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

Tilo Schwientek, Eric P. Bennett, Carlos Flores, John Thacker, Martin Hollmann, Celso A. Reis, Jane Behrens, Ulla Mandel, Birgit Keck, A. Mireille, Schäfer, Kim Haselmann, Roman Zubarev, Peter Roepstorff, Joy M. Burchell, Joyce Taylor-Papadimitriou, Michael A. Hollingsworth, Henrik Clausena

Research output: Contribution to journalArticle

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Abstract

The completed fruit fly genome was found to contain up to 15 putative UDP-N-acetyl- α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-transferase) genes. Phylogenetic analysis of the putative catalytic domains of the large GalNAc-transferase enzyme families of Drosophila melanogaster (13 available), Caenorhabditis elegans (9 genes), and mammals (12 genes) indicated that distinct subfamilies of orthologous genes are conserved in each species. In support of this hypothesis, we provide evidence that distinctive functional properties of Drosophila and human GalNAc-transferase isoforms were exhibited by evolutionarily conserved members of two subfamilies (dGalNAc-T1 (l(2)35Aa) and GalNAc-T11; dGalNAc-T2 (CG6394) and GalNAc-T7). dGalNAc-T1 and novel human GalNAc-T11 were shown to encode functional GalNAc-transferases with the same polypeptide acceptor substrate specificity, and dGalNAc-T2 was shown to encode a Gal-NAc-transferase with similar GalNAc glycopeptide substrate specificity as GalNAc-T7. Previous data suggested that the putative GalNAc-transferase encoded by l(2)35Aa had a lethal phenotype (Flores, C., and Engels, W. (1999) Proc. NatL Acad Sci. U. S. A. 96, 2964-2969), and this was substantiated by sequencing of three lethal alleles l(2)35AaHG8, l(2)35AaSF12, and l(2)35AaSF32. The finding that subfamilies of GalNAc-transferases with distinct catalytic functions are evolutionarily conserved stresses that GalNAc-transferase isoforms may serve unique biological functions rather than providing functional redundancy, and this is further supported by the lethal phenotype of l(2)35Aa.

Original languageEnglish (US)
Pages (from-to)22623-22638
Number of pages16
JournalJournal of Biological Chemistry
Volume277
Issue number25
DOIs
StatePublished - Jun 21 2002

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Uridine Diphosphate N-Acetylgalactosamine
Acetylgalactosamine
Mammals
Uridine Diphosphate
Caenorhabditis elegans
Drosophila
Conservation
Genes
Substrate Specificity
Protein Isoforms
Lethal Genes
Phenotype
Glycopeptides
polypeptide N-acetylgalactosaminyltransferase
Substrates
Transferases
Fruits
Drosophila melanogaster
Diptera
Redundancy

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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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. / Schwientek, Tilo; Bennett, Eric P.; Flores, Carlos; Thacker, John; Hollmann, Martin; Reis, Celso A.; Behrens, Jane; Mandel, Ulla; Keck, Birgit; Mireille, A.; Schäfer; Haselmann, Kim; Zubarev, Roman; Roepstorff, Peter; Burchell, Joy M.; Taylor-Papadimitriou, Joyce; Hollingsworth, Michael A.; Clausena, Henrik.

In: Journal of Biological Chemistry, Vol. 277, No. 25, 21.06.2002, p. 22623-22638.

