UDP-N-Acetyl-Alpha-D-Galactosamine: Polypeptide N-Acetylgalactosaminyltransferases (ppGalNAc-Ts)

  • Liping Zhang
  • E. Tian
  • Kelly G. Ten Hagen
Reference work entry


Mucin-type O-linked glycosylation is initiated by the UDP-N-acetyl-α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferases (ppGalNAc-Ts), which catalyze the addition of N-acetylgalactosamine (GalNAc) in an alpha-anomeric linkage to the hydroxyl groups of serines or threonines (Fig. 46.1). The ppGalNAc-Ts belong to family 27 of the retaining nucleotide-diphospho-sugar transferases, based on amino acid sequence similarities. The initial transfer of GalNAc from the nucleotide sugar UDP-GalNAc onto protein substrates occurs in the Golgi apparatus and can then be followed by the subsequent addition of other saccharides to form extended and branched mucin-type O-glycans.


Bovine Colostrum Lectin Domain Radioisotopic Method Lymphocyte Homing Ascites Hepatoma 
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. Araya K, Fukumoto S, Backenroth R, Takeuchi Y, Nakayama K, Ito N, Yoshii N, Yamazaki Y, Yamashita T, Silver J, Igarashi T, Fujita T (2005) A novel mutation in fibroblast growth factor 23 gene as a cause of tumoral calcinosis. J Clin Endocrinol Metab 90:5523–5527PubMedCrossRefGoogle Scholar
  2. Benet-Pagès A, Orlik P, Strom TM, Lorenz-Depiereux B (2005) An FGF23 missense mutation causes familial tumoral calcinosis with hyperphosphatemia. Hum Mol Genet 14:385–390PubMedCrossRefGoogle Scholar
  3. Bennett EP, Hassan H, Clausen H (1996) cDNA cloning and expression of a novel human UDP-N-acetyl-α-d-galactosamine Polypeptide N-acetylgalactosaminyltransferase, GalNAc-T3. J Biol Chem 271:17006–17012PubMedCrossRefGoogle Scholar
  4. Bennett EP, Hassan H, Mandel U, Mirgorodskaya E, Roepstorff P, Burchell J, Taylor-Papadimitriou J, Hollingsworth MA, Merkx G, van Kessel AG, Eiberg H, Steffensen R, Clausen H (1998) Cloning of a human UDP-N-acetyl-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase that complements other GalNAc-transferases in complete O-glycosylation of the MUC1 tandem repeat. J Biol Chem 273:30472–30481PubMedCrossRefGoogle Scholar
  5. Bennett EP, Hassan H, Mandel U, Hollingsworth MA, Akisawa N, Ikematsu Y, Merkx G, van Kessel AG, Olofsson S, Clausen H (1999) Cloning and characterization of a close homologue of human UDP-N-acetyl-alpha-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase-T3, designated GalNAc-T6. Evidence for genetic but not functional redundancy. J Biol Chem 274:25362–25370PubMedCrossRefGoogle Scholar
  6. Bennett EP, Mandel U, Clausen H, Gerken TA, Fritz TA, Tabak LA (2012) Control of mucin-type O-glycosylation: a classification of the polypeptide GalNAc-transferase gene family. Glycobiology 22:736–756PubMedCrossRefGoogle Scholar
  7. Berois N, Mazal D, Ubillos L, Trajtenberg F, Nicolas A, Sastre-Garau X, Magdelenat H, Osinaga E (2006) UDP-N-acetyl-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase-6 as a new immunohistochemical breast cancer marker. J Histochem Cytochem 54:317–328PubMedCrossRefGoogle Scholar
  8. Brockhausen I, Toki D, Brockhausen J, Peters S, Bielfeldt T, Kleen A, Paulsen H, Meldal M, Hagen F, Tabak LA (1996) Specificity of O-glycosylation by bovine colostrum UDP-GalNAc: polypeptide a-N-acetylgalactosaminyltransferase using synthetic glycopeptide substances. Glycoconj J 13:849–856PubMedCrossRefGoogle Scholar
