TY - JOUR
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, T
AU - Bennett, E P
AU - Flores, C
AU - Thacker, J
AU - Hollmann, M
AU - Reis, C A
AU - Behrens, J
AU - Mandel, U
AU - Keck, B
AU - Schafer, M A
AU - Haselmann, K
AU - Zubarev, R
AU - Roepstorff, P
AU - Burchell, J M
AU - Taylor-Papadimitriou, J
AU - Hollingsworth, M A
AU - Clausen, H
PY - 2002/6/21
Y1 - 2002/6/21
N2 - The completed fruit fly genome was found to contain up to 15 putative UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetvlgalactosaminyltransferase (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-tranferase 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 GalNAc-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)35Aa(HG8), l(2)35Aa(SF12), and l(2)35Aa(SF32). 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.
AB - The completed fruit fly genome was found to contain up to 15 putative UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetvlgalactosaminyltransferase (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-tranferase 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 GalNAc-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)35Aa(HG8), l(2)35Aa(SF12), and l(2)35Aa(SF32). 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.
UR - http://www.scopus.com/inward/record.url?scp=0037151059&partnerID=8YFLogxK
U2 - 10.1074/jbc.M202684200
DO - 10.1074/jbc.M202684200
M3 - Article
SN - 1083-351X
VL - 277
SP - 22623
EP - 22638
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 25
ER -