Cystatin-A (CSTA) Human Active Protein

The cystatin superfamily encompasses proteins that contain multiple cystatin-like sequences. Some of the members are active cysteine protease inhibitors, while others have lost or perhaps never acquired this inhibitory activity. There are three inhibitory families in the superfamily, including the type 1 cystatins (stefins), type 2 cystatins, and kininogens. This gene encodes a stefin that functions as a cysteine protease inhibitor, forming tight complexes with papain and the cathepsins B, H, and L. The protein is one of the precursor proteins of cornified cell envelope in keratinocytes and plays a role in epidermal development and maintenance. Stefins have been proposed as prognostic and diagnostic tools for cancer. [provided by RefSeq, Jul 2008]

CSTA: This is an intracellular thiol proteinase inhibitor. Has an important role in desmosome-mediated cell-cell adhesion in the lower levels of the epidermis. Defects in CSTA are the cause of ichthyosis exfoliative autosomal recessive ichthyosis bullosa of Siemens-like (AREI). A form of congenital exfoliative ichthyosis, sharing some features with ichthyosis bullosa of Siemens and annular epidermolytic ichthyosis. AREI presents shortly after birth as dry, scaly skin over most of the body with coarse peeling of non- erythematous skin on the palms and soles, which is exacerbated by excessive moisture and minor trauma. Electron microscopy analysis of skin biopsies, reveals mostly normal-appearing upper layers of the epidermis, but prominent intercellular edema of the basal and suprabasal cell layers with aggregates of tonofilaments in the basal keratinocytes. Belongs to the cystatin family.

Chromosomal Location of Human Ortholog: 3q21

Cellular Component: nucleoplasm; extracellular space; cytoplasm; cornified envelope; nucleus

Molecular Function: protein binding, bridging; protease binding; cysteine protease inhibitor activity; structural molecule activity

Biological Process: negative regulation of proteolysis; keratinocyte differentiation; cell-cell adhesion; negative regulation of peptidase activity; peptide cross-linking

Disease: Exfoliative Ichthyosis, Autosomal Recessive, Ichthyosis Bullosa Of Siemens-like