title: N-acetylglucosamine modification in the lumen of the endoplasmic reticulum.
abstract: BACKGROUND
  O-linked β-N-acetylglucosamine (O-GlcNAc) modification of epidermal growth factor (EGF) domains catalyzed by EGF domain O-GlcNAc transferase (EOGT) is the first example of GlcNAc modification in the lumen of the endoplasmic reticulum (ER).
  
  
  METHODS
  This review summarizes current knowledge on the EOGT-catalyzed O-GlcNAc modification of EGF domains obtained through biochemical characterization, genetic analysis in Drosophila, and identification of human EOGT mutation. Additionally, this review discusses GTDC2-another ER protein homologous to EOGT that catalyzes the GlcNAc modification of O-mannosylated α-dystroglycan-and other components of the biosynthetic pathway involved in GlcNAc modification in the ER lumen.
  
  
  CONCLUSIONS
  GlcNAc modification in the ER lumen has been identified as a novel type of protein modification that regulates specific protein function. Moreover, abnormal GlcNAc modification in the ER lumen is responsible for Adams-Oliver syndrome and Walker-Warburg syndrome.
  
  
  CONCLUSIONS
  Elucidation of the biological function of GlcNAc modification in the ER lumen will provide new insights into the unique roles of O-glycans, whose importance has been demonstrated in multifunctional glycoproteins such as Notch receptors and α-dystroglyan.
authors: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan; Department of Bioscience, Nagahama Institute of Bio-Science and Technology, 1266 Tamura, Nagahama, Shiga 526-0829, Japan.
authors: Mitsutaka
authors: M
authors: Ogawa
authors: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors: Shogo
authors: S
authors: Sawaguchi
authors: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan.
authors: Koichi
authors: K
authors: Furukawa
authors: Department of Biochemistry II, Nagoya University Graduate School of Medicine, 65 Tsurumai, Showa-ku, Nagoya 466-0065, Japan. Electronic address: tokajima@med.nagoya-u.ac.jp.
authors: Tetsuya
authors: T
authors: Okajima
mesh_terms: D000117:Acetylglucosamine / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004476:Ectodermal Dysplasia / Q000201:enzymology / Q000235:genetics; D004721:Endoplasmic Reticulum / Q000201:enzymology / Q000378:metabolism*; D004815:Epidermal Growth Factor / Q000737:chemistry / Q000378:metabolism*; D006031:Glycosylation; D016695:Glycosyltransferases / Q000378:metabolism; D006801:Humans; D017880:Limb Deformities, Congenital / Q000201:enzymology / Q000235:genetics; D008969:Molecular Sequence Data; D009154:Mutation; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics / Q000378:metabolism; D011487:Protein Conformation; D011499:Protein Processing, Post-Translational; D017434:Protein Structure, Tertiary; D012536:Scalp Dermatoses / Q000151:congenital / Q000201:enzymology / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D029721:Drosophila Proteins; D004815:Epidermal Growth Factor; D016695:Glycosyltransferases; C576562:POMGNT2 protein, human; C585194:Eogt protein, Drosophila; D017351:N-Acetylglucosaminyltransferases; D000117:Acetylglucosamine
keywords: EOGT; GTDC2; Notch; O-GlcNAc; UDP-GlcNAc transporter; α-Dystroglycan