Glycosyltransferase family A (GT-A) includes diverse families of glycosyl transferases with a common GT-A type structural fold; Glycosyltransferases (GTs) are enzymes that synthesize oligosaccharides, polysaccharides, and glycoconjugates by transferring the sugar moiety from an activated nucleotide-sugar donor to an acceptor molecule, which may be a growing oligosaccharide, a lipid, or a protein. Based on the stereochemistry of the donor and acceptor molecules, GTs are classified as either retaining or inverting enzymes. To date, all GT structures adopt one of two possible folds, termed GT-A fold and GT-B fold. This hierarchy includes diverse families of glycosyl transferases with a common GT-A type structural fold, which has two tightly associated beta/alpha/beta domains that tend to form a continuous central sheet of at least eight beta-strands. The majority of the proteins in this superfamily are Glycosyltransferase family 2 (GT-2) proteins. But it also includes families GT-43, GT-6, GT-8, GT13 and GT-7; which are evolutionarily related to GT-2 and share structure similarities.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21751142   3 VSAQDIFNAVIKEHPGLVQRLPCVWNVQLSDHTLAERCYSEASDLKVIHWNSPKKLRVKNKHVEFFRNFYLTFLEYDGNL 82
Cdd:cd06431 195 LADQDIFNAVIKQNPFLVYQLPCAWNVQLSDHTRSEQCYRDVSDLKVIHWNSPKKLRVKNKHVEFFRNLYLTFLEYDGNL 274

                ....*.
gi 21751142  83 LRRELF 88
Cdd:cd06431 275 LRRELF 280

LARGE catalytic domain has closest homology to GT8 glycosyltransferase involved in lipooligosaccharide synthesis; The catalytic domain of LARGE is a putative glycosyltransferase. Mutations of LARGE in mouse and human cause dystroglycanopathies, a disease associated with hypoglycosylation of the membrane protein alpha-dystroglycan (alpha-DG) and consequent loss of extracellular ligand binding. LARGE needs to both physically interact with alpha-dystroglycan and function as a glycosyltransferase in order to stimulate alpha-dystroglycan hyperglycosylation. LARGE localizes to the Golgi apparatus and contains three conserved DxD motifs. While two of the motifs are indispensible for glycosylation function, one is important for localization of th eenzyme. LARGE was originally named because it covers approximately large trunck of genomic DNA, more than 600bp long. The predicted protein structure contains an N-terminal cytoplasmic domain, a transmembrane region, a coiled-coil motif, and two putative catalytic domains. This catalytic domain has closest homology to GT8 glycosyltransferase involved in lipooligosaccharide synthesis.

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                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21751142   3 VSAQDIFNAVIKEHPGLVQRLPCVWNVQLSDHTLAERCYSEASDLKVIHWNSPKKLRVKNKHVEFFRNFYLTFLEYDGNL 82
Cdd:cd06431 195 LADQDIFNAVIKQNPFLVYQLPCAWNVQLSDHTRSEQCYRDVSDLKVIHWNSPKKLRVKNKHVEFFRNLYLTFLEYDGNL 274

                ....*.
gi 21751142  83 LRRELF 88
Cdd:cd06431 275 LRRELF 280

Glycosyl transferase family 8; This family includes enzymes that transfer sugar residues to donor molecules. Members of this family are involved in lipopolysaccharide biosynthesis and glycogen synthesis. This family includes Lipopolysaccharide galactosyltransferase, lipopolysaccharide glucosyltransferase 1, and glycogenin glucosyltransferase.

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                  ....*....|....*....|....*....|....*....|....*....|...
gi 21751142     6 QDIFNAVIKehpGLVQRLPCVWNVQLSDHTLAERCYSEASD-LKVIHWNSPKK 57
Cdd:pfam01501 197 QDPLNIVFY---GKVKPLDPRWNVLGLGYYNKKKSLNEITEnAAVIHYNGPTK 246

LARGE catalytic domain has closest homology to GT8 glycosyltransferase involved in lipooligosaccharide synthesis; The catalytic domain of LARGE is a putative glycosyltransferase. Mutations of LARGE in mouse and human cause dystroglycanopathies, a disease associated with hypoglycosylation of the membrane protein alpha-dystroglycan (alpha-DG) and consequent loss of extracellular ligand binding. LARGE needs to both physically interact with alpha-dystroglycan and function as a glycosyltransferase in order to stimulate alpha-dystroglycan hyperglycosylation. LARGE localizes to the Golgi apparatus and contains three conserved DxD motifs. While two of the motifs are indispensible for glycosylation function, one is important for localization of th eenzyme. LARGE was originally named because it covers approximately large trunck of genomic DNA, more than 600bp long. The predicted protein structure contains an N-terminal cytoplasmic domain, a transmembrane region, a coiled-coil motif, and two putative catalytic domains. This catalytic domain has closest homology to GT8 glycosyltransferase involved in lipooligosaccharide synthesis.

                        10        20        30        40        50        60        70        80
                ....*....|....*....|....*....|....*....|....*....|....*....|....*....|....*....|
gi 21751142   3 VSAQDIFNAVIKEHPGLVQRLPCVWNVQLSDHTLAERCYSEASDLKVIHWNSPKKLRVKNKHVEFFRNFYLTFLEYDGNL 82
Cdd:cd06431 195 LADQDIFNAVIKQNPFLVYQLPCAWNVQLSDHTRSEQCYRDVSDLKVIHWNSPKKLRVKNKHVEFFRNLYLTFLEYDGNL 274

                ....*.
gi 21751142  83 LRRELF 88
Cdd:cd06431 275 LRRELF 280

Members of glycosyltransferase family 8 (GT-8) are involved in lipopolysaccharide biosynthesis and glycogen synthesis; Members of this family are involved in lipopolysaccharide biosynthesis and glycogen synthesis. GT-8 comprises enzymes with a number of known activities: lipopolysaccharide galactosyltransferase, lipopolysaccharide glucosyltransferase 1, glycogenin glucosyltransferase, and N-acetylglucosaminyltransferase. GT-8 enzymes contains a conserved DXD motif which is essential in the coordination of a catalytic divalent cation, most commonly Mn2+.

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                ....*....|....*....|....*....|....*....|....*....|....*..
gi 21751142   6 QDIFNAVIKEHPGLVQRLPCVWNVQLSDHTLAERC-YSEASDLKVIHWNSPKKLRVK 61
Cdd:cd00505 190 QDLLNTFFKQVPFIVKSLPCIWNVRLTGCYRSLNCfKAFVKNAKVIHFNGPTKPWNK 246