Prosaposin (PSAP) Antibody – Mouse Monoclonal

This gene encodes a highly conserved glycoprotein which is a precursor for 4 cleavage products: saposins A, B, C, and D. 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 compartment where they facilitate the catabolism of glycosphingolipids with short oligosaccharide groups. The precursor protein exists both as a secretory protein and as an integral membrane protein and has neurotrophic activities. Mutations in this gene have been associated with Gaucher disease, Tay-Sachs disease, and metachromatic leukodystrophy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]

PSAP: The lysosomal degradation of sphingolipids takes place by the sequential action of specific hydrolases. Some of these enzymes require specific low-molecular mass, non-enzymic proteins: the sphingolipids activator proteins (coproteins). Defects in PSAP are the cause of combined saposin deficiency (CSAPD); also known as prosaposin deficiency. CSAPD is due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement. Defects in PSAP saposin-B region are the cause of leukodystrophy metachromatic due to saposin-B deficiency (MLD- SAPB). MLD-SAPB is an atypical form of metachromatic leukodystrophy. It is characterized by tissue accumulation of cerebroside-3-sulfate, demyelination, periventricular white matter abnormalities, peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotr regression, seizures, cognitive decline and spastic quadriparesis. Defects in PSAP saposin-C region are the cause of atypical Gaucher disease (AGD). Affected individuals have marked glucosylceramide accumulation in the spleen without having a deficiency of glucosylceramide-beta glucosidase characteristic of classic Gaucher disease, a lysosomal storage disorder. Defects in PSAP saposin-A region are the cause of atypical Krabbe disease (AKRD). AKRD is a disorder of galactosylceramide metabolism. AKRD features include progressive encephalopathy and abnormal myelination in the cerebral white matter resembling Krabbe disease. Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis). 3 isoforms of the human protein are produced by alternative splicing.

Chromosomal Location of Human Ortholog: 10q21-q22

Cellular Component: nucleoplasm; Golgi apparatus; extracellular space; lysosomal lumen; mitochondrion; intracellular membrane-bound organelle; lysosomal membrane; nucleolus; integral to membrane; extracellular region

Molecular Function: protein binding; enzyme activator activity; lipid binding

Biological Process: positive regulation of catalytic activity; platelet activation; regulation of lipid metabolic process; platelet degranulation; sphingolipid metabolic process; regulation of MAPKKK cascade; glycosphingolipid metabolic process; lipid transport; blood coagulation

Disease: Gaucher Disease, Atypical, Due To Saposin C Deficiency; Metachromatic Leukodystrophy Due To Saposin B Deficiency; Krabbe Disease, Atypical, Due To Saposin A Deficiency; Combined Saposin Deficiency