Gene/Proteome Database (LMPD)
LMPD ID
LMP002838
Gene ID
Species
Homo sapiens (Human)
Gene Name
prosaposin
Gene Symbol
Synonyms
GLBA; SAP1
Alternate Names
prosaposin; proactivator polypeptide; sphingolipid activator protein-1
Chromosome
10
Map Location
10q21-q22
Summary
This gene encodes a highly conserved glycoprotein which is a precursor for 4 cleavage products: saposins A, B, C, and D. 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. Mutations in this gene have been associated with Gaucher disease, Tay-Sachs disease, and metachromatic leukodystrophy. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jul 2008]
Orthologs
Proteins
| prosaposin isoform a preproprotein | |
|---|---|
| Refseq ID | NP_002769 |
| Protein GI | 11386147 |
| UniProt ID | P07602 |
| mRNA ID | NM_002778 |
| Length | 524 |
| RefSeq Status | REVIEWED |
| MYALFLLASLLGAALAGPVLGLKECTRGSAVWCQNVKTASDCGAVKHCLQTVWNKPTVKSLPCDICKDVVTAAGDMLKDNATEEEILVYLEKTCDWLPKPNMSASCKEIVDSYLPVILDIIKGEMSRPGEVCSALNLCESLQKHLAELNHQKQLESNKIPELDMTEVVAPFMANIPLLLYPQDGPRSKPQPKDNGDVCQDCIQMVTDIQTAVRTNSTFVQALVEHVKEECDRLGPGMADICKNYISQYSEIAIQMMMHMQPKEICALVGFCDEVKEMPMQTLVPAKVASKNVIPALELVEPIKKHEVPAKSDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEVVDTYGSSILSILLEEVSPELVCSMLHLCSGTRLPALTVHVTQPKDGGFCEVCKKLVGYLDRNLEKNSTKQEILAALEKGCSFLPDPYQKQCDQFVAEYEPVLIEILVEVMDPSFVCLKIGACPSAHKPLLGTEKCIWGPSYWCQNTETAAQCNAVEHCKRHVWN | |
| sig_peptide: 1..16 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1638 peptide sequence: MYALFLLASLLGAALA mat_peptide: 60..142 product: saposin A note: protein A calculated_mol_wt: 9108 peptide sequence: SLPCDICKDVVTAAGDMLKDNATEEEILVYLEKTCDWLPKPNMSASCKEIVDSYLPVILDIIKGEMSRPGEVCSALNLCESLQ mat_peptide: 195..276 product: saposin B note: sphingolipid activator protein 1, SAP-1, cerebroside sulfate activator, CSAct, dispersin, sulfatide/GM1 activator calculated_mol_wt: 9247 peptide sequence: GDVCQDCIQMVTDIQTAVRTNSTFVQALVEHVKEECDRLGPGMADICKNYISQYSEIAIQMMMHMQDQQPKEICALVGFCDE mat_peptide: 314..394 product: saposin C note: co-beta-glucosidase, A1 activator, glucosylceramidase activator, sphingolipid activator protein 2, SAP-2 calculated_mol_wt: 9051 peptide sequence: SDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEVVDTYGSSILSILLEEVSPELVCSMLHLCSGT mat_peptide: 408..489 product: saposin D note: protein C, component C calculated_mol_wt: 9127 peptide sequence: DGGFCEVCKKLVGYLDRNLEKNSTKQEILAALEKGCSFLPDPYQKQCDQFVAEYEPVLIEILVEVMDPSFVCLKIGACPSAH sig_peptide: 1..16 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1638 peptide sequence: MYALFLLASLLGAALA mat_peptide: 60..142 product: saposin A note: protein A calculated_mol_wt: 9108 peptide sequence: SLPCDICKDVVTAAGDMLKDNATEEEILVYLEKTCDWLPKPNMSASCKEIVDSYLPVILDIIKGEMSRPGEVCSALNLCESLQ mat_peptide: 195..275 product: saposin B note: sphingolipid activator protein 1, SAP-1, cerebroside sulfate activator, CSAct, dispersin, sulfatide/GM1 activator calculated_mol_wt: 9119 peptide sequence: GDVCQDCIQMVTDIQTAVRTNSTFVQALVEHVKEECDRLGPGMADICKNYISQYSEIAIQMMMHMDQQPKEICALVGFCDE mat_peptide: 313..393 product: saposin C note: co-beta-glucosidase, A1 activator, glucosylceramidase