Alternative titles; symbols
HGNC Approved Gene Symbol: KLK7
Cytogenetic location: 19q13.41 Genomic coordinates (GRCh38) : 19:50,976,468-50,984,064 (from NCBI)
KLK7 belongs to the kallikrein subfamily of serine proteases, which are involved in a variety of enzymatic processes (Gan et al., 2000).
The stratum corneum is the outermost layer of the epidermis, i.e., the stratified squamous epithelium lining the body surface. The cells of the stratum corneum, the corneocytes, represent the end stage of the epidermal differentiation process. Corneocytes are highly resistant anucleated cells mainly consisting of keratin filaments surrounded by a crosslinked protein envelope. The mechanical resistance of the stratum corneum is dependent on the cohesion between individual corneocytes, which is mediated to a major extent by modified desmosomes. Since a fraction of epidermal cells continuously leaves the proliferating basal layer and goes through differentiation, there is a continuous de novo production of corneocytes. This is balanced to give a constant and well-regulated stratum corneum thickness by cell shedding at the skin surface in a process called desquamation. Desquamation means elimination of stratum corneum cell cohesion in superficial cell layers. It has been established that proteolysis of intercellular cohesive structures is of major importance in the series of events preceding desquamation. Stratum corneum chymotryptic enzyme (SCCE), or kallikrein-7 (KLK7), is a serine proteinase with an inhibitor profile, pH dependence, and tissue localization compatible with a role in desquamation. Egelrud (1993) purified SCCE from human plantar corneocytes. SDS-PAGE indicated that the purified preparation contained 1 major component with an apparent molecular mass of 25 kD and 1 minor component with a slightly higher apparent molecular mass. Both of these components were associated with chymotrypsin-like activity, although SCCE differed significantly from bovine chymotrypsin, human cathepsin G (116830), and human mast cell chymases (see 118938) in its relative activity toward various substrates and in its inhibitor profile. Hansson et al. (1994) sequenced the N-terminal region of the native SCCE enzyme. By screening a human keratinocyte cDNA library with a degenerate oligonucleotide based on the amino acid sequence of SCCE, they isolated 2 forms of SCCE cDNA that differed only in the 3-prime untranslated region. The predicted 253-amino acid protein consists of a 22-amino acid signal peptide and a 7-amino acid propeptide followed by the active enzyme. SCCE contains the conserved active site regions of serine proteinases and a potential N-glycosylation site. The amino acid sequence homology between SCCE and human chymotrypsin, cathepsin G, and mast cell chymase, all of which have chymotryptic activity, did not exceed 40%. Hansson et al. (1994) demonstrated that SCCE is heterogenously glycosylated. Northern blot analysis detected 1.2- and 2.0-kb SCCE transcripts in human skin. Abundant SCCE mRNA expression was restricted to skin, with very low levels of expression found in brain and kidney. Immunohistochemical analyses had shown that the SCCE protein is present in high suprabasal keratinocytes in the epidermis and in the keratinizing inner root sheet of the hair follicle (Sondell et al., 1994). In the human oral cavity, only suprabasal keratinocytes at sites where a stratum corneum is formed contained SCCE.
Yousef et al. (2000) noted the presence of 12 cysteine residues in KLK7, 10 of which are conserved in all serine proteases, and 2 of which are also found in other KLK proteins. RT-PCR analysis revealed expression primarily in brain, mammary gland, cerebellum, spinal cord, kidney, and skin, with lower levels or none detected in other tissues.
Yousef et al. (2000) observed the upregulation of KLK7 expression in a breast cancer cell in response to estrogens and glucocorticoids.
By genomic sequence analysis, Yousef et al. (2000) determined that the KLK7 gene contains 6 exons, 5 of which are coding. The gene spans 6 kb.
By computational analysis, Yousef et al. (2000) mapped the KLK7 gene to chromosome 19q13.3-q13.4 between KLK6 (602652) and KLK8 (605644).
Egelrud, T. Purification and preliminary characterization of stratum corneum chymotryptic enzyme: a proteinase that may be involved in desquamation. J. Invest. Derm. 101: 200-204, 1993. [PubMed: 8393902] [Full Text: https://doi.org/10.1111/1523-1747.ep12363804]
Gan, L., Lee, I., Smith, R., Argonza-Barrett, R., Lei, H., McCuaig, J., Moss, P., Paeper, B., Wang, K. Sequencing and expression analysis of the serine protease gene cluster located in chromosome 19q13 region. Gene 257: 119-130, 2000. [PubMed: 11054574] [Full Text: https://doi.org/10.1016/s0378-1119(00)00382-6]
Hansson, L., Stromqvist, M., Backman, A., Wallbrandt, P., Carlstein, A., Egelrud, T. Cloning, expression, and characterization of stratum corneum chymotryptic enzyme: a skin-specific human serine proteinase. J. Biol. Chem. 269: 19420-19426, 1994. [PubMed: 8034709]
Sondell, B., Thornell, L. E., Stigbrand, T., Egelrud, T. Immunolocalization of stratum corneum chymotryptic enzyme in human skin and oral epithelium with monoclonal antibodies: evidence of a proteinase specifically expressed in keratinizing squamous epithelia. J. Histochem. Cytochem. 42: 459-465, 1994. [PubMed: 7510318] [Full Text: https://doi.org/10.1177/42.4.7510318]
Yousef, G. M., Scorilas, A., Magklara, A., Soosaipillai, A., Diamandis, E. P. The KLK7 (PRSS6) gene, encoding for the stratum corneum chymotryptic enzyme is a new member of the human kallikrein gene family-genomic characterization, mapping, tissue expression and hormonal regulation. Gene 254: 119-128, 2000. [PubMed: 10974542] [Full Text: https://doi.org/10.1016/s0378-1119(00)00280-8]