Property Summary

NCBI Gene PubMed Count 37
PubMed Score 510.97
PubTator Score 108.53

Knowledge Summary

Patent

No data available

Expression

Protein-protein Interaction (2)

Gene RIF (27)

PMID Text
26318044 Data show that silencing tumor-endothelial cells (EC) for trypsinogen 4 accumulated tissue factor pathway inhibitor-2 (TFPI-2) in the matrix.
26175157 These findings suggest that inhibitor cleavage represents a functional adaptation of mesotrypsin that may have evolved in response to positive selection pressure.
25735255 High PRSS3 expression in EOC tissues was significantly associated with advanced FIGO stage and lymph node metastasis.
25301953 Data suggest that mesotrypsin cleavage of Kunitz domains may contribute to cancer progression.
24872419 Mesotrypsin generated saposins A-D from prosaposin, and mature caspase-14 contributed to this process by activating mesotrypsinogen to mesotrypsin. Knockdown of these proteases markedly down-regulated saposin A synthesis in skin equivalent models.
24146905 extra-pancreatic trypsinogen 3 is produced by esophageal adenocarcinoma cells and activates PAR-2 in an autocrine manner.
22042864 IFN regulatory factor 2 (Irf2) has a regulatory role in trypsinogen5 gene transcription, which is resistant to a major endogenous trypsin inhibitor, Spink3
20947888 PRSS3 plays an important role in the progression, metastasis and prognosis of human pancreatic cancer.
20484962 Investigation did not reveal an association between PRSS3 variants and chronic pancreatitis.
20484962 Observational study of gene-disease association. (HuGE Navigator)
20035377 Report PRSS3/mesotrypsin upregulation in breast cancer cells and identify CD109 as the functional proteolytic target of mesotrypsin.
19924134 Because mesotrypsin is resistant to naturally occurring trypsin inhibitors, confined expression of the isoforms of mesotrypsinogens and enteropeptidase may indicate that mesotrypsin is involved in keratinocyte terminal differentiation
19920152 Processing by mesotrypsin may ablate the protease inhibitory function of APP/protease nexin 2 in vivo and may also modulate other activities of APP/protease nexin 2 that involve the Kunitz domain.
19249338 Here, we report that nexin-1 inhibits trypsin-4, and forms stable complexes only with this trypsin-isoenzyme. This result suggests that nexin-1 could modulate trypsin activity in brain where both nexin-1 and trypsin-4 are expressed.
18665091 Absence of mesotrypsinogen gene (PRSS3) copy number variations in patients with chronic pancreatitis.
18363639 This study reveals enhanced mRNA expression of trypsinogen IV and SERT and a higher 5-HT content in the small intestine of IBS patients compared to healthy subjects.
17623652 trypsin IV and p23 are inhibitor-resistant trypsins that can cleave and activate PARs, causing PAR(1)- and PAR(2)-dependent inflammation and PAR(2)-dependent hyperalgesia.
17406981 human trypsinogen 4 is widely but unevenly distributed in the human brain. It is localized in neurons and glial cells, predominantly in astrocytes & the extracellular matrix.
16759229 mesotrypsin cannot activate pancreatic zymogens, but might activate certain proteinase-activated receptors because of its thrombin-like subsite specificity; alpha1AT Pittsburgh is an effective mesotrypsin inhibitor
16492676 analysis of structural rearrangement during the acylation step in human trypsin 4 on 4-methylumbelliferyl 4-guanidinobenzoate substrate analogue
16412431 Results suggest that human trypsin 4 may be one of the candidate proteases involved in the pathomechanism of multiple sclerosis via cleavage of myelin basic protein.
16013053 we determined the promoter hypermethylation status of PRSS3 in a case series study of primary NSCLC, and found methylation of this gene to be common, occurring in 53% (86 of 166) of tumors examined.
15987713 PRSS3 promoter methylation is associated with advanced bladder cancer
15855826 Observational study of gene-disease association. (HuGE Navigator)
15855826 The results classify E32del mesotrypsinogen as a frequent polymorphic variant, which is not associated with chronic alcoholic pancreatitis
14507909 biological function of human mesotrypsin is digestive degradation of trypsin inhibitors
11827488 X-ray structure in complex with the inhibitor benzamidine at 1.7 A resolution; crystal structure reveals basis for inhibitor resistance

AA Sequence

MCGPDDRCPARWPGPGRAVKCGKGLAAARPGRVERGGAQRGGAGLELHPLLGGRTWRAARDADGCEALGT      1 - 70
VAVPFDDDDKIVGGYTCEENSLPYQVSLNSGSHFCGGSLISEQWVVSAAHCYKTRIQVRLGEHNIKVLEG     71 - 140
NEQFINAAKIIRHPKYNRDTLDNDIMLIKLSSPAVINARVSTISLPTTPPAAGTECLISGWGNTLSFGAD    141 - 210
YPDELKCLDAPVLTQAECKASYPGKITNSMFCVGFLEGGKDSCQRDSGGPVVCNGQLQGVVSWGHGCAWK    211 - 280
NRPGVYTKVYNYVDWIKDTIAANS                                                  281 - 304
//

