Defective ST3GAL3 does not transfer SA to keratan

Stable Identifier
R-HSA-3656258
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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CMP-N-acetylneuraminate-beta-1,4-galactoside alpha-2,3-sialyltransferase (ST3GAL3) mediates the transfer of sialic acid from CMP-sialic acid to galactose-containing glycoproteins and forms the sialyl Lewis, an epitope on proteins which are required for attaining and/or maintaining higher cognitive functions. Some defects in ST3GAL3 result in mental retardation, autosomal recessive 12 (MRT12; MIM:611090), a disorder characterised by below average general intellectual function and impaired adaptative behaviour. Another defect of ST3GAL3 can cause early infantile epileptic encephalopathy-15 (EIEE15: MIM:615006), resulting in severe mental retardation.

In two ST3GAL3 homozygous mutations causing MRT12, A13D and D370Y, most of the mutant protein was improperly localized to the endoplasmic reticulum. This prevented the protein from interacting with its substrates in the Golgi, resulting in a loss of function and loss of the sialyl Lewis, an epitope important for higher cognative functions (Najmabadi et al. 2007, Hu et al. 2011). Another homozygous mutation, A320P, causing EIEE15, functional expression studies showed a 75% reduction in the secretion of the mutant protein and no detectable enzymatic activity (Edvardson et al. 2012). This mutation affects the highly conserved sialyl motif S, which is crucial for binding both donor and acceptor substrates.

Literature References
PubMed ID Title Journal Year
23252400 West syndrome caused by ST3Gal-III deficiency

Edvardson, S, Baumann, AM, Mühlenhoff, M, Stephan, O, Kuss, AW, Shaag, A, He, L, Zenvirt, S, Tanzi, R, Gerardy-Schahn, R, Elpeleg, O

Epilepsia 2013
21907012 ST3GAL3 mutations impair the development of higher cognitive functions

Hu, H, Eggers, K, Chen, W, Garshasbi, M, Motazacker, MM, Wrogemann, K, Kahrizi, K, Tzschach, A, Hosseini, M, Bahman, I, Hucho, T, Mühlenhoff, M, Gerardy-Schahn, R, Najmabadi, H, Ropers, HH, Kuss, AW

Am. J. Hum. Genet. 2011
17120046 Homozygosity mapping in consanguineous families reveals extreme heterogeneity of non-syndromic autosomal recessive mental retardation and identifies 8 novel gene loci

Najmabadi, H, Motazacker, MM, Garshasbi, M, Kahrizi, K, Tzschach, A, Chen, W, Behjati, F, Hadavi, V, Nieh, SE, Abedini, SS, Vazifehmand, R, Firouzabadi, SG, Jamali, P, Falah, M, Seifati, SM, Grüters, A, Lenzner, S, Jensen, LR, Rüschendorf, F, Kuss, AW, Ropers, HH

Hum. Genet. 2007
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
beta-galactoside (CMP) alpha-2,3-sialyltransferase activity of ST3GAL3 mutants [Golgi membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
developmental disorder of mental health 0060037
Authored
Reviewed
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