The expanding beta 4-galactosyltransferase gene family: messages from the databanks

Lo, Neng Wen; Shaper, Joël H.; Pevsner, Jonathan; Shaper, Nancy L.

doi:10.1093/glycob/8.5.517

Cited by 186 publications

(129 citation statements)

References 25 publications

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“…These and other unpublished experiments in the laboratory support a model of defective synthesis of glycans with β (1-4)N-acetylglucosamine linkages. The β(1-4)galactosyltransferase I gene is part of a substantial gene family (Lo et al, 1998). This report tests the hypothesis that a glycosyltransferase allele is linked to predisposition to this disease.…”

Section: Commentsmentioning

confidence: 55%

A novel b(1-4)galactosyltransferase gene silent mutation (594C>T) associated with Hutchinson-Gilford progeria Communicated by Mark H. Paalman Online Citation: Human Mutation, Mutation and Polymorphism Report #231 (2001) Online http://journals.wiley.com/1059-7794/pdf/mutation/mpr231.pdf Acknowledgments: We are very grateful to the individuals and progeria families whose cooperation made this study possible, and to members of the Weiss laboratory.

O’Brien¹,

Weiss

2001

Hum. Mutat.

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Section: Commentsmentioning

confidence: 55%

A novel b(1-4)galactosyltransferase gene silent mutation (594C>T) associated with Hutchinson-Gilford progeria Communicated by Mark H. Paalman Online Citation: Human Mutation, Mutation and Polymorphism Report #231 (2001) Online http://journals.wiley.com/1059-7794/pdf/mutation/mpr231.pdf Acknowledgments: We are very grateful to the individuals and progeria families whose cooperation made this study possible, and to members of the Weiss laboratory.

O’Brien¹,

Weiss

2001

Hum. Mutat.

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“…To date, seven members of the human ␤1,4-galactosyltransferase (␤4Gal-T) 1 family and six members of the human ␤1,4-N-acetylgalactosaminyltransferase (␤4GalNAc-T) family have been identified. ␤4Gal-T1 to -T6 exhibit activity to transfer Gal to GlcNAc with a ␤1,4-linkage in N-and O-glycans and glycolipids (1)(2)(3)(4).…”

mentioning

confidence: 99%

“…␤4Gal-T1 to -T6 exhibit activity to transfer Gal to GlcNAc with a ␤1,4-linkage in N-and O-glycans and glycolipids (1)(2)(3)(4). ␤4Gal-T7 synthesizes the Gal␤1-4Xyl structure that occurs in the linkage portion of glycosaminoglycans (5,6).…”

mentioning

confidence: 99%

“…Elimination of a hydrogen bond by mutating the Tyr-289 residue to Leu, Ile, or Asn enhances the GalNAc-T activity. One GalNAc-T of Caenorhabditis elegans, which can synthesize GalNAc␤1-4GlcNAc 1 The abbreviations used are: (␤4)Gal-T, (␤1,4-)galactosyltransferase; (␤4 or CS)GalNAc-T, (␤1,4-or CS)N-acetylgalactosaminyltransferase; CS, chondroitin sulfate; Cer, ceramide; GM3, NeuAc␣2-3Gal␤1-4Glc␤1-1ЈCer; GD3, NeuAc␣2-8NeuAc␣2-3Gal␤1-4Glc␤1-1ЈCer; GM2, GalNAc␤1-4(NeuAc␣2-3)Gal␤1-4Glc␤1-1ЈCer; GD2, GalNAc␤1-4(NeuAc␣2-8NeuAc␣2-3)Gal␤1-4Glc␤1-1ЈCer; CSS, chondroitin synthase; LacdiNAc, N, NЈ-diacetyllactosediamine (GalNAc␤1-4GlcNAc); LH, lutropin; TSH, thyrotropin; TFPI, tissue factor pathway inhibitor; HEK, human embryonic kidney; HPC, human protein C; ␤4GT, ␤1,4-glycosyltransferase; ORF, open reading frame; RACE, rapid amplification of cDNA ends; TBS, Tris-buffered saline; pNp, para-nitrophenyl; Bz, benzyl; HPLC, high performance liquid chromatography; MS, mass spectrometry; MALDI-TOF, matrix assisted laser desorption/ ionization-time of flight; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; FCF, fetal calf fetuin; GPF, glycopeptidase F; HRP, horseradish peroxidase; WFA, W. floribunda agglutinin; MES, 4-morpholineethanesulfonic acid; NOE, nuclear Overhauser effect.…”

