Prosaposin (PSAP)
The protein contains 524 amino acids for an estimated molecular weight of 58113 Da.
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).', '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. (updated: Dec. 11, 2019)
Protein identification was indicated in the following studies:
- Wilson and co-workers. (2016) Comparison of the Proteome of Adult and Cord Erythroid Cells, and Changes in the Proteome Following Reticulocyte Maturation. Mol Cell Proteomics. 15(6), 1938-1946.
- Bryk and co-workers. (2017) Quantitative Analysis of Human Red Blood Cell Proteome. J Proteome Res. 16(8), 2752-2761.
- D'Alessandro and co-workers. (2017) Red blood cell proteomics update: is there more to discover? Blood Transfus. 15(2), 182-187.
Methods
The following articles were analysed to gather the proteome content of erythrocytes.
The gene or protein list provided in the studies were processed using the ID mapping API of Uniprot in September 2018. The number of proteins identified and mapped without ambiguity in these studies is indicated below.
Only Swiss-Prot entries (reviewed) were considered for protein evidence assignation.
| Publication | Identification 1 | Uniprot mapping 2 | Not mapped / Obsolete | TrEMBL | Swiss-Prot |
|---|---|---|---|---|---|
| Goodman (2013) | 2289 (gene list) | 2278 | 53 | 20599 | 2269 |
| Lange (2014) | 1234 | 1234 | 7 | 28 | 1224 |
| Hegedus (2015) | 2638 | 2622 | 0 | 235 | 2387 |
| Wilson (2016) | 1658 | 1528 | 170 | 291 | 1068 |
| d'Alessandro (2017) | 1826 | 1817 | 2 | 0 | 1815 |
| Bryk (2017) | 2090 | 2060 | 10 | 108 | 1942 |
| Chu (2018) | 1853 | 1804 | 55 | 362 | 1387 |
1 as available in the article and/or in supplementary material
2 uniprot mapping returns all protein isoforms as one entry
The compilation of older studies can be retrieved from the Red Blood Cell Collection database.
The data and differentiation stages presented below come from the proteomic study and analysis performed by our partners of the GReX consortium, more details are available in their published work.
This protein is annotated as membranous in Gene Ontology.
Biological Process
Adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway
Antigen processing and presentation
Cellular response to organic substance
Cerebellar Purkinje cell differentiation
Cochlea development
Corneocyte development
Cornified envelope assembly
Epithelial cell differentiation involved in prostate gland development
G protein-coupled receptor signaling pathway
Galactosylceramide catabolic process
Ganglioside GM1 transport to membrane
Gene expression
Glucosylceramide metabolic process
Glycosphingolipid metabolic process
Inclusion body assembly
Intracellular protein transport
Lipid transport
Lysosomal protein catabolic process
Lysosomal transport
Micturition
Myelination
Negative regulation of hydrogen peroxide-induced cell death
Neuromuscular process controlling balance
Neutrophil degranulation
NK T cell differentiation
Platelet degranulation
Positive regulation of beta-galactosidase activity
Positive regulation of hydrolase activity
Positive regulation of MAPK cascade
Prostate gland growth
Protein secretion
Regulation of autophagy
Regulation of lipid metabolic process
Sensory perception of sound
Walking behavior
Cellular Component
Aggresome
Azurophil granule membrane
Collagen-containing extracellular matrix
Extracellular exosome
Extracellular region
Extracellular space
Intracellular membrane-bounded organelle
Late endosome
Lysosomal lumen
Lysosomal membrane
Lysosome
Plasma membrane
Molecular Function
Beta-galactosidase activity
Enzyme activator activity
G protein-coupled receptor binding
Ganglioside GM1 binding
Ganglioside GM2 binding
Ganglioside GM3 binding
Ganglioside GP1c binding
Ganglioside GT1b binding
Identical protein binding
Lipid antigen binding
Lipid binding
Phospholipid binding
Protease binding
Protein homodimerization activity
The reference OMIM entry for this protein is 176801
Prosaposin; psap saposin a, included; sapa, included
