Defective POMT2 does not transfer Man from Dol-P-Man to DAG1

Stable Identifier
R-HSA-5615556
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 POMT2 (MIM:607439) results in defective glycosylation of DAG1 and can cause severe congenital muscular dystrophy dystroglycanopathies ranging from a severe type A, MDDGA2 (brain and eye abnormalities; MIM:613150), through a less severe type B, MDDGB2 (congenital form with mental retardation; MIM:613156) to a milder type C, MDDGC2 (limb girdle form; MIM:603158) (Bertini et al. 2011, Wells 2013). Several mutations are known (MIM:607439), and mutations causing the severest type A2 form include R638*, T433* (van Reeuwijk et al. 2005), I444_N445insLLWQ, Y666C (Yanagisawa et al. 2009), V373F and I198N (Godfrey et al. 2007).

Literature References
PubMed ID Title Journal Year
15894594 POMT2 mutations cause alpha-dystroglycan hypoglycosylation and Walker-Warburg syndrome

van Reeuwijk, J, Janssen, M, van den Elzen, C, Beltran-Valero de Bernabé, D, Sabatelli, P, Merlini, L, Boon, M, Scheffer, H, Brockington, M, Muntoni, F, Huynen, MA, Verrips, A, Walsh, CA, Barth, PG, Brunner, HG, van Bokhoven, H

J. Med. Genet. 2005
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
22172424 Congenital muscular dystrophies: a brief review

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

Semin Pediatr Neurol 2011
19138766 POMT2 intragenic deletions and splicing abnormalities causing congenital muscular dystrophy with mental retardation

Yanagisawa, A, Bouchet, C, Quijano-Roy, S, Vuillaumier-Barrot, S, Clarke, N, Odent, S, Rodriguez, D, Romero, NB, Osawa, M, Endo, T, Taratuto, AL, Seta, N, Guicheney, P

Eur J Med Genet 2009
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
dolichyl-phosphate-mannose-protein mannosyltransferase activity of POMT1:POMT2 mutants [endoplasmic reticulum membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
muscular dystrophy-dystroglycanopathy 0050588
Authored
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