Research output: Contribution to journalArticle

Schwientek, T, Bennett, EP, Flores, C, Thacker, J, Hollmann, M, Reis, CA, Behrens, J, Mandel, U, Keck, B, Mireille, A, Schäfer, Haselmann, K, Zubarev, R, Roepstorff, P, Burchell, JM, Taylor-Papadimitriou, J, Hollingsworth, MA & Clausena, 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', Journal of Biological Chemistry, vol. 277, no. 25, pp. 22623-22638. https://doi.org/10.1074/jbc.M202684200
Schwientek, Tilo ; Bennett, Eric P. ; Flores, Carlos ; Thacker, John ; Hollmann, Martin ; Reis, Celso A. ; Behrens, Jane ; Mandel, Ulla ; Keck, Birgit ; Mireille, A. ; Schäfer ; Haselmann, Kim ; Zubarev, Roman ; Roepstorff, Peter ; Burchell, Joy M. ; Taylor-Papadimitriou, Joyce ; Hollingsworth, Michael A. ; Clausena, Henrik. / 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. In: Journal of Biological Chemistry. 2002 ; Vol. 277, No. 25. pp. 22623-22638.
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abstract = "The completed fruit fly genome was found to contain up to 15 putative UDP-N-acetyl- α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-transferase) genes. Phylogenetic analysis of the putative catalytic domains of the large GalNAc-transferase enzyme families of Drosophila melanogaster (13 available), Caenorhabditis elegans (9 genes), and mammals (12 genes) indicated that distinct subfamilies of orthologous genes are conserved in each species. In support of this hypothesis, we provide evidence that distinctive functional properties of Drosophila and human GalNAc-transferase isoforms were exhibited by evolutionarily conserved members of two subfamilies (dGalNAc-T1 (l(2)35Aa) and GalNAc-T11; dGalNAc-T2 (CG6394) and GalNAc-T7). dGalNAc-T1 and novel human GalNAc-T11 were shown to encode functional GalNAc-transferases with the same polypeptide acceptor substrate specificity, and dGalNAc-T2 was shown to encode a Gal-NAc-transferase with similar GalNAc glycopeptide substrate specificity as GalNAc-T7. Previous data suggested that the putative GalNAc-transferase encoded by l(2)35Aa had a lethal phenotype (Flores, C., and Engels, W. (1999) Proc. NatL Acad Sci. U. S. A. 96, 2964-2969), and this was substantiated by sequencing of three lethal alleles l(2)35AaHG8, l(2)35AaSF12, and l(2)35AaSF32. The finding that subfamilies of GalNAc-transferases with distinct catalytic functions are evolutionarily conserved stresses that GalNAc-transferase isoforms may serve unique biological functions rather than providing functional redundancy, and this is further supported by the lethal phenotype of l(2)35Aa.",
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T1 - 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

AU - Schwientek, Tilo

AU - Bennett, Eric P.

AU - Flores, Carlos

AU - Thacker, John

AU - Hollmann, Martin

AU - Reis, Celso A.

AU - Behrens, Jane

AU - Mandel, Ulla

AU - Keck, Birgit

AU - Mireille, A.

AU - Schäfer,

AU - Haselmann, Kim

AU - Zubarev, Roman

AU - Roepstorff, Peter

AU - Burchell, Joy M.

AU - Taylor-Papadimitriou, Joyce

AU - Hollingsworth, Michael A.

AU - Clausena, Henrik

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N2 - The completed fruit fly genome was found to contain up to 15 putative UDP-N-acetyl- α-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase (GalNAc-transferase) genes. Phylogenetic analysis of the putative catalytic domains of the large GalNAc-transferase enzyme families of Drosophila melanogaster (13 available), Caenorhabditis elegans (9 genes), and mammals (12 genes) indicated that distinct subfamilies of orthologous genes are conserved in each species. In support of this hypothesis, we provide evidence that distinctive functional properties of Drosophila and human GalNAc-transferase isoforms were exhibited by evolutionarily conserved members of two subfamilies (dGalNAc-T1 (l(2)35Aa) and GalNAc-T11; dGalNAc-T2 (CG6394) and GalNAc-T7). dGalNAc-T1 and novel human GalNAc-T11 were shown to encode functional GalNAc-transferases with the same polypeptide acceptor substrate specificity, and dGalNAc-T2 was shown to encode a Gal-NAc-transferase with similar GalNAc glycopeptide substrate specificity as GalNAc-T7. Previous data suggested that the putative GalNAc-transferase encoded by l(2)35Aa had a lethal phenotype (Flores, C., and Engels, W. (1999) Proc. NatL Acad Sci. U. S. A. 96, 2964-2969), and this was substantiated by sequencing of three lethal alleles l(2)35AaHG8, l(2)35AaSF12, and l(2)35AaSF32. The finding that subfamilies of GalNAc-transferases with distinct catalytic functions are evolutionarily conserved stresses that GalNAc-transferase isoforms may serve unique biological functions rather than providing functional redundancy, and this is further supported by the lethal phenotype of l(2)35Aa.

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