  9. Cheng L, Tachibana K, Zhang Y, Guo J, Kahori Tachibana K, Kameyama A, Wang H, Hiruma T, Iwasaki H, Togayachi A, Kudo T, Narimatsu H (2002) Characterization of a novel human UDP-GalNAc transferase, pp-GalNAc-T10. FEBS Lett 531:115–121PubMedCrossRefGoogle Scholar
  10. Cheng L, Tachibana K, Iwasaki H, Kameyama A, Zhang Y, Kubota T, Hiruma T, Tachibana K, Kudo T, Guo JM, Narimatsu H (2004) Characterization of a novel human UDP-GalNAc transferase, pp-GalNAc-T15. FEBS Lett 566:17–24PubMedCrossRefGoogle Scholar
  11. Duncan EL, Danoy P, Kemp JP, Leo PJ, McCloskey E, Nicholson GC, Eastell R, Prince RL, Eisman JA, Jones G et al (2011) Genome-wide association study using extreme truncate selection identifies novel genes affecting bone mineral density and fracture risk. PLoS Genet 7:e1001372PubMedCentralPubMedCrossRefGoogle Scholar
  12. Elhammer A, Kornfeld S (1986) Purification and characterization of UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferase from bovine colostrum and murine lymphoma BW5147 cells. J Biol Chem 261:5249–5255PubMedGoogle Scholar
  13. Estrada K, Styrkarsdottir U, Evangelou E, Hsu YH, Duncan EL, Ntzani EE, Oei L, Albagha OM, Amin N, Kemp JP et al (2012) Genome-wide meta-analysis identifies 56 bone mineral density loci and reveals 14 loci associated with risk of fracture. Nat Genet 44:491–501PubMedCentralPubMedCrossRefGoogle Scholar
  14. Fakhro KA, Choi M, Ware SM, Belmont JW, Towbin JA, Lifton RP, Khokha MK, Brueckner M (2011) Rare copy number variations in congenital heart disease patients identify unique genes in left-right patterning. Proc Natl Acad Sci USA 108:2915–2920PubMedCrossRefGoogle Scholar
  15. Fritz TA, Hurley JH, Trinh LB, Shiloach J, Tabak LA (2004) The beginnings of mucin biosynthesis: the crystal structure of UDP-GalNAc:polypeptide α-N-acetylgalactosaminyltransferase-T1. Proc Natl Acad Sci USA 101:15307–15312PubMedCrossRefGoogle Scholar
  16. Fritz TA, Raman J, Tabak LA (2006) Dynamic association between the catalytic and lectin domains of human UDP-GalNAc:polypeptide α-N-acetylgalactosaminyltransferase-2. J Biol Chem 281:8613–8619PubMedCrossRefGoogle Scholar
  17. Gerken TA, Raman J, Fritz TA, Jamison O (2006) Identification of common and unique peptide substrate preferences for the UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferases T1 and T2 derived from oriented random peptide substrates. J Biol Chem 281:32403–32416PubMedCrossRefGoogle Scholar
  18. Gerken TA, Ten Hagen KG, Jamison O (2008) Conservation of peptide acceptor preferences between Drosophila and mammalian polypeptide-GalNAc transferase orthologue pairs. Glycobiology 18:861–870PubMedCrossRefGoogle Scholar
  19. Gerken TA, Jamison O, Perrine CL, Collette JC, Moinova H, Ravi L, Markowitz SD, Shen W, Patel H, Tabak LA (2011) Emerging paradigms for the initiation of mucin-type protein O-glycosylation by the polypeptide GalNAc transferase family of glycosyltransferases. J Biol Chem 286:14493–14507PubMedCrossRefGoogle Scholar
  20. Gomes J, Marcos NT, Berois N, Osinaga E, Magalhães A, Pinto-de-Sousa J, Almeida R, Gärtner F, Reis CA (2009) Expression of UDP-N-acetyl-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase-6 in gastric mucosa, intestinal metaplasia, and gastric carcinoma. J Histochem Cytochem 57:79–86PubMedCrossRefGoogle Scholar
