Cathepsin A

Lysosomal carboxypeptidase, cathepsin A (protective protein, CathA), is a component of the lysosomal multienzyme complex along with beta-galactosidase (GAL) and sialidase Neu1, where it activates Neu1 and protects GAL and Neu1 against the rapid proteolytic degradation. Cathepsin A is a multicatalytic enzyme with deamidase and esterase in addition to carboxypeptidase activities. It was recently identified in human platelets as deamidase. In vitro, it hydrolyzes a variety of bioactive peptide hormones including tachykinins, suggesting that extralysosomal cathepsin A plays a role in regulation of bioactive peptide functions. It is a member of the alpha/beta hydrolase fold family and has been suggested to share a common ancestral relationship with other alpha/beta hydrolase fold enzymes, such as cholinesterases. Cathepsin A defects are linked to multiple forms of Galactosialidosis with a combined secondary deficiency of beta-galactosidase and neuraminidase. Cathepsin A is a key molecule in the onset of galactosialidosis and also highlight the therapeutic acts in vivo as an endothelin-1-inactivating enzyme and strongly confirm a crucial role of this enzyme in effective elastic fiber formation.

Cathepsin A Related Areas

Enzyme>>Protease & Regulator>>Serine Protease & Regulator>>Cathepsin A/CTSA

Cancer>>Angiogenesis>>Cathepsin Family>>Cathepsin A/CTSA

Immunology>>Innate Immunity>>Lysosomal Enzyme>>Cathepsin Family>>Cathepsin A/CTSA

Cathepsin A Alternative Names

Cathepsin A, CTSA, RP3-337O18.1, GLB2, GSL, NGBE, PPCA, PPGB [Homo sapiens]

Cathepsin A, Ctsa, RP23-61O3.6, AU019505, PPCA, Ppgb [Mus musculus]

Summaries for Cathepsin A

Entrez Gene summary for Cathepsin A:

This gene encodes a glycoprotein which associates with lysosomal enzymes beta-galactosidase and neuraminidase to form a complex of high molecular weight multimers. The formation of this complex provides a protective role for stability and activity. Deficiencies in this gene are linked to multiple forms of galactosialidosis. Alternatively spliced transcript variants encoding different isoforms have been found for this gene

OMIM - description for Cathepsin A:

Cathepsin A (protective protein) is a ubiquitously expressed multifunctional enzyme, with deamidase, esterase, and carboxypeptidase activities and a preference for substrates with hydrophobic amino acid residues at the P1-prime position. Association with CTSA, as part of the lysosomal multienzyme complex, is essential for stabilization of lysosomal beta-galactosidase (GLB1; 611458), as well as for activation of the lysosomal neuraminidase (NEU1; 608272) (summary by Seyrantepe et al., 2008).

Wikipedia summary for Cathepsin A:

Cathepsin A is an enzyme that is classified both as a cathepsin and a carboxypeptidase. In humans, it is encoded by the CTSA gene

Human Cathepsin A Protein General Information

 

• Protein names: Recommended name: Lysosomal protective protein
• Sequence length: 480 AA.
• Domain: Signal
• Sequence similarities: Belongs to the peptidase S10 family.
• Catalytic activity: Heterodimer of a 32 kDa chain and a 20 kDa chain; disulfide-linked.
• Subunit structure: Heterodimer of a 32 kDa chain and a 20 kDa chain; disulfide-linked.
• Subcellular location: Lysosome.
• Involvement in disease: Defects in CTSA are the cause of galactosialidosis (GSL) [MIM:256540]. A lysosomal storage disease associated with a combined deficiency of beta-galactosidase and neuraminidase, secondary to a defect in cathepsin A. All patients have clinical manifestations typical of a lysosomal disorder, such as coarse facies, cherry red spots, vertebral changes, foam cells in the bone marrow, and vacuolated lymphocytes. Three phenotypic subtypes are recognized. The early infantile form is associated with fetal hydrops, edema, ascites, visceromegaly, skeletal dysplasia, and early death. The late infantile type is characterized by hepatosplenomegaly, growth retardation, cardiac involvement, and a normal or mildly affected mental state. The juvenile/adult form is characterized by myoclonus, ataxia, angiokeratoma, mental retardation, neurologic deterioration, absence of visceromegaly, and long survival.

General information above from UniProt

Function for Cathepsin A Protein

UniProtKB:

Protective protein appears to be essential for both the activity of beta-galactosidase and neuraminidase, it associates with these enzymes and exerts a protective function necessary for their stability and activity. This protein is also a carboxypeptidase and can deamidate tachykinins

Genatlas:

• serine carboxypeptidase S10 family
• Cathepsin A galactosidase, associated with esterase, deamidase, serine carboxypeptidase, cathepsin A activity,
• serine carboxypeptidase activity triggering the degradation of the lysosome-associated membrane protein type 2a (Cuervo 2003)
• carboxypeptidase that can deamidate tachykinins (Galjart 1991)

Homology for human Cathepsin A

• homolog to murine Ctsa (87.8pc)
• homolog to rattus Ppgb (85.3pc)

Phenotype Information for Cathepsin A

• Gene/Locus: CTSA, PPGB, GSL, NGBE, GLB2
• Phenotype: Galactosialidosis

Phenotype Information for Cathepsin A from OMIM (Online Mendelian Inheritance in Man)