NEU1 hydrolyses Neu5Ac from glycoconjugates

Stable Identifier
R-HSA-4084999
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Sialidases 1-4 (NEU1-4, neuraminidases, receptor-destroying enzymes, RDEs) hydrolyse sialic acids (N-acetylneuraminic acid, Neu5Ac) to produce asialo compounds, a step in the degradation process of glycoproteins and gangliosides and are expressed in a variety of cellular locations. NEU4 is an extrinsic membrane protein associated with lysosomes, mitochondria and endoplasmic reticulum. It has broad sialidase activity against glycoconjugates with alpha2,3-, alpha2,6- or alpha2,8-linkages (Bigi et al. 2010, Monti et al. 2004, Seyrantepe et al. 2004). NEU1 (lysosomal sialidase) hydrolyses Neu5Ac from glycoconjugates with alpha2,3-, alpha2,6- or alpha2,8-linked terminal sialated residues 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), a lysosomal storage disorder manifesting as type I (late-onset) or type II (earlier-onset) (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).

Literature References
PubMed ID Title Journal Year
14962670 Molecular cloning and characterization of NEU4, the fourth member of the human sialidase gene family

Monti, E, Bassi, MT, Bresciani, R, Civini, S, Croci, GL, Papini, N, Riboni, M, Zanchetti, G, Ballabio, A, Preti, A, Tettamanti, G, Venerando, B, Borsani, G

Genomics 2004
19797320 Human sialidase NEU4 long and short are extrinsic proteins bound to outer mitochondrial membrane and the endoplasmic reticulum, respectively

Bigi, A, Morosi, L, Pozzi, C, Forcella, M, Tettamanti, G, Venerando, B, Monti, E, Fusi, P

Glycobiology 2010
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
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
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
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
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
Participant Of
Catalyst Activity
Catalyst Activity
Title
exo-alpha-sialidase activity of NEU1:GLB1:CTSA dimer [lysosomal lumen]
Physical Entity
Activity
Orthologous Events
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Reviewed
Created