Serine Peptidase Inhibitor, Kunitz Type 2 (SPINT2), also known as Hepatocyte Growth Factor Activator Inhibitor Type 2 (HAI-2), is a protein encoded by the SPINT2 gene in humans. This protein plays a crucial role in inhibiting a variety of serine proteases, which are enzymes that cleave peptide bonds in proteins.
The SPINT2 gene is located on chromosome 19q13.2 and encodes a transmembrane protein with two extracellular Kunitz domains . These Kunitz domains are responsible for the inhibitory activity of the protein. The protein has a calculated molecular mass of approximately 28.2 kDa and contains an N-terminal signal peptide, a hydrophobic membrane-associated C-terminal region, and two potential N-glycosylation sites .
SPINT2 inhibits several serine proteases, including the Hepatocyte Growth Factor Activator (HGFAC), plasmin, and tissue kallikrein . By inhibiting HGFAC, SPINT2 prevents the formation of active hepatocyte growth factor, which is involved in cell growth, motility, and morphogenesis. This inhibition is crucial for regulating various physiological processes and maintaining tissue homeostasis.
SPINT2 is considered a putative tumor suppressor. Mutations in the SPINT2 gene have been associated with congenital sodium diarrhea, a condition characterized by severe diarrhea and electrolyte imbalance . Additionally, overexpression of SPINT2 has been observed in pancreatic cancer tissues and cell lines, suggesting its potential role in cancer biology .
Recombinant SPINT2 is produced using recombinant DNA technology, which involves inserting the SPINT2 gene into a suitable expression system, such as bacteria or mammalian cells, to produce the protein in large quantities. This recombinant protein is used in various research and clinical applications to study its inhibitory effects on serine proteases and its potential therapeutic uses.