Disease relevance of MAN1A1

• Heterogeneity of urinary oligosaccharides from mannosidosis: mass spectrometric analysis of permethylated Man9, Man8, and Man7 derivatives [1].
• We produced the human kidney Man9-mannosidase in Escherichia coli and studied the effect of the alpha-1,2-mannosidic linkage located in the alpha branch of Manalpha1-6(Manalpha1-2Manalpha1-3)Manalpha1-6(Manalpha1-3)Manbeta1-4GlcNAcbeta1-4-GlcNAc, an N-linked oligosaccharide, on the enzyme activity [2].

High impact information on MAN1A1

• Second, the binding to the C3-derived glycoprotein iC3b appears to be exclusively mediated through the Man8 or Man9 oligosaccharide on the alpha chain; there is no evidence for other N-linked oligosaccharides on C3 that are uniquely bound by conglutinin [3].
• In the structure, each monomeric asymmetric unit contains a Man9 oligomannose-type chain at Asn 75, with only the first two GlcNAc residues visible [4].
• Recently, we have shown that highly ordered cross-linked lattices are formed between the tetrameric glycoprotein soybean agglutinin (SBA), which possesses a Man9 oligomannose chain per monomer, and the Glc/Man-specific plant lectin concanavalin A (Con A) [Khan, M. I., Mandal, D. K., & Brewer, C. F. (1991) Carbohydr. Res. 213, 69-77] [5].
• ER localization was also observed with an M9GI chimera consisting of the cytosolic and transmembrane domain of Man9-mannosidase and the glucosidase I catalytic domain [6].
• To identify sequence motifs responsible for ER localization, we prepared a protein chimera by transferring the cytosolic and transmembrane domain of glucosidase I to the luminal domain of Golgi-Man9-mannosidase [6].

Biological context of MAN1A1

• Analysis of the coding sequence predicts that Man9-mannosidase is a type II transmembrane protein consisting of a short cytoplasmic polypeptide tail, a single transmembrane domain acting as a non-cleavable signal sequence and a large luminal catalytic domain [7].
• Man9-mannosidase, an alpha 1,2-specific exo-enzyme involved in N-linked oligosaccharide processing, has been cloned recently from a human kidney cDNA library [Bause, E., Bieberich, E., Rolfs, A., Völker, C. & Schmidt, B. (1993) Eur. J. Biochem. 217, 533-540] [8].
• The calculated mass of an intact lectin monomer from the amino acid sequence (253 residues) derived from cDNA of the lectin including a Man9 oligomannose chain is 29438 Da [9].

Anatomical context of MAN1A1

• Man9-mannosidase from human kidney is expressed in COS cells as a Golgi-resident type II transmembrane N-glycoprotein [8].
• This localization clearly differs from that of pig liver Man9-mannosidase which appears to be located in the endoplasmic reticulum and transient vesicles [8].

Associations of MAN1A1 with chemical compounds

• Several lines of evidence suggest that Man9-mannosidase, as expressed, is N-glycosylated at one of three potential Asn-Xaa-Thr/Ser/Cys acceptor sites [8].
• Man9-mannosidase, a processing enzyme found in the endoplasmic reticulum (ER), catalyses the removal of three distinct mannose residues from peptide-bound Man9-GlcNAc2 oligosaccharides producing a single Man6 isomer [Bause, E., Breuer, W., Schweden, J., Roesser, R. & Geyer, R. (1992) Eur. J. Biochem. 208, 451-457] [7].
• Unlike ConA, DGL does not show enhanced affinity for a large N-linked oligomannose carbohydrate (Man9 glycopeptide) relative to the trimannoside [10].
• However, a variable proportion (5% to 15%) of high-mannose (Man5 to Man9) oligosaccharides were present [11].
• Two mechanisms of binding at the primary sites of oligomannose-type glycopeptides have been identified which account for the 3000-fold increase in affinity of a Man9 glycopeptide relative to that of methyl alpha-D-mannopyranoside [12].

Analytical, diagnostic and therapeutic context of MAN1A1

• Molecular cloning and primary structure of Man9-mannosidase from human kidney [7].
• This observation is consistent with the results of indirect immunofluorescence studies, pointing to a localization of the Man9-mannosidase predominantly in the juxtanuclear Golgi region [8].
• Separation of the per-O-benzoylated high-mannose oligosaccharides by high-pressure liquid chromatography revealed the same polymeric structures in a molar ratio (from Man5 to Man9) of 10:2:3:2:3 [13].

References