SPINK5(490-624) binds KLK5

Stable Identifier
R-HSA-8849646
Type
Reaction
Species
Homo sapiens
Compartment
Locations in the PathwayBrowser
Summation

The D8D9 fragment of SPINK5 (Serine protease inhibitor Kazal-type 5, also known as LEKTI, Lympho-epithelial Kazal-type-related inhibitor), consisting of residues 490 - 624 of the full-length protein, binds to KLK5 (Kallikrein-5), inactivating the latter. At neutral pH, complex formation is effectively irreversible. In normal skin, this event occurs extracellularly in the stratum corneum of the skin. As the complex is carried into layers nearer the surface of the skin, falling pH triggers its dissociation and release of active KLK5. Mutations that inactivate SPINK5 are associated with a severe skin disorder, Netherton syndrome (NS, MIM 256500), whose symptoms include premature desquamation (Deraison et al, 2007; Fortugno et al. 2011). Consistent with the hypothesis that SPINK5-mediated inhibition of KLK5 activity is a key feature of regulating normal desquamation, the NS-like phenotype of mice whose SPINK5-homologous gene has been knocked out is reversed in mice missing both SPINK5 and KLK5 activitiies (Furio et al. 2015).

Literature References
PubMed ID Title Journal Year
17596512 LEKTI fragments specifically inhibit KLK5, KLK7, and KLK14 and control desquamation through a pH-dependent interaction

Deraison, C, Bonnart, C, Lopez, F, Besson, C, Robinson, R, Jayakumar, A, Wagberg, F, Brattsand, M, Hachem, JP, Leonardsson, G, Hovnanian, A

Mol. Biol. Cell 2007
26390218 KLK5 Inactivation Reverses Cutaneous Hallmarks of Netherton Syndrome

Furio, L, Pampalakis, G, Michael, IP, Nagy, A, Sotiropoulou, G, Hovnanian, A

PLoS Genet. 2015
Participants
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