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Gene Review

HGFAC  -  HGF activator

Homo sapiens

Synonyms: HGFA, HGFAP, Hepatocyte growth factor activator
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Disease relevance of HGFAC

  • Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma [1].
  • The subcellular localization of HGFA immunoreactivity was altered in carcinoma cells showing basal or cell-stroma interface staining patterns, compared with normal and adenoma cells with a supranuclear or apical staining pattern [2].
  • Therefore, extrahepatic expression of HGFA in the colorectal carcinoma cells could be responsible for the single-chain HGF/SF-processing activity of the cells [2].
  • Multiple myeloma cells catalyze hepatocyte growth factor (HGF) activation by secreting the serine protease HGF-activator [3].
  • In our study, we examined the effects of engineered expression of HGFA on 2 human glioblastoma cell lines (YKG-1 and U251) [4].

High impact information on HGFAC

  • The activity was also inhibited by recombinant HGFA inhibitor type 1 (HAI-1) [2].
  • This processing activity was enhanced by thrombin treatment but was inhibited significantly by a neutralizing antibody against HGF activator (HGFA), a factor XIIa-like serine proteinase believed to be expressed mainly in the liver [2].
  • The presence of HGFA mRNA and secretion of HGFA protein were confirmed in the cell lines [2].
  • We examined the expression of HGFA and HAI-1 in human colorectal mucosa and adenoma-carcinoma sequence [2].
  • Immunohistochemically, HGFA was stained weakly in the normal enterocytes, and immunoreactivity was increased modestly in the neoplastic differentiation [2].

Biological context of HGFAC


Anatomical context of HGFAC

  • In fact, pro-HGFA and the active form of HGFA proteins increased in carcinoma tissue compared with the corresponding normal mucosa [2].
  • Hepatocyte growth factor activator (HGFA) is responsible for proteolytic activation of the precursor form of hepatocyte growth factor in injured tissues [5].
  • In addition to HAI-1, low but distinct expression of HGFA mRNA was observed in the placenta tissue and cultured cytotrophoblasts by using a sensitive RT-PCR method [9].
  • These results suggest that HAI-1 is a cell-surface acceptor of activated HGFA in regenerative epithelial cells, and functions on the cell surface to localize the active HGFA that is going to enter the repair process [10].
  • The latter property might paradoxically ensure the concentrated pericellular HGFA activity in certain cellular conditions in which shedding of HAI-1/HGFA complex from the plasma membrane is upregulated [11].

Associations of HGFAC with chemical compounds

  • We also analyzed the heparin binding properties of the precursor and mature forms of HGFA [7].
  • These results suggest that the NH2-terminal Kunitz domain is mainly responsible for the HGF activator inhibitory activity of HAI-2 [12].
  • Factor XIIa exhibited a significant level of HGF-converting activity in the presence of dextran sulfate, although the specific activity of factor XIIa was slightly lower than that of the HGF activator [13].

Regulatory relationships of HGFAC


Other interactions of HGFAC

  • The binding of HGFA to HAI-1 was reversible, and no irreversible modifications affecting the enzyme activity occurred during the binding [5].
  • This review is a summary and interpretation of recent data regarding the regulation of pericellular HGF/SF activation mediated by HGFA and HAIs and includes a discussion of the possible role of the type I transmembrane Kunitz-type inhibitor in pericellular proteolysis [16].
  • Both are Kunitz-type serine proteinase inhibitors and inhibit not only HGFA but also other serine proteinases, such as membrane-type serine protease 1 (matriptase), plasmin, trypsin and kallikreins [16].
  • Two genes were assigned since they were present in clones that contained mapped markers (HGFAC and HMX1) [17].
  • We evaluated the expression of HGFA and its endogenous inhibitors HAI-1 and HAI-2 in normal kidney and RCC [14].

