Prosaposin

From Wikipedia, the free encyclopedia

Prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy)

PDB rendering based on 1m12.

Available structures: 1m12, 1n69, 1sn6, 2dob, 2gtg

Identifiers

Symbol(s)

PSAP; SAP1; FLJ00245; GLBA; MGC110993

External IDs

OMIM: 176801 MGI: 97783 HomoloGene: 37680

Gene ontology
Molecular Function:	• cerebroside-sulfatase activity • galactosylceramidase activity • glucosylceramidase activity • alpha-galactosidase activity • beta-galactosidase activity • sphingomyelin phosphodiesterase activity • enzyme activator activity • lipid binding
Cellular Component:	• extracellular space • lysosome • integral to membrane
Biological Process:	• lipid metabolic process • sphingolipid metabolic process • glycosphingolipid metabolic process • lipid transport • lysosome organization and biogenesis

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_001042465 (mRNA)
NP_001035930 (protein)

NM_011179 (mRNA)
NP_035309 (protein)

Location

Chr 10: 73.25 - 73.28 Mb

Chr 10: 59.67 - 59.7 Mb

Pubmed search

[1]

[2]

Prosaposin is a protein associated with Gaucher disease.

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.^[1]

[edit] References

^ Entrez Gene: PSAP prosaposin (variant Gaucher disease and variant metachromatic leukodystrophy).

[edit] Further reading

Gieselmann V, Zlotogora J, Harris A, et al. (1995). "Molecular genetics of metachromatic leukodystrophy.". Hum. Mutat. 4 (4): 233–42. doi:10.1002/humu.1380040402. PMID 7866401.
Schnabel D, Schröder M, Fürst W, et al. (1992). "Simultaneous deficiency of sphingolipid activator proteins 1 and 2 is caused by a mutation in the initiation codon of their common gene.". J. Biol. Chem. 267 (5): 3312–5. PMID 1371116.
Hiraiwa M, Soeda S, Kishimoto Y, O'Brien JS (1993). "Binding and transport of gangliosides by prosaposin.". Proc. Natl. Acad. Sci. U.S.A. 89 (23): 11254–8. PMID 1454804.
Rorman EG, Scheinker V, Grabowski GA (1992). "Structure and evolution of the human prosaposin chromosomal gene.". Genomics 13 (2): 312–8. PMID 1612590.
Kondoh K, Hineno T, Sano A, Kakimoto Y (1992). "Isolation and characterization of prosaposin from human milk.". Biochem. Biophys. Res. Commun. 181 (1): 286–92. PMID 1958198.
Holtschmidt H, Sandhoff K, Fürst W, et al. (1991). "The organization of the gene for the human cerebroside sulfate activator protein.". FEBS Lett. 280 (2): 267–70. PMID 2013321.
Holtschmidt H, Sandhoff K, Kwon HY, et al. (1991). "Sulfatide activator protein. Alternative splicing that generates three mRNAs and a newly found mutation responsible for a clinical disease.". J. Biol. Chem. 266 (12): 7556–60. PMID 2019586.
Hineno T, Sano A, Kondoh K, et al. (1991). "Secretion of sphingolipid hydrolase activator precursor, prosaposin.". Biochem. Biophys. Res. Commun. 176 (2): 668–74. PMID 2025281.
Schnabel D, Schröder M, Sandhoff K (1991). "Mutation in the sphingolipid activator protein 2 in a patient with a variant of Gaucher disease.". FEBS Lett. 284 (1): 57–9. PMID 2060627.
Zhang XL, Rafi MA, DeGala G, Wenger DA (1991). "The mechanism for a 33-nucleotide insertion in mRNA causing sphingolipid activator protein (SAP-1)-deficient metachromatic leukodystrophy.". Hum. Genet. 87 (2): 211–5. PMID 2066109.
Fürst W, Schubert J, Machleidt W, et al. (1990). "The complete amino-acid sequences of human ganglioside GM2 activator protein and cerebroside sulfate activator protein.". Eur. J. Biochem. 192 (3): 709–14. PMID 2209618.
Rafi MA, Zhang XL, DeGala G, Wenger DA (1990). "Detection of a point mutation in sphingolipid activator protein-1 mRNA in patients with a variant form of metachromatic leukodystrophy.". Biochem. Biophys. Res. Commun. 166 (2): 1017–23. PMID 2302219.
Kretz KA, Carson GS, Morimoto S, et al. (1990). "Characterization of a mutation in a family with saposin B deficiency: a glycosylation site defect.". Proc. Natl. Acad. Sci. U.S.A. 87 (7): 2541–4. PMID 2320574.
Nakano T, Sandhoff K, Stümper J, et al. (1989). "Structure of full-length cDNA coding for sulfatide activator, a Co-beta-glucosidase and two other homologous proteins: two alternate forms of the sulfatide activator.". J. Biochem. 105 (2): 152–4. PMID 2498298.
Rorman EG, Grabowski GA (1990). "Molecular cloning of a human co-beta-glucosidase cDNA: evidence that four sphingolipid hydrolase activator proteins are encoded by single genes in humans and rats.". Genomics 5 (3): 486–92. PMID 2515150.
Morimoto S, Martin BM, Yamamoto Y, et al. (1989). "Saposin A: second cerebrosidase activator protein.". Proc. Natl. Acad. Sci. U.S.A. 86 (9): 3389–93. PMID 2717620.
Dewji NN, Wenger DA, O'Brien JS (1988). "Nucleotide sequence of cloned cDNA for human sphingolipid activator protein 1 precursor.". Proc. Natl. Acad. Sci. U.S.A. 84 (23): 8652–6. PMID 2825202.
O'Brien JS, Kretz KA, Dewji N, et al. (1988). "Coding of two sphingolipid activator proteins (SAP-1 and SAP-2) by same genetic locus.". Science 241 (4869): 1098–101. PMID 2842863.
Morimoto S, Martin BM, Kishimoto Y, O'Brien JS (1988). "Saposin D: a sphingomyelinase activator.". Biochem. Biophys. Res. Commun. 156 (1): 403–10. PMID 2845979.
Dewji N, Wenger D, Fujibayashi S, et al. (1986). "Molecular cloning of the sphingolipid activator protein-1 (SAP-1), the sulfatide sulfatase activator.". Biochem. Biophys. Res. Commun. 134 (2): 989–94. PMID 2868718.