  21. Guda K, Moinova H, He J, Jamison O, Ravi L, Natale L, Lutterbaugh J, Lawrence E, Lewis S, Willson JK et al (2009) Inactivating germ-line and somatic mutations in polypeptide N-acetylgalactosaminyltransferase 12 in human colon cancers. Proc Natl Acad Sci USA 106:12921–12925PubMedCrossRefGoogle Scholar
  22. Guo JM, Zhang Y, Cheng L, Iwasaki H, Wang H, Kubota T, Tachibana K, Narimatsu H (2002) Molecular cloning and characterization of a novel member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family, pp-GalNAc-T12. FEBS Lett 524:211–218PubMedCrossRefGoogle Scholar
  23. Hagen FK, Nehrke K (1998) cDNA cloning and expression of a family of UDP-N-acetyl-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase sequence homologs from Caenorhabditis elegans. J Biol Chem 273:8268–8277PubMedCrossRefGoogle Scholar
  24. Hagen FK, Van Wuyckhuyse B, Tabak LA (1993) Purification, cloning, and expression of a bovine UDP-GalNAc:polypeptide N-acetyl-galactosaminyltransferase. J Biol Chem 268:18960–18965PubMedGoogle Scholar
  25. Hagen FK, Gregoire CA, Tabak LA (1995) Cloning and sequence homology of a rat UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase. Glycoconj J 12:901–909PubMedCrossRefGoogle Scholar
  26. Hagen FK, Ten Hagen KG, Beres TM, Balys MM, Van Wuyckhuyse BC, Tabak LA (1997) cDNA cloning and expression of a novel UDP-N-acetyl-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase. J Biol Chem 272:13843–13848PubMedCrossRefGoogle Scholar
  27. Hagopian A, Eylar EH (1968) Glycoprotein biosynthesis: studies on the receptor specificity of the polypeptidyl:N-acetylgalactosaminyl transferase from bovine submaxillary glands. Arch Biochem Biophys 128:422–433PubMedCrossRefGoogle Scholar
  28. Hagopian A, Eylar EH (1969) Glycoprotein biosynthesis: the purification and characterization of a polypeptidyl:N-acetylgalactosaminyl transferase from bovine submaxillary glands. Arch Biochem Biophys 129:515–524PubMedCrossRefGoogle Scholar
  29. Hanisch FG, Muller S, Hassan H, Clausen H, Zachara N, Gooley AA, Paulsen H, Alving K, Peter-Katalinic J (1999) Dynamic epigenetic regulation of initial O-glycosylation by UDP-N-acetylgalactosamine: peptide N-acetylgalactosaminyltransferases. J Biol Chem 274:9946–9954PubMedCrossRefGoogle Scholar
  30. Hazes B (1996) The (QxW)3 domain: a flexible lectin scaffold. Protein Sci 5:1490–1501PubMedCrossRefGoogle Scholar
  31. Herr P, Korniychuk G, Yamamoto Y, Grubisic K, Oelgeschläger M (2008) Regulation of TGF-(beta) signalling by N-acetylgalactosaminyltransferase-like 1. Development 135:1813–1822PubMedCrossRefGoogle Scholar
  32. Holleboom AG, Karlsson H, Lin RS, Beres TM, Sierts JA, Herman DS, Stroes ES, Aerts JM, Kastelein JJ, Motazacker MM, Dallinga-Thie GM, Levels JH, Zwinderman AH, Seidman JG, Seidman CE, Ljunggren S, Lefeber DJ, Morava E, Wevers RA, Fritz TA, Tabak LA, Lindahl M, Hovingh GK, Kuivenhoven JA (2011) Heterozygosity for a loss-of-function mutation in GALNT2 improves plasma triglyceride clearance in man. Cell Metab 14:811–818PubMedCentralPubMedCrossRefGoogle Scholar
  33. Homa FL, Hollander T, Lehman DJ, Thomsen DR, Elhammer AP (1993) Isolation and expression of a cDNA clone encoding a bovine UDPGalNAc: polypeptide N-acetylgalactosaminyltransferase. J Biol Chem 268:12609–12616PubMedGoogle Scholar
  34. Huang HC, Yu C, Pratt MR, Bertozzi CR (2004) Probing glycosyltransferase activities with the Staudinger ligation. J Am Chem Soc 126:6–7CrossRefGoogle Scholar
