SPINT2 explained

Kunitz-type protease inhibitor 2 is an enzyme inhibitor that in humans is encoded by the SPINT2 gene.^{[1] [2] [3]} SPINT2 is a transmembrane protein with two extracellular Kunitz domains to inhibit serine proteases. This gene is a presumed tumor suppressor by inhibiting HGF activator which prevents the formation of active hepatocyte growth factor. Mutations in SPINT2 could result in congenital sodium diarrhea (CSD).

Further reading

• Morelle W, Capon C, Balduyck M, Sautiere P, Kouach M, Michalski C, Fournet B, Mizon J . Chondroitin sulphate covalently cross-links the three polypeptide chains of inter-alpha-trypsin inhibitor . European Journal of Biochemistry . 221 . 2 . 881–8 . Apr 1994 . 7513643 . 10.1111/j.1432-1033.1994.tb18803.x .
• Mizon C, Balduyck M, Albani D, Michalski C, Burnouf T, Mizon J . Development of an enzyme-linked immunosorbent assay for human plasma inter-alpha-trypsin inhibitor (ITI) using specific antibodies against each of the H1 and H2 heavy chains . Journal of Immunological Methods . 190 . 1 . 61–70 . Mar 1996 . 8601712 . 10.1016/0022-1759(95)00257-X .
• Gress TM, Müller-Pillasch F, Geng M, Zimmerhackl F, Zehetner G, Friess H, Büchler M, Adler G, Lehrach H . A pancreatic cancer-specific expression profile . Oncogene . 13 . 8 . 1819–30 . Oct 1996 . 8895530 .
• 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 . The Journal of Biological Chemistry . 272 . 10 . 6370–6 . Mar 1997 . 9045658 . 10.1074/jbc.272.10.6370 . free .
• Blom AM, Thuveson M, Fries E . Intracellular coupling of bikunin and the heavy chain of rat pre-alpha-inhibitor in COS-1 cells . The Biochemical Journal . 328 (Pt 1) . Pt 1 . 185–91 . Nov 1997 . 9359851 . 1218904 . 10.1042/bj3280185.
• Müller-Pillasch F, Wallrapp C, Bartels K, Varga G, Friess H, Büchler M, Adler G, Gress TM . Cloning of a new Kunitz-type protease inhibitor with a putative transmembrane domain overexpressed in pancreatic cancer . Biochimica et Biophysica Acta (BBA) - Gene Structure and Expression . 1395 . 1 . 88–95 . Jan 1998 . 9434156 . 10.1016/s0167-4781(97)00129-2 .
• 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 . The Journal of Biological Chemistry . 275 . 51 . 40453–62 . Dec 2000 . 11013244 . 10.1074/jbc.M006412200 . free .
• Itoh H, Kataoka H, Yamauchi M, Naganuma S, Akiyama Y, Nuki Y, Shimomura T, Miyazawa K, Kitamura N, Koono M . Identification of hepatocyte growth factor activator inhibitor type 2 (HAI-2)-related small peptide (H2RSP): its nuclear localization and generation of chimeric mRNA transcribed from both HAI-2 and H2RSP genes . Biochemical and Biophysical Research Communications . 288 . 2 . 390–9 . Oct 2001 . 11606055 . 10.1006/bbrc.2001.5767 .
• Suzuki M, Kobayashi H, Fujie M, Nishida T, Takigawa M, Kanayama N, Terao T . Kunitz-type protease inhibitor bikunin disrupts phorbol ester-induced oligomerization of CD44 variant isoforms containing epitope v9 and subsequently suppresses expression of urokinase-type plasminogen activator in human chondrosarcoma cells . The Journal of Biological Chemistry . 277 . 10 . 8022–32 . Mar 2002 . 11777908 . 10.1074/jbc.M108545200 . free .