Text Mined References (40)

PMID Year Title
26318044 2015 Trypsinogen 4 boosts tumor endothelial cells migration through proteolysis of tissue factor pathway inhibitor-2.
26175157 2015 Mesotrypsin Has Evolved Four Unique Residues to Cleave Trypsin Inhibitors as Substrates.
25735255 2015 PRSS3 expression is associated with tumor progression and poor prognosis in epithelial ovarian cancer.
25301953 2014 Sequence and conformational specificity in substrate recognition: several human Kunitz protease inhibitor domains are specific substrates of mesotrypsin.
24872419 2014 Mesotrypsin and caspase-14 participate in prosaposin processing: potential relevance to epidermal permeability barrier formation.
24146905 2013 Autocrine extra-pancreatic trypsin 3 secretion promotes cell proliferation and survival in esophageal adenocarcinoma.
23376485 2013 Proteomic analysis of podocyte exosome-enriched fraction from normal human urine.
22042864 2011 Characterization of dsRNA-induced pancreatitis model reveals the regulatory role of IFN regulatory factor 2 (Irf2) in trypsinogen5 gene transcription.
20947888 2010 PRSS3 promotes tumour growth and metastasis of human pancreatic cancer.
20484962 2010 Complete analysis of the human mesotrypsinogen gene (PRSS3) in patients with chronic pancreatitis.
20035377 2010 Mesotrypsin promotes malignant growth of breast cancer cells through shedding of CD109.
19924134 2010 Keratinocytes synthesize enteropeptidase and multiple forms of trypsinogen during terminal differentiation.
19920152 2010 The amyloid precursor protein/protease nexin 2 Kunitz inhibitor domain is a highly specific substrate of mesotrypsin.
19249338 2009 Nexin-1 inhibits the activity of human brain trypsin.
18711365 2008 Collaborative genome-wide association analysis supports a role for ANK3 and CACNA1C in bipolar disorder.
18665091 2008 Absence of mesotrypsinogen gene (PRSS3) copy number variations in patients with chronic pancreatitis.
18363639 2008 Trypsinogen IV, serotonin transporter transcript levels and serotonin content are increased in small intestine of irritable bowel syndrome patients.
17623652 2007 Trypsin IV or mesotrypsin and p23 cleave protease-activated receptors 1 and 2 to induce inflammation and hyperalgesia.
17406981 2007 Regional distribution of human trypsinogen 4 in human brain at mRNA and protein level.
17207965 2007 hORFeome v3.1: a resource of human open reading frames representing over 10,000 human genes.
16759229 2006 Human mesotrypsin exhibits restricted S1' subsite specificity with a strong preference for small polar side chains.
16492676 2006 Thermodynamic analysis reveals structural rearrangement during the acylation step in human trypsin 4 on 4-methylumbelliferyl 4-guanidinobenzoate substrate analogue.
16412431 2006 Myelin basic protein, an autoantigen in multiple sclerosis, is selectively processed by human trypsin 4.
16013053 2005 Epigenetic silencing of the PRSS3 putative tumor suppressor gene in non-small cell lung cancer.
15987713 2006 Carcinogen exposure and gene promoter hypermethylation in bladder cancer.
15855826 2005 Genetic and biochemical characterization of the E32del polymorphism in human mesotrypsinogen.
15489334 2004 The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC).
15313892 2004 S100 family members and trypsinogens are predictors of distant metastasis and survival in early-stage non-small cell lung cancer.
15164053 2004 DNA sequence and analysis of human chromosome 9.
14507909 2003 Human mesotrypsin is a unique digestive protease specialized for the degradation of trypsin inhibitors.
12860985 2003 Canonical inhibitor-like interactions explain reactivity of alpha1-proteinase inhibitor Pittsburgh and antithrombin with proteinases.
12477932 2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.
12021776 2002 Paneth cell trypsin is the processing enzyme for human defensin-5.
11827488 2002 Crystal structure reveals basis for the inhibitor resistance of human brain trypsin.
11057674 2000 Structure of a serpin-protease complex shows inhibition by deformation.
9099703 1997 Identification and expression of the cDNA-encoding human mesotrypsin(ogen), an isoform of trypsin with inhibitor resistance.
8294000 1993 Cloning of the cDNA encoding human brain trypsinogen and characterization of its product.
7498454 1995 Crystal structures of factor Xa specific inhibitors in complex with trypsin: structural grounds for inhibition of factor Xa and selectivity against thrombin.
6698368 1984 Mesotrypsin: a new inhibitor-resistant protease from a zymogen in human pancreatic tissue and fluid.
2326201 1990 Nucleotide sequence of the human pancreatic trypsinogen III cDNA.