SPINK1 gene

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 the specific proteases, the Kazal-type SPINK protease inhibitor family (SPINK). 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.

The SPINK1 gene is located on chromosome 5q32 and consists of four exons. SPINK1 encodes the SPINK1 protein, a protein product 79 amino acids in length, the serine protease inhibitor Kazal type 1, also known as pancreatic secretory trypsin inhibitor (PSTI). SPINK1 was originally isolated as "tumor-associated trypsin inhibitor -TATI - from the urine of a patient with ovarian cancer.

In pancreatic tissue, SPINK1 exerts an inhibitory function in trypsin-catalyzed premature activation of zymogens.

Polymorphisms in the SPINK1 gene are associated with hereditary pancreatitis (see below.Pancreatitis chronic) and tropical calcified pancreatitis. They appear to play a pathogenetic role (Averbukh LD et al.2019).

SPINK1 acts not only as a protease inhibitor, but also as an "acute phase reactant" as well as a growth factor (Räsänen K et al. 2016). It has also been shown to modulate apoptosis.

Overexpression of SPINK1 has been demonstrated in several cancers, including prostate cancer (Attard G et al. 2016). Overexpression may be associated with an unfavorable course (Räsänen K et al. 2016).

1. Attard G et al.(2016) Prostate cancer. Lancet. 2016 Jan 2;387(10013):70-82
2. Averbukh LD et al.(2019) SPINK-1 polymorphism as a pancreatitis risk factor. Cureus. 11(1):e3852.
3. Räsänen K et al (2016) Emerging roles of SPINK1 in cancer. Clin Chem 62:449-457.