SPINK gene family

SPINK is the acronym for "Serine Peptidase Inhibitor Kazal" and comprises a gene family placed on different chromosomes. The members of this gene family code for specific proteases, the SPINK protease inhibitor Kazal-type (SPINK) family. These are serine peptidase inhibitors. They contain at least one inhibitory Kazal domain. This domain binds to their targets, the serine proteases, and inhibits their proteolytic functions. This regulatory inhibitory function and its fine-tuning is fundamental for many epithelia.

SPINK family members 1, 2, and 4 have comparable size and structure, encoded by 4 exons with a single Kazal-type serine protease inhibitor domain. SPINK5, on the other hand, contains 33 exons encoding 15 inhibitory domains. These SPINK protease inhibitors are thought to be involved in protection against proteolytic degradation of epithelial and mucosal tissues, although their respective major sites of expression may differ.

Some SPINK protease inhibitors (e.g., SPINK7, also known as esophageal cancer-related gene 2) has a role as a tumor suppressor through its ability to inhibit urokinase plasminogen-type activator (uPA) binding to the uPA receptor (uPAR) and cleavage of uPAR, which suppresses cell migration/invasion and signaling pathways including increased cytosolic calcium.

SPINK family members 1, 2, and 4 have comparable size and structure, encoded by 4 exons with a single Kazal-type serine protease inhibitory domain. SPINK5, on the other hand, contains 33 exons encoding 15 inhibitory domains. These SPINK protease inhibitors are thought to be involved in protection against proteolytic degradation of epithelial and mucosal tissues, although their respective major sites of expression may differ.

Some SPINK protease inhibitors (e.g., SPINK7, also known as esophageal cancer-related gene 2) has a role as a tumor suppressor through its ability to inhibit urokinase plasminogen-type activator (uPA) binding to the uPA receptor (uPAR) and cleavage of uPAR, which suppresses cell migration/invasion and signaling pathways including increased cytosolic calcium.

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7. Wapenaar MC et al (2007) The SPINK-gene family. Immunogenetics 59: 349-357