Analytical, diagnostic and therapeutic context of HGFAC


  1. Functional analysis of HGF/MET signaling and aberrant HGF-activator expression in diffuse large B-cell lymphoma. Tjin, E.P., Groen, R.W., Vogelzang, I., Derksen, P.W., Klok, M.D., Meijer, H.P., van Eeden, S., Pals, S.T., Spaargaren, M. Blood (2006) [Pubmed]
  2. Activation of hepatocyte growth factor/scatter factor in colorectal carcinoma. Kataoka, H., Hamasuna, R., Itoh, H., Kitamura, N., Koono, M. Cancer Res. (2000) [Pubmed]
  3. Multiple myeloma cells catalyze hepatocyte growth factor (HGF) activation by secreting the serine protease HGF-activator. Tjin, E.P., Derksen, P.W., Kataoka, H., Spaargaren, M., Pals, S.T. Blood (2004) [Pubmed]
  4. Role of hepatocyte growth factor activator (HGF activator) in invasive growth of human glioblastoma cells in vivo. Uchinokura, S., Miyata, S., Fukushima, T., Itoh, H., Nakano, S., Wakisaka, S., Kataoka, H. Int. J. Cancer (2006) [Pubmed]
  5. Hepatocyte growth factor activator inhibitor type 1 is a specific cell surface binding protein of hepatocyte growth factor activator (HGFA) and regulates HGFA activity in the pericellular microenvironment. Kataoka, H., Shimomura, T., Kawaguchi, T., Hamasuna, R., Itoh, H., Kitamura, N., Miyazawa, K., Koono, M. J. Biol. Chem. (2000) [Pubmed]
  6. Molecular cloning and sequence analysis of the cDNA for a human serine protease reponsible for activation of hepatocyte growth factor. Structural similarity of the protease precursor to blood coagulation factor XII. Miyazawa, K., Shimomura, T., Kitamura, A., Kondo, J., Morimoto, Y., Kitamura, N. J. Biol. Chem. (1993) [Pubmed]
  7. Activation of hepatocyte growth factor in the injured tissues is mediated by hepatocyte growth factor activator. Miyazawa, K., Shimomura, T., Kitamura, N. J. Biol. Chem. (1996) [Pubmed]
  8. Tissue expression, protease specificity, and Kunitz domain functions of hepatocyte growth factor activator inhibitor-1B (HAI-1B), a new splice variant of HAI-1. Kirchhofer, D., Peek, M., Li, W., Stamos, J., Eigenbrot, C., Kadkhodayan, S., Elliott, J.M., Corpuz, R.T., Lazarus, R.A., Moran, P. J. Biol. Chem. (2003) [Pubmed]
  9. Localization of hepatocyte growth factor activator inhibitor type 1 in Langhans' cells of human placenta. Kataoka, H., Meng, J.Y., Itoh, H., Hamasuna, R., Shimomura, T., Suganuma, T., Koono, M. Histochem. Cell Biol. (2000) [Pubmed]
  10. Roles of hepatocyte growth factor activator (HGFA) and its inhibitor HAI-1 in the regeneration of injured gastrointestinal mucosa. Itoh, H., Kataoka, H. J. Gastroenterol. (2002) [Pubmed]
  11. Pericellular activation of hepatocyte growth factor/scatter factor (HGF/SF) in colorectal carcinomas: roles of HGF activator (HGFA) and HGFA inhibitor type 1 (HAI-1). Kataoka, H., Itoh, H., Hamasuna, R., Meng, J.Y., Koono, M. Hum. Cell (2001) [Pubmed]
  12. Functional characterization of Kunitz domains in hepatocyte growth factor activator inhibitor type 2. Qin, L., Denda, K., Shimomura, T., Kawaguchi, T., Kitamura, N. FEBS Lett. (1998) [Pubmed]
  13. Activation of hepatocyte growth factor by two homologous proteases, blood-coagulation factor XIIa and hepatocyte growth factor activator. Shimomura, T., Miyazawa, K., Komiyama, Y., Hiraoka, H., Naka, D., Morimoto, Y., Kitamura, N. Eur. J. Biochem. (1995) [Pubmed]
  14. Hepatocyte growth factor activator inhibitor types 1 and 2 are expressed by tubular epithelium in kidney and down-regulated in renal cell carcinoma. Yamauchi, M., Kataoka, H., Itoh, H., Seguchi, T., Hasui, Y., Osada, Y. J. Urol. (2004) [Pubmed]
  15. Concomitant expression of hepatocyte growth factor (HGF), HGF activator and c-met genes in human glioma cells in vitro. Moriyama, T., Kataoka, H., Tsubouchi, H., Koono, M. FEBS Lett. (1995) [Pubmed]
  16. Roles of hepatocyte growth factor (HGF) activator and HGF activator inhibitor in the pericellular activation of HGF/scatter factor. Kataoka, H., Miyata, S., Uchinokura, S., Itoh, H. Cancer Metastasis Rev. (2003) [Pubmed]
  17. Fine mapping a quantitative trait locus affecting ovulation rate in swine on chromosome 8. Campbell, E.M., Nonneman, D., Rohrer, G.A. J. Anim. Sci. (2003) [Pubmed]
  18. Activation of the zymogen of hepatocyte growth factor activator by thrombin. Shimomura, T., Kondo, J., Ochiai, M., Naka, D., Miyazawa, K., Morimoto, Y., Kitamura, N. J. Biol. Chem. (1993) [Pubmed]
  19. Defect of pro-hepatocyte growth factor activation by fibroblasts in idiopathic pulmonary fibrosis. Marchand-Adam, S., Fabre, A., Mailleux, A.A., Marchal, J., Quesnel, C., Kataoka, H., Aubier, M., Dehoux, M., Soler, P., Crestani, B. Am. J. Respir. Crit. Care Med. (2006) [Pubmed]
  20. Hepatocyte growth factor (HGF), HGF activator, and c-Met in synovial tissues in rheumatoid arthritis and osteoarthritis. Nagashima, M., Hasegawa, J., Kato, K., Yamazaki, J., Nishigai, K., Ishiwata, T., Asano, G., Yoshino, S. J. Rheumatol. (2001) [Pubmed]
  21. Astroglial expression of hepatocyte growth factor and hepatocyte growth factor activator in human brain tissues. Yamada, T., Yoshiyama, Y., Tsuboi, Y., Shimomura, T. Brain Res. (1997) [Pubmed]
  22. Hepatocyte growth factor (HGF) activator expressed in hair follicles is involved in in vitro HGF-dependent hair follicle elongation. Lee, Y.R., Yamazaki, M., Mitsui, S., Tsuboi, R., Ogawa, H. J. Dermatol. Sci. (2001) [Pubmed]
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