Annotation inferences using phylogenetic trees
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
The X-ray crystal structures of human alpha-phosphomannomutase 1 reveal the structural basis of congenital disorder of glycosylation type 1a.
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The two isozymes alpha-PMM1 and alpha-PMM2 share a conserved active-site structure and similar kinetic properties; analysis of mutation sites explains the genotype-phenotype relationship of CDG-1a.
"The two isozymes, alpha-PMM1 and alpha-PMM2, are shown to have a conserved active-site structure and to display similar kinetic properties."
A proteome-scale map of the human interactome network.
Widespread Expansion of Protein Interaction Capabilities by Alternative Splicing.
A reference map of the human binary protein interactome.
Evolutionary rescue of phosphomannomutase deficiency in yeast models of human disease.
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The most common cause of human CDG are mutations in PMM2 that impair protein N-linked glycosylation; the yeast SEC53 gene is a homolog of human PMM2, and disease-associated alleles (including F126L, equivalent to human p.Phe119Leu) cause a slow-growth/glycosylation phenotype that can be evolutionarily rescued.
"mutations in the phosphomannomutase gene PMM2, which affect protein N-linked"
In Silico Analysis of Phosphomannomutase-2 Dimer Interface Stability and Heterodimerization with Phosphomannomutase-1.
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PMM2 functions as an obligate homodimer; the catalytic p.Arg141His variant impairs activity whereas the interface variant p.Phe119Leu disrupts homodimer formation, leading to destabilization/degradation. Man-1-P formation is a pivotal step in GDP-mannose and dolichol-phosphate-mannose biosynthesis. PMM1/PMM2 heterodimers are predicted to be structurally plausible but PMM1 does not compensate for PMM2 deficiency in vivo.
"Structurally, PMM2 functions as an obligate homodimer"
Tracer metabolomics reveals the role of aldose reductase in glycosylation.
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PMM2-CDG (caused by PMM2 deficiency) presents with depleted GDP-mannose and abnormal glycosylation; PMM2 itself is not directly involved in polyol metabolism. Aldose-reductase inhibition (epalrestat) diverts glucose flux toward sugar nucleotide synthesis, increasing GDP-mannose and improving glycosylation.
"Considering that the PMM2 enzyme is not"
Mutations in PMM2, a phosphomannomutase gene on chromosome 16p13, in carbohydrate-deficient glycoprotein type I syndrome (Jaeken syndrome).
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PMM2 on 16p13 encodes a phosphomannomutase necessary for GDP-mannose synthesis; missense mutations cause CDG type I (Jaeken syndrome), establishing PMM deficiency as the basis of the disease.
"phosphomannomutase (PMM)8, an enzyme necessary for"
Carbohydrate-deficient glycoprotein syndrome type Ib. Phosphomannose isomerase deficiency and mannose therapy.
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Describes phosphomannose ISOMERASE (PMI/MPI) deficiency causing CDG type Ib and mannose therapy - a different enzyme and gene than PMM2.
"Phosphomannose isomerase (PMI) deficiency is the cause of a new type of carbohydrate-deficient glycoprotein syndrome"
Defective PMM2 does not isomerise Man6P to Man1P
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PMM2 catalyses the cytosolic isomerization of Man6P to Man1P; Man1P is the precursor of GDP-mannose and dolichol-phosphate-mannose required for N-glycosylation. PMM2 mutations cause PMM2-CDG (CDG-1a).
"catalyses the isomerisation of mannose 6-phosphate (Man6P) to mannose 1-phosphate (Man1P) in the cytosol of cells"
PMM1,2 isomerise Man6P to Man1P
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Cytosolic PMM1 and PMM2 catalyze the Man6P->Man1P isomerization; PMM2 mutations cause Jaeken syndrome (CDG-Ia).
"Cytosolic phosphomannomutases 1 and 2 (PMM1 and PMM2) catalyse the isomerisation of mannose 6-phosphate (Man6P) to mannose 1-phosphate (Man1P)"
Synthesis of GDP-mannose
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GDP-mannose, the mannose donor for early N-glycan and Dol-P-Man synthesis, is made from fructose 6-phosphate and GTP in three steps (PMM2 catalyzes the mutase step).
"GDP-mannose is the mannose donor for the first 5 mannose addition reactions"