Neu5Ac is cleaved from GM3 by NEU1 and 4 to form a globoside (lysosomal lumen)

Stable Identifier
R-HSA-1605724
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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 are the cause of Sialidosis (MIM:256550) (Bonten et al. 1996). CTSA is thought to exert a protective function necessary for 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, doesn't require association with other proteins for enzymatic activity. Isoform 2 is thought to be the lysosomal sialidase (Seyrantepe et al. 2004).

Literature References
PubMed ID Title Journal Year
8591035 Three-dimensional structure of the human 'protective protein': structure of the precursor form suggests a complex activation mechanism

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

Structure 1995
15213228 Neu4, a novel human lysosomal lumen sialidase, confers normal phenotype to sialidosis and galactosialidosis cells

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

J Biol Chem 2004
1756715 A mutation in a mild form of galactosialidosis impairs dimerization of the protective protein and renders it unstable

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

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

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

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

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

Cell 1988
Participants
Participates
Catalyst Activity

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

Orthologous Events
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