PSAP
Function
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.
Involvement in disease
Combined saposin deficiency
PSAPD
An autosomal recessive storage disorder characterized by hepatosplenomegaly and severe neurologic disease, due to absence of all saposins. PSAPD has a fatal outcome in infancy.
None
The disease is caused by variants affecting the gene represented in this entry.
Metachromatic leukodystrophy due to saposin B deficiency
MLDSAPB
A form of metachromatic leukodystrophy biochemically characterized by tissue accumulation of cerebroside-3-sulfate, saposin B deficiency, and normal arylsulfatase A activity. Clinical manifestations include periventricular white matter abnormalities, demyelination, and peripheral neuropathy. Additional neurological features include dysarthria, ataxic gait, psychomotor regression, seizures, cognitive decline and spastic quadriparesis.
None
The disease is caused by variants affecting the gene represented in this entry.
Gaucher disease, atypical, due to saposin C deficiency
GDSAPC
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.
None
The disease is caused by variants affecting the gene represented in this entry.
Krabbe disease, atypical, due to saposin A deficiency
KRBSAPA
An autosomal recessive 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.
None
The disease is caused by variants affecting the gene represented in this entry.
Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).
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.
None
Disease susceptibility is associated with variants affecting the gene represented in this entry.
Post-translational modifications
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.
Cellular localization
- Lysosome
- Prosaposin
- Secreted
- Secreted as a fully glycosylated 70 kDa protein composed of complex glycans.
Alternative names
GLBA, SAP1, PSAP, Prosaposin, Proactivator polypeptide