Proteopedia

Hepatocyte growth factor activator inhibitor


Function

Hepatocyte growth factor activator inhibitor (HAI) or Kunitz-type protease inhibitor contains 2 Kunitz domains[1].

  • HAI-1 is a cell surface-binding protein and regulates hepatocyte growth factor activator activity in the patricellular microenvironment[2]. HAI-1 is the cognate inhibitor of HGFA and matripase.
  • HAI-2 is more efficient inhibitor of pepsin and displays a broader inhibitory spectrum[3]

Relevance

Abnormal levels of HAI-1 were observed in various types of human cancer[4].

Structural highlights

in the manner of other trypsin-like proteases inhibitors[5].


Human hepatocyte growth factor activator inhibitor 1 Kunitz domain 1 (green) complex with HGFA (blue) and phosphate (PDB code 1yc0)

Drag the structure with the mouse to rotate

3D structures of hepatocyte growth factor activator inhibitor3D structures of hepatocyte growth factor activator inhibitor

Updated on 01-July-2024

    • 1yc0 – hHAI1 Kunitz domain 1 + HGFA – human
    • 5ezd – hHAI1 PDK-like and Kunitz domain 1
    • 2msx – hHAI1 MANEC-type domain - NMR
    • 5h7v – hHAI1 ligand-binding domain
    • 4isl, 4isn, 4iso – hHAI1 Kunitz domain 1 + matriptase
  • Hepatocyte growth factor activator inhibitor 2
    • 4u32 – hHAI2 Kunitz domain 1 + mesotrypsin

ReferencesReferences

  1. ↑ Shimomura T, Denda K, Kitamura A, Kawaguchi T, Kito M, Kondo J, Kagaya S, Qin L, Takata H, Miyazawa K, Kitamura N. Hepatocyte growth factor activator inhibitor, a novel Kunitz-type serine protease inhibitor. J Biol Chem. 1997 Mar 7;272(10):6370-6. PMID:9045658
  2. ↑ Kataoka H, Shimomura T, Kawaguchi T, Hamasuna R, Itoh H, Kitamura N, Miyazawa K, Koono M. 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. J Biol Chem. 2000 Dec 22;275(51):40453-62. PMID:11013244 doi:http://dx.doi.org/10.1074/jbc.M006412200
  3. ↑ Nakamura K, Abarzua F, Hongo A, Kodama J, Nasu Y, Kumon H, Hiramatsu Y. Hepatocyte growth factor activator inhibitor-2 (HAI-2) is a favorable prognosis marker and inhibits cell growth through the apoptotic pathway in cervical cancer. Ann Oncol. 2009 Jan;20(1):63-70. PMID:18689863 doi:10.1093/annonc/mdn556
  4. ↑ Zheng Q, Wu H, Cao J, Ye J. Hepatocyte growth factor activator inhibitor type1 in cancer: advances and perspectives (Review). Mol Med Rep. 2014 Dec;10(6):2779-85. doi: 10.3892/mmr.2014.2628. Epub 2014 Oct, 13. PMID:25310042 doi:http://dx.doi.org/10.3892/mmr.2014.2628
  5. ↑ Shia S, Stamos J, Kirchhofer D, Fan B, Wu J, Corpuz RT, Santell L, Lazarus RA, Eigenbrot C. Conformational lability in serine protease active sites: structures of hepatocyte growth factor activator (HGFA) alone and with the inhibitory domain from HGFA inhibitor-1B. J Mol Biol. 2005 Mar 11;346(5):1335-49. Epub 2005 Jan 28. PMID:15713485 doi:10.1016/j.jmb.2004.12.048

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