CASP14
This gene encodes a member of the cysteine-aspartic acid protease (caspase) family. Sequential activation of caspases plays a central role in the execution-phase of cell apoptosis. Caspases exist as inactive proenzymes which undergo proteolytic processing at conserved aspartic residues to produce two subunits, large and small, that dimerize to form the active enzyme. This caspase has been shown to be processed and activated by caspase 8 and caspase 10 in vitro, and by anti-Fas agonist antibody or TNF-related apoptosis inducing ligand in vivo. The expression and processing of this caspase may be involved in keratinocyte terminal differentiation, which is important for the formation of the skin barrier. [provided by RefSeq]
Full Name
caspase 14, apoptosis-related cysteine peptidase
Function
Non-apoptotic caspase involved in epidermal differentiation. Is the predominant caspase in epidermal stratum corneum (PubMed:15556625).
Seems to play a role in keratinocyte differentiation and is required for cornification. Regulates maturation of the epidermis by proteolytically processing filaggrin (By similarity).
In vitro has a preference for the substrate [WY]-X-X-D motif and is active on the synthetic caspase substrate WEHD-ACF (PubMed:16854378, PubMed:19960512).
Involved in processing of prosaposin in the epidermis (By similarity).
May be involved in retinal pigment epithelium cell barrier function (PubMed:25121097).
Involved in DNA degradation in differentiated keratinocytes probably by cleaving DFFA/ICAD leading to liberation of DFFB/CAD (PubMed:24743736).
Biological Process
Cornification Source: UniProtKB
Epidermis development Source: ProtInc
Keratinization Source: UniProtKB
Cellular Location
Cytoplasm; Nucleus
Involvement in disease
Ichthyosis, congenital, autosomal recessive 12 (ARCI12): A form of autosomal recessive congenital ichthyosis, a disorder of keratinization with abnormal differentiation and desquamation of the epidermis, resulting in abnormal skin scaling over the whole body. The main skin phenotypes are lamellar ichthyosis (LI) and non-bullous congenital ichthyosiform erythroderma (NCIE), although phenotypic overlap within the same patient or among patients from the same family can occur. Lamellar ichthyosis is a condition often associated with an embedment in a collodion-like membrane at birth; skin scales later develop, covering the entire body surface. Non-bullous congenital ichthyosiform erythroderma characterized by fine whitish scaling on an erythrodermal background; larger brownish scales are present on the buttocks, neck and legs.
PTM
Maturation by proteolytic processing appears to be a two-step process. The precursor is processed by KLK7 to yield the p20/p8 intermediate form which acts on the precursor to yield the p17/p10 mature form (PubMed:22825846). Initially, cleavage between Ile-152 and Lys-153 has been proposed to yield the large and small subunits of the active enzyme (PubMed:12200134).
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