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Gene Review

MAN2A1  -  mannosidase, alpha, class 2A, member 1

Homo sapiens

Synonyms: AMan II, Alpha-mannosidase 2, GOLIM7, Golgi alpha-mannosidase II, MANA2, ...

Functions (from Uniprot)

Catalyzes the first committed step in the biosynthesis of complex N-glycans. It controls conversion of high mannose to complex N-glycans; the final hydrolytic step in the N-glycan maturation pathway.


Catalytic activity (from Uniprot)

Hydrolysis of the terminal (1->3)- and (1->6)-linked alpha-D-mannose residues in the mannosyl-oligosaccharide Man5(GlcNAc)3.


Disease relevance of MAN2A1


High impact information on MAN2A1

  • Alpha-mannosidase-II (alphaM-II) catalyzes the first committed step in the biosynthesis of complex asparagine-linked (N-linked) oligosaccharides (N-glycans) [6].
  • After 1 h at 37 degrees C, VT1B accumulated in a juxtanuclear structure that colocalized with several Golgi markers, including alpha-mannosidase II, beta-COP, and NBD-ceramide [7].
  • Isolation, characterization, and expression of cDNAs encoding murine alpha-mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans [8].
  • Transient expression of the alpha-mannosidase II cDNA in COS cells resulted in 8-12-fold overexpression of enzyme activity, and the appearance of cross-reactive material in a perinuclear membrane array consistent with a Golgi localization [8].
  • We have isolated overlapping clones from a murine cDNA library encoding the full length alpha-mannosidase II open reading frame and most of the 5' and 3' untranslated region [8].

Chemical compound and disease context of MAN2A1


Biological context of MAN2A1

  • Partial human alpha-mannosidase II cDNA clones were also isolated and the gene was localized to human chromosome 5 [8].
  • Many proteins synthesized through the secretory pathway receive posttranslational modifications, including N-glycosylation. alpha-Mannosidase II (MII) is a key enzyme converting precursor high-mannose-type N-glycans to matured complex-type structures [10].
  • Novel purification of the catalytic domain of Golgi alpha-mannosidase II. Characterization and comparison with the intact enzyme [11].
  • This results in reduced levels and/or altered Golgi localization of alpha-mannosidase II and beta-1,4 galactosyltransferase I, which links it to the glycosylation deficiency [12].
  • Previously, we cloned and characterized an insect (Sf9) cell cDNA encoding a class II alpha-mannosidase with amino acid sequence and biochemical similarities to mammalian Golgi alpha-mannosidase II [13].

Anatomical context of MAN2A1


Associations of MAN2A1 with chemical compounds

  • Golgi alpha-mannosidase II (GlcNAc transferase I-dependent alpha 1,3[alpha 1,6] mannosidase, EC catalyzes the final hydrolytic step in the N-glycan maturation pathway acting as the committed step in the conversion of high mannose to complex type structures [8].
  • (a) The catalytic activity of the intact and cleaved forms of alpha-mannosidase II were indistinguishable in Km, Vmax, inhibition by the alkaloid, swainsonine, and in their activity toward the natural substrate GlcNAc-Man5GlcNAc [11].
  • The GalNAc bearing hybrid structures, either with or without sulfate, cannot be processed to mono- or disulfated complex oligosaccharides due to the inability of either alpha-mannosidase II or GlcNAc-transferase II to act on GalNAc containing oligosaccharides [18].
  • When N-acetyl-beta-glucosaminidase or alpha-mannosidase II was inhibited by specific inhibitors, the amount of terminal N-acetylglucosamine in hemagglutinin from Sf9 cells was significantly enhanced [19].
  • Thus novel glycosylation pathways have been uncovered in two such knockouts, namely alpha-mannosidase II null mice and UDP-N-acetylglucosamine: alpha 6-D-mannoside beta 1,2-N-acetylglucosaminyltransferase II null mice [20].

