Search by BoMiProt ID - Bomi2391

Primary Information

BoMiProt ID Bomi2391
Protein Name Lysosomal alpha-mannosidase
Organism Bos taurus
Uniprot IDQ29451
Milk FractionWhey
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,
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.
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).