activator, sphingolipid activator protein 2, SAP-2 calculated_mol_wt: 9051 peptide sequence: SDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEVVDTYGSSILSILLEEVSPELVCSMLHLCSGT mat_peptide: 406..488 product: saposin D note: protein C, component C calculated_mol_wt: 9255 peptide sequence: KDGGFCEVCKKLVGYLDRNLEKNSTKQEILAALEKGCSFLPDPYQKQCDQFVAEYEPVLIEILVEVMDPSFVCLKIGACPSAH sig_peptide: 1..16 inference: COORDINATES: ab initio prediction:SignalP:4.0 calculated_mol_wt: 1638 peptide sequence: MYALFLLASLLGAALA mat_peptide: 60..142 product: saposin A note: protein A calculated_mol_wt: 9108 peptide sequence: SLPCDICKDVVTAAGDMLKDNATEEEILVYLEKTCDWLPKPNMSASCKEIVDSYLPVILDIIKGEMSRPGEVCSALNLCESLQ mat_peptide: 195..273 product: saposin B note: sphingolipid activator protein 1, SAP-1, cerebroside sulfate activator, CSAct, dispersin, sulfatide/GM1 activator calculated_mol_wt: 8875 peptide sequence: GDVCQDCIQMVTDIQTAVRTNSTFVQALVEHVKEECDRLGPGMADICKNYISQYSEIAIQMMMHMQPKEICALVGFCDE mat_peptide: 311..391 product: saposin C note: co-beta-glucosidase, A1 activator, glucosylceramidase activator, sphingolipid activator protein 2, SAP-2 calculated_mol_wt: 9051 peptide sequence: SDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEVVDTYGSSILSILLEEVSPELVCSMLHLCSGT mat_peptide: 405..486 product: saposin D note: protein C, component C calculated_mol_wt: 9127 peptide sequence: DGGFCEVCKKLVGYLDRNLEKNSTKQEILAALEKGCSFLPDPYQKQCDQFVAEYEPVLIEILVEVMDPSFVCLKIGACPSAH | |
| prosaposin isoform b preproprotein | |
|---|---|
| Refseq ID | NP_001035930 |
| Protein GI | 110224476 |
| UniProt ID | P07602 |
| mRNA ID | NM_001042465 |
| Length | 527 |
| RefSeq Status | REVIEWED |
| MYALFLLASLLGAALAGPVLGLKECTRGSAVWCQNVKTASDCGAVKHCLQTVWNKPTVKSLPCDICKDVVTAAGDMLKDNATEEEILVYLEKTCDWLPKPNMSASCKEIVDSYLPVILDIIKGEMSRPGEVCSALNLCESLQKHLAELNHQKQLESNKIPELDMTEVVAPFMANIPLLLYPQDGPRSKPQPKDNGDVCQDCIQMVTDIQTAVRTNSTFVQALVEHVKEECDRLGPGMADICKNYISQYSEIAIQMMMHMQDQQPKEICALVGFCDEVKEMPMQTLVPAKVASKNVIPALELVEPIKKHEVPAKSDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEVVDTYGSSILSILLEEVSPELVCSMLHLCSGTRLPALTVHVTQPKDGGFCEVCKKLVGYLDRNLEKNSTKQEILAALEKGCSFLPDPYQKQCDQFVAEYEPVLIEILVEVMDPSFVCLKIGACPSAHKPLLGTEKCIWGPSYWCQNTETAAQCNAVEHCKRHVWN | |
| prosaposin isoform c preproprotein | |
|---|---|
| Refseq ID | NP_001035931 |
| Protein GI | 110224476 |
| UniProt ID | P07602 |
| mRNA ID | NM_001042466 |
| Length | 527 |
| RefSeq Status | REVIEWED |
| MYALFLLASLLGAALAGPVLGLKECTRGSAVWCQNVKTASDCGAVKHCLQTVWNKPTVKSLPCDICKDVVTAAGDMLKDNATEEEILVYLEKTCDWLPKPNMSASCKEIVDSYLPVILDIIKGEMSRPGEVCSALNLCESLQKHLAELNHQKQLESNKIPELDMTEVVAPFMANIPLLLYPQDGPRSKPQPKDNGDVCQDCIQMVTDIQTAVRTNSTFVQALVEHVKEECDRLGPGMADICKNYISQYSEIAIQMMMHMQDQQPKEICALVGFCDEVKEMPMQTLVPAKVASKNVIPALELVEPIKKHEVPAKSDVYCEVCEFLVKEVTKLIDNNKTEKEILDAFDKMCSKLPKSLSEECQEVVDTYGSSILSILLEEVSPELVCSMLHLCSGTRLPALTVHVTQPKDGGFCEVCKKLVGYLDRNLEKNSTKQEILAALEKGCSFLPDPYQKQCDQFVAEYEPVLIEILVEVMDPSFVCLKIGACPSAHKPLLGTEKCIWGPSYWCQNTETAAQCNAVEHCKRHVWN | |
Gene Information
Gene Ontology (GO Annotations)
| GO ID | Source | Type | Description |
|---|---|---|---|
| GO:0005576 | TAS:Reactome | C | extracellular region |
