Search results for HPN

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Species

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Protein (2 results from a total of 2)

Identifier: R-HSA-6800195
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: HPN: P05981
Identifier: R-HSA-8849219
Species: Homo sapiens
Compartment: plasma membrane
Primary external reference: UniProt: HPN: P05981

Complex (1 results from a total of 1)

Identifier: R-HSA-8849220
Species: Homo sapiens
Compartment: plasma membrane

Reaction (2 results from a total of 2)

Identifier: R-HSA-6800200
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
Hepsin (HPN, aka TMPRSS1) is a cell surface-expressed chymotrypsin-like serine protease and a member of the family of type II transmembrane serine proteases (TTSP). The HPN zymogen is activated autocatalytically by cleavage at Arg162-Ile163, forming a heterodimeric enzyme (Tsuji et al. 1991, Torres-Rosado et al. 1993). HPN plays an essential role in cell growth and maintenance of cell morphology and is highly upregulated in prostate cancer and promotes tumor progression and metastasis (Klezovitch et al. 2004). Located on the cell surface, HPN can activate fibrinolytic enzymes, matrix metalloproteases and latent forms of growth factors, such as hepatocyte growth factor (HGF). HGF is a pleiotropic factor and activates hepatocyte growth factor receptor (MET). HGF is secreted into the extracellular matrix as an inactive single chain precursor (pro-HGF (32-728)) and requires cleavage at Arg494–Val495 to form the biologically active alpha-beta heterodimer (Hartmann et al. 1992, Kirchhofer et al. 2005). The Kunitz-type protease inhibitors 1 and 2 (SPINT1 and 2, aka HAI1 and 2) are inhibitors of HPN activity (Kawaguchi et al. 1997, Shimomoura et al. 1997, Kirchhofer et al. 2005).
Identifier: R-HSA-6800198
Species: Homo sapiens
Compartment: extracellular region, plasma membrane
Hepsin (HPN, aka TMPRSS1) is a cell surface-expressed chymotrypsin-like serine protease and a member of the family of type II transmembrane serine proteases (TTSP). The HPN zymogen is activated autocatalytically by cleavage at Arg162–Ile163, forming a heterodimeric enzyme (Tsuji et al. 1991, Torres-Rosado et al. 1993). HPN plays an essential role in cell growth and maintenance of cell morphology and is highly upregulated in prostate cancer and promotes tumor progression and metastasis. Located on the cell surface, HPN can activate fibrinolytic enzymes, matrix metalloproteases and latent forms of growth factors such as hepatocyte growth factor-like protein (MST1, aka macrophage stimulatory protein, MSP). MST1 is a plasminogen-related growth factor and ligand for the receptor tyrosine kinase (MST1R, RON). The MST1/MST1R (MSP/RON) signaling system promotes wound healing and invasive tumor growth and suppresses proinflammatory immune response. For MST1 to bind MST1R, the inactive single-chain form (pro-MST1) must be cleaved into the disulfide-linked alpha-beta heterodimer by HPN (Ganesan et al. 2011). The Kunitz-type protease inhibitors 1 and 2 (SPINT1 and 2, aka HAI1 and 2) are inhibitors of HPN activity (Kirchhofer et al. 2005).

The non-synonymous coding variant in MST1 (R689C) has been associated with genetic susceptibility to both Crohn's disease and ulcerative colitis, two major types of inflammatory bowel disease (IBD). The R689C variant reduces the amount of circulating MST1 thereby reducing MST1R activity and down-regulation of the MST1/MST1R signaling pathway (McGovern et al. 2010, Gorlatova et al. 2011, Kauder et al. 2013).

Pathway (1 results from a total of 1)

Identifier: R-HSA-6806942
Species: Homo sapiens
Hepatocyte growth factor (HGF), the ligand for MET receptor tyrosine kinase (RTK), is secreted into the extracellular matrix (ECM) as an inactive single chain precursor (pro-HGF). The biologically active HGF is the heterodimer of alpha and beta chains that are produced via proteolytic cleavage of pro-HGF by the plasma membrane bound serine protease Hepsin (HPN) (Kirchhofer et al. 2005, Owen et al. 2010) or the ECM-associated serine protease Hepatocyte growth factor activator (HGFAC, commonly known as HGFA) (Shia et al. 2005). HGF binds to the extracellular SEMA and PSI domains of MET RTK, inducing a conformational change that enables MET dimerization or oligomerization (Kirchhofer et al. 2004, Stamos et al. 2004, Hays and Watowich 2004, Gherardi et al. 2006). MET dimers trans-autophosphorylate on tyrosine residues in the activation loop, leading to increased kinase activity, and on tyrosine residues at the cytoplasmic tail that serve as docking sites for adapter proteins involved in MET signal transduction (Ferracini et al. 1991, Longati et al. 1994, Rodrigues and Park 1994, Ponzetto et al. 1994).
CD44v6 was implicated as a MET co-receptor, but its role has been disputed (Orian-Rousseau et al. 2002, Dortet et al. 2010, Olaku et al. 2011, Hasenauer et al. 2013, Elliot et al. 2014).
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