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N-Acetylglucosamine-1-Phosphodiester Alpha-N-Acetylglucosaminidase (NAGPA)

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Handbook of Glycosyltransferases and Related Genes

Abstract

N-Acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase (phosphodiester α-GlcNAcase, also known as “uncovering enzyme”) is a type I membrane-spanning glycoprotein enzyme of the Golgi apparatus. It exists as a homotetramer (272 kDa) composed of two dimers, each containing a pair of disulfide-linked monomers of 68 kDa. The enzyme catalyzes the second step in the formation of the mannose 6-phosphate recognition marker on lysosomal enzyme oligosaccharides. It removes the “covering” GlcNAc residue from GlcNAc-P added during the first step to C-6-hydroxyl groups of selected mannose residues by the enzyme UDP-N-acetylglucosamine: lysosomal enzyme N-acetylglucosamine-1-phosphotransferase (phosphotransferase). The Man-6-P moiety exposed by phosphodiester α-GlcNAcase action is responsible for the specific, high-affinity binding of lysosomal enzymes to one of the two mannose 6-phosphate receptors in the trans-Golgi network (TGN) that transport the lysosomal enzymes to endosomes and subsequently to lysosomes. Phosphodiester α-GlcNAcase activity is present in all tissues of higher eukaryotes examined but is absent in the slime mold Dictyostelium discoideum and in Acanthamoeba castellanii, each of which contains phosphotransferase activity (Couso et al. 1986).

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References

  • Boonen M, Vogel P, Platt KA, Dahms N, Kornfeld S (2009) Mice lacking mannose 6-phosphate uncovering enzyme activity have a milder phenotype than mice deficient for N-acetylglucosamine-1-phosphotransferase activity. Mol Biol Cell 20:4381–4389

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Couso R, Lang L, Roberts RM, Kornfeld S (1986) Phosphorylation of the oligosaccharides of uteroferrin by UDP-GlcNAc:glycoprotein N-acetylglucosamine-1-phosphotransferases from rat liver, Acanthamoeba castellanii, and Dictyostelium discoideum requires α1,2 linked mannose residues. J Biol Chem 261:6326–6331

    CAS  PubMed  Google Scholar 

  • Das D, Lee W-S, Grant J, Chiu H-J, Farr C, Vance J, Klock H, Knuth M, Miller M, Elsliger M-A, Deacon A, Godzik A, Lesley S, Kornfeld S, Wilson IA (2013) Structure and function of the DUF 2233 domain in bacteria and in the human mannose 6-phosphate-uncovering enzyme. J Biol Chem 288:16789–16799

    Article  CAS  PubMed  Google Scholar 

  • Do H, Lee W-S, Ghosh P, Hollowell T, Canfield W, Kornfeld S (2002) Human mannose 6-phosphate-uncovering enzyme is synthesized as a proenzyme that is activated by the endoprotease furin. J Biol Chem 277:29737–29744

    Article  CAS  PubMed  Google Scholar 

  • Hasilik A, Klein V, Waheed A, Strecker G, von Figura K (1980) Phosphorylated oligosaccharides in lysosomal enzymes: identification of α-N-acetylglucosamine(1) phospho(6) mannose diester groups. Proc Natl Acad Sci USA 77:7074–7078

    Article  CAS  PubMed  Google Scholar 

  • Kang C, Riazuddin S, Mundorff J, Krasnewich D, Friedman P, Mullikin JC, Drayna D (2010) Mutations in the lysosomal enzyme-targeting pathway and persistent stuttering. New Engl J Med 362:677–685

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Kornfeld R, Bao M, Brewer K, Noll C, Canfield WM (1998) Purification and multimeric structure of bovine N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase. J Biol Chem 273:23203–23210

    Article  CAS  PubMed  Google Scholar 

  • Kornfeld R, Bao M, Brewer K, Noll C, Canfield W (1999) Molecular cloning and functional expression of two splice forms of human N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase. J Biol Chem 274:32778–32785

    Article  CAS  PubMed  Google Scholar 

  • Lee JK, Pierce M (1995) Purification and characterization of human serum N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase. Arch Biochem Biophys 319:413–425

    Article  CAS  PubMed  Google Scholar 

  • Lee W-S, Rohrer J, Kornfeld R, Kornfeld S (2002) Multiple signals regulate trafficking of the mannose 6-Phosphate-uncovering enzyme. J Biol Chem 277:3544–3551

    Article  CAS  PubMed  Google Scholar 

  • Lee W-S, Kang C, Drayna D, Kornfeld S (2011) Analysis of mannose 6-phosphate uncovering enzyme mutations associated with persistent stuttering. J Biol Chem 286:39786–39793