Co-localisations of MAN2A1


Other interactions of MAN2A1


Analytical, diagnostic and therapeutic context of MAN2A1


  1. Incomplete synthesis of N-glycans in congenital dyserythropoietic anemia type II caused by a defect in the gene encoding alpha-mannosidase II. Fukuda, M.N., Masri, K.A., Dell, A., Luzzatto, L., Moremen, K.W. Proc. Natl. Acad. Sci. U.S.A. (1990) [Pubmed]
  2. Fragmentation and dispersal of Golgi proteins and redistribution of glycoproteins and glycolipids processed through the Golgi apparatus after infection with herpes simplex virus 1. Campadelli, G., Brandimarti, R., Di Lazzaro, C., Ward, P.L., Roizman, B., Torrisi, M.R. Proc. Natl. Acad. Sci. U.S.A. (1993) [Pubmed]
  3. Unusually high expression of N-acetylglucosaminyltransferase-IVa in human choriocarcinoma cell lines: a possible enzymatic basis of the formation of abnormal biantennary sugar chain. Takamatsu, S., Oguri, S., Minowa, M.T., Yoshida, A., Nakamura, K., Takeuchi, M., Kobata, A. Cancer Res. (1999) [Pubmed]
  4. A phase I study of swainsonine in patients with advanced malignancies. Goss, P.E., Baptiste, J., Fernandes, B., Baker, M., Dennis, J.W. Cancer Res. (1994) [Pubmed]
  5. Phase IB clinical trial of the oligosaccharide processing inhibitor swainsonine in patients with advanced malignancies. Goss, P.E., Reid, C.L., Bailey, D., Dennis, J.W. Clin. Cancer Res. (1997) [Pubmed]
  6. Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis. Chui, D., Oh-Eda, M., Liao, Y.F., Panneerselvam, K., Lal, A., Marek, K.W., Freeze, H.H., Moremen, K.W., Fukuda, M.N., Marth, J.D. Cell (1997) [Pubmed]
  7. Dynamic measurement of the pH of the Golgi complex in living cells using retrograde transport of the verotoxin receptor. Kim, J.H., Lingwood, C.A., Williams, D.B., Furuya, W., Manolson, M.F., Grinstein, S. J. Cell Biol. (1996) [Pubmed]
  8. Isolation, characterization, and expression of cDNAs encoding murine alpha-mannosidase II, a Golgi enzyme that controls conversion of high mannose to complex N-glycans. Moremen, K.W., Robbins, P.W. J. Cell Biol. (1991) [Pubmed]
  9. Human melanoma cell invasion is inhibited in vitro by swainsonine and deoxymannojirimycin with a concomitant decrease in collagenase IV expression. Seftor, R.E., Seftor, E.A., Grimes, W.J., Liotta, L.A., Stetler-Stevenson, W.G., Welch, D.R., Hendrix, M.J. Melanoma Res. (1991) [Pubmed]
  10. Essential and mutually compensatory roles of {alpha}-mannosidase II and {alpha}-mannosidase IIx in N-glycan processing in vivo in mice. Akama, T.O., Nakagawa, H., Wong, N.K., Sutton-Smith, M., Dell, A., Morris, H.R., Nakayama, J., Nishimura, S., Pai, A., Moremen, K.W., Marth, J.D., Fukuda, M.N. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  11. Novel purification of the catalytic domain of Golgi alpha-mannosidase II. Characterization and comparison with the intact enzyme. Moremen, K.W., Touster, O., Robbins, P.W. J. Biol. Chem. (1991) [Pubmed]
  12. Conserved oligomeric Golgi complex subunit 1 deficiency reveals a previously uncharacterized congenital disorder of glycosylation type II. Foulquier, F., Vasile, E., Schollen, E., Callewaert, N., Raemaekers, T., Quelhas, D., Jaeken, J., Mills, P., Winchester, B., Krieger, M., Annaert, W., Matthijs, G. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  13. Insect cells encode a class II alpha-mannosidase with unique properties. Kawar, Z., Karaveg, K., Moremen, K.W., Jarvis, D.L. J. Biol. Chem. (2001) [Pubmed]
  14. Immunocytochemical localization of the Menkes copper transport protein (ATP7A) to the trans-Golgi network. Dierick, H.A., Adam, A.N., Escara-Wilke, J.F., Glover, T.W. Hum. Mol. Genet. (1997) [Pubmed]