• Kobayashi H, Suzuki M, Kanayama N, Nishida T, Takigawa M, Terao T . Suppression of urokinase receptor expression by bikunin is associated with inhibition of upstream targets of extracellular signal-regulated kinase-dependent cascade . European Journal of Biochemistry . 269 . 16 . 3945–57 . Aug 2002 . 12180971 . 10.1046/j.1432-1033.2002.03068.x . free .
• Mizon C, Piva F, Queyrel V, Balduyck M, Hachulla E, Mizon J . Urinary bikunin determination provides insight into proteinase/proteinase inhibitor imbalance in patients with inflammatory diseases . Clinical Chemistry and Laboratory Medicine . 40 . 6 . 579–86 . Jun 2002 . 12211652 . 10.1515/CCLM.2002.100 . 22630736 .
• Isogai R, Matsukura A, Aragane Y, Maeda A, Matsukura M, Yudate T, Sugihara K, Takahashi M, Aisu K, Tezuka T . Quantitative analysis of bikunin-laden mast cells in follicular eruptions and chronic skin lesions of atopic dermatitis . Archives of Dermatological Research . 294 . 9 . 387–92 . Dec 2002 . 12522575 . 10.1007/s00403-002-0336-9 . 9514861 .
• Yamauchi M, Itoh H, Naganuma S, Koono M, Hasui Y, Osada Y, Kataoka H . Expression of hepatocyte growth factor activator inhibitor type 2 (HAI-2) in human testis: identification of a distinct transcription start site for the HAI-2 gene in testis . Biological Chemistry . 383 . 12 . 1953–7 . Dec 2002 . 12553733 . 10.1515/BC.2002.220 . 19734313 .
• Suzuki M, Kobayashi H, Tanaka Y, Hirashima Y, Kanayama N, Takei Y, Saga Y, Suzuki M, Itoh H, Terao T . Suppression of invasion and peritoneal carcinomatosis of ovarian cancer cell line by overexpression of bikunin . International Journal of Cancer . 104 . 3 . 289–302 . Apr 2003 . 12569552 . 10.1002/ijc.10950 . 10271/1250 . 84583247 . free .
• Suzuki M, Kobayashi H, Tanaka Y, Hirashima Y, Kanayama N, Takei Y, Saga Y, Suzuki M, Itoh H, Terao T . Bikunin target genes in ovarian cancer cells identified by microarray analysis . The Journal of Biological Chemistry . 278 . 17 . 14640–6 . Apr 2003 . 12571229 . 10.1074/jbc.M300239200 . free .
• Schuster JM, Longo M, Nelson PS . Differential expression of bikunin (HAI-2/PB), a proposed mediator of glioma invasion, by demethylation treatment . Journal of Neuro-Oncology . 64 . 3 . 219–25 . Sep 2003 . 14558597 . 10.1023/A:1025674227750 . 22607445 .
• Fukai K, Yokosuka O, Chiba T, Hirasawa Y, Tada M, Imazeki F, Kataoka H, Saisho H . Hepatocyte growth factor activator inhibitor 2/placental bikunin (HAI-2/PB) gene is frequently hypermethylated in human hepatocellular carcinoma . Cancer Research . 63 . 24 . 8674–9 . Dec 2003 . 14695180 .

Notes and References

1. Marlor CW, Delaria KA, Davis G, Muller DK, Greve JM, Tamburini PP . Identification and cloning of human placental bikunin, a novel serine protease inhibitor containing two Kunitz domains . The Journal of Biological Chemistry . 272 . 18 . 12202–8 . May 1997 . 9115294 . 10.1074/jbc.272.18.12202 . free .
2. Kawaguchi T, Qin L, Shimomura T, Kondo J, Matsumoto K, Denda K, Kitamura N . Purification and cloning of hepatocyte growth factor activator inhibitor type 2, a Kunitz-type serine protease inhibitor . The Journal of Biological Chemistry . 272 . 44 . 27558–64 . Oct 1997 . 9346890 . 10.1074/jbc.272.44.27558 . free .
3. Web site: Entrez Gene: SPINT2 serine peptidase inhibitor, Kunitz type, 2.