    Article  CAS  PubMed  Google Scholar 

  • Mullis KG, Ketcham CM (1992) The synthesis of substrates and two assays for the detection of N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase (uncovering enzyme). Anal Biochem 205:200–207

    Article  CAS  PubMed  Google Scholar 

  • Mullis KG, Huynh M, Kornfeld RH (1994) Purification and kinetic parameters of bovine liver N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase. J Biol Chem 269:1718–1726

    CAS  PubMed  Google Scholar 

  • Nair P, Schaub BE, Huang K, Chen X, Murphy RF, Griffith JM, Geuze HJ, Rohrer J (2005) Characterization of the TGN exit signal of the human mannose 6-phosphate uncovering enzyme. J Cell Sci 118:2949–2956

    Article  CAS  PubMed  Google Scholar 

  • Olson LJ, Peterson FC, Castonguay A, Bohnsack RN, Kudo M, Gotschall RR, Canfield WM, Volkman BF, Dahms NM (2010) Structural basis for recognition of phosphodiester-containing lysosomal enzymes by the cation-independent mannose 6-phosphate receptor. Proc Natl Acad Sci 107:12493–12498

    Article  CAS  PubMed  Google Scholar 

  • Page T, Zhao KW, Tao L, Miller AL (1996) Purification and characterization of human lymphoblast N-acetylglucosamine-1-phosphodiester α-N-acetylglucosaminidase. Glycobiology 6:619–626

    Article  CAS  PubMed  Google Scholar 

  • Rohrer J, Kornfeld R (2001) Lysosomal hydrolase mannose 6-phosphate uncovering enzyme resides in the trans-Golgi network. Mol Biol Cell 12:1623–1631

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  • Tabas I, Kornfeld S (1980) Biosynthetic intermediates of β-glucuronidase contain high mannose oligosaccharides with blocked phosphate residues. J Biol Chem 255:6633–6639

    CAS  PubMed  Google Scholar 

  • Varki A, Kornfeld S (1980) Identification of a rat liver α-N-acetylglucosaminyl phosphodiesterase capable of removing “blocking” α-N-acetylglucosamine residues from phosphorylated high mannose oligosaccharides of lysosomal enzymes. J Biol Chem 255:8398–8401

    CAS  PubMed  Google Scholar 

  • Varki A, Kornfeld S (1981) Purification and characterization of rat liver α-N-acetylglucosaminyl phosphodiesterase. J Biol Chem 256:9937–9943

    CAS  PubMed  Google Scholar 

  • Varki A, Sherman W, Kornfeld S (1983) Demonstration of the enzymatic mechanisms of α-N-acetyl-d-glucosamine-1-phosphodiester N-acetylglucosaminidase (formerly called α-N-acetylglucosaminylphosphodiesterase) and lysosomal α-N-acetylglucosaminidase. Arch Biochem Biophys 222:145–149

    Article  CAS  PubMed  Google Scholar 

  • Waheed A, Hasilik A, von Figura K (1981) Processing of the phosphorylated recognition marker in lysosomal enzymes: characterization and partial purification of a microsomal α-N-acetylglucosaminyl phosphodiesterase. J Biol Chem 256:5717–5721

    CAS  PubMed  Google Scholar 

  • Wei Y, Yen T-Y, Cai J, Trent JO, Pierce WM, Young WW (2005) Structural features of the lysosomal hydrolase mannose 6-phosphate uncovering enzyme. Glycoconj J 22:13–19

    Article  CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Internal Medicine, Washington University School of Medicine, St. Louis, MO, 63110, USA

    Dr. Stuart Kornfeld

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  1. Dr. Stuart Kornfeld
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Correspondence to Stuart Kornfeld .

Editor information

Editors and Affiliations

  1. RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN, Wako, Saitama, Japan

    Naoyuki Taniguchi

  2. Department of Biochemistry, Kochi University, Medical School, Nankoku, Kochi, Japan

    Koichi Honke

  3. Sanford Burnham Medical Research Institute, La Jolla, California, USA

    Minoru Fukuda

  4. Research Center for Medical Glycoscience (RCMG), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Ibaraki, Japan

    Hisashi Narimatsu

  5. RIKEN-Max-Planck Joint Research Center for Systems Chemical Biology, RIKEN, Wako, Saitama, Japan

    Yoshiki Yamaguchi

  6. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan

    Takashi Angata

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© 2014 Springer Japan

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Kornfeld, S. (2014). N-Acetylglucosamine-1-Phosphodiester Alpha-N-Acetylglucosaminidase (NAGPA). In: Taniguchi, N., Honke, K., Fukuda, M., Narimatsu, H., Yamaguchi, Y., Angata, T. (eds) Handbook of Glycosyltransferases and Related Genes. Springer, Tokyo. https://doi.org/10.1007/978-4-431-54240-7_78

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