SPINK6 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 its target, the serine proteases, and inhibits their proteolytic functions. This regulatory inhibitory function and its fine-tuning is fundamental for many epithelia.

SPINK6 (Kazal-type 6 serine protease inhibitor) was identified as a selective inhibitor of "Extracellular kallikrein-related peptidases (KLKs) in human stratum corneum extracts.

Immunohistochemical analysis revealed SPINK6 expression in the stratum granulosum of human skin at various anatomical locations and in skin appendages, including sebaceous and sweat glands. SPINK6 expression is decreased in lesions of atopic dermatitis (Meyer-Hoffert U et al. 2010).

SPINK6 plays a role in modulating the activity of KLKs (kallikrein-related peptidases) in human skin. Selective inhibition of KLKs by SPINK6 may have therapeutic potential when KLK activity is elevated. KLKs are involved in the desquamation process of the epidermis and in the initiation of epidermal inflammation through different mechanisms. Their action is tightly controlled by specific protease inhibitors.

SPINK6 is expressed in the same localization as transglutaminases (TGM). The protease inhibitor also contains TGM substrate motifs. Recombinant SPINK6 was shown to be cross-linked to fibronectin (FN) by TGM1. Conjugated SPINK6 showed protease inhibitory activity in keratinocytes and stratum corneum extracts. Cross-linked SPINK6 protected fibronectin from extracellular kallikrein-related peptidase (KLK5)-mediated cleavage.

1. Fischer J et al (2013) Cross-linking of SPINK6 by transglutaminases protects from epidermal proteases. J Invest Dermatol 133:1170-1177.
2. Meyer-Hoffert U et al (2010) Isolation of SPINK6 in human skin: selective inhibitor of kallikrein-related peptidases. J Biol Chem 285:32174-32181.