Primary Information | |
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BoMiProt ID | Bomi2391 |
Protein Name | Lysosomal alpha-mannosidase |
Organism | Bos taurus |
Uniprot ID | Q29451 |
Milk Fraction | Whey |
Ref Sequence ID | NP_776986.2 |
Aminoacid Length | 999 |
Molecular Weight | 112919 |
FASTA Sequence | Download |
Gene Name | MAN2B1 |
Gene ID | 282272 |
Protein Existence Status | Reviewed: Experimental evidence at protein level |
Secondary Information | |
Protein Function | Lysosomal alpha-mannosidase takes part in the sequential degradation of complex, hybrid and high-mannose N-linked oligosaccharides. |
Biochemical Properties | It contains 1011 amino acids sequence containing a putative signal peptide of 48 amino acids followed by a polypeptide sequence of 962 amino acids and 11 potential N-glycosylation sites.The three-dimensional structure of bovine alpha-mannosidase has been resolved (PDB ID:1O7D), providing a close structural model for the human enzyme. Lysosomal alpha-mannosidase consists of four domains: a N-terminal alpha/beta –domain, and three all-beta-domains. The N-terminal alpha/beta domain contains the active site and is formed by the a- and b-peptides. It is followed by a three-helix bundle joining the b and c-peptides, and three mainly β-sheet domains formed by peptides c, d and e. The mature enzyme is a dimer. |
PTMs | Disulfide bond,N-Linked Glycosylation at Asn-134,634,681 and 755, Zymogen formation |
Site(s) of PTM(s) N-glycosylation, O-glycosylation, Phosphorylation | |
Predicted Disorder Regions | (1-25) |
DisProt Annotation | |
TM Helix Prediction | No TM helices |
Significance of PTMs | Processed into 5 peptides of 35/38 kDa (A), 11/13 kDa (B) and 22 kDa (C), 38 kDa (D) and 13/15 kDa (E). The A, B and C peptides are disulfide-linked into a 67 kDa complex. |
PDB ID | 1O7D, |
Additional Comments | Lack of lysosomal alpha-mannosidase activity causes the autosomal recessive disease alpha-mannosidosis. |
Bibliography | 1.Heikinheimo P, Helland R, Leiros HK, Leiros I, Karlsen S, Evjen G, Ravelli R, Schoehn G, Ruigrok R, Tollersrud OK, McSweeney S, Hough E. The structure of bovine lysosomal alpha-mannosidase suggests a novel mechanism for low-pH activation. J Mol Biol. 2003 Mar 28;327(3):631-44. doi: 10.1016/s0022-2836(03)00172-4. PMID: 12634058. 2.Paciotti S, Codini M, Tasegian A, Ceccarini MR, Cataldi S, Arcuri C, Fioretti B, Albi E, Beccari T. Lysosomal alpha-mannosidase and alpha-mannosidosis. Front Biosci (Landmark Ed). 2017 Jan 1;22:157-167. doi: 10.2741/4478. PMID: 27814608. 3.O. Nilssen, T. Berg, H. M. Riise, U. Ramachandran, G. Evjen, G. M. Hansen, D. Malm, L. Tranebjaerg and O. K. Tollersrud: alpha-Mannosidosis: functional cloning of the lysosomal alpha-mannosidase cDNA and identification of a mutation in two affected siblings. Hum Mol Genet, 6, 717-26 (1997). 4.P. Heikinheimo, R. Helland, H. K. Leiros, I. Leiros, S. Karlsen, G. Evjen, R. Ravelli, G. Schoehn, R. Ruigrok, O. K. Tollersrud, S. McSweeney and E. Hough: The structure of bovine lysosomal alpha-mannosidase suggests a novel mechanism for low-pH activation. J Mol Biol, 327, 631-44 (2003). 5.O. K. Tollersrud, T. Berg, P. Healy, G. Evjen, U. Ramachandran and O. Nilssen: Purification of bovine lysosomal alpha-mannosidase, characterization of its gene and determination of two mutations that cause alpha-mannosidosis. Eur J Biochem, 246, 410-9 (1997). |