Defective POMGNT1 does not transfer GlcNAc from UDP-GlcNAc to Man-O-Ser-DAG1

Stable Identifier
R-HSA-5617096
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Protein O-linked-mannose beta-1,2-N-acetylglucosaminyltransferase 1 (POMGNT1; CAZy family GT61; MIM:606822) mediates the transfer of N-acetylglucosaminyl (GlcNAc) residues to mannosylated proteins such as mannose-O-serine-dystroglycan (man-O-Ser-DAG1). DAG1 is a cell surface protein that plays an important role in the assembly of the extracellular matrix in muscle, brain, and peripheral nerves by linking the basal lamina to cytoskeletal proteins. Defects in POMGNT1 (MIM:606822) result in disrupted glycosylation of DAG1 and can cause severe congenital muscular dystrophy-dystroglycanopathies ranging from a severe type A3 (MDDGA3; MIM:253280), through a less severe type B3 (MDDGB3; MIM:613151) to a milder type C3 (MDDGC3; MIM:613157) (Bertini et al. 2011, Wells 2013). Several mutations in POMGNT1 are known (MIM:606822) and mutations causing the severest type A3 include S550N, P493R, R605Vfs*29 (Yoshida et al. 2001), R63* (Taniguchi et al. 2003, Mercuri et al. 2009) and W475* (Godfrey et al. 2007).

Literature References
PubMed ID Title Journal Year
19299310 Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study

Mercuri, E, Messina, S, Bruno, C, Mora, M, Pegoraro, E, Comi, GP, D'Amico, A, Aiello, C, Biancheri, R, Berardinelli, A, Boffi, P, Cassandrini, D, Laverda, A, Moggio, M, Morandi, L, Moroni, I, Pane, M, Pezzani, R, Pichiecchio, A, Pini, A, Minetti, C, Mongini, T, Mottarelli, E, Ricci, E, Ruggieri, A, Saredi, S, Scuderi, C, Tessa, A, Toscano, A, Tortorella, G, Trevisan, CP, Uggetti, C, Vasco, G, Santorelli, FM, Bertini, E

Neurology 2009
17878207 Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan

Godfrey, C, Clement, E, Mein, R, Brockington, M, Smith, J, Talim, B, Straub, V, Robb, S, Quinlivan, R, Feng, L, Jimenez-Mallebrera, C, Mercuri, E, Manzur, AY, Kinali, M, Torelli, S, Brown, SC, Sewry, CA, Bushby, K, Topaloglu, H, North, K, Abbs, S, Muntoni, F

Brain 2007
23329833 The o-mannosylation pathway: glycosyltransferases and proteins implicated in congenital muscular dystrophy

Wells, L

J. Biol. Chem. 2013
12588800 Worldwide distribution and broader clinical spectrum of muscle-eye-brain disease

Taniguchi, K, Kobayashi, K, Saito, K, Yamanouchi, H, Ohnuma, A, Hayashi, YK, Manya, H, Jin, DK, Lee, M, Parano, E, Falsaperla, R, Pavone, P, Van Coster, R, Talim, B, Steinbrecher, A, Straub, V, Nishino, I, Topaloglu, H, Voit, T, Endo, T, Toda, T

Hum. Mol. Genet. 2003
22172424 Congenital muscular dystrophies: a brief review

Bertini, E, D'Amico, A, Gualandi, F, Petrini, S

Semin Pediatr Neurol 2011
11709191 Muscular dystrophy and neuronal migration disorder caused by mutations in a glycosyltransferase, POMGnT1

Yoshida, A, Kobayashi, K, Manya, H, Taniguchi, K, Kano, H, Mizuno, M, Inazu, T, Mitsuhashi, H, Takahashi, S, Takeuchi, M, Herrmann, R, Straub, V, Talim, B, Voit, T, Topaloglu, H, Toda, T, Endo, T

Dev. Cell 2001
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
beta-1,3-galactosyl-O-glycosyl-glycoprotein beta-1,3-N-acetylglucosaminyltransferase activity of POMGNT1 mutants [Golgi membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
muscular dystrophy-dystroglycanopathy 0050588
Authored
Reviewed
Created