Saposin b, included; sapb, included
Saposin c, included; sapc, included
Saposin d, included; sapd, included
Sphingolipid activator protein 1, formerly; sap1, formerly
Sphingolipid activat
DESCRIPTION
The PSAP gene encodes prosaposin, a precursor of several small nonenzymatic glycoproteins termed 'sphingolipid activator proteins' (SAPs) that assist in the lysosomal hydrolysis of sphingolipids (O'Brien and Kishimoto, 1991). O'Brien and Kishimoto (1991) proposed a classification of the saposins based on the placement of 4 activating polypeptides in the PSAP precursor protein from the amino to carboxy termini: A, B, C, and D. After proteolytic processing of the presaposin protein, these 4 released polypeptides are functional activators. The authors noted that there has been a confusing array of terms for these proteins, and provided a table of updated nomenclature. For example, saposin B was formerly referred to as 'SAP1,' saposin C was formerly referred to as 'SAP2,' and saposin D was originally called 'component C.'CLONING
Dewji et al. (1986) cloned the 'SAP1' gene, and Dewji et al. (1987) reported its nucleotide sequence. O'Brien et al. (1988) determined that saposin B (SAP1) and C (SAP2) are encoded by the same locus. Several cDNAs clones were isolated from a human hepatoma cDNA library and found to match the 70-kD precursor of saposin B and the derived amino acid sequence of saposin C. The coding sequence for mature saposin C was located 3-prime to that coding for saposin B in the precursor cDNA. The findings indicated that saposin B and C are derived by proteolytic processing from a common precursor. The precursor protein contained 2 additional similar domains that were postulated to have functional significance. Each of the 4 domains was approximately 80 residues long and had nearly identical placement of cysteine residues, glycosylation sites, proline residues, and helicoregions. The domains were flanked by proteolytic cleavage sites. Morimoto et al. (1989) isolated and characterized saposin A, a 16-kD protein derived from domain 1 of prosaposin. Homologies of protein and nucleotide sequence between saposins A and C indicated that they were derived from a common ancestral gene segment that was duplicated in the saposin gene. Rorman and Grabowski (1989) cloned cDNAs encoding saposin C from human cDNA libraries. The full-length clone corresponded to the full-length 524-residue PSAP precursor protein with a typical 16-residue hydrophobic signal sequence. They demonstrated that saposin B (SAP1) was encoded by sequences 5-prime to those for saposin C, and that a new SAP protein termed 'protein C' (later designated saposin D) was coded by sequences 3-prime to those for saposin C. A fourth region of sequence similarity, encoding a theoretical peptide of undefined function, was located most 5-prime in the cDNA (later designated saposin A). The encoded polypeptide showed 80% amino acid similarity to sulfated glycoprotein-1 encoded by a rat Sertoli cell cDNA. Rorman and Grabowski (1989) concluded that a single highly conserved gene encodes the precursor for 4 potential sphingolipid activator proteins in rat and man. Saposin A is encoded by residues 60 to 143 of PSAP, saposin B by 195 to 275, saposin C by 311 to 390, and saposin D by 405 to 487 (O'Brien and Kishimoto, 1991).GENE STRUCTURE
Rorman et al. (1992) determined that the PSAP gene contains 13 exons. The regions encoding saposins A, B, and D have 3 exons each, while that for saposin C has only 2. Over 99% of the coding sequence is contained in about 20 kb. Analysis of intronic positions indicated that the gene evolved from an ancestral ... More on the omim web site
Jan. 22, 2020: Protein entry updated
Automatic update: Entry updated from uniprot information.
Oct. 20, 2018: Protein entry updated
Automatic update: OMIM entry 176801 was added.
Oct. 19, 2018: Additional information
Initial protein addition to the database. This entry was referenced in Bryk and co-workers. (2017).