MGP Database

MGP002466

UniProt Annotations

Entry Information

Gene Name	prosaposin
Protein Entry	SAP_HUMAN
UniProt ID	P07602
Species	Human

Comments

Comment type	Description
Alternative Products	Event=Alternative splicing; Named isoforms=3; Comment=Additional isoforms seem to exist.; Name=Sap-mu-0; IsoId=P07602-1; Sequence=Displayed; Name=Sap-mu-6; IsoId=P07602-2; Sequence=VSP_006014; Name=Sap-mu-9; IsoId=P07602-3; Sequence=VSP_006015;
Disease	Combined saposin deficiency (CSAPD) [MIM:611721]: Due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement. {ECO:0000269\|PubMed:11309366, ECO:0000269\|PubMed:1371116}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Gaucher disease, atypical, due to saposin C deficiency (AGD) [MIM:610539]: 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. {ECO:0000269\|PubMed:17919309, ECO:0000269\|PubMed:2060627}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Krabbe disease, atypical, due to saposin A deficiency (AKRD) [MIM:611722]: 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. {ECO:0000269\|PubMed:15773042}. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Leukodystrophy metachromatic due to saposin-B deficiency (MLD-SAPB) [MIM:249900]: 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. Note=The disease is caused by mutations affecting the gene represented in this entry.
Disease	Note=Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).
Function	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. {ECO:0000250\|UniProtKB:Q61207}.
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.
Function	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.
Function	Saposin-D is a specific sphingomyelin phosphodiesterase activator (EC 3.1.4.12).
Function	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.
Miscellaneous	Saposin-B co-purifies with 1 molecule of phosphatidylethanolamine.
Ptm	N-linked glycans show a high degree of microheterogeneity. {ECO:0000269\|PubMed:19159218, ECO:0000269\|PubMed:19167329}.
Ptm	The lysosomal precursor is proteolytically processed to 4 small peptides, which are similar to each other and are sphingolipid hydrolase activator proteins.
Ptm	The one residue extended Saposin-B-Val is only found in 5% of the chains.
Similarity	Contains 2 saposin A-type domains. {ECO:0000255\|PROSITE-ProRule:PRU00414}.
Similarity	Contains 4 saposin B-type domains. {ECO:0000255\|PROSITE-ProRule:PRU00415}.
Subcellular Location	Lysosome {ECO:0000269\|PubMed:14657016, ECO:0000269\|PubMed:21835174}.
Subcellular Location	Prosaposin: Secreted. Note=Secreted as a fully glycosylated 70 kDa protein composed of complex glycans. {ECO:0000250\|UniProtKB:Q61207}.
Subunit	Saposin-B is a homodimer. Prosaposin exists as a roughly half-half mixture of monomers and disulfide-linked dimers. Monomeric prosaposin interacts (via C-terminus) with sortilin/SORT1, the interaction is required for targeting to lysosomes. {ECO:0000269\|PubMed:10406958, ECO:0000269\|PubMed:12510003, ECO:0000269\|PubMed:14657016, ECO:0000269\|PubMed:21835174, ECO:0000269\|PubMed:7730378}.
Web Resource	Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PSAPID42980ch10q22.html";