| GO:0005615 | IDA:BHF-UCL | C | extracellular space |
| GO:0070062 | IDA:UniProtKB | C | extracellular vesicular exosome |
| GO:0016021 | TAS:ProtInc | C | integral component of membrane |
| GO:0043202 | TAS:Reactome | C | lysosomal lumen |
| GO:0005765 | TAS:Reactome | C | lysosomal membrane |
| GO:0005739 | IEA:Ensembl | C | mitochondrion |
| GO:0008047 | TAS:ProtInc | F | enzyme activator activity |
| GO:0008289 | TAS:ProtInc | F | lipid binding |
| GO:0007596 | TAS:Reactome | P | blood coagulation |
| GO:0071310 | IEA:Ensembl | P | cellular response to organic substance |
| GO:0060742 | IEA:Ensembl | P | epithelial cell differentiation involved in prostate gland development |
| GO:0006687 | TAS:Reactome | P | glycosphingolipid metabolic process |
| GO:0006869 | TAS:ProtInc | P | lipid transport |
| GO:0030168 | TAS:Reactome | P | platelet activation |
| GO:0002576 | TAS:Reactome | P | platelet degranulation |
| GO:0043085 | TAS:GOC | P | positive regulation of catalytic activity |
| GO:0060736 | IEA:Ensembl | P | prostate gland growth |
| GO:0043408 | IEA:Ensembl | P | regulation of MAPK cascade |
| GO:0019216 | IEA:Ensembl | P | regulation of lipid metabolic process |
| GO:0044281 | TAS:Reactome | P | small molecule metabolic process |
| GO:0006665 | TAS:Reactome | P | sphingolipid metabolic process |
KEGG Pathway Links
| KEGG Pathway ID | Description |
|---|---|
| hsa04142 | Lysosome |
REACTOME Pathway Links
| REACTOME Pathway ID | Description |
|---|---|
| REACT_21340 | GPCR ligand binding |
| REACT_116105 | Glycosphingolipid metabolism |
| REACT_318 | Platelet degranulation |
Domain Information
UniProt Annotations
Entry Information
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 |
| Disease | Gaucher disease, atypical, due to saposin C deficiency (AGD) [MIM |
| Disease | Krabbe disease, atypical, due to saposin A deficiency (AKRD) [MIM |
| Disease | Leukodystrophy metachromatic due to saposin-B deficiency (MLD-SAPB) [MIM |
| 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. |
| 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. |
| 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. |
| Similarity | Contains 4 saposin B-type domains. |
| Subcellular Location | Lysosome {ECO |
| Subcellular Location | Prosaposin: Secreted. Note=Secreted as a fully glycosylated 70 kDa protein composed of complex glycans. |
| 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 |
| Web Resource | Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL="http://atlasgeneticsoncology.org/Genes/PSAPID42980ch10q22.html"; |
Identical and Related Proteins
Unique RefSeq proteins for LMP002838 (as displayed in Record Overview)
| Protein GI | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| 11386147 | RefSeq | NP_002769 | 524 | prosaposin isoform a preproprotein |
| 110224476 | RefSeq | NP_001035930 | 527 | prosaposin isoform b preproprotein |
| 110224476 | RefSeq | NP_001035931 | 527 | prosaposin isoform c preproprotein |
Identical Sequences to LMP002838 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:110224476 | DBBJ | BAA00321.1 | 527 | sphingolipid activator proteins [Homo sapiens] |
