Literature summary for 2.7.7.13 extracted from

Carss, K.J.; Stevens, E.; Foley, A.R.; Cirak, S.; Riemersma, M.; Torelli, S.; Hoischen, A.; Willer, T.; van Scherpenzeel, M.; Moore, S.A.; Messina, S.; Bertini, E.; Boennemann, C.G.; Abdenur, J.E.; Grosmann, C.M.; Kesari, A.; Punetha, J.; Quinlivan, R.; Waddell, L.B.; Young, H.K.; Wraige, E.; Yau, S.; Bro, L. et al.
Mutations in GDP-mannose pyrophosphorylase B cause congenital and limb-girdle muscular dystrophies associated with hypoglycosylation of alpha-dystroglycan (2013), Am. J. Hum. Genet., 93, 29-41.

Application

Application	Comment	Organism
medicine	mutations in guanosine diphosphate mannose diphosphorylase GMPPB can result in muscular dystrophy variants with hypoglycosylated alpha-dystroglycan. Produkt GDP-mannose is required for O-mannosylation of proteins, including alpha-dystroglycan, and it is the substrate of cytosolic mannosyltransferases. In the muscle biopsies of affected individuals and in available fibroblasts, reduced alpha-dystroglycan glycosylation is found. Overexpression of wild-type GMPPB in fibroblasts from an affected individual partially restores glycosylation of alpha-dystroglycan. Whereas wild-type GMPPB localizes to the cytoplasm, five of the identified missense mutations cause formation of aggregates in the cytoplasm or near membrane protrusions	Homo sapiens
medicine	mutations in guanosine diphosphate mannose diphosphorylase B (GMPPB) can result in muscular dystrophy variants with hypoglycosylated alpha-dystroglycan. Reduced alpha-dystroglycan glycosylation is found in the muscle biopsies of individuals suffering from congenital and limb-girdle muscular dystrophies and in available fibroblasts. Overexpression of wild-type GMPPB in fibroblasts from an affected individual partially restored glycosylation of alpha-dystroglycan. Wild-type GMPPB localizes to the cytoplasm, but five of the identified missense mutations cause formation of aggregates in the cytoplasm or near membrane protrusions	Homo sapiens

Protein Variants	Comment	Organism
D27H/V330I	mutation identified in patient with muscular dystrophy	Homo sapiens
P22S/D334N	mutation identified in patient with muscular dystrophy	Homo sapiens
P32L	mutation identified in patient with muscular dystrophy	Homo sapiens
R185C	mutation identified in patient with muscular dystrophy	Homo sapiens
R287Q	mutation identified in patient with muscular dystrophy	Homo sapiens
R74*/D334N	mutation identified in patient with muscular dystrophy	Homo sapiens

Localization	Comment	Organism	GeneOntology No.	Textmining
cytoplasm	-	Homo sapiens	5737	-
cytoplasm	-	Danio rerio	5737	-

Natural Substrates	Organism	Comment (Nat. Sub.)	Natural Products	Comment (Nat. Pro.)	Rev.	Reac.
GTP + alpha-D-mannose 1-phosphate	Homo sapiens	-	diphosphate + GDP-mannose	-	?

Organism	UniProt	Comment	Textmining
Danio rerio	Q6DBU5	-	-
Homo sapiens	Q9Y5P6	-	-

Substrates	Comment Substrates	Organism	Products	Comment (Products)	Rev.	Reac.
GTP + alpha-D-mannose 1-phosphate	-	Homo sapiens	diphosphate + GDP-mannose	-	?

Synonyms	Comment	Organism
GDP-mannose pyrophosphorylase B	-	Homo sapiens
GMPBB	-	Homo sapiens
GMPPB	-	Homo sapiens
GMPPB	-	Danio rerio
guanosine diphosphate mannose pyrophosphorylase B	-	Homo sapiens
mannose-1-phosphate guanyltransferase beta	-	Danio rerio

General Information	Comment	Organism
malfunction	enzyme deficiency leads to reduced alpha-dystroglycan glycosylation in the muscle biopsies of affected individuals and in available fibroblasts. Mutations in GDP-mannose pyrophosphorylase B (GMPPB) can result in muscular dystrophy variants with hypoglycosylated alpha-dystroglycan. Overexpression of wild-type GMPPB in fibroblasts from an affected individual partially restores glycosylation of alpha-dystroglycan in muscle. Five of the identified missense mutations cause formation of aggregates in the cytoplasm or near membrane protrusions. Enzyme mutant phenotypes with brain and muscle abnormalities, overview	Homo sapiens
physiological function	knockdown of GMPPB in zebrafish causes structural muscle defects with decreased motility, eye abnormalities, and reduced glycosylation of alpha-dystroglycan	Danio rerio
physiological function	the enzyme catalyzes the formation of GDP-mannose from GTP and mannose-1-phosphate. GDP-mannose is required for O-mannosylation of proteins, including alpha-dystroglycan, and it is the substrate of cytosolic mannosyltransferases	Homo sapiens