Glucosidase, Alpha Neutral AB; Glucosidase II Subunit Beta (GANAB, PRKCSH, α-Glucosidase II)

  • Alison V. Nairn
  • Kelley W. Moremen
Reference work entry


The synthesis of N-linked glycans is initiated by the synthesis of a Glc3Man9GlcNAc2 lipid-linked precursor and the co-translational transfer to nascent polypeptide chains in the lumen of the endoplasmic reticulum (ER) (Kornfeld and Kornfeld 1985). Immediately after transfer of the glycan to Asn side chains glucose (Glc), trimming is initiated by the cleavage of the terminal α1,2-Glc residue by α-glucosidase I (MOGS). Subsequent cleavage of the two internal α1,3-Glc residues is accomplished by the heterodimeric enzyme α-glucosidase II (GANAB/PRKCSH) (Burns and Touster 1982; Grinna and Robbins 1979, 1980) to produce the Man9GlcNAc2-Asn processing intermediate (Fig. 114.1).


Glycan Structure Mannose Residue Nascent Polypeptide Chain Lectin Chaperone Autosomal Dominant Polycystic Liver Disease 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


  1. Alonso JM, Santa-Cecilia A, Calvo P (1991) Glucosidase II from rat liver microsomes. Kinetic model for binding and hydrolysis. Biochem J 278:721–727PubMedGoogle Scholar
  2. Arendt CW, Ostergaard HL (1997) Identification of the CD45-associated 116-kDa and 80-kDa proteins as the α- and β-subunits of α-glucosidase II. J Biol Chem 272:13117–13125PubMedCrossRefGoogle Scholar
  3. Arendt CW, Ostergaard HL (2000) Two distinct domains of the β-subunit of glucosidase II interact with the catalytic α-subunit. Glycobiology 10:487–492PubMedCrossRefGoogle Scholar
  4. Arendt CW, Dawicki W, Ostergaard HL (1999) Alternative splicing of transcripts encoding the α- and β-subunits of mouse glucosidase II in T lymphocytes. Glycobiology 9:277–283PubMedCrossRefGoogle Scholar
  5. Brada D, Dubach UC (1984) Isolation of a homogeneous glucosidase II from pig kidney microsomes. Eur J Biochem 141:149–156PubMedCrossRefGoogle Scholar
  6. Brada D, Kerjaschki D, Roth J (1990) Cell type-specific post-Golgi apparatus localization of a “resident” endoplasmic reticulum glycoprotein, glucosidase II. J Cell Biol 110:309–318PubMedCrossRefGoogle Scholar
  7. Burns DM, Touster O (1982) Purification and characterization of glucosidase II, an endoplasmic reticulum hydrolase involved in glycoprotein biosynthesis. J Biol Chem 257:9990–10000PubMedGoogle Scholar
  8. Chiu CC, Lin CY, Lee LY, Chen YJ, Lu YC, Wang HM, Liao CT, Chang JT, Cheng AJ (2011) Molecular chaperones as a common set of proteins that regulate the invasion phenotype of head and neck cancer. Clin Cancer Res 17:4629–4641PubMedCrossRefGoogle Scholar
  9. Datema R, Romero PA, Legler G, Schwarz RT (1982) Inhibition of formation of complex oligosaccharides by the glucosidase inhibitor bromoconduritol. Proc Natl Acad Sci USA 79:6787–6791PubMedCrossRefGoogle Scholar
  10. Deprez P, Gautschi M, Helenius A (2005) More than one glycan is needed for ER glucosidase II to allow entry of glycoproteins into the calnexin/calreticulin cycle. Mol Cell 19:183–195PubMedCrossRefGoogle Scholar
  11. Fedeles SV, Tian X, Gallagher AR, Mitobe M, Nishio S, Lee SH, Cai Y, Geng L, Crews CM, Somlo S (2013) A genetic interaction network of five genes for human polycystic kidney and liver diseases defines polycystin-1 as the central determinant of cyst formation. Nat Genet 43:639–647CrossRefGoogle Scholar
  12. Feng J, Romaniouk AV, Samal SK, Vijay IK (2004) Processing enzyme glucosidase II: proposed catalytic residues and developmental regulation during the ontogeny of the mouse mammary gland. Glycobiology 14:909–921PubMedCrossRefGoogle Scholar
