PSAP

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]

PSAP

Saposin-A and saposin-C stimulate the hydrolysis of glucosylceramide by beta-glucosylceramidase (EC 3.2.1.45) and galactosylceramide by beta-galactosylceramidase (EC 3.2.1.46). Saposin-C apparently acts by combining with the enzyme and acidic lipid to form an activated complex, rather than by solubilizing the substrate.
Saposin-B stimulates the hydrolysis of galacto-cerebroside sulfate by arylsulfatase A (EC 3.1.6.8), GM1 gangliosides by beta-galactosidase (EC 3.2.1.23) and globotriaosylceramide by alpha-galactosidase A (EC 3.2.1.22). Saposin-B forms a solubilizing complex with the substrates of the sphingolipid hydrolases.
Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).
Prosaposin
Behaves as a myelinotrophic and neurotrophic factor, these effects are mediated by its G-protein-coupled receptors, GPR37 and GPR37L1, undergoing ligand-mediated internalization followed by ERK phosphorylation signaling.
Saposins are specific low-molecular mass non-enzymic proteins, they participate in the lysosomal degradation of sphingolipids, which takes place by the sequential action of specific hydrolases.

Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathwayManual Assertion Based On ExperimentIBA:GO_Central
Epithelial cell differentiation involved in prostate gland developmentManual Assertion Based On ExperimentIBA:GO_Central
Ganglioside GM1 transport to membraneManual Assertion Based On ExperimentIDA:CAFA
Lysosomal transportManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of beta-galactosidase activityManual Assertion Based On ExperimentIDA:CAFA
Prostate gland growthManual Assertion Based On ExperimentIBA:GO_Central
Regulation of autophagyManual Assertion Based On ExperimentTAS:ParkinsonsUK-UCL
Regulation of lipid metabolic processManual Assertion Based On ExperimentIBA:GO_Central
Sphingolipid metabolic processIEA:UniProtKB-KW

Lysosome
Prosaposin
Secreted
Secreted as a fully glycosylated 70 kDa protein composed of complex glycans.

Combined saposin deficiency (CSAPD):
Due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement.
Metachromatic leukodystrophy due to saposin-B deficiency (MLD-SAPB):
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, psychomotor regression, seizures, cognitive decline and spastic quadriparesis.
Gaucher disease, atypical, due to saposin C deficiency (AGD):
A disease characterized by marked glucosylceramide accumulation in the spleen without having a deficiency of glucosylceramide-beta glucosidase characteristic of classic Gaucher disease. Gaucher disease is a lysosomal storage disorder characterized by skeletal deterioration, hepatosplenomegaly, and organ dysfunction. There are several subtypes based on the presence and severity of neurological involvement.
Krabbe disease, atypical, due to saposin A deficiency (AKRD):
A disorder of galactosylceramide metabolism. Clinical features include neurologic regression around age 3 months, loss of spontaneous movements, hyporeflexia, generalized brain atrophy, and diffuse white matter dysmyelination.
Parkinson disease 24, autosomal dominant (PARK24):
An autosomal dominant form of Parkinson disease, a complex neurodegenerative disorder characterized by bradykinesia, resting tremor, muscular rigidity and postural instability, as well as by a clinically significant response to treatment with levodopa. The pathology involves the loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies (intraneuronal accumulations of aggregated proteins), in surviving neurons in various areas of the brain. PARK24 shows incomplete penetrance.

The lysosomal precursor is proteolytically processed to 4 small peptides, which are similar to each other and are sphingolipid hydrolase activator proteins.
N-linked glycans show a high degree of microheterogeneity.
The one residue extended Saposin-B-Val is only found in 5% of the chains.