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Glycobiology Advance Access originally published online on September 22, 2004
Glycobiology 2005 15(2):153-164; doi:10.1093/glycob/cwh151
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Glycobiology vol. 15 no. 2 © Oxford University Press 2005; all rights reserved.

Prediction, conservation analysis, and structural characterization of mammalian mucin-type O-glycosylation sites

Karin Julenius1, Anne Mølgaard, Ramneek Gupta and Søren Brunak

Center for Biological Sequence Analysis, BioCentrum, Building 208, Technical University of Denmark, DK-2800 Lyngby, Denmark


1 To whom correspondence should be addressed; e-mail: karin.julenius{at}sbc.su.se

Received on January 9, 2004; revised on September 15, 2004; accepted on September 15, 2004

O-GalNAc-glycosylation is one of the main types of glycosylation in mammalian cells. No consensus recognition sequence for the O-glycosyltransferases is known, making prediction methods necessary to bridge the gap between the large number of known protein sequences and the small number of proteins experimentally investigated with regard to glycosylation status. From O-GLYCBASE a total of 86 mammalian proteins experimentally investigated for in vivo O-GalNAc sites were extracted. Mammalian protein homolog comparisons showed that a glycosylated serine or threonine is less likely to be precisely conserved than a nonglycosylated one. The Protein Data Bank was analyzed for structural information, and 12 glycosylated structures were obtained. All positive sites were found in coil or turn regions. A method for predicting the location for mucin-type glycosylation sites was trained using a neural network approach. The best overall network used as input amino acid composition, averaged surface accessibility predictions together with substitution matrix profile encoding of the sequence. To improve prediction on isolated (single) sites, networks were trained on isolated sites only. The final method combines predictions from the best overall network and the best isolated site network; this prediction method correctly predicted 76% of the glycosylated residues and 93% of the nonglycosylated residues. NetOGlyc 3.1 can predict sites for completely new proteins without losing its performance. The fact that the sites could be predicted from averaged properties together with the fact that glycosylation sites are not precisely conserved indicates that mucin-type glycosylation in most cases is a bulk property and not a very site-specific one. NetOGlyc 3.1 is made available at www.cbs.dtu.dk/services/netoglyc.

Key words: machine learning / mucin-type / neural networks / O-glycosylation / prediction


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Hum. Mol. Genet., April 15, 2006; 15(suppl_1): R81 - R87.
[Abstract] [Full Text] [PDF]


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Clin. Chem.Home page
S. Wopereis, D. J. Lefeber, E. Morava, and R. A. Wevers
Mechanisms in Protein O-Glycan Biosynthesis and Clinical and Molecular Aspects of Protein O-Glycan Biosynthesis Defects: A Review
Clin. Chem., April 1, 2006; 52(4): 574 - 600.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
T. A. Fritz, J. Raman, and L. A. Tabak
Dynamic Association between the Catalytic and Lectin Domains of Human UDP-GalNAc:Polypeptide {alpha}-N-Acetylgalactosaminyltransferase-2
J. Biol. Chem., March 31, 2006; 281(13): 8613 - 8619.
[Abstract] [Full Text] [PDF]


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Mol Biol EvolHome page
R. H. Y. Jiang, B. M. Tyler, S. C. Whisson, A. R. Hardham, and F. Govers
Ancient Origin of Elicitin Gene Clusters in Phytophthora Genomes
Mol. Biol. Evol., February 1, 2006; 23(2): 338 - 351.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
I. Ahmad, D. C. Hoessli, E. Walker-Nasir, S. M. Rafik, A. R. Shakoori, and Nasir-ud-Din
Oct-2 DNA binding transcription factor: functional consequences of phosphorylation and glycosylation
Nucleic Acids Res., January 8, 2006; 34(1): 175 - 184.
[Abstract] [Full Text] [PDF]