  35. Ichikawa S, Lyles KW, Econs MJ (2005) A novel GALNT3 mutation in a pseudoautosomal dominant form of tumoral calcinosis: evidence that the disorder is autosomal recessive. J Clin Endocrinol Metab 90:2420–2423PubMedCrossRefGoogle Scholar
  36. Ichikawa S, Sorenson AH, Austin AM, Mackenzie DS, Fritz TA, Moh A, Hui SL, Econs MJ (2009) Ablation of the Galnt3 gene leads to low-circulating intact fibroblast growth factor 23 (Fgf23) concentrations and hyperphosphatemia despite increased Fgf23 expression. Endocrinology 150:2543–2550PubMedCrossRefGoogle Scholar
  37. Ichikawa S, Austin AM, Gray AK, Allen MR, Econs MJ (2011) Dietary phosphate restriction normalizes biochemical and skeletal abnormalities in a murine model of tumoral calcinosis. Endocrinology 152:4504–4513PubMedCrossRefGoogle Scholar
  38. Imberty A, Piller V, Piller F, Breton C (1997) Fold recognition and molecular modeling of a lectin-like domain in UDP-GalNac:polypeptide N-acetylgalactosaminyltransferase. Protein Eng 10:1353–1356PubMedCrossRefGoogle Scholar
  39. Ishikawa M, Kitayama J, Nariko H, Kohno K, Nagawa H (2004) The expression pattern of UDP-N-acetyl-alpha-d-galactosamine:polypeptide N-acetylgalactosaminyl transferase-3 in early gastric carcinoma. J Surg Oncol 86:28–33PubMedCrossRefGoogle Scholar
  40. Ju T, Cummings RD (2005) Protein glycosylation: chaperone mutation in Tn syndrome. Nature 437:1252PubMedCrossRefGoogle Scholar
  41. Kathiresan S, Melander O, Guiducci C, Surti A, Burtt NP, Rieder MJ, Cooper GM, Roos C, Voight BF, Havulinna AS et al (2008) Six new loci associated with blood low-density lipoprotein cholesterol, high-density lipoprotein cholesterol or triglycerides in humans. Nat Genet 40:189–197PubMedCentralPubMedCrossRefGoogle Scholar
  42. Kato K, Jeanneau C, Tarp MA, Benet-Pages A, Lorenz-Depiereux B, Bennett EP, Mandel U, Strom TM, Clausen H (2006) Polypeptide GalNAc-transferase T3 and familial tumoral calcinosis. Secretion of fibroblast growth factor 23 requires O-glycosylation. J Biol Chem 281:18370–18377PubMedCrossRefGoogle Scholar
  43. Kingsley PD, Ten Hagen KG, Maltby KM, Zara J, Tabak LA (2000) Diverse spatial expression patterns of UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase family members mRNAs during mouse development. Glycobiology 10:1317–1323PubMedCrossRefGoogle Scholar
  44. Kubota T, Shiba T, Sugioka S, Furukawa S, Sawaki H, Kato R, Wakatsuki S, Narimatsu H (2006) Structural basis of carbohydrate transfer activity by human UDP-GalNAc:polypeptide alpha-N-acetylgalactosaminyltransferase (pp-GalNAc-T10). J Mol Biol 359:708–727PubMedCrossRefGoogle Scholar
  45. Mandel U, Hassan H, Therkildsen MH, Rygaard J, Jakobsen MH, Juhl BR, Dabelsteen E, Clausen H (1999) Expression of polypeptide GalNAc-transferases in stratified epithelia and squamous cell carcinomas: immunohistological evaluation using monoclonal antibodies to three members of the GalNAc-transferase family. Glycobiology 9:43–52PubMedCrossRefGoogle Scholar
  46. Manzi AE, Norgard-Sumnicht K, Argade S, Marth JD, van Halbeek H, Varki A (2000) Exploring the glycan repertoire of genetically modified mice by isolation and profiling of the major glycan classes and nano-NMR analysis of glycan mixtures. Glycobiology 10:669–689PubMedCrossRefGoogle Scholar
  47. McGuire EJ, Roseman S (1967) Enzymatic synthesis of the protein-hexosamine linkage in sheep submaxillary mucin. J Biol Chem 242:3745–3747PubMedGoogle Scholar