  13. Flura T, Brada D, Ziak M, Roth J (1997) Expression of a cDNA encoding the glucose trimming enzyme glucosidase II in CHO cells and molecular characterization of the enzyme deficiency in a mutant mouse lymphoma cell line. Glycobiology 7:617–624PubMedCrossRefGoogle Scholar
  14. Ganan S, Cazzulo JJ, Parodi AJ (1991) A major proportion of N-glycoproteins are transiently glucosylated in the endoplasmic reticulum. Biochemistry 30:3098–3104PubMedCrossRefGoogle Scholar
  15. Grinna LS, Robbins PW (1979) Glycoprotein biosynthesis. Rat liver microsomal glucosidases which process oligosaccharides. J Biol Chem 254:8814–8818PubMedGoogle Scholar
  16. Grinna LS, Robbins PW (1980) Substrate specificities of rat liver microsomal glucosidases which process glycoproteins. J Biol Chem 255:2255–2258PubMedGoogle Scholar
  17. Hammond C, Helenius A (1995) Quality control in the secretory pathway. Curr Opin Cell Biol 7:523–529PubMedCrossRefGoogle Scholar
  18. Henrissat B, Bairoch A (1993) New families in the classification of glycosyl hydrolases based on amino acid sequence similarities. Biochem J 293:781–788PubMedGoogle Scholar
  19. Henrissat B, Davies G (1997) Structural and sequence-based classification of glycoside hydrolases. Curr Opin Struct Biol 7:637–644PubMedCrossRefGoogle Scholar
  20. Henrissat B, Romeu A (1995) Families, superfamilies and subfamilies of glycosyl hydrolases. Biochem J 311:350–351PubMedGoogle Scholar
  21. Hentges A, Bause E (1997) Affinity purification and characterization of glucosidase II from pig liver. Biol Chem 378:1031–1038PubMedCrossRefGoogle Scholar
  22. Hettkamp H, Bause E, Legler G (1982) Inhibition by nojirimycin and 1-deoxynojirimycin of microsomal glucosidases from calf liver acting on the glycoprotein oligosaccharides Glc1-3Man9GlcNAc2. Biosci Rep 2:899–906PubMedCrossRefGoogle Scholar
  23. Hino Y, Rothman JE (1985) Glucosidase II, a glycoprotein of the endoplasmic reticulum membrane. Proteolytic cleavage into enzymatically active fragments. Biochemistry 24:800–805PubMedCrossRefGoogle Scholar
  24. Hirai M, Shimizu N (1990) Purification of two distinct proteins of approximate Mr 80,000 from human epithelial cells and identification as proper substrates for protein kinase C. Biochem J 270:583–589PubMedGoogle Scholar
  25. Hirano K, Ziak M, Kamoshita K, Sukenaga Y, Kametani S, Shiga Y, Roth J, Akanuma H (2000) N-linked oligosaccharide processing enzyme glucosidase II produces 1,5-anhydrofructose as a side product. Glycobiology 10:1283–1289PubMedCrossRefGoogle Scholar
  26. Kornfeld R, Kornfeld S (1985) Assembly of asparagine-linked oligosaccharides. Annu Rev Biochem 54:631–664PubMedCrossRefGoogle Scholar
  27. Li A, Davila S, Furu L, Qian Q, Tian X, Kamath PS, King BF, Torres VE, Somlo S (2003) Mutations in PRKCSH cause isolated autosomal dominant polycystic liver disease. Am J Hum Genet 72:691–703PubMedCentralPubMedCrossRefGoogle Scholar
  28. Martiniuk F, Ellenbogen A, Hirschhorn R (1985) Identity of neutral α-glucosidase AB and the glycoprotein processing enzyme glucosidase II. Biochemical and genetic studies. J Biol Chem 260:1238–1242PubMedGoogle Scholar
  29. Michael JM, Kornfeld S (1980) Partial purification and characterization of the glucosidases involved in the processing of asparagine-linked oligosaccharides. Arch Biochem Biophys 199:249–258PubMedCrossRefGoogle Scholar
  30. Munro S (2001) The MRH domain suggests a shared ancestry for the mannose 6-phosphate receptors and other N-glycan-recognising proteins. Curr Biol 11:R499–R501PubMedCrossRefGoogle Scholar
