Disease relevance of POMGNT1

• These findings emphasize the importance of considering MEB and searching for POMGnT1 mutations in WWS or other congenital muscular dystrophy patients worldwide [1].
• We also observed a slight correlation between the location of the mutation and clinical severity in the brain: patients with mutations near the 5' terminus of the POMGnT1 coding region show relatively severe brain symptoms such as hydrocephalus, while patients with mutations near the 3' terminus have milder phenotypes [1].

High impact information on POMGNT1

• The protein products of POMGnT1 and Fukutin have both been implicated in protein glycosylation [2].
• Since POMGnT1 encodes an O-mannoside N-acetylglucosaminyltransferase, we analyzed the possible implication of O-mannosyl glycan synthesis in WWS [2].
• Furthermore, incorporation of an additional GlcNAc residue into a synthetic mannosyl peptide Ac-Ala-Ala-Pro-Thr(Man)-Pro-Val-Ala-Ala-Pro-NH(2) by GnT-IX was only observed in the presence of POMGnT1 [3].
• It has been demonstrated that the transfer of GlcNAc to the 2-OH position of the mannose residue is catalyzed by the enzyme, protein O-mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1), but the enzymatic basis of the transfer to the 6-OH position is unknown [3].
• POMGnT1 Mutations in Congenital Muscular Dystrophy: Genotype-Phenotype Correlation and Expanded Clinical Spectrum [4].

Biological context of POMGNT1

• We evaluated several truncated mutants of POMGnT1 to determine the minimal catalytic domain [5].
• Single amino acid substitutions in the stem domain of POMGnT1 from MEB patients abolished the activity of the membrane-bound form but not the soluble form [5].
• Molecular interaction between fukutin and POMGnT1 in the glycosylation pathway of alpha-dystroglycan [6].
• Y371C, a missense mutation found in FCMD, retains fukutin in the ER and also redirects POMGnT1 to the ER [6].
• MEB is caused by mutations in the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1) gene on chromosome 1q33 [7].

Associations of POMGNT1 with chemical compounds

• Previously, we found that MEB is caused by mutations in the gene encoding the protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1), which is responsible for the formation of the GlcNAcbeta1-2Man linkage of O-mannosyl glycan [8].
• Protein O-linked mannose beta1,2-N-acetylglucosaminyltransferase 1 (POMGnT1) catalyzes the transfer of GlcNAc to O-mannose of glycoproteins [5].
• We have identified and characterized a glycosyltransferase, UDP-N-acetylglucosamine: protein O-mannose beta1,2-N-acetylglucosaminyltransferase (POMGnT1), involved in the biosynthesis of O-mannosyl glycans [9].

Other interactions of POMGNT1

• This protocol describes assay methods for the mammalian POMT and POMGnT [10].

Analytical, diagnostic and therapeutic context of POMGNT1

• Direct interaction between fukutin and POMGnT1 was confirmed by co-immunoprecipitation and two-hybrid analyses [6].
• CONCLUSIONS: The assay of POMGnT1 activity in MEB muscle provides a rapid and relatively simple diagnostic test for this disease [11].

References