Mannosidase, Alpha, Class 2a2 (MAN2A2)

Reference work entry


Many proteins synthesized through the secretory pathway are posttranslationally modified by N-glycosylation. Alpha-mannosidase II (MAN2A1) and alpha-mannosidase IIx (MAN2A2) are key enzymes that convert precursor high mannose-type N-glycans to mature complex-type structures. While alpha-mannosidase II activity had been characterized by the time the mechanism of N-glycan processing was recognized (Kornfeld and Kornfeld 1985), investigators did not discover an alternative processing pathway until Man2a1 null mutant mice were generated and found capable of synthesizing complex-type N-glycans (Chui et al. 1997). Man2a2 then became a candidate for mediating that alternate pathway of N-glycan synthesis, but support for the pathway was lacking until creation of Man2a1/Man2a2 double knockout mice, which showed a complete loss in the ability to synthesize complex-type N-glycans (Fig. 117.1) (Akama et al. 2006).


Sertoli Cell Spermatogenic Cell Double Knockout Mouse Cleavable Signal Sequence Xenobiotic Responsive Element 


  1. Akama TO, Fukuda MN (2006) N-Glycan structure analysis using lectins and an alpha-mannosidase activity assay. Methods Enzymol 416:304–314PubMedCrossRefGoogle Scholar
  2. Akama TO, Nakagawa H, Sugihara K, Narisawa S, Ohyama C, Nishimura S, O’Brien DA, Moremen KW, Millan JL, Fukuda MN (2002) Germ cell survival through carbohydrate-mediated interaction with sertoli cells. Science 295:124–127PubMedCrossRefGoogle Scholar
  3. Akama TO, Nakagawa H, Wong NK, Sutton-Smith M, Dell A, Morris HR, Nakayama J, Nishimura S, Pai A, Moremen KW et al (2006) Essential and mutually compensatory roles of alpha-mannosidase II and alpha-mannosidase IIx in N-glycan processing in vivo in mice. Proc Natl Acad Sci USA 103:8983–8988PubMedCrossRefGoogle Scholar
  4. Bulun SE, Zeitoun KM, Takayama K, Sasano H (2000) Estrogen biosynthesis in endometriosis: molecular basis and clinical relevance. J Mol Endocrinol 25:35–42PubMedCrossRefGoogle Scholar
  5. Chui D, Oh-Eda M, Liao YF, Panneerselvam K, Lal A, Marek KW, Freeze HH, Moremen KW, Fukuda MN, Marth JD (1997) Alpha-mannosidase-II deficiency results in dyserythropoiesis and unveils an alternate pathway in oligosaccharide biosynthesis. Cell 90:157–167PubMedCrossRefGoogle Scholar
  6. Dall’Olio GM, Laayouni H, Luisi P, Sikora M, Montanucci L, Bertranpetit J (2012) Distribution of events of positive selection and population differentiation in a metabolic pathway: the case of asparagine N-glycosylation. BMC Evol Biol 12:98PubMedCentralPubMedCrossRefGoogle Scholar
  7. Flores I, Rivera E, Mousses S, Chen Y, Rozenblum E (2006) Identification of molecular markers for endometriosis in blood lymphocytes by using deoxyribonucleic acid microarrays. Fertil Steril 85:1676–1683PubMedCrossRefGoogle Scholar
  8. Kornfeld R, Kornfeld S (1985) Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem 54:631–664PubMedCrossRefGoogle Scholar
  9. Kroes RA, Dawson G, Moskal JR (2007) Focused microarray analysis of glyco-gene expression in human glioblastomas. J Neurochem 103(Suppl 1):14–24PubMedCrossRefGoogle Scholar
  10. Misago M, Liao Y-F, Kudo S, Eto S, Mattei M-G, Moremen KW, Fukuda MN (1995) Molecular cloning and expression of cDNAs encoding human a-mannosidase II and a novel a-mannosidase IIx isozyme. Proc Natl Acad Sci USA 92:11766–11770PubMedCrossRefGoogle Scholar
  11. Ogawa R, Misago M, Fukuda MN, Kudo S, Tsukada J, Morimoto I, Eto S (1996) Structure and transcriptional regulation of human alpha-mannosidase IIX (alpha-mannosidase II isotype) gene. Eur J Biochem 242:446–453PubMedCrossRefGoogle Scholar
  12. Wei YL, Li CX, Li SB, Liu Y, Hu L (2011) Association study of monoamine oxidase A/B genes and schizophrenia in Han Chinese. Behav Brain Funct: BBF 7:42PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Sanford-Burnham Medical Research InstituteLa JollaUSA
  2. 2.Department of Obsteterics and GynecologyHaamamatsu University School of MedicineHamamatsu CityJapan
  3. 3.Department of PharmacologyKansai Medical UniversityHirakataJapan
  4. 4.Sanford-Burnham Medical Research InstituteLa JollaUSA

Personalised recommendations