Disease relevance of Man2b1

• Targeted disruption of the lysosomal alpha-mannosidase gene results in mice resembling a mild form of human alpha-mannosidosis [1].
• Alpha-mannosidosis is a lysosomal storage disease with autosomal recessive inheritance caused by a deficiency of the lysosomal alpha-mannosidase, which is involved in the degradation of asparagine-linked carbohydrate cores of glycoproteins [1].
• Mannosidosis: assignment of the lysosomal alpha-mannosidase B gene to chromosome 19 in man [2].
• Injection of 250 mU human LAMAN/g body weight followed by a subsequent injection 3.5 days later was sufficient to clear liver, kidney and heart from neutral oligosaccharides [3].
• Retrovirus vector-mediated correction and cross-correction of lysosomal alpha-mannosidase deficiency in human and feline fibroblasts [4].

High impact information on Man2b1

• Here we report on the correction of storage in a mouse model of alpha-mannosidosis after intravenous administration of lysosomal acid alpha-mannosidase (LAMAN) from bovine kidney, and human and mouse recombinant LAMAN [3].
• The bovine and the human enzyme were barely phosphorylated, whereas the bulk of the mouse LAMAN contained mannose 6-phosphate recognition markers [3].
• The indolizidine alkaloid swainsonine (SW) is an inhibitor of lysosomal alpha-mannosidase reported to have antimetastatic activity in animal models [5].
• The effect of swainsonine, an inhibitor of Golgi alpha-mannosidase II and lysosomal alpha-mannosidase, on the synthesis, processing, and turnover of two glycoproteins, lysosomal beta-galactosidase and lysosomal beta-glucuronidase, has been studied in cultured mouse peritoneal macrophages [6].
• Lysosomal alpha-mannosidase (EC 3.2.1.24) is an exoglycosidase in the glycoprotein degradation pathway [4].

Chemical compound and disease context of Man2b1

• Human mannosidosis, an inherited glycoprotein storage disorder, has been associated with severe deficiency of both lysosomal alpha-mannosidase B molecular forms [2].

Biological context of Man2b1

• The deduced amino acid sequence was 76.5% identical to the human lysosomal alpha-mannosidase and 38.1% identical to the lysosomal alpha-mannosidase from D. discoideum [7].
• We have previously reported on a mouse liver-specific genetic polymorphism associated with altered sialylation of lysosomal alpha-mannosidase [8].

Associations of Man2b1 with chemical compounds

• Catabolism of alpha-linked mannose residues on eukaryotic glycoproteins is accomplished by a broad specificity lysosomal alpha-mannosidase (EC 3.2.1.24) [7].
• Based on regions of protein sequence conservation between the lysosomal alpha-mannosidase from Dictyostelium discoideum and the murine Golgi glycoprotein processing alpha 1,3/1,6-mannosidase, alpha-mannosidase II, we have cloned a cDNA encoding the murine lysosomal alpha-mannosidase [7].
• Lysosomal alpha-mannosidase (EC 3.2.1.24) is required in the degradation of the asparagine-linked carbohydrates of glycoproteins [9].

Analytical, diagnostic and therapeutic context of Man2b1

• N-terminal sequence analysis of the purified enzyme revealed that the proteolysis occurred close to a cleavage site previously identified in the intracellular form of lysosomal alpha-mannosidase [9].

References