HGSNAT oligomer acetylates Heparan sulfate chain(3)

Stable Identifier
Reaction [transition]
Homo sapiens
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Heparan-alpha-glucosaminide N-acetyltransferase (HGSNAT) acetylates the non-reducing terminal alpha-glucosamine residue of heparan sulfate. This is a critical reaction for the degradation of heparan sulfate because there is no enzyme that can act on the unacetylated glucosamine molecule. The mechanism by which HGSNAT uses cytosolic acetyl-CoA to transfer the acetyl group to the lysosomal luminal substrate is unknown (Fan et al. 2006). A catalytically inactive 77kDa precursor is transported to the lysosome and is cleaved into a 29kDa N-terminal alpha-chain and a 48kDa C-terminal beta-chain, which are assembled into active 440kDa oligomers in the lysosomal membrane (Durand et al. 2010). Defects in HGSNAT cause mucopolysaccharidosis type IIIC (MPSIIIC, MIM:252930), also called Sanfilippo C syndrome (Fan et al. 2006, Hrebicek et al. 2006).

Literature References
PubMed ID Title Journal Year
17033958 Mutations in TMEM76* cause mucopolysaccharidosis IIIC (Sanfilippo C syndrome)

Hrebícek, M, Mrázová, L, Seyrantepe, V, Durand, S, Roslin, NM, Nosková, L, Hartmannová, H, Ivánek, R, Cízkova, A, Poupetová, H, Sikora, J, Urinovská, J, Stranecký, V, Zeman, J, Lepage, P, Roquis, D, Verner, A, Ausseil, J, Beesley, CE, Maire, I, Poorthuis, BJ, van de Kamp, J, van Diggelen, OP, Wevers, RA, Hudson, TJ, Fujiwara, TM, Majewski, J, Morgan, K, Kmoch, S, Pshezhetsky, AV

Am J Hum Genet 2006
16960811 Identification of the gene encoding the enzyme deficient in mucopolysaccharidosis IIIC (Sanfilippo disease type C)

Fan, X, Zhang, H, Zhang, S, Bagshaw, RD, Tropak, MB, Callahan, JW, Mahuran, DJ

Am J Hum Genet 2006
20650889 Analysis of the biogenesis of heparan sulfate acetyl-CoA:alpha-glucosaminide N-acetyltransferase provides insights into the mechanism underlying its complete deficiency in mucopolysaccharidosis IIIC

Durand, S, Feldhammer, M, Bonneil, E, Thibault, P, Pshezhetsky, AV

J Biol Chem 2010
Participant Of
Catalyst Activity
Catalyst Activity
heparan-alpha-glucosaminide N-acetyltransferase activity of HGSNAT oligomer [lysosomal membrane]
Physical Entity
Orthologous Events
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