04Li-Mei Chen, Karl X Chai
Burnett School of Biomedical Sciences, University of Central Florida College of Medicine, Orlando, FL 32816, USA

(Note : for Links provided by Atlas : click)


Alias (NCBI)CAP1
HGNC Alias nameprostasin
HGNC Previous nameprotease, serine 8
LocusID (NCBI) 5652
Atlas_Id 41880
Location 16p11.2  [Link to chromosome band 16p11]
Location_base_pair Starts at 31131433 and ends at 31135727 bp from pter ( according to GRCh38/hg38-Dec_2013)  [Mapping PRSS8.png]
Local_order Centromere to telomere.
Fusion genes
(updated 2017)
Data from Atlas, Mitelman, Cosmic Fusion, Fusion Cancer, TCGA fusion databases with official HUGO symbols (see references in chromosomal bands)
IFI6 (1p36.11)::PRSS8 (16p11.2)PRSS8 (16p11.2)::S100A14 (1q21.3)


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 gene's 3'-untranslated region (UTR) overlaps with the 3'-UTR of the 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 gene's 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.


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 prostasin's 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).


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 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 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 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 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 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 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 prostasin's role in skin inflammation (Frateschi et al., 2011).
Entity Aldosteronism and hypertension
Note ENaC function related condition.
Disease Consistent with aldosterone's 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 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 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 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).


Activation of epithelial sodium channels by prostasin in Xenopus oocytes.
Adachi M, Kitamura K, Miyoshi T, Narikiyo T, Iwashita K, Shiraishi N, Nonoguchi H, Tomita K.
J Am Soc Nephrol. 2001 Jun;12(6):1114-21.
PMID 11373334
The Charles River "hairless" rat mutation maps to chromosome 1: allelic with fuzzy and a likely orthologue of mouse frizzy.
Ahearn K, Akkouris G, Berry PR, Chrissluis RR, Crooks IM, Dull AK, Grable S, Jeruzal J, Lanza J, Lavoie C, Maloney RA, Pitruzzello M, Sharma R, Stoklasek TA, Tweeddale J, King TR.
J Hered. 2002 May-Jun;93(3):210-3.
PMID 12195039
Activation 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, Vuagniaux G, Fowler-Jaeger N, Hummler E, Rossier BC.
J Am Soc Nephrol. 2006 Apr;17(4):968-76. Epub 2006 Mar 8.
PMID 16524950
Strong expression association between matriptase and its substrate prostasin in breast cancer.
Bergum C, Zoratti G, Boerner J, List K.
J Cell Physiol. 2012 Apr;227(4):1604-9. doi: 10.1002/jcp.22877.
PMID 21678412
Local protease signaling contributes to neural tube closure in the mouse embryo.
Camerer E, Barker A, Duong DN, Ganesan R, Kataoka H, Cornelissen I, Darragh MR, Hussain A, Zheng YW, Srinivasan Y, Brown C, Xu SM, Regard JB, Lin CY, Craik CS, Kirchhofer D, Coughlin SR.
Dev Cell. 2010 Jan 19;18(1):25-38.
PMID 20152175
Proteolytic processing of the epithelial sodium channel gamma subunit has a dominant role in channel activation.
Carattino MD, Hughey RP, Kleyman TR.
J Biol Chem. 2008 Sep 12;283(37):25290-5. Epub 2008 Jul 23.
PMID 18650438
Characterization of human gamma-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families.
Caughey GH, Raymond WW, Blount JL, Hau LW, Pallaoro M, Wolters PJ, Verghese GM.
J Immunol. 2000 Jun 15;164(12):6566-75.
PMID 10843716
Analysis of gene expression profiles reveals novel correlations with the clinical course of colorectal cancer.
Cavalieri D, Dolara P, Mini E, Luceri C, Castagnini C, Toti S, Maciag K, De Filippo C, Nobili S, Morganti M, Napoli C, Tonini G, Baccini M, Biggeri A, Tonelli F, Valanzano R, Orlando C, Gelmini S, Cianchi F, Messerini L, Luzzatto L.
Oncol Res. 2007;16(11):535-48.
PMID 18306933
Prostasin serine protease inhibits breast cancer invasiveness and is transcriptionally regulated by promoter DNA methylation.
Chen LM, Chai KX.
Int J Cancer. 2002 Jan 20;97(3):323-9.
PMID 11774283
Prostasin regulates iNOS and cyclin D1 expression by modulating protease-activated receptor-2 signaling in prostate epithelial cells.
