ASPRV1 Human

Aspartic Peptidase, Retroviral-Like 1 (ASPRV1), also known as Skin Aspartic Protease (SASPase), is a protein-coding gene that plays a crucial role in the development and maintenance of the skin barrier. This enzyme is particularly significant in the processing of profilaggrin to filaggrin, which is essential for proper epidermal organization .

The ASPRV1 gene is located on chromosome 2p13.3 and spans approximately 2.35 kb. It contains a single exon with no introns . The gene encodes a protein that consists of 343 amino acids with a calculated molecular mass of 37 kDa. An alternative isoform of 259 amino acids has a molecular mass of 28.5 kDa . The protein shares similarity with aspartyl proteases with a retroviral-type signature, such as the equine anemia virus (EIAV) protease .

ASPRV1 is primarily expressed in the epidermis and the inner root sheath of hair follicles . Northern blot analysis has detected its expression mainly in the skin, with lower levels in the brain . The protein is specifically localized in the granular layer of the skin, which is why it is also referred to as skin-specific aspartic protease .

ASPRV1 is responsible for the catalytic activity that processes profilaggrin to filaggrin, a crucial step in maintaining the skin barrier . Filaggrin is a structural protein that aggregates keratin filaments in epidermal cells, contributing to the skin’s barrier function. The enzyme’s activity is essential for proper epidermal differentiation and organization .

The ASPRV1 protein contains several functional domains, including a predicted N-myristoylation domain, a dileucine site, N-glycosylation, sulfation, phosphorylation, myristoylation, and amidation sites, as well as a putative transmembrane domain . The enzyme exhibits aspartic-type endopeptidase activity, which is crucial for its role in filaggrin processing .

Mutations in the ASPRV1 gene have been associated with skin disorders such as autosomal dominant lamellar ichthyosis and autosomal recessive congenital ichthyosis . These conditions are characterized by abnormal skin barrier function, leading to dry, scaly skin.