SPINK5

This gene encodes a multidomain serine protease inhibitor that contains 15 potential inhibitory domains. The encoded preproprotein is proteolytically processed to generate multiple protein products, which may exhibit unique activities and specificities. These proteins may play a role in skin and hair morphogenesis, as well as anti-inflammatory and antimicrobial protection of mucous epithelia. Mutations in this gene may result in Netherton syndrome, a disorder characterized by ichthyosis, defective cornification, and atopy. This gene is present in a gene cluster on chromosome 5. Alternative splicing results in multiple transcript variants.

Full Name

Serine Peptidase Inhibitor, Kazal Type 5

Function

Serine protease inhibitor, probably important for the anti-inflammatory and/or antimicrobial protection of mucous epithelia. Contribute to the integrity and protective barrier function of the skin by regulating the activity of defense-activating and desquamation-involved proteases. Inhibits KLK5, it's major target, in a pH-dependent manner. Inhibits KLK7, KLK14 CASP14, and trypsin.

Biological Process

Biological Process cell differentiationManual Assertion Based On ExperimentIBA:GO_Central
Biological Process central nervous system developmentManual Assertion Based On ExperimentIBA:GO_Central
Biological Process epidermal cell differentiationManual Assertion Based On ExperimentIDA:UniProtKB
Biological Process epithelial cell differentiationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process extracellular matrix organizationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process hair cell differentiationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process negative regulation of angiogenesisManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process negative regulation of antibacterial peptide productionIEA:Ensembl
Biological Process negative regulation of immune responseManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process negative regulation of serine-type endopeptidase activityIEA:Ensembl
Biological Process negative regulation of serine-type peptidase activityManual Assertion Based On ExperimentIBA:GO_Central
Biological Process regulation of cell adhesionIEA:Ensembl
Biological Process regulation of T cell differentiationManual Assertion Based On ExperimentTAS:UniProtKB
Biological Process regulation of timing of anagenManual Assertion Based On ExperimentTAS:UniProtKB

Cellular Location

Secreted

Involvement in disease

Netherton syndrome (NETH):
An autosomal recessive congenital ichthyosis associated with hair shaft abnormalities and anomalies of the immune system. Typical features are ichthyosis linearis circumflexa, ichthyosiform erythroderma, trichorrhexis invaginata (bamboo hair), atopic dermatitis, and hayfever. High postnatal mortality is due to failure to thrive, infections and hypernatremic dehydration.

PTM

Proteolytically processed by furin in individual domains (D1, D5, D6, D8 through D11, and D9 through D15) exhibiting various inhibitory potentials for multiple proteases.