Chen LM, Hatfield ML, Fu YY, Chai KX.
Prostate. 2009a Dec 1;69(16):1790-801.
PMID 19670249
Down-regulation of prostasin serine protease: a potential invasion suppressor in prostate cancer.
Chen LM, Hodge GB, Guarda LA, Welch JL, Greenberg NM, Chai KX.
Prostate. 2001a Jul 1;48(2):93-103.
PMID 11433419
Prostasin is a glycosylphosphatidylinositol-anchored active serine protease.
Chen LM, Skinner ML, Kauffman SW, Chao J, Chao L, Thaler CD, Chai KX.
J Biol Chem. 2001b Jun 15;276(24):21434-42. Epub 2001 Mar 26.
PMID 11274175
Loss of prostasin (PRSS8) in human bladder transitional cell carcinoma cell lines is associated with epithelial-mesenchymal transition (EMT).
Chen LM, Verity NJ, Chai KX.
BMC Cancer. 2009b Oct 22;9:377.
PMID 19849847
Prostasin attenuates inducible nitric oxide synthase expression in lipopolysaccharide-induced urinary bladder inflammation.
Chen LM, Wang C, Chen M, Marcello MR, Chao J, Chao L, Chai KX.
Am J Physiol Renal Physiol. 2006a Sep;291(3):F567-77. Epub 2006 Apr 25.
PMID 16638913
Regulation of prostasin expression and function in the prostate.
Chen LM, Zhang X, Chai KX.
Prostate. 2004 Apr 1;59(1):1-12.
PMID 14991861
Hepsin activates prostasin and cleaves the extracellular domain of the epidermal growth factor receptor.
Chen M, Chen LM, Lin CY, Chai KX.
Mol Cell Biochem. 2010a Apr;337(1-2):259-66.
PMID 19911255
Regulation of the matriptase-prostasin cell surface proteolytic cascade by hepatocyte growth factor activator inhibitor-1 during epidermal differentiation.
Chen YW, Wang JK, Chou FP, Chen CY, Rorke EA, Chen LM, Chai KX, Eckert RL, Johnson MD, Lin CY.
J Biol Chem. 2010b Oct 8;285(41):31755-62. Epub 2010 Aug 9.
PMID 20696767
Camostat attenuates airway epithelial sodium channel function in vivo through the inhibition of a channel-activating protease.
Coote K, Atherton-Watson HC, Sugar R, Young A, MacKenzie-Beevor A, Gosling M, Bhalay G, Bloomfield G, Dunstan A, Bridges RJ, Sabater JR, Abraham WM, Tully D, Pacoma R, Schumacher A, Harris J, Danahay H.
J Pharmacol Exp Ther. 2009 May;329(2):764-74. Epub 2009 Feb 3.
PMID 19190233
Identification of hepatocyte growth factor activator inhibitor-1B as a potential physiological inhibitor of prostasin.
Fan B, Wu TD, Li W, Kirchhofer D.
J Biol Chem. 2005 Oct 14;280(41):34513-20. Epub 2005 Aug 15.
PMID 16103126
PAR2 absence completely rescues inflammation and ichthyosis caused by altered CAP1/Prss8 expression in mouse skin.
Frateschi S, Camerer E, Crisante G, Rieser S, Membrez M, Charles RP, Beermann F, Stehle JC, Breiden B, Sandhoff K, Rotman S, Haftek M, Wilson A, Ryser S, Steinhoff M, Coughlin SR, Hummler E.
Nat Commun. 2011 Jan 18;2:161.
PMID 21245842
Transport via the transcytotic pathway makes prostasin available as a substrate for matriptase.
Friis S, Godiksen S, Bornholdt J, Selzer-Plon J, Rasmussen HB, Bugge TH, Lin CY, Vogel LK.
J Biol Chem. 2011 Feb 18;286(7):5793-802. Epub 2010 Dec 10.
PMID 21148558
Analysis of the comprehensive effects of polyunsaturated fatty acid on mRNA expression using a gene chip.
Fujiwara Y, Yokoyama M, Sawada R, Seyama Y, Ishii M, Tsutsumi S, Aburatani H, Hanaka S, Itakura H, Matsumoto A.
J Nutr Sci Vitaminol (Tokyo). 2003 Apr;49(2):125-32.
PMID 12887159
In vivo induction of prostasin mRNA in colonic epithelial cells by dietary sodium depletion and aldosterone infusion in rats.
