PSAP
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1M12, 1N69, 1SN6, 2DOB, 2GTG, 2QYP, 2R0R, 2R1Q, 2RB3, 2Z9A, 3BQP, 3BQQ, 4DDJ, 4UEX, 4V2O
Identifiers
Aliases	PSAP, GLBA, SAP1, prosaposin, SAP2, PSAPD, PARK24
External IDs	OMIM: 176801 MGI: 97783 HomoloGene: 37680 GeneCards: PSAP
Gene location (Human) Chr. Chromosome 10 (human)[1] Band 10q22.1 Start 71,816,298 bp[1] End 71,851,251 bp[1]
Gene location (Mouse) Chr. Chromosome 10 (mouse)[2] Band 10 B4|10 30.02 cM Start 60,113,449 bp[2] End 60,138,376 bp[2]
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in monocyte gallbladder internal globus pallidus stromal cell of endometrium Achilles tendon left adrenal gland visceral pleura prefrontal cortex optic nerve cerebellar hemisphere Top expressed in superior frontal gyrus cerebellar cortex calvaria utricle ventromedial nucleus cerebellar vermis dorsomedial hypothalamic nucleus mammillary body lateral hypothalamus mucosa of urinary bladder More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor binding protein binding lipid binding enzyme activator activity beta-galactosidase activity phospholipid binding protein homodimerization activity ganglioside GM1 binding ganglioside GM2 binding ganglioside GM3 binding ganglioside GT1b binding ganglioside GP1c binding identical protein binding protease binding Cellular component lysosomal membrane integral component of membrane mitochondrion lysosomal lumen extracellular exosome extracellular space lysosome plasma membrane azurophil granule membrane intracellular membrane-bounded organelle extracellular matrix extracellular region cytoplasm collagen-containing extracellular matrix late endosome Biological process lipid metabolism lipid transport epithelial cell differentiation involved in prostate gland development regulation of MAPK cascade glycosphingolipid metabolic process developmental growth adenylate cyclase-inhibiting G protein-coupled receptor signaling pathway regulation of autophagy positive regulation of MAPK cascade cellular response to organic substance negative regulation of hydrogen peroxide-induced cell death regulation of lipid metabolic process prostate gland growth platelet degranulation sphingolipid metabolic process positive regulation of catalytic activity neutrophil degranulation ganglioside GM1 transport to membrane corneocyte development galactosylceramide catabolic process G protein-coupled receptor signaling pathway sensory perception of sound myelination neuromuscular process controlling balance positive regulation of hydrolase activity urination cochlea development walking behavior cornified envelope assembly lysosomal transport Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 5660 19156 Ensembl ENSG00000197746 ENSMUSG00000004207 UniProt P07602 Q5BJH1 Q61207 RefSeq (mRNA) NM_002778 NM_001042465 NM_001042466 NM_001146120 NM_001146121 NM_001146122 NM_001146123 NM_001146124 NM_011179 RefSeq (protein) NP_001035930 NP_001035931 NP_002769 NP_002769.1 NP_001139592 NP_001139593 NP_001139594 NP_001139595 NP_001139596 NP_035309 Location (UCSC) Chr 10: 71.82 – 71.85 Mb Chr 10: 60.11 – 60.14 Mb PubMed search [3] [4]
Wikidata
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Prosaposin, also known as PSAP, is a protein which in humans is encoded by the PSAP gene.^[5]

This highly conserved glycoprotein is a precursor for 4 cleavage products: saposins A, B, C, and D. Saposin is an acronym for Sphingolipid Activator PrO[S]teINs.^[6] 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.^[5]

Saposins A–D are required for the hydrolysis of certain sphingolipids by specific lysosomal hydrolases.^[7]

Family members

• Saposin A was identified as an N-terminal domain in the prosaposin cDNA prior to its isolation. It is known to stimulate the enzymatic hydrolysis of 4-methylumbelliferyl-β-glucoside, glucocerebroside, and galactocerebroside.^[8]
• Saposin B was the first to be discovered and was found to be required as a heat-stable factor for hydrolysis of sulfatides by arylsulfatase A. It is known by many different names, such as, sphingolipid activator protein-1 (SAP-1), sulfatide activator protein, GM₁ ganglioside activator, dispersin, and nonspecific.^[9] It has been observed that this particular saposin activates many enzymes through interaction with the substrates not the enzymes themselves.
• Saposin C was the second saposin to be discovered and stimulates the hydrolysis of glycocerebroside by glycosylceramidase and galactocerebroside by galactosylceramidase.
• Saposin D is not well known to due lack of investigation at this point in time. It was predicted from the cDNA sequence of prosaposin, like saposin A. Enzymatic stimulation is very specific for this particular glycoprotein and it not understood completely.^[7]
• GM2A (GM2 ganglioside activator) has been viewed as a member of the SAP family and has been called SAP-3 (sphingolipid activator protein 3)^[10]

Structure

Every saposin contains about 80 amino acid residues and has six equally placed cysteines, two prolines, and a glycosylation site (two in saposin A, one each in saposins B, C, and D).^[7] Since saposins characteristics of extreme heat-stability, abundance of disulfide linkages, and resistance to most proteases, they are assumed to be extremely compact and rigidly disulfide-linked molecules. Each saposin has an α-helical structure that is seen as being important for stimulation because this structure is maximal at a pH of 4.5; which is optimal for many lysosomal hydrolases.^[7] This helical structure is seen in all (especially with the first region), but saposin has been predicted to have β-sheet configuration due to it first 24 amino acids of the N-end.^[9]

Function

They probably act by isolating the lipid substrate from the membrane surroundings, thus making it more accessible to the soluble degradative enzymes. which contains four Saposin-B domains, yielding the active saposins after proteolytic cleavage, and two Saposin-A domains that are removed in the activation reaction. The Saposin-B domains also occur in other proteins, many of them active in the lysis of membranes.^[14][15]

Clinical significance

Mutations in this gene have been associated with Gaucher disease, Tay–Sachs disease, and metachromatic leukodystrophy.^[6]