  48. Mendicino J, Sangadala S (1998) Purification and characterization of UDP-GalNAc:polypeptide N-acetylgalactosaminyl transferase from swine trachea epithelium. Mol Cell Biochem 185:135–145PubMedCrossRefGoogle Scholar
  49. Mitoma J, Bao X, Petryanik B, Schaerli P, Gauguet JM, Yu SY, Kawashima H, Saito H, Ohtsubo K, Marth JD, Khoo KH, von Andrian UH, Lowe JB, Fukuda M (2007) Critical functions of N-glycans in L-selectin-mediated lymphocyte homing and recruitment. Nat Immunol 8:409–418PubMedCrossRefGoogle Scholar
  50. Miyazaki T, Mori M, Yoshida CA, Ito C, Yamatoya K, Moriishi T, Kawai Y, Komori H, Kawane T, Izumi SI, Toshimori K, Komori T (2012) Galnt3 deficiency disrupts acrosome formation and leads to oligoasthenoteratozoospermia. Histochem Cell Biol 139:339–354.PubMedCrossRefGoogle Scholar
  51. Nakamura N, Toba S, Hirai M, Morishita S, Mikami T, Konishi M, Itoh N, Kurosaka A (2005) Cloning and expression of a brain-specific putative UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase gene. Biol Pharm Bull 28:429–433PubMedCrossRefGoogle Scholar
  52. O’Halloran AM, Patterson CC, Horan P, Maree A, Curtin R, Stanton A, McKeown PP, Shields DC (2009) Genetic polymorphisms in platelet-related proteins and coronary artery disease: investigation of candidate genes, including N-acetylgalactosaminyltransferase 4 (GALNT4) and sulphotransferase 1A1/2 (SULT1A1/2). J Thromb Thrombolysis 27:175–184PubMedCrossRefGoogle Scholar
  53. Pedersen JW, Bennett EP, Schjoldager KT, Meldal M, Holmér AP, Blixt O, Cló E, Levery SB, Clausen H, Wandall HH (2011) Lectin domains of polypeptide GalNAc transferases exhibit glycopeptide binding specificity. J Biol Chem 286:32684–32696PubMedCrossRefGoogle Scholar
  54. Peng C, Togayachi A, Kwon YD, Xie C, Wu G, Zou X, Sato T, Ito H, Tachibana K, Kubota T, Noce T, Narimatsu H, Zhang Y (2010) Identification of a novel human UDPGalNAc transferase with unique catalytic activity and expression profile. Biochem Biophys Res Commun 402:680–686PubMedCrossRefGoogle Scholar
  55. Perrine CL, Ganguli A, Wu P, Bertozzi CR, Fritz TA, Raman J, Tabak LA, Gerken TA (2009) Glycopeptide-preferring polypeptide GalNAc transferase 10 (ppGalNAc T10), involved in mucin-type O-glycosylation, has a unique GalNAc-O-Ser/Thr-binding site in its catalytic domain not found in ppGalNAc T1 or T2. J Biol Chem 284:20387–20397PubMedCrossRefGoogle Scholar
  56. Pratt MR, Hang HC, Ten Hagen KG, Rarick J, Gerken TA, Tabak LA, Bertozzi CR (2004) Deconvoluting the functions of polypeptide N-alpha-acetylgalactosaminyltransferase family members by glycopeptide substrate profiling. Chem Biol 11:1009–1016PubMedCrossRefGoogle Scholar
  57. Raman J, Fritz TA, Gerken TA, Jamison O, Live D, Lu M, Tabak LA (2008) The catalytic and lectin domains of UDP-GalNAc:polypeptide alpha-Nacetylgalactosaminyltransferase function in concert to direct glycosylation site selection. J Biol Chem 283:22942–22951PubMedCrossRefGoogle Scholar
  58. Raman J, Guan Y, Perrine CL, Gerken TA, Tabak LA (2012) UDP-N-Acetyl- α-d-galactosamine:polypeptide N-acetylgalactosaminyltransferases: completion of the family tree. Glycobiology 22:768–777PubMedCrossRefGoogle Scholar
  59. Roth J, Wang Y, Eckhardt AE, Hill RL (1994) Subcellular localization of the UDP-N-acetyl-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase-mediated O-glycosylation reaction in the submaxillary gland. Proc Natl Acad Sci USA 91:8935–8939PubMedCrossRefGoogle Scholar