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Infect. Immun.Home page
C. K. Doyle, K. A. Nethery, V. L. Popov, and J. W. McBride
Differentially Expressed and Secreted Major Immunoreactive Protein Orthologs of Ehrlichia canis and E. chaffeensis Elicit Early Antibody Responses to Epitopes on Glycosylated Tandem Repeats
Infect. Immun., January 1, 2006; 74(1): 711 - 720.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
D. Hubmacher, K. Tiedemann, R. Bartels, J. Brinckmann, T. Vollbrandt, B. Batge, H. Notbohm, and D. P. Reinhardt
Modification of the Structure and Function of Fibrillin-1 by Homocysteine Suggests a Potential Pathogenetic Mechanism in Homocystinuria
J. Biol. Chem., October 14, 2005; 280(41): 34946 - 34955.
[Abstract] [Full Text] [PDF]


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Proc. Natl. Acad. Sci. USAHome page
B. Musicki, M. F. Kramer, R. E. Becker, and A. L. Burnett
Inactivation of phosphorylated endothelial nitric oxide synthase (Ser-1177) by O-GlcNAc in diabetes-associated erectile dysfunction
PNAS, August 16, 2005; 102(33): 11870 - 11875.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
M. Semenov, K. Tamai, and X. He
SOST Is a Ligand for LRP5/LRP6 and a Wnt Signaling Inhibitor
J. Biol. Chem., July 22, 2005; 280(29): 26770 - 26775.
[Abstract] [Full Text] [PDF]


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J. Virol.Home page
K. T. Zlateva, P. Lemey, E. Moes, A.-M. Vandamme, and M. Van Ranst
Genetic Variability and Molecular Evolution of the Human Respiratory Syncytial Virus Subgroup B Attachment G Protein
J. Virol., July 15, 2005; 79(14): 9157 - 9167.
[Abstract] [Full Text] [PDF]


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Hum Mol GenetHome page
E. O'Connor, B. Eisenhaber, J. Dalley, T. Wang, C. Missen, N. Bulleid, P. N. Bishop, and D. Trump
Species specific membrane anchoring of nyctalopin, a small leucine-rich repeat protein
Hum. Mol. Genet., July 1, 2005; 14(13): 1877 - 1887.
[Abstract] [Full Text] [PDF]


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Nucleic Acids ResHome page
P. I. Olason
Integrating protein annotation resources through the Distributed Annotation System
Nucleic Acids Res., July 1, 2005; 33(suppl_2): W468 - W470.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
S. K. Patnaik and P. Stanley
Mouse Large Can Modify Complex N- and Mucin O-Glycans on {alpha}-Dystroglycan to Induce Laminin Binding
J. Biol. Chem., May 27, 2005; 280(21): 20851 - 20859.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
S. Nakav, A. Jablonka-Shariff, S. Kaner, P. Chadna-Mohanty, H. E. Grotjan, and D. Ben-Menahem
The LH{beta} Gene of Several Mammals Embeds a Carboxyl-terminal Peptide-like Sequence Revealing a Critical Role for Mucin Oligosaccharides in the Evolution of Lutropin to Chorionic Gonadotropin in the Animal Phyla
J. Biol. Chem., April 29, 2005; 280(17): 16676 - 16684.
[Abstract] [Full Text] [PDF]


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Mol. Cell. ProteomicsHome page
S. H. Olesen, L. L. Christensen, F. B. Sorensen, T. Cabezon, S. Laurberg, T. F. Orntoft, and K. Birkenkamp-Demtroder
Human FK506 Binding Protein 65 Is Associated with Colorectal Cancer
Mol. Cell. Proteomics, April 1, 2005; 4(4): 534 - 544.
[Abstract] [Full Text] [PDF]


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J. Biol. Chem.Home page
J. I. MacRae, A. Acosta-Serrano, N. A. Morrice, A. Mehlert, and M. A. J. Ferguson
Structural Characterization of NETNES, a Novel Glycoconjugate in Trypanosoma cruzi Epimastigotes
J. Biol. Chem., April 1, 2005; 280(13): 12201 - 12211.
[Abstract] [Full Text] [PDF]



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