| GI:110224476 | DBBJ | BAA00321.1 | 527 | sphingolipid activator proteins [Homo sapiens] |
| GI:110224476 | DBBJ | BAI45469.1 | 527 | prosaposin, partial [synthetic construct] |
| GI:110224476 | DBBJ | BAI45469.1 | 527 | prosaposin, partial [synthetic construct] |
| GI:110224476 | GenBank | ABI07131.1 | 527 | Sequence 27 from patent US 7081345 |
| GI:110224476 | GenBank | ABI07131.1 | 527 | Sequence 27 from patent US 7081345 |
| GI:110224476 | GenBank | ACQ18000.1 | 527 | Sequence 27 from patent US 7510843 |
| GI:110224476 | GenBank | ACQ18000.1 | 527 | Sequence 27 from patent US 7510843 |
| GI:11386147 | GenBank | ADT01398.1 | 524 | Sequence 1 from patent US 7834147 |
| GI:11386147 | GenBank | ADT50390.1 | 524 | Sequence 2407 from patent US 7842467 |
| GI:11386147 | GenBank | ADT50391.1 | 524 | Sequence 2408 from patent US 7842467 |
| GI:11386147 | GenBank | ADT50392.1 | 524 | Sequence 2409 from patent US 7842467 |
| GI:11386147 | GenBank | AEK13664.1 | 524 | Sequence 76 from patent US 7972785 |
| GI:11386147 | GenBank | AHD74739.1 | 524 | Sequence 14756 from patent US 8586006 |
| GI:110224476 | PRF | - | 527 | sphingolipid activator [Homo sapiens] |
| GI:110224476 | PRF | - | 527 | sphingolipid activator [Homo sapiens] |
Related Sequences to LMP002838 proteins
| Reference | Database | Accession | Length | Protein Name |
|---|---|---|---|---|
| GI:110224476 | DBBJ | BAD93013.1 | 530 | prosaposin variant, partial [Homo sapiens] |
| GI:110224476 | DBBJ | BAD93013.1 | 530 | prosaposin variant, partial [Homo sapiens] |
| GI:110224476 | EMBL | CAI29728.1 | 527 | hypothetical protein [Pongo abelii] |
| GI:110224476 | EMBL | CAI29728.1 | 527 | hypothetical protein [Pongo abelii] |
| GI:110224476 | GenBank | AAA36594.1 | 527 | cerebroside sulfate activator protein [Homo sapiens] |
| GI:110224476 | GenBank | AAA36594.1 | 527 | cerebroside sulfate activator protein [Homo sapiens] |
| GI:11386147 | GenBank | AAP36206.1 | 525 | Homo sapiens prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy), partial [synthetic construct] |
| GI:11386147 | GenBank | AAX29636.1 | 525 | prosaposin, partial [synthetic construct] |
| GI:11386147 | GenBank | AAX29637.1 | 525 | prosaposin, partial [synthetic construct] |
| GI:11386147 | GenBank | ACM83105.1 | 535 | Sequence 8603 from patent US 6812339 |
| GI:110224476 | RefSeq | NP_001035931.1 | 526 | prosaposin isoform c preproprotein [Homo sapiens] |
| GI:110224476 | RefSeq | NP_001035931.1 | 526 | prosaposin isoform c preproprotein [Homo sapiens] |
| GI:110224476 | RefSeq | XP_507840.2 | 527 | PREDICTED: prosaposin isoform X1 [Pan troglodytes] |
| GI:110224476 | RefSeq | XP_507840.2 | 527 | PREDICTED: prosaposin isoform X1 [Pan troglodytes] |
| GI:11386147 | RefSeq | XP_003312667.1 | 524 | PREDICTED: prosaposin isoform X3 [Pan troglodytes] |
| GI:110224476 | RefSeq | XP_008967227.1 | 527 | PREDICTED: prosaposin isoform X1 [Pan paniscus] |
| GI:110224476 | RefSeq | XP_008967227.1 | 527 | PREDICTED: prosaposin isoform X1 [Pan paniscus] |
| GI:11386147 | RefSeq | XP_008967229.1 | 524 | PREDICTED: prosaposin isoform X3 [Pan paniscus] |