  60. Rottger S, White J, Wandall HH, Olivo JC, Stark A, Bennett EP, Whitehouse C, Berger EG, Clausen H, Nilsson T (1998) Localization of three human polypeptide GalNAc-transferases in HeLa cells suggests initiation of O-linked glycosylation throughout the Golgi apparatus. J Cell Sci 111:45–60PubMedGoogle Scholar
  61. Schjoldager KT, Vester-Christensen MB, Bennett EP, Levery SB, Schwientek T, Yin W, Blixt O, Clausen H (2010) O-glycosylation modulates proprotein convertase activation of angiopoietin-like protein 3: possible role of polypeptide GalNAc-transferase-2 in regulation of concentrations of plasma lipids. J Biol Chem 285:36293–36303PubMedCrossRefGoogle Scholar
  62. Schwientek T, Bennett EP, Flores C, Thacker J, Hollmann M, Reis CA, Behrens J, Mandel U, Keck B, Schafer MA, Haselmann K, Zubarev R, Roepstorff P, Burchell JM, Taylor-Papadimitriou J, Hollingsworth MA, Clausen H (2002) Functional conservation of subfamilies of putative UDP-N-acetylgalactosamine:polypeptide N-acetylgalactosaminyltransferases in Drosophila, Caenorhabditis elegans, and mammals. One subfamily composed of l(2)35Aa is essential in Drosophila. J Biol Chem 277:22623–22638PubMedCrossRefGoogle Scholar
  63. Sellers TA, Huang Y, Cunningham J, Goode EL, Sutphen R, Vierkant RA, Kelemen LE, Fredericksen ZS, Liebow M, Pankratz VS, Hartmann LC, Myer J, Iversen ES Jr, Schildkraut JM, Phelan C (2008) Association of single nucleotide polymorphisms in glycosylation genes with risk of epithelial ovarian cancer. Cancer Epidemiol Biomarkers Prev 17:397–404PubMedCentralPubMedCrossRefGoogle Scholar
  64. Shibao K, Izumi H, Nakayama Y, Ohta R, Nagata N, Nomoto M, Matsuo K, Yamada Y, Kitazato K, Itoh H, Kohno K (2002) Expression of UDP-N-acetyl-α-d-galactosamine- polypeptide galNAc N-acetylgalactosaminyl transferase-3 in relation to differentiation and prognosis in patients with colorectal carcinoma. Cancer 94:1939–1946PubMedCrossRefGoogle Scholar
  65. Shogren R, Gerken TA, Jentoft N (1989) Role of glycosylation on the conformation and chain dimensions of O-linked glycoproteins: light-scattering studies of ovine submaxillary mucin. Biochemistry 28:5525–5536PubMedCrossRefGoogle Scholar
  66. Sugiura M, Kawasaki T, Yamashina I (1982) Purification and characterization of UDP-GalNAc:polypeptide N-acetylgalactosamine transferase from an ascites hepatoma, AH 66. J Biol Chem 257:9501–9507PubMedGoogle Scholar
  67. Tabak LA (2010) The role of mucin-type O-glycans in eukaryotic development. Semin Cell Dev Biol 21:616–621PubMedCentralPubMedCrossRefGoogle Scholar
  68. Ten Hagen KG, Tran DT (2002) A UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase is essential for viability in Drosophila melanogaster. J Biol Chem 277:22616–22622PubMedCrossRefGoogle Scholar
  69. Ten Hagen KG, Hagen FK, Balys MM, Beres TM, Van Wuyckhuyse B, Tabak LA (1998) Cloning and expression of a novel, tissue specifically expressed member of the UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase family. J Biol Chem 273:27749–27754PubMedCrossRefGoogle Scholar
  70. Ten Hagen KG, Tetaert D, Hagen FK, Richet C, Beres TM, Gagnon J, Balys MM, VanWuyckhuyse B, Bedi GS, Degand P, Tabak LA (1999) Characterization of a UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase that displays glycopeptide N-acetylgalactosaminyltransferase activity. J Biol Chem 274:27867–27874PubMedCrossRefGoogle Scholar
