InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: PSAP

Summary

InnateDB Protein

IDBP-240545.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

PSAP

Protein Name

prosaposin

Synonyms

GLBA; SAP1;

Species

Homo sapiens

Ensembl Protein

ENSP00000378394

InnateDB Gene

IDBG-77686 (PSAP)

Protein Structure

UniProt Annotation

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.

Subcellular Localization

Lysosome {ECO:0000269PubMed:14657016, ECO:0000269PubMed:21835174, ECO:0000269PubMed:23690594}.Prosaposin: Secreted. Note=Secreted as a fully glycosylated 70 kDa protein composed of complex glycans.

Disease Associations

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:0000269PubMed:11309366, ECO:0000269PubMed:1371116}. Note=The disease is caused by mutations affecting the gene represented in this entry.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.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:0000269PubMed:17919309, ECO:0000269PubMed:2060627}. Note=The disease is caused by mutations affecting the gene represented in this entry.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:0000269PubMed:15773042}. Note=The disease is caused by mutations affecting the gene represented in this entry.Note=Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).

Tissue Specificity

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 48 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	48 [view]
Protein-Protein	48 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005515	protein binding
GO:0008047	enzyme activator activity
GO:0008289	lipid binding

Biological Process

GO:0002576	platelet degranulation
GO:0006629	lipid metabolic process
GO:0006665	sphingolipid metabolic process
GO:0006687	glycosphingolipid metabolic process
GO:0006869	lipid transport
GO:0007596	blood coagulation
GO:0019216	regulation of lipid metabolic process
GO:0030168	platelet activation
GO:0043085	positive regulation of catalytic activity
GO:0043408	regulation of MAPK cascade
GO:0044281	small molecule metabolic process
GO:0048589	developmental growth
GO:0060736	prostate gland growth
GO:0060742	epithelial cell differentiation involved in prostate gland development
GO:0071310	cellular response to organic substance

Cellular Component

GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005739	mitochondrion
GO:0005764	lysosome
GO:0005765	lysosomal membrane
GO:0016021	integral component of membrane
GO:0043202	lysosomal lumen
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

InterPro

IPR003119 Saposin type A
IPR007856 Saposin-like type B, 1
IPR008138 Saposin-like type B, 2
IPR008139 Saposin B
IPR008373 Saposin
IPR011001 Saposin-like
IPR021165 Saposin, chordata

PFAM

PF02199
PF05184
PF03489

PRINTS

PR01797

PIRSF

PIRSF002431

SMART

SM00162
SM00741

TIGRFAMs

Post-translational Modifications

Modification

Cross-References