  15. Nordihydroguaiaretic acid blocks protein transport in the secretory pathway causing redistribution of Golgi proteins into the endoplasmic reticulum. Fujiwara, T., Takami, N., Misumi, Y., Ikehara, Y. J. Biol. Chem. (1998) [Pubmed]
  16. Site-directed mutagenesis and deletion of three phosphorylation sites of calsequestrin of skeletal muscle sarcoplasmic reticulum. Effects on intracellular targeting. Nori, A., Furlan, S., Patiri, F., Cantini, M., Volpe, P. Exp. Cell Res. (2000) [Pubmed]
  17. The structural basis of the inhibition of human alpha-mannosidases by azafuranose analogues of mannose. Winchester, B., al Daher, S., Carpenter, N.C., Cenci di Bello, I., Choi, S.S., Fairbanks, A.J., Fleet, G.W. Biochem. J. (1993) [Pubmed]
  18. Biosynthesis of sulfated asparagine-linked oligosaccharides on bovine lutropin. Green, E.D., Boime, I., Baenziger, J.U. J. Biol. Chem. (1986) [Pubmed]
  19. N-acetyl-beta-glucosaminidase accounts for differences in glycosylation of influenza virus hemagglutinin expressed in insect cells from a baculovirus vector. Wagner, R., Geyer, H., Geyer, R., Klenk, H.D. J. Virol. (1996) [Pubmed]
  20. MS screening strategies: investigating the glycomes of knockout and myodystrophic mice and leukodystrophic human brains. Sutton-Smith, M., Morris, H.R., Grewal, P.K., Hewitt, J.E., Bittner, R.E., Goldin, E., Schiffmann, R., Dell, A. Biochem. Soc. Symp. (2002) [Pubmed]
  21. Overexpression of the Golgi-localized enzyme alpha-mannosidase IIx in Chinese hamster ovary cells results in the conversion of hexamannosyl-N-acetylchitobiose to tetramannosyl-N-acetylchitobiose in the N-glycan-processing pathway. Oh-Eda, M., Nakagawa, H., Akama, T.O., Lowitz, K., Misago, M., Moremen, K.W., Fukuda, M.N. Eur. J. Biochem. (2001) [Pubmed]
  22. A novel strategy for preventing PERV transmission to human cells by remodeling the viral envelope glycoprotein. Miyagawa, S., Nakatsu, S., Hazama, K., Nakagawa, T., Kondo, A., Matsunami, K., Yamamoto, A., Yamada, J., Miyazawa, T., Shirakura, R. Xenotransplantation (2006) [Pubmed]
  23. Molecular cloning and primary structure of Man9-mannosidase from human kidney. Bause, E., Bieberich, E., Rolfs, A., Völker, C., Schmidt, B. Eur. J. Biochem. (1993) [Pubmed]
  24. Exclusion of three candidate genes as determinants of congenital dyserythropoietic anemia type II (CDA-II). Iolascon, A., Miraglia del Giudice, E., Perrotta, S., Granatiero, M., Zelante, L., Gasparini, P. Blood (1997) [Pubmed]
  25. HEMPAS disease: genetic defect of glycosylation. Fukuda, M.N. Glycobiology (1990) [Pubmed]
  26. Molecular cloning and expression of cDNAs encoding human alpha-mannosidase II and a previously unrecognized alpha-mannosidase IIx isozyme. Misago, M., Liao, Y.F., Kudo, S., Eto, S., Mattei, M.G., Moremen, K.W., Fukuda, M.N. Proc. Natl. Acad. Sci. U.S.A. (1995) [Pubmed]
  27. Cloning and recombinant expression of active full-length xylosyltransferase I (XT-I) and characterization of subcellular localization of XT-I and XT-II. Schön, S., Prante, C., Bahr, C., Kuhn, J., Kleesiek, K., Götting, C. J. Biol. Chem. (2006) [Pubmed]
  28. Measuring swainsonine in serum of cancer patients: phase I clinical trial. Baptista, J.A., Goss, P., Nghiem, M., Krepinsky, J.J., Baker, M., Dennis, J.W. Clin. Chem. (1994) [Pubmed]
  29. Isolation and characterization of a class II alpha-mannosidase cDNA from lepidopteran insect cells. Jarvis, D.L., Bohlmeyer, D.A., Liao, Y.F., Lomax, K.K., Merkle, R.K., Weinkauf, C., Moremen, K.W. Glycobiology (1997) [Pubmed]
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