Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.21 (beta-glucosidase)
 3,280 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prosaposin is the precursor protein for saposins, which are small lysosomal proteins required for the hydrolysis of sphingolipids by specific lysosomal hydrolases. Prosaposin, in addition to generating the saposins in the lysosomes, also exists as an unprocessed approximately 70-kDa protein in many tissues and secretory fluids. In this study, we isolated prosaposin from human milk. Milk was fractioned by ammonium sulfate precipitation, then chromatographed with DEAE-Sephacel and G-3000 SW gel permeation-HPLC. A fraction containing prosaposin was finally purified with the anti-saposin C IgG attached affinity column. The protein staining of the purified preparation on SDS-PAGE and the Western blotting showed a single band. The sequence of the initial 10 amino acids from N-terminus of the purified protein was identical to the sequence of prosaposin deduced from cDNA. Although prosaposin itself showed beta-glucosidase activator activity at a slight degree, the activity increased much after trypsin treatment. Western blotting of the trypsin-treated sample confirmed the formation of small saposin-like bands from prosaposin by the action of trypsin.
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PMID:Isolation and characterization of prosaposin from human milk. 195 98

Prosaposin contains separate domains in tandem for four saposins, A, B, C, and D. These mature saposins are produced by limited proteolysis of prosaposin. They are involved in lysosomal hydrolysis of GM1 ganglioside, gluco- and galactocerebrosides, sulfatides, and sphingomyelin and other sphingolipids. Prosaposin also exists as a secretory protein in body fluids. In this investigation prosaposin was expressed in Spodoptera frugiperda cells (Sf9) by infection with baculovirus containing a full length cDNA coding for human prosaposin. Prosaposin was isolated and purified from spent culture medium of the recombinant Sf9 cell cultures as well as from human seminal plasma and milk. From sodium dodecyl sulfate-polyacrylamide gel electrophoresis, the molecular weight of both native human prosaposins is estimated to be 66 kDa and that of recombinant prosaposin as 58 kDa. Deglycosylation of native and recombinant prosaposins yielded a protein with a molecular weight of 54 kDa and isoelectric point of 5.4. The N-terminal sequence of both native and recombinant prosaposins was identical (G-P-V-L-L-G-L-K). Like mature saposins, all prosaposins possessed stimulative activity for cerebroside beta-glucosidase (saposins A and C activity), GM1 ganglioside beta-galactosidase (saposin B activity), and sphingomyelinase (saposin D activity) but not sulfatide sulfatase (saposin B activity). Partially proteolyzed products derived from prosaposins were isolated and identified. From seminal plasma, two proteins of 48 and 29 kDa and from Sf9 culture media, two proteins of 39 and 26 kDa were characterized. N-terminal amino acid sequencing and Western blot analysis of each protein indicated that the 39-and 48-kDa proteins are cleavage products containing domains for saposins B, C, and D (trisaposins), and the 26- and 29-kDa proteins are cleavage products containing domains for saposins C and D (disaposin). These observations suggest that proteolysis of prosaposin in these tissues occurs sequentially from the N-terminal region. Proteins involved in the initial proteolysis of prosaposin were partially characterized in human testis.
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PMID:Isolation, characterization, and proteolysis of human prosaposin, the precursor of saposins (sphingolipid activator proteins). 832 76

An infant presented with multifocal myoclonus and cyanotic hypoxemia immediately after birth, and severe feeding problems, a protein-losing enteropathy, massive ascites and grand-mal epilepsy marked his rapid downhill course, with death at 17 weeks. At 2 weeks, brain MRI revealed grey matter heterotopias in the parieto-occipital regions suggestive of a cortical morphogenetic disorder. In cultured skin fibroblasts, lipid storage and reduced activities of ceramidase, galactosylceramide beta-galactosidase and glucosylceramide beta-glucosidase were evident. Autopsy disclosed generalised lysosomal lipid storage with macrophages and adrenal cortex prominently affected. The pattern of stored lipids in cultured fibroblasts and in dewaxed spleen tissue blocks was compatible with a diagnosis of prosaposin (pSap) deficiency (pSap-d). Neuropathologically, there was a pronounced generalised neurolysosomal storage combined with a severe depletion of cortical neurons and extreme paucity of myelin and oligodendroglia. This pathology, in particular the massive neuronal loss, differed from that in other neurolipidoses and could be explained by the reduced hydrolysis of multiple sphingolipids and the loss of pSap's neurotrophic function. The absence of immunostainable saposins on tissue sections and the presence of a homozygous c.1 A > T mutation in the prosaposin gene confirmed the diagnosis. PSap-d may be an underdiagnosed condition in infants with severe neurological and dystrophic signs starting immediately after birth.
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PMID:Prosaposin deficiency -- a rarely diagnosed, rapidly progressing, neonatal neurovisceral lipid storage disease. Report of a further patient. 1594 2

Gaucher disease is generally caused by a deficiency of the lysosomal enzyme glucocerebrosidase. The degradation of glycosphingolipids requires also the participation of sphingolipid activator proteins. The prosaposin PSAP gene codes for a single protein which undergoes post-translational cleavage to yield four proteins named saposins A, B, C and D. Saposin (SAP-) C is required for glucosylceramide degradation, and its deficiency results in a variant form of Gaucher disease. In this report, we present clinical, biochemical, and molecular findings in a 36-year-old man and his 30-year-old sister with non-neuronopathic Gaucher disease due to SAP-C deficiency. Very high levels of chitotriosidase activity, chemokine CCL18, and increased concentration of glucosylceramide in plasma and normal beta-glucosidase activity in skin fibroblasts were observed in the patients. A molecular genetics study of the PSAP gene enabled the identification of one missense mutation, p.L349P, located in the SAP-C domain and another mutation, p.M1L, located in the initiation codon of the prosaposin precursor protein. The presented findings describe the first cases where the non-neuronopathic Gaucher disease has been definitely demonstrated to be a consequence of SAP-C deficiency. Three previously described cases in the literature displayed a Gaucher type 3 phenotype.
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PMID:Non-neuronopathic Gaucher disease due to saposin C deficiency. 1791 9