  31. Olson LJ, Orsi R, Alculumbre SG, Peterson FC, Stigliano ID, Parodi A, D’Alessio C, Dahms NM (2013) Structure of the lectin MRH domain of Glucosidase II, an enzyme that regulates glycoprotein folding quality control in the endoplasmic reticulum. J Biol Chem 288:16460–16475PubMedCrossRefGoogle Scholar
  32. Pelletier MF, Marcil A, Sevigny G, Jakob CA, Tessier DC, Chevet E, Menard R, Bergeron JJ, Thomas DY (2000) The heterodimeric structure of glucosidase II is required for its activity, solubility, and localization in vivo. Glycobiology 10:815–827PubMedCrossRefGoogle Scholar
  33. Reitman ML, Trowbridge IS, Kornfeld S (1982) A lectin-resistant mouse lymphoma cell line is deficient in glucosidase II, a glycoprotein-processing enzyme. J Biol Chem 257:10357–10363PubMedGoogle Scholar
  34. Robledo-Ortiz CI, Flores-Carreon A, Hernandez-Cervantes A, Alvarez-Vargas A, Lee KK, Diaz-Jimenez DF, Munro CA, Cano-Canchola C, Mora-Montes HM (2012) Isolation and functional characterization of Sporothrix schenckii ROT2, the encoding gene for the endoplasmic reticulum glucosidase II. Fungal Biol 116:910–918PubMedCrossRefGoogle Scholar
  35. Sakai K, Hirai M, Minoshima S, Kudoh J, Fukuyama R, Shimizu N (1989) Isolation of cDNAs encoding a substrate for protein kinase C: nucleotide sequence and chromosomal mapping of the gene for a human 80 K protein. Genomics 5:309–315PubMedCrossRefGoogle Scholar
  36. Saunier B, Kilker RD Jr, Tkacz JS, Quaroni A, Herscovics A (1982) Inhibition of N-linked complex oligosaccharide formation by 1-deoxynojirimycin, an inhibitor of processing glucosidases. J Biol Chem 257:14155–14161PubMedGoogle Scholar
  37. Saxena S, Shailubhai K, Dong-Yu B, Vijay IK (1987) Purification and characterization of glucosidase II involved in N-linked glycoprotein processing in bovine mammary gland. Biochem J 247:563–570PubMedGoogle Scholar
  38. Sousa M, Parodi AJ (1995) The molecular basis for the recognition of misfolded glycoproteins by the UDP-Glc:glycoprotein glucosyltransferase. EMBO J 14:4196–4203PubMedGoogle Scholar
  39. Sousa MC, Ferrero-Garcia MA, Parodi AJ (1992) Recognition of the oligosaccharide and protein moieties of glycoproteins by the UDP-Glc: glycoprotein glucosyltransferase. Biochemistry 31:97–105PubMedCrossRefGoogle Scholar
  40. Stigliano ID, Alculumbre SG, Labriola CA, Parodi AJ, D’Alessio C (2011) Glucosidase II and N-glycan mannose content regulate the half-lives of monoglucosylated species in vivo. Mol Biol Cell 22:1810–1823PubMedCentralPubMedCrossRefGoogle Scholar
  41. Strous GJ, Van Kerkhof P, Brok R, Roth J, Brada D (1987) Glucosidase II, a protein of the endoplasmic reticulum with high mannose oligosaccharide chains and a rapid turnover. J Biol Chem 262:3620–3625PubMedGoogle Scholar
  42. Treml K, Meimaroglou D, Hentges A, Bause E (2000) The a- and b-subunits are required for expression of catalytic activity in the hetero-dimeric glucosidase II complex from human liver. Glycobiology 10:493–502PubMedCrossRefGoogle Scholar
  43. Trombetta ES, Simons JF, Helenius A (1996) Endoplasmic reticulum glucosidase II is composed of a catalytic subunit, conserved from yeast to mammals, and a tightly bound noncatalytic HDEL-containing subunit. J Biol Chem 271:27509–27516PubMedCrossRefGoogle Scholar
  44. Ugalde RA, Staneloni RJ, Leloir LF (1980) Microsomal glucosidases of rat liver. Partial purification and inhibition by disaccharides. Eur J Biochem 113:97–103PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  1. 1.Complex Carbohydrate Research CenterThe University of GeorgiaAthensUSA

Personalised recommendations