Fukushima K, Naito H, Funayama Y, Yonezawa H, Haneda S, Shibata C, Sasaki I.
J Gastroenterol. 2004 Oct;39(10):940-7.
PMID 15549446
Testisin, a new human serine proteinase expressed by premeiotic testicular germ cells and lost in testicular germ cell tumors.
Hooper JD, Nicol DL, Dickinson JL, Eyre HJ, Scarman AL, Normyle JF, Stuttgen MA, Douglas ML, Loveland KA, Sutherland GR, Antalis TM.
Cancer Res. 1999 Jul 1;59(13):3199-205.
PMID 10397266
Regulation of adrenal aldosterone production by serine protease prostasin.
Ko T, Kakizoe Y, Wakida N, Hayata M, Uchimura K, Shiraishi N, Miyoshi T, Adachi M, Aritomi S, Konda T, Tomita K, Kitamura K.
J Biomed Biotechnol. 2010;2010:793843. Epub 2010 Mar 2.
PMID 20204133
Urinary prostasin in humans: relationships among prostasin, aldosterone and epithelial sodium channel activity.
Koda A, Wakida N, Toriyama K, Yamamoto K, Iijima H, Tomita K, Kitamura K.
Hypertens Res. 2009 Apr;32(4):276-81. Epub 2009 Feb 27.
PMID 19262497
Blood-borne RT-PCR assay for prostasin- specific transcripts to identify circulating prostate cells in cancer patients.
Laribi A, Berteau P, Gala J, Eschwege P, Benoit G, Tombal B, Schmitt F, Loric S.
Eur Urol. 2001 Jan;39(1):65-71.
PMID 11173941
The epidermal barrier function is dependent on the serine protease CAP1/Prss8.
Leyvraz C, Charles RP, Rubera I, Guitard M, Rotman S, Breiden B, Sandhoff K, Hummler E.
J Cell Biol. 2005 Aug 1;170(3):487-96.
PMID 16061697
Interleukin-6 stimulates epithelial sodium channels in mouse cortical collecting duct cells.
Li K, Guo D, Zhu H, Hering-Smith KS, Hamm LL, Ouyang J, Dong Y.
Am J Physiol Regul Integr Comp Physiol. 2010 Aug;299(2):R590-5. Epub 2010 May 26.
PMID 20504903
Association of genetic variations of the prostasin gene with essential hypertension in the Xinjiang Kazakh population.
Li NF, Zhang JH, Chang JH, Yang J, Wang HM, Zhou L, Luo WL.
Chin Med J (Engl). 2011 Jul;124(14):2107-12.
PMID 21933610
Expression of prostasin and protease nexin-1 in rhesus monkey (Macaca mulatta) endometrium and placenta during early pregnancy.
Lin HY, Zhang H, Yang Q, Wang HX, Wang HM, Chai KX, Chen LM, Zhu C.
J Histochem Cytochem. 2006 Oct;54(10):1139-47. Epub 2006 Jun 26.
PMID 16801525
Prostasin inhibits cell invasion in human choriocarcinomal JEG-3 cells.
Ma XJ, Fu YY, Li YX, Chen LM, Chai K, Wang YL.
Histochem Cell Biol. 2009 Dec;132(6):639-46. Epub 2009 Oct 22.
PMID 19847458
Camostat mesilate inhibits prostasin activity and reduces blood pressure and renal injury in salt-sensitive hypertension.
Maekawa A, Kakizoe Y, Miyoshi T, Wakida N, Ko T, Shiraishi N, Adachi M, Tomita K, Kitamura K.
J Hypertens. 2009 Jan;27(1):181-9.
PMID 19145783
Prostasin, a potential serum marker for ovarian cancer: identification through microarray technology.
Mok SC, Chao J, Skates S, Wong K, Yiu GK, Muto MG, Berkowitz RS, Cramer DW.
J Natl Cancer Inst. 2001 Oct 3;93(19):1458-64.
PMID 11584061
Prostasin expression is regulated by airway surface liquid volume and is increased in cystic fibrosis.
Myerburg MM, McKenna EE, Luke CJ, Frizzell RA, Kleyman TR, Pilewski JM.
Am J Physiol Lung Cell Mol Physiol. 2008 May;294(5):L932-41. Epub 2008 Feb 29.
PMID 18310226
Regulation of prostasin by aldosterone in the kidney.
