Reactome | POMT1:POMT2 transfers Man from Dol-P-Man to DAG1(30-653)

POMT1:POMT2 transfers Man from Dol-P-Man to DAG1(30-653)

Stable Identifier

R-HSA-5615637

Type

Reaction [transition]

Species

Homo sapiens

Compartment

endoplasmic reticulum membrane, endoplasmic reticulum lumen

ReviewStatus

5/5

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POMT1:POMT2 transfers Man from Dol-P-Man to DAG1(30-653)

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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 (Manya et al. 2004), that is mediating the transfer of mannosyl residues to the hydroxyl group of threonine residues of proteins such as alpha-dystroglycan (DAG1; MIM:128239). This process occurs in the ER lumen and both POMT isozymes are ER membrane residents. O-Mannosyl residues are also called M0. 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). Analogously, mutations in POMT1 can lead to the muscular dystrophy-dystroglycanopathies MDDGA1 (MIM:236670; Beltran-Valero de Bernabe et al., 2002), MDDGB1 (MIM:613155; van Reeuwijk et al., 2006), MDDGC1 (MIM:609308; Balci et al., 2005).

Literature References

PubMed ID	Title	Journal	Year
14699049	Demonstration of mammalian protein O-mannosyltransferase activity: coexpression of POMT1 and POMT2 required for enzymatic activity Manya, H, Chiba, A, Yoshida, A, Wang, X, Chiba, Y, Jigami, Y, Margolis, RU, Endo, T	Proc. Natl. Acad. Sci. U.S.A.	2004
16575835	The expanding phenotype of POMT1 mutations: from Walker-Warburg syndrome to congenital muscular dystrophy, microcephaly, and mental retardation van Reeuwijk, J, Maugenre, S, van den Elzen, C, Verrips, A, Bertini, E, Muntoni, F, Merlini, L, Scheffer, H, Brunner, HG, Guicheney, P, van Bokhoven, H	Hum Mutat	2006
15792865	An autosomal recessive limb girdle muscular dystrophy (LGMD2) with mild mental retardation is allelic to Walker-Warburg syndrome (WWS) caused by a mutation in the POMT1 gene Balci, B, Uyanik, G, Dincer, P, Gross, C, Willer, T, Talim, B, Haliloglu, G, Kale, G, Hehr, U, Winkler, J, Topaloglu, H	Neuromuscul Disord	2005
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
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