MGP Database

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MGP005021

UniProt Annotations

Entry Information
Gene NameGDP-mannose pyrophosphorylase A
Protein EntryGMPPA_HUMAN
UniProt IDQ96IJ6
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=2; Name=1; IsoId=Q96IJ6-1; Sequence=Displayed; Name=2; IsoId=Q96IJ6-2; Sequence=VSP_032741;
CautionGMPPA is a close homolog of GMPPB, that has been shown to catalyze the formation of GDP-mannose, an essential precursor of glycan moieties of glycoproteins and glycolipids. However, lymphocytes from AAMR patients, that exhibit very low GMPPA protein levels, have unchanged GDP-mannose pyrophosphorylase activity and higher GDP-mannose levels than those from healthy controls. Affected individuals and control subjects show similar N-glycosylation profiles, both for transferrin glycosylation and for N-glycans derived from either total serum protein or immunoglobulin G. These observations led to the hypothesis that GMPPA might serve as a regulatory subunit and allow allosteric feedback inhibition of GMPPB by GDP-mannose. Alignment of GMPPAs and GMPPBs from various species shows that GMPPAs are characterized by a 2 amino acid-insertion (residues 11-12) in a highly conserved motif that borders the catalytic pocket and binds the nucleotide substrate in homologous enzymes. This insertion might inactivate the ancestral catalytic site, converting it to an allosteric site (PubMed:24035193). {ECO:0000305|PubMed:24035193}.
DiseaseAlacrima, achalasia, and mental retardation syndrome (AAMR) [MIM:615510]: An autosomal recessive disorder characterized by onset of alacrima, achalasia, and mental retardation at birth or in early infancy. More variable features include hypotonia, gait abnormalities, anisocoria, and visual or hearing deficits. The disorder shows similarity to the triple A syndrome, but patients with AAMR do not have adrenal insufficiency. {ECO:0000269|PubMed:24035193}. Note=The disease is caused by mutations affecting the gene represented in this entry.
FunctionMay serve as a regulatory subunit and allow allosteric feedback inhibition of GMPPB by GDP-mannose. {ECO:0000269|PubMed:24035193}.
Sequence CautionSequence=AAD38517.1; Type=Frameshift; Positions=355; Evidence={ECO:0000305};
SimilarityBelongs to the transferase hexapeptide repeat family. {ECO:0000305}.
Subcellular LocationCytoplasm {ECO:0000269|PubMed:24035193}. Note=Myc-tagged GMPPA shows a diffuse cytoplasmic and nuclear pattern in transfected COS-7 cells.
SubunitAssociates with GMPPB. {ECO:0000250}.
Tissue SpecificityExpressed in fibroblasts (at protein level). {ECO:0000269|PubMed:24035193}.
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