Narikiyo T, Kitamura K, Adachi M, Miyoshi T, Iwashita K, Shiraishi N, Nonoguchi H, Chen LM, Chai KX, Chao J, Tomita K.
J Clin Invest. 2002 Feb;109(3):401-8.
PMID 11828000
Urinary prostasin: a candidate marker of epithelial sodium channel activation in humans.
Olivieri O, Castagna A, Guarini P, Chiecchi L, Sabaini G, Pizzolo F, Corrocher R, Righetti PG.
Hypertension. 2005 Oct;46(4):683-8. Epub 2005 Sep 19.
PMID 16172430
Gene expression profiling separates chromophobe renal cell carcinoma from oncocytoma and identifies vesicular transport and cell junction proteins as differentially expressed genes.
Rohan S, Tu JJ, Kao J, Mukherjee P, Campagne F, Zhou XK, Hyjek E, Alonso MA, Chen YT.
Clin Cancer Res. 2006 Dec 1;12(23):6937-45.
PMID 17145811
A conditional allele at the mouse channel activating protease 1 (Prss8) gene locus.
Rubera I, Meier E, Vuagniaux G, Merillat AM, Beermann F, Rossier BC, Hummler E.
Genesis. 2002 Feb;32(2):173-6.
PMID 11857812
Expression of prostasin and its inhibitors during colorectal cancer carcinogenesis.
Selzer-Plon J, Bornholdt J, Friis S, Bisgaard HC, Lothe IM, Tveit KM, Kure EH, Vogel U, Vogel LK.
BMC Cancer. 2009 Jun 25;9:201.
PMID 19555470
Biochemical characterization of prostasin, a channel activating protease.
Shipway A, Danahay H, Williams JA, Tully DC, Backes BJ, Harris JL.
Biochem Biophys Res Commun. 2004 Nov 12;324(2):953-63.
PMID 15474520
The mouse frizzy (fr) and rat 'hairless' (frCR) mutations are natural variants of protease serine S1 family member 8 (Prss8).
Spacek DV, Perez AF, Ferranti KM, Wu LK, Moy DM, Magnan DR, King TR.
Exp Dermatol. 2010 Jun;19(6):527-32. Epub 2010 Feb 25.
PMID 20201958
Active site conformational changes of prostasin provide a new mechanism of protease regulation by divalent cations.
Spraggon G, Hornsby M, Shipway A, Tully DC, Bursulaya B, Danahay H, Harris JL, Lesley SA.
Protein Sci. 2009 May;18(5):1081-94.
PMID 19388054
Apical serine protease activity is necessary for assembly of a high-resistance renal collecting duct epithelium.
Steensgaard M, Svenningsen P, Tinning AR, Nielsen TD, Jorgensen F, Kjaersgaard G, Madsen K, Jensen BL.
Acta Physiol (Oxf). 2010 Dec;200(4):347-59. doi: 10.1111/j.1748-1716.2010.02170.x.
PMID 20645929
Prostasin-dependent activation of epithelial Na+ channels by low plasmin concentrations.
Svenningsen P, Uhrenholt TR, Palarasah Y, Skjodt K, Jensen BL, Skott O.
Am J Physiol Regul Integr Comp Physiol. 2009 Dec;297(6):R1733-41. Epub 2009 Sep 30.
PMID 19793956
Down-regulated expression of prostasin in high-grade or hormone-refractory human prostate cancers.
Takahashi S, Suzuki S, Inaguma S, Ikeda Y, Cho YM, Hayashi N, Inoue T, Sugimura Y, Nishiyama N, Fujita T, Chao J, Ushijima T, Shirai T.
Prostate. 2003 Feb 15;54(3):187-93.
PMID 12518323
Prostasin, a membrane-anchored serine peptidase, regulates sodium currents in JME/CF15 cells, a cystic fibrosis airway epithelial cell line.
Tong Z, Illek B, Bhagwandin VJ, Verghese GM, Caughey GH.
Am J Physiol Lung Cell Mol Physiol. 2004 Nov;287(5):L928-35. Epub 2004 Jul 9.
PMID 15246975
Inhibition of prostasin expression by TGF-beta1 in renal epithelial cells.
Tuyen DG, Kitamura K, Adachi M, Miyoshi T, Wakida N, Nagano J, Nonoguchi H, Tomita K.
Kidney Int. 2005 Jan;67(1):193-200.
PMID 15610243
An epithelial serine protease activates the amiloride-sensitive sodium channel.
Vallet V, Chraibi A, Gaeggeler HP, Horisberger JD, Rossier BC.
