Defective POMT1 does not transfer Man from Dol-P-Man to DAG1

Stable Identifier
Reaction [transition]
Homo sapiens
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Co-expression of both protein O-mannosyl-transferases 1 and 2 (POMT1 and POMT2; CAZy family GT39) is necessary for enzyme activity, that is mediating the transfer of mannosyl residues to the hydroxyl group of serine or threonine residues of proteins such as alpha-dystroglycan (DAG1; MIM:128239). 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 POMT1 (MIM:607423) results in defective glycosylation of DAG1 and can cause severe congenital muscular dystrophy-dystroglycanopathies ranging from a severe type A, MDDGA1 (brain and eye abnormalities; MIM:236670), through a less severe type B, MDDGB1 (congenital form with mental retardation; MIM:613155) to a milder type C, MDDGC1 (limb girdle form; MIM:609308) (Bertini et al. 2011, Wells 2013).
Several mutations are known and mutations causing the severest type A1 form include G76R, Q303*, S727Afs*3, W705Lfs*26 and D723Efs*8 (Beltran-Valero de Bernabe et al. 2002, Godfrey et al. 2007, Mercuri et al. 2009).
Literature References
PubMed ID Title Journal Year
17878207 Refining genotype phenotype correlations in muscular dystrophies with defective glycosylation of dystroglycan

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

Brain 2007
19299310 Congenital muscular dystrophies with defective glycosylation of dystroglycan: a population study

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

Neurology 2009
23329833 The o-mannosylation pathway: glycosyltransferases and proteins implicated in congenital muscular dystrophy

Wells, L

J. Biol. Chem. 2013
12369018 Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome

Merlini, L, Brunner, HG, van Bokhoven, H, Chitayat, D, van Beusekom, E, Celli, J, Lehesjoki, AE, Dobyns, WB, Steinbrecher, A, Cormand, B, Currier, S, Walsh, CA, Voit, T, Cruces, J, Kayserili, H, van der Zwaag, B, Beltrán-Valero de Bernabé, D

Am. J. Hum. Genet. 2002
22172424 Congenital muscular dystrophies: a brief review

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

Semin Pediatr Neurol 2011
Catalyst Activity

dolichyl-phosphate-mannose-protein mannosyltransferase activity of POMT1 mutants:POMT2 [endoplasmic reticulum membrane]

Normal reaction
Functional status

Loss of function of POMT1 mutants:POMT2 [endoplasmic reticulum membrane]

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