Prosaposin also known as PSAP is a protein

Protein

Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...

 which in humans is encoded by the PSAP gene

Gene

A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...

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This gene encodes a highly conserved glycoprotein

Glycoprotein

Glycoproteins are proteins that contain oligosaccharide chains covalently attached to polypeptide side-chains. The carbohydrate is attached to the protein in a cotranslational or posttranslational modification. This process is known as glycosylation. In proteins that have segments extending...

 which is a precursor for 4 cleavage products: saposins A, B, C, and D. Saposin is an acronym for Sphingolipid Activator PrO[S]teINs. Each domain of the precursor protein is approximately 80 amino acid residues long with nearly identical placement of cysteine residues and glycosylation sites. Saposins A-D localize primarily to the lysosomal

Lysosome

thumb|350px|Schematic of typical animal cell, showing subcellular components. [[Organelle]]s: [[nucleoli]] [[cell nucleus|nucleus]] [[ribosomes]] [[vesicle |vesicle]] rough [[endoplasmic reticulum]]...

 compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide

Oligosaccharide

An oligosaccharide is a saccharide polymer containing a small number of component sugars, also known as simple sugars...

 groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic

Neurotrophin

Neurotrophins are a family of proteins that induce the survival, development, and function of neurons.They belong to a class of growth factors, secreted proteins that are capable of signaling particular cells to survive, differentiate, or grow. Growth factors such as neurotrophins that promote the...

 activities.

Saposins A-D are required for the hydrolysis of certain sphingolipids by specific lysosomal hydrolases.

Family members

• Saposin A was identified as an N-terminal domain in the prosaposin cDNA prior to its isolation. It is known to stimulate the enzymatic hydrolysis of 4-methlyumbelliferyl-β-glucoside, glucocerebroside, and galactocerebroside.

• Saposin B was the first to be discovered and was found to be required as a heat-stable factor for hydrolysis of sulfatides by arylsulfatase A. It is known by many different names, such as, sphingolipid activator protein-1 (SAP-1), sulfatide activator protein, GM₁ ganglioside activator, dispersin, and nonspecific. It has been observed that this particular saposin activates many enzymes through interaction with the substrates not the enzymes themselves.

• Saposin C was the second saposin to be discovered and stimulates the hydrolysis of glycocerebroside by glycosylceramidase and galactocerebroside by galactoslyceramidase.

• Saposin D is not well known to due lack of investigation at this point in time. It was predicted from the cDNA sequence of prosaposin, like saposin A. Ezymatic stimulation is very specific for this particular glycoprotein and it not understood completely.

Structure

Every saposin contains about 80 amino acid residues and has six equally placed cytesines, two prolines, and a glycosylation site (two in saposin A, one each in saposins B, C, and D). Since saposins characteristics of extreme heat-stability, adundance of disulfide linkages, and resistance to most proteases, they are assumed to be extremely compact and rigidly disulfide-linked molecules. Each saposin has an α-helical structure that is seen as being important for stimulation because this structure is maximal at a pH of 4.5; which is optimal for many lysosomal hydrolases. This helical structure is seen in all (especially with the first region), but saposin has been predicted to have β-sheet configuration due to it first 24 amino acids of the N-end.

Function

They probably act by isolating the lipid substrate from the membrane surroundings, thus making it more accessible to the soluble degradative enzymes. which contains four Saposin-B domains, yielding the active saposins after proteolytic cleavage, and two Saposin-A domains that are removed in the activation reaction. The Saposin-B domains also occur in other proteins, many of them active in the lysis of membranes.

Clinical significance

Mutations in this gene have been associated with Gaucher disease, Tay-Sachs disease

Tay-Sachs disease

Tay–Sachs disease is an autosomal recessive genetic disorder...

, and metachromatic leukodystrophy

Metachromatic leukodystrophy

Metachromatic leukodystrophy is a lysosomal storage disease which is commonly listed in the family of leukodystrophies. Leukodystrophies affect the growth and/or development of myelin, the fatty covering which acts as an insulator around nerve fibers throughout the central and peripheral nervous...

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Further reading

External links