10         20         30         40         50         60
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MYALFLLASL LGAALAGPVL GLKECTRGSA VWCQNVKTAS DCGAVKHCLQ TVWNKPTVKS - 60
LPCDICKDVV TAAGDMLKDN ATEEEILVYL EKTCDWLPKP NMSASCKEIV DSYLPVILDI - 120
IKGEMSRPGE VCSALNLCES LQKHLAELNH QKQLESNKIP ELDMTEVVAP FMANIPLLLY - 180
PQDGPRSKPQ PKDNGDVCQD CIQMVTDIQT AVRTNSTFVQ ALVEHVKEEC DRLGPGMADI - 240
CKNYISQYSE IAIQMMMHMQ PKEICALVGF CDEVKEMPMQ TLVPAKVASK NVIPALELVE - 300
PIKKHEVPAK SDVYCEVCEF LVKEVTKLID NNKTEKEILD AFDKMCSKLP KSLSEECQEV - 360
VDTYGSSILS ILLEEVSPEL VCSMLHLCSG TRLPALTVHV TQPKDGGFCE VCKKLVGYLD - 420
RNLEKNSTKQ EILAALEKGC SFLPDPYQKQ CDQFVAEYEP VLIEILVEVM DPSFVCLKIG - 480
ACPSAHKPLL GTEKCIWGPS YWCQNTETAA QCNAVEHCKR HVWN

Function: The lysosomal degradation of sphingolipids takes place by the sequential action of specific hydrolases. Some of these enzymes require specific low-molecular mass, non-enzymic proteins: the sphingolipids activator proteins (coproteins).

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).
SUBUNIT: Saposin-B is a homodimer.


Subcellular Location: Lysosome. 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;
PTM: This precursor is proteolytically processed to 4 small peptides, which are similar to each other and are sphingolipid hydrolase activator proteins.
PTM: N-linked glycans show a high degree of microheterogeneity.
PTM: The one residue extended Saposin-B-Val is only found in 5% of the chains.
DISEASE: Defects in PSAP are the cause of combined saposin deficiency (CSAPD) [MIM:611721]; also known as prosaposin deficiency. CSAPD is due to absence of all saposins, leading to a fatal storage disorder with hepatosplenomegaly and severe neurological involvement.
DISEASE: Defects in PSAP saposin-B region are the cause of leukodystrophy metachromatic due to saposin-B deficiency (MLD- SAPB) [MIM:249900]. MLD-SAPB is 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, psychomotr regression, seizures, cognitive decline and spastic quadriparesis.
DISEASE: Defects in PSAP saposin-C region are the cause of atypical Gaucher disease (AGD) [MIM:610539]. Affected individuals have marked glucosylceramide accumulation in the spleen without having a deficiency of glucosylceramide-beta glucosidase characteristic of classic Gaucher disease, a lysosomal storage disorder.
DISEASE: Defects in PSAP saposin-A region are the cause of atypical Krabbe disease (AKRD) [MIM:611722]. AKRD is a disorder of galactosylceramide metabolism. AKRD features include progressive encephalopathy and abnormal myelination in the cerebral white matter resembling Krabbe disease.
DISEASE: Note=Defects in PSAP saposin-D region are found in a variant of Tay-Sachs disease (GM2-gangliosidosis).
MISCELLANEOUS: Saposin-B co-purifies with 1 molecule of phosphatidylethanolamine.
SIMILARITY: Contains 2 saposin A-type domains.
SIMILARITY: Contains 4 saposin B-type domains.
WEB RESOURCE: Name=Atlas of Genetics and Cytogenetics in Oncology and Haematology; URL='http://atlasgeneticsoncology.org/Genes/PSAPID42980ch10q22.html';
WEB RESOURCE: Name=GeneReviews; URL='http://www.ncbi.nlm.nih.gov/sites/GeneTests/lab/gene/PSAP';
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Characterization of disorder is found on Saposin-B (DP00733_C003) which is cleavage product 3 of full-length Proactivator polypeptide, and on Saposin-C (DP00733_C004) which is cleavage product 4 of full-length Proactivator polypeptide,