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

Stable Identifier
R-HSA-5615604
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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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
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
12369018 Mutations in the O-mannosyltransferase gene POMT1 give rise to the severe neuronal migration disorder Walker-Warburg syndrome

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

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

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

Semin Pediatr Neurol 2011
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
dolichyl-phosphate-mannose-protein mannosyltransferase activity of POMT1 mutants:POMT2 [endoplasmic reticulum membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
muscular dystrophy-dystroglycanopathy 0050588
Authored
Reviewed
Created
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