  71. Ten Hagen KG, Bedi GS, Tetaert D, Kingsley PD, Hagen FK, Balys MM, Beres TM, Degand P, Tabak LA (2001) Cloning and characterization of a ninth member of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family, ppGaNTase-T9. J Biol Chem 276:17395–17404PubMedCrossRefGoogle Scholar
  72. Ten Hagen KG, Tran DT, Gerken TA, Stein DS, Zhang Z (2003a) Functional characterization and expression analysis of members of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family from Drosophila melanogaster. J Biol Chem 278:35039–35048PubMedCrossRefGoogle Scholar
  73. Ten Hagen KG, Fritz TA, Tabak LA (2003b) All in the family: the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases. Glycobiology 13:1R–16RPubMedCrossRefGoogle Scholar
  74. Tenno M, Ohtsubo K, Hagen FK, Ditto D, Zarbock A, Schaerli P, von Andrian UH, Ley K, Le D, Tabak LA, Marth JD (2007) Initiation of protein O glycosylation by the polypeptide GalNAcT-1 in vascular biology and humoral immunity. Mol Cell Biol 27:8783–8796PubMedCentralPubMedCrossRefGoogle Scholar
  75. Teslovich TM, Musunuru K, Smith AV, Edmondson AC, Stylianou IM, Koseki M (2010) Biological, clinical and population relevance of 95 loci for blood lipids. Nature 466:707–713PubMedCentralPubMedCrossRefGoogle Scholar
  76. Tian E, Ten Hagen KG (2006) Expression of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase family is spatially and temporally regulated during Drosophila development. Glycobiology 16:83–95PubMedCrossRefGoogle Scholar
  77. Tian E, Ten Hagen KG (2007) A UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase is required for epithelial tube formation. J Biol Chem 282:606–614PubMedCrossRefGoogle Scholar
  78. Tian E, Ten Hagen KG (2009) Recent insights into the biological roles of mucin-type O-glycosylation. Glycoconj J 26:325–334PubMedCentralPubMedCrossRefGoogle Scholar
  79. Tian E, Hoffman MP, Ten Hagen KG (2012) O-glycosylation modulates integrin and FGF signaling by influencing the secretion of basement membrane components. Nat Commun 3:869. doi:10.1038/ncomms1874PubMedCentralPubMedCrossRefGoogle Scholar
  80. Toba S, Tenno M, Konishi M, Mikami T, Itoh N, Kurosaka A (2000) Brain specific expression of a novel human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase (GalNAc-T9). Biochim Biophys Acta 1493:264–268PubMedCrossRefGoogle Scholar
  81. Topaz O, Shurman DL, Bergman R, Indelman M, Ratajczak P, Mizrachi M, Khamaysi Z, Behar D, Petronius D, Friedman V, Zelikovic I, Raimer S, Metzker A, Richard G, Sprecher E (2004) Mutations in GALNT3, encoding a protein involved in O-linked glycosylation, cause familial tumoral calcinosis. Nat Genet 36:579–581PubMedCrossRefGoogle Scholar
  82. Tran DT, Ten Hagen KG (2013) Mucin-type O-glycosylation during development. J Biol Chem 288:6921–6929PubMedCrossRefGoogle Scholar
  83. Tran DT, Zhang L, Zhang Y, Tian E, Earl LA, Ten Hagen KG (2012) Multiple members of the UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase family are essential for viability in Drosophila. J Biol Chem 287:5243–5252PubMedCrossRefGoogle Scholar
  84. Wandall HH, Irazoqui F, Tarp MA, Bennett EP, Mandel U, Takeuchi H, Kato K, Irimura T, Suryanarayanan G, Hollingsworth MA, Clausen H (2007) The lectin domains of polypeptide GalNAc-transferases exhibit carbohydrate-binding specificity for GalNAc: lectin binding to GalNAc-glycopeptide substrates is required for high density GalNAc-O-glycosylation. Glycobiology 17:374–387PubMedCrossRefGoogle Scholar
