NEU1,4 hydrolyze PSAP(195-273):GM3:PE

Stable Identifier
Reaction [transition]
Homo sapiens
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Ganglioside GM3, mobilized by Saposin B (PSAP(195-273)), is hydrolyzed by sialidases to lactosylceramide (LacCer). Sialidases (NEU, neuraminidases) hydrolyze sialic acids (N-acetylneuramic acid, Neu5Ac, NANA) to produce asialo compounds, a step in the degradation process of glycoproteins and gangliosides. NEU1 and NEU4 hydrolyse NANA in the lysosomal lumen. NEU1 is active in a multienzyme complex comprising cathepsin A protective protein (CTSA) and beta-galactosidase (Bonten et al. 1996, Rudenko et al. 1995). Defects in NEU1 cause Sialidosis (MIM:256550) (Bonten et al. 1996). CTSA appears to exert a protective function necessary for the stability and activity of these enzymes (Galjart et al. 1988). Defects in CTSA are the cause of galactosialidosis (GSL, MIM:256540) (Zhou et al. 1991). NEU4 is also a lysosomal sialidase which, unlike NEU1, does not require association with other proteins for enzymatic activity. Isoform 2 seems to be the lysosomal sialidase (Seyrantepe et al. 2004). Researchers observed elevated GM3 in prosaposin deficiency (PSAPD, MIM: 611721) cases, a rare disease with low levels of all saposins. The essential cofactor missing appears to be Saposin B (PSAP(195-273)) (Schmidt et al., 1992; Bradova et al., 1993).
Literature References
PubMed ID Title Journal Year
1634229 Metabolism of GM1 ganglioside in cultured skin fibroblasts: anomalies in gangliosidoses, sialidoses, and sphingolipid activator protein (SAP, saposin) 1 and prosaposin deficient disorders

Schmid, B, Paton, BC, Harzer, K, Sandhoff, K

Hum Genet 1992
8370580 Prosaposin deficiency: further characterization of the sphingolipid activator protein-deficient sibs. Multiple glycolipid elevations (including lactosylceramidosis), partial enzyme deficiencies and ultrastructure of the skin in this generalized sphingolipid storage disease

Paton, BC, Harzer, K, Smíd, F, Bradová, V, Ulrich-Bott, B, Roggendorf, W

Hum Genet 1993
15213228 Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells

Landry, K, Hassan, JA, Trudel, S, Pshezhetsky, AV, Seyrantepe, V, Morales, CR

J Biol Chem 2004
8591035 Three-dimensional structure of the human 'protective protein': structure of the precursor form suggests a complex activation mechanism

Hol, WG, Rudenko, G, d'Azzo, A, Bonten, E

Structure 1995
1756715 A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable

Zhou, XY, Gillemans, N, Willemsen, R, d'Azzo, A, Galjart, NJ, Galjaard, H

EMBO J 1991
8985184 Characterization of human lysosomal neuraminidase defines the molecular basis of the metabolic storage disorder sialidosis

van der Spoel, A, Grosveld, G, d'Azzo, A, Fornerod, M, Bonten, E

Genes Dev 1996
3136930 Expression of cDNA encoding the human "protective protein" associated with lysosomal beta-galactosidase and neuraminidase: homology to yeast proteases

Verheijen, FW, Harris, A, van der Horst, GT, Gillemans, N, d'Azzo, A, Galjart, NJ, Galjaard, H

Cell 1988
Catalyst Activity

exo-alpha-sialidase activity of NEU1,4 [lysosomal lumen]

Orthologous Events
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