Nature. 1997 Oct 9;389(6651):607-10.
PMID 9335501
Cell-surface expression of the channel activating protease xCAP-1 is required for activation of ENaC in the Xenopus oocyte.
Vallet V, Pfister C, Loffing J, Rossier BC.
J Am Soc Nephrol. 2002 Mar;13(3):588-94.
PMID 11856761
Prostasin regulates epithelial monolayer function: cell-specific Gpld1-mediated secretion and functional role for GPI anchor.
Verghese GM, Gutknecht MF, Caughey GH.
Am J Physiol Cell Physiol. 2006 Dec;291(6):C1258-70. Epub 2006 Jul 5.
PMID 16822939
Adenovirus-mediated human prostasin gene delivery is linked to increased aldosterone production and hypertension in rats.
Wang C, Chao J, Chao L.
Am J Physiol Regul Integr Comp Physiol. 2003 Apr;284(4):R1031-6. Epub 2002 Dec 19.
PMID 12626364
Comprehensive serum profiling for the discovery of epithelial ovarian cancer biomarkers.
Yip P, Chen TH, Seshaiah P, Stephen LL, Michael-Ballard KL, Mapes JP, Mansfield BC, Bertenshaw GP.
PLoS One. 2011;6(12):e29533. Epub 2011 Dec 21.
PMID 22216306
Structure and chromosomal localization of the human prostasin (PRSS8) gene.
Yu JX, Chao L, Ward DC, Chao J.
Genomics. 1996 Mar 15;32(3):334-40.
PMID 8838796
Prostasin: a possible candidate gene for human hypertension.
Zhu H, Guo D, Li K, Yan W, Tan Y, Wang X, Treiber FA, Chao J, Snieder H, Dong Y.
Am J Hypertens. 2008 Sep;21(9):1028-33. Epub 2008 Jun 26.
PMID 18583984


This paper should be referenced as such :
Chen, LM ; Chai, KX
PRSS8 (protease, serine, 8)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(9):658-664.
Free journal version : [ pdf ]   [ DOI ]

External links


HGNC (Hugo)PRSS8   9491
Atlas Explorer : (Salamanque)PRSS8
Entrez_Gene (NCBI)PRSS8    serine protease 8
GeneCards (Weizmann)PRSS8
Ensembl hg19 (Hinxton)ENSG00000052344 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000052344 [Gene_View]  ENSG00000052344 [Sequence]  chr16:31131433-31135727 [Contig_View]  PRSS8 [Vega]
ICGC DataPortalENSG00000052344
TCGA cBioPortalPRSS8
Genatlas (Paris)PRSS8
SOURCE (Princeton)PRSS8
Genetics Home Reference (NIH)PRSS8
Genomic and cartography
GoldenPath hg38 (UCSC)PRSS8  -     chr16:31131433-31135727 -  16p11.2   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)PRSS8  -     16p11.2   [Description]    (hg19-Feb_2009)
GoldenPathPRSS8 - 16p11.2 [CytoView hg19]  PRSS8 - 16p11.2 [CytoView hg38]
Genome Data Viewer NCBIPRSS8 [Mapview hg19]  
Gene and transcription
Genbank (Entrez)AK296656 AK301619 AK309955 AU142128 BC001462
RefSeq transcript (Entrez)NM_002773
Consensus coding sequences : CCDS (NCBI)PRSS8
Gene ExpressionPRSS8 [ NCBI-GEO ]   PRSS8 [ EBI - ARRAY_EXPRESS ]   PRSS8 [ SEEK ]   PRSS8 [ MEM ]
Gene Expression Viewer (FireBrowse)PRSS8 [ Firebrowse - Broad ]
GenevisibleExpression of PRSS8 in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)5652
GTEX Portal (Tissue expression)PRSS8
Human Protein AtlasENSG00000052344-PRSS8 [pathology]   [cell]   [tissue]
Protein : pattern, domain, 3D structure
UniProt/SwissProtQ16651   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtQ16651  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProQ16651
Catalytic activity : Enzyme3.4.21.- [ Enzyme-Expasy ]   3.4.21.-3.4.21.- [ IntEnz-EBI ]   3.4.21.- [ BRENDA ]   3.4.21.- [ KEGG ]   [ MEROPS ]
Domaine pattern : Prosite (Expaxy)TRYPSIN_DOM (PS50240)    TRYPSIN_HIS (PS00134)    TRYPSIN_SER (PS00135)   
Domains : Interpro (EBI)Peptidase_S1_PA    Peptidase_S1_PA_chymotrypsin    Peptidase_S1A    Trypsin_dom    TRYPSIN_HIS    TRYPSIN_SER   
