KLK7

Kallikrein-related peptidase 7 (KLK7) is a is_associated_with::serine protease that in humans is encoded by the KLK7 is_associated_with::gene. KLK7 was initially purified from the epidermis and characterised as stratum corneum chymotryptic enzyme (SCCE). It was later identified as the seventh member of the human is_associated_with::kallikrein family, which includes fifteen homologous serine proteases located on is_associated_with::chromosome 19q13.

Gene
Alternative splicing of the KLK7 gene results in two transcript variants encoding the same protein.

Function
KLK7 is secreted as an inactive is_associated_with::zymogen in the is_associated_with::stratum granulosum layer of the epidermis, requiring proteolytic cleavage of the short N-terminal pro-region to liberate activated enzyme. This may be performed by is_associated_with::KLK5 or is_associated_with::matriptase, which are in vitro activators of KLK7.

Once active, KLK7 is able to cleave is_associated_with::desmocollin and is_associated_with::corneodesmosin. These proteins constitute the extracellular component of corneodesmosomes, intercellular cohesive structures which link the is_associated_with::intermediate filaments of adjacent cells in the is_associated_with::stratum corneum. Proteolysis of corneodesmosomes is required for is_associated_with::desquamation, the shedding of corneocytes from the outer layer of the epidermis. This indicates a role for KLK7 in maintaining skin is_associated_with::homeostasis.

Both KLK5 and is_associated_with::KLK14, other skin-expressed proteases, also cleave corneodesmosomal proteins. KLK5 is able to undergo autoactivation, as well as activating KLK7 and KLK14, suggesting a KLK skin cascade is responsible for coordinating desquamation.

KLK7 activity is regulated by a number of endogenous protein inhibitors including is_associated_with::LEKTI, is_associated_with::SPINK6, is_associated_with::elafin and is_associated_with::alpha-2-Macroglobulin-like 1. Both Zn2+ and Cu2+ ions are also able to inhibit KLK7.

KLK7 is a chymotrypsin-like serine protease, preferring to cleave proteins at the residues is_associated_with::tyrosine, is_associated_with::phenylalanine or is_associated_with::leucine. Analysis of peptide substrate hydrolysis indicates a strong preference for tyrosine at P1.

Skin disease
Dysregulation of KLK7 has been linked to several skin disorders including is_associated_with::atopic dermatitis, is_associated_with::psoriasis and is_associated_with::Netherton syndrome. These diseases are characterised by excessively dry, scaly and inflamed skin, due to a disruption of skin homeostasis and correct barrier function.

Cancer
Overexpression of KLK7 may provide a route for is_associated_with::metastasis in ovarian, breast, pancreatic, cervix, and is_associated_with::melanoma is_associated_with::cancers by excessive cleavage of cell junction proteins. It may also be underexpressed in is_associated_with::lung cancer.