Defective NEU1 does not hydrolyse Neu5Ac from glycoconjugates

Stable Identifier
Reaction [transition]
Homo sapiens
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NEU1 Sialidase 1 (NEU1, neuraminidase, receptor-destroying enzyme, RDE) normally hydrolyses N-acetylneuraminic acid (Neu5Ac) from glycoconjugates with alpha2,3-, alpha2,6- or alpha2,8-linked terminal sialated residues in the lysosomal lumen, a step in the degradation process of glycoproteins and gangliosides. 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), a lysosomal storage disorder manifesting as type I (late-onset) or type II (earlier-onset) (Bonten et al. 1996). Generally, patients with the more severe type II disease have catalytically inactive enzymes whereas patients with the milder type I disease have some residual activity. Mutations causing the severest type II disease include E377*, L303P, W29*, R225P and W23* (Bonten et al. 1996, Pshezhetsky et al. 1997, Sergi et al. 2001, Pattison et al. 2004).
Literature References
PubMed ID Title Journal Year
14695530 Five novel mutations in the lysosomal sialidase gene (NEU1) in type II sialidosis patients and assessment of their impact on enzyme activity and intracellular targeting using adenovirus-mediated expression

Pankarican, M, Igdoura, SA, Rupar, CA, Graham, FL, Pattison, S

Hum. Mutat. 2004
11702224 Prenatal diagnosis and fetal pathology in a Turkish family harboring a novel nonsense mutation in the lysosomal alpha-N-acetyl-neuraminidase (sialidase) gene

Sergi, C, Zoubaa, S, Rieger, P, Otto, HF, Dietrich, H, Cantz, M, Decker, N, Penzel, R, Kopitz, J, Kiessling, M, Uhl, J

Hum. Genet. 2001
9054950 Cloning, expression and chromosomal mapping of human lysosomal sialidase and characterization of mutations in sialidosis

Igdoura, S, Dallaire, L, Elsliger, MA, Qu, J, Wang, S, Richard, C, Pshezhetsky, AV, Leclerc, D, Michaud, L, Gravel, R, Potier, M

Nat. Genet. 1997
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
Catalyst Activity

exo-alpha-sialidase activity of NEU1 mutants:GLB1:CTSA dimer [lysosomal lumen]

Normal reaction
Functional status

Loss of function of NEU1 mutants:GLB1:CTSA dimer [lysosomal lumen]

Name Identifier Synonyms
lysosomal storage disease DOID:3211 lysosomal storage metabolism disorder, inborn lysosomal enzyme disorder, disorder of lysosomal enzyme (disorder)
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