Domain families : Pfam (Sanger)Trypsin (PF00089)   
Domain families : Pfam (NCBI)pfam00089   
Domain families : Smart (EMBL)Tryp_SPc (SM00020)  
Conserved Domain (NCBI)PRSS8
PDB (RSDB)3DFJ    3DFL    3E0N    3E0P    3E16    3E1X    3FVF    3GYL    3GYM   
PDB Europe3DFJ    3DFL    3E0N    3E0P    3E16    3E1X    3FVF    3GYL    3GYM   
PDB (PDBSum)3DFJ    3DFL    3E0N    3E0P    3E16    3E1X    3FVF    3GYL    3GYM   
PDB (IMB)3DFJ    3DFL    3E0N    3E0P    3E16    3E1X    3FVF    3GYL    3GYM   
Structural Biology KnowledgeBase3DFJ    3DFL    3E0N    3E0P    3E16    3E1X    3FVF    3GYL    3GYM   
SCOP (Structural Classification of Proteins)3DFJ    3DFL    3E0N    3E0P    3E16    3E1X    3FVF    3GYL    3GYM   
CATH (Classification of proteins structures)3DFJ    3DFL    3E0N    3E0P    3E16    3E1X    3FVF    3GYL    3GYM   
AlphaFold pdb e-kbQ16651   
Human Protein Atlas [tissue]ENSG00000052344-PRSS8 [tissue]
Protein Interaction databases
IntAct (EBI)Q16651
Ontologies - Pathways
Ontology : AmiGOserine-type endopeptidase activity  protein binding  extracellular region  extracellular space  plasma membrane  plasma membrane  proteolysis  serine-type peptidase activity  positive regulation of sodium ion transport  integral component of membrane  sodium channel regulator activity  extracellular exosome  
Ontology : EGO-EBIserine-type endopeptidase activity  protein binding  extracellular region  extracellular space  plasma membrane  plasma membrane  proteolysis  serine-type peptidase activity  positive regulation of sodium ion transport  integral component of membrane  sodium channel regulator activity  extracellular exosome  
REACTOMEQ16651 [protein]
REACTOME PathwaysR-HSA-6809371 [pathway]   
NDEx NetworkPRSS8
Atlas of Cancer Signalling NetworkPRSS8
Wikipedia pathwaysPRSS8
Orthology - Evolution
GeneTree (enSembl)ENSG00000052344
Phylogenetic Trees/Animal Genes : TreeFamPRSS8
Homologs : HomoloGenePRSS8
Homology/Alignments : Family Browser (UCSC)PRSS8
Gene fusions - Rearrangements
Fusion : FusionHubIFI6--PRSS8    PRB1--PRSS8    PRSS8--AGAP1    PRSS8--MYBBP1A    PRSS8--PRSS36    PRSS8--S100A14   
Fusion : QuiverPRSS8
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerPRSS8 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)PRSS8
Exome Variant ServerPRSS8
GNOMAD BrowserENSG00000052344
Varsome BrowserPRSS8
ACMGPRSS8 variants
Genomic Variants (DGV)PRSS8 [DGVbeta]
DECIPHERPRSS8 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisPRSS8 
ICGC Data PortalPRSS8 
TCGA Data PortalPRSS8 
Broad Tumor PortalPRSS8
OASIS PortalPRSS8 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICPRSS8  [overview]  [genome browser]  [tissue]  [distribution]  
Somatic Mutations in Cancer : COSMIC3DPRSS8
Mutations and Diseases : HGMDPRSS8
LOVD (Leiden Open Variation Database)[gene] [transcripts] [variants]
DgiDB (Drug Gene Interaction Database)PRSS8
DoCM (Curated mutations)PRSS8
CIViC (Clinical Interpretations of Variants in Cancer)PRSS8
Impact of mutations[PolyPhen2] [Provean] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Genetic Testing Registry PRSS8
NextProtQ16651 [Medical]
Target ValidationPRSS8
Huge Navigator PRSS8 [HugePedia]
Clinical trials, drugs, therapy
Protein Interactions : CTDPRSS8
Pharm GKB GenePA33840
Clinical trialPRSS8
DataMed IndexPRSS8
PubMed72 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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