Reactome | NEU1 hydrolyses Neu5Ac from glycoconjugates

NEU1 hydrolyses Neu5Ac from glycoconjugates

Stable Identifier

R-HSA-4084999

Type

Reaction [transition]

Species

Homo sapiens

Compartment

lysosomal lumen

ReviewStatus

5/5

Locations in the PathwayBrowser

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Metabolism of proteins (Homo sapiens)

- Post-translational protein modification (Homo sapiens)
  - Asparagine N-linked glycosylation (Homo sapiens)
    - Biosynthesis of the N-glycan precursor (dolichol lipid-linked oligosaccharide, LLO) and transfer to a nascent protein (Homo sapiens)
      - Synthesis of substrates in N-glycan biosythesis (Homo sapiens)
        
        Sialic acid metabolism (Homo sapiens)
        
        NEU1 hydrolyses Neu5Ac from glycoconjugates (Homo sapiens)

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NEU1 hydrolyses Neu5Ac from glycoconjugates

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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
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
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
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