  85. Wang Y, Abernethy JL, Eckhardt AE, Hill RL (1992) Purification and characterization of a GalNAc:polypeptide N-acetylgalactosaminyltransferases specific for glycosylation of threonine residues. J Biol Chem 267:12709–12716PubMedGoogle Scholar
  86. Wang H, Tachibana K, Zhang Y, Iwasaki H, Kameyama A, Cheng L, Guo JM, Hiruma T, Togayachi A, Kudo T (2003) Cloning and characterization of a novel UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, pp-GalNAc-T14. Biochem Biophys Res Commun 300:738–744PubMedCrossRefGoogle Scholar
  87. White T, Bennett EP, Takio K, Sørensen T, Bonding N, Clausen H (1995) Purification and cDNA cloning of a human UDP-N-acetyl-alpha-d-galactosamine: polypeptide N-acetylgalactosaminyltransferase. J Biol Chem 270:24156–24165PubMedCrossRefGoogle Scholar
  88. White KE, Lorenz B, Evans WE, Meitinger T, Strom TM, Econs M (2000) Molecular cloning of a novel human UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase, GalNAc-T8, and analysis as a candidate autosomal dominant hypophosphatemic rickets (ADHR) gene. Gene 246:347–356PubMedCrossRefGoogle Scholar
  89. Wood LD, Parsons DW, Jones S, Lin J, Sjoblom T, Leary RJ, Shen D, Boca SM, Barber T, Ptak J et al (2007) The genomic landscapes of human breast and colorectal cancers. Science 318:1108–1113PubMedCrossRefGoogle Scholar
  90. Yoshida A, Hara T, Ikenaga H, Takeuchi M (1995) Cloning and expression of a porcine UDP-GalNAc:polypeptide N-acetylgalactosaminyl transferase. Glycoconj J 12:824–828PubMedCrossRefGoogle Scholar
  91. Young WW Jr, Holcomb DR, Ten Hagen KG, Tabak LA (2003) Expression of UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferase isoforms in murine tissues determined by real-time PCR: a new view of a large family. Glycobiology 13:549–557PubMedCrossRefGoogle Scholar
  92. Zara J, Hagen FK, Ten Hagen KG, Van Wuyckhuyse BC, Tabak LA (1996) Cloning and expression of mouse UDP-GalNAc: polypeptide N-acetylgalactosaminyltransferase-T3. Biochem BiophysRes Commun 228:38–44CrossRefGoogle Scholar
  93. Zhang L, Ten Hagen KG (2010) Dissecting the biological role of mucin-type O-glycosylation using RNA interference in Drosophila cell culture. J Biol Chem 285:34477–34484PubMedCrossRefGoogle Scholar
  94. Zhang Y, Iwasaki H, Wang H, Kudo T, Kalka TB, Hennet T, Kubota T, Cheng L, Inaba N, Gotoh M, Togayachi A, Guo J, Hisatomi H, Nakajima K, Nishihara S, Nakamura M, Marth JD, Narimatsu H (2003) Cloning and characterization of a new human UDP-N-acetyl-alpha-d-galactosamine:polypeptide N-acetylgalactosaminyltransferase designated pp-GalNAc-T13, that is specifically expressed in neurons and synthesizes GalNAc alpha-serine/threonine antigen. J Biol Chem 278:573–584PubMedCrossRefGoogle Scholar
  95. Zhang L, Zhang Y, Ten Hagen KG (2008) A mucin-type O-glycosyltransferase modulates cell adhesion during Drosophila development. J Biol Chem 283:34076–34086PubMedCrossRefGoogle Scholar
  96. Zhang L, Tran DT, Ten Hagen KG (2010) An O-glycosyltransferase promotes cell adhesion during development by influencing secretion of an extracellular matrix integrin ligand. J Biol Chem 285:19491–19501PubMedCrossRefGoogle Scholar

Copyright information

© Springer Japan 2014

Authors and Affiliations

  • Liping Zhang
    • 1
  • E. Tian
    • 1
  • Kelly G. Ten Hagen
    • 1
  1. 1.NIDCR/National Institutes of HealthBethesdaUSA

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