Cathepsin A is an

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

that is classified both as a

cathepsin Cathepsins (Ancient Greek ''kata-'' "down" and ''hepsein'' "boil"; abbreviated CTS) are proteases (enzymes that degrade proteins) found in all animals as well as other organisms. There are approximately a dozen members of this family, which are d ...

and a

carboxypeptidase A carboxypeptidase ( EC number 3.4.16 - 3.4.18) is a protease enzyme that hydrolyzes (cleaves) a peptide bond at the carboxy-terminal (C-terminal) end of a protein or peptide. This is in contrast to an aminopeptidases, which cleave peptide b ...

. In humans, it is encoded by the ''CTSA''

gene In biology, the word gene has two meanings. The Mendelian gene is a basic unit of heredity. The molecular gene is a sequence of nucleotides in DNA that is transcribed to produce a functional RNA. There are two types of molecular genes: protei ...

. The enzyme is also known as Human Protective Protein. It is a lysosomal serine carboxypeptidase. The enzyme is a zymogen and must be processed to produce a 32 kDa and 20 kDa large and small subunit, respectively, to become catalytically active. Cathespin L can activate Cathepsin A in vitro.

Structure

Cathepsin A contains a large and small subunit. The active site contains unusual pairs of carboxylic acids hydrogen bonded to one another, sometimes referred to as "Rebek pairs". CatA

The pairing of these carboxylic acids raises the pKa of one glutamate to ~13 while the other has a predicted pKa of ~6.

Function

This gene encodes a glycoprotein that associates with lysosomal enzymes beta-galactosidase and

neuraminidase Exo-α-sialidase (, sialidase, neuraminidase; systematic name acetylneuraminyl hydrolase) is a glycoside hydrolase that cleaves the glycosidic linkages of neuraminic acids: : Hydrolysis of α-(2→3)-, α-(2→6)-, α-(2→8)- glycosidic linkag ...

to form a complex of high-molecular-weight multimers. The formation of this complex provides a protective role for stability and activity. It is protective for

β-galactosidase β-Galactosidase (EC 3.2.1.23, beta-gal or β-gal; systematic name β-D-galactoside galactohydrolase) is a glycoside hydrolase enzyme that catalyzes hydrolysis of terminal non-reducing β-D-galactose residues in β-D-galactosides. (This enzym ...

and

Substrates

CTSA is part of the

Renin Angiotensin System Renin (etymology and pronunciation), also known as an angiotensinogenase, is an aspartic protease protein and enzyme secreted by the kidneys that participates in the body's renin-angiotensin-aldosterone system (RAAS)—also known as the renin ...

(RAS). Substrates of the enzyme that have been identified in vitro include endothelin I, angiotensin I, bradykinin, Substance P, and oxytocin. CatASubstrate

Inhibition

Cathepsin A is one of 14 human enzymes commonly inhibited by

organophosphate In organic chemistry, organophosphates (also known as phosphate esters, or OPEs) are a class of organophosphorus compounds with the general structure , a central phosphate molecule with alkyl or aromatic substituents. They can be considered ...

pesticides and phosphonate nerve agents. Cathepsin A can be inhibited by sarin, soman, cyclosarin, VX, and VR. After inhibition, it undergoes aging. The enzyme can be found in urine and blood.

Clinical significance

Deficiencies in this gene are linked to multiple forms of

galactosialidosis Galactosialidosis, also known as neuraminidase deficiency with beta-galactosidase deficiency, is a genetic lysosomal storage disease. It is caused by a mutation in the CTSA gene which leads to a deficiency of enzymes β-galactosidase and neuram ...

and

CARASAL Cathepsin-A Related Arteriopathy with Strokes And Leukoencephalopathy (CARASAL) is a rare genetic disorder that is caused by mutation in a gene Cathepsin A, ''CTSA'' which is located on a chromosome 20. This disease is allelic to Galactosialidosis ...

Interactions

Cathepsin A has been shown to

interact Advocates for Informed Choice, dba interACT or interACT Advocates for Intersex Youth, is a 501(c)(3) nonprofit organization advocating for the legal and human rights of children with intersex traits. The organization was founded in 2006 and fo ...

with

NEU1 Sialidase-1, is a mammalian lysosomal neuraminidase enzyme which in humans is encoded by the ''NEU1'' gene. Function The protein SIALIDASE-1 encoded by the NEU-1 gene encodes the lysosomal enzyme SIALIDASE-1, which cleaves terminal sialic acid ...

and

GLB1 Galactosidase, beta 1, also known as GLB1, is a protein which in humans is encoded by the ''GLB1'' gene. The GLB1 protein is a beta-galactosidase that cleaves the terminal beta-galactose from ganglioside substrates and other glycoconjugates. The ...

References

External links

* {{Portal bar, Biology, border=no EC 3.4.16 Proteases Cathepsins