mentioning

confidence: 99%

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Molecular Cloning and Characterization of a Novel Human β1,4-N-Acetylgalactosaminyltransferase, β4GalNAc-T3, Responsible for the Synthesis of N,N′-Diacetyllactosediamine, GalNAcβ1–4GlcNAc

Sato

Gotoh

Kiyohara

et al. 2003

Journal of Biological Chemistry

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We found a novel human glycosyltransferase gene carrying a hypothetical ␤1,4-glycosyltransferase motif during a BLAST search, and we cloned its full-length open reading frame by using the 5 -rapid amplification of cDNA ends method. It encodes a type II transmembrane protein of 999 amino acids with homology to chondroitin sulfate synthase in its C-terminal region (GenBank TM accession number AB089940). Its putative orthologous gene was also found in mouse (accession number AB114826). The truncated form of the human enzyme was expressed in HEK293T cells as a soluble protein. The recombinant enzyme transferred GalNAc to GlcNAc ␤-benzyl. The product was deduced to be GalNAc␤1-4GlcNAc␤-benzyl based on mass spectrometry and NMR spectroscopy. We renamed the enzyme ␤1,4-N-acetylgalactosaminyltransferase-III (␤4GalNAc-T3). ␤4GalNAc-T3 effectively synthesized N,N -diacetylgalactosediamine, GalNAc␤1-4GlcNAc, at non-reducing termini of various acceptors derived not only from N-glycans but also from O-glycans. Quantitative real time PCR analysis showed that its transcript was highly expressed in stomach, colon, and testis. As some glycohormones contain N,N -diacetylgalactosediamine structures in their N-glycans, we examined the ability of ␤4GalNAc-T3 to synthesize N,N -diacetylgalactosediamine structures in N-glycans on a model protein.When fetal calf fetuin treated with neuraminidase and ␤1,4-galactosidase was utilized as an acceptor protein, ␤4GalNAc-T3 transferred GalNAc to it. Furthermore, the majority of the signal from GalNAc disappeared on treatment with glycopeptidase F. These results suggest that ␤4GalNAc-T3 could transfer GalNAc residues, producing N,N -diacetylgalactosediamine structures at least in Nglycans and probably in both N-and O-glycans.

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“…Although the ␤4GalT family is known to have seven members (␤4GalT-I to VII) in vivo (17,18), the biological role of each is not fully understood. Some of them are able to synthesize N-acetyllactosamine on glycoproteins.…”

mentioning

confidence: 99%

Specific Enzyme Complex of β-1,4-Galactosyltransferase-II and Glucuronyltransferase-P Facilitates Biosynthesis of N-linked Human Natural Killer-1 (HNK-1) Carbohydrate

Kouno

Kizuka

Nakagawa

et al. 2011

Journal of Biological Chemistry

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Human natural killer-1 (HNK-1) carbohydrate is highly expressed in the nervous system and is involved in synaptic plasticity and dendritic spine maturation. This unique carbohydrate, consisting of a sulfated trisaccharide (HSO 3 -3GlcA␤1-3Gal␤1-4GlcNAc-), is biosynthesized by the successive actions of ␤-1,4-galactosyltransferase (␤4GalT), glucuronyltransferase (GlcAT-P and GlcAT-S), and sulfotransferase (HNK-1ST). A previous study showed that mice lacking ␤4GalT-II, one of seven ␤4GalTs, exhibited a dramatic loss of HNK-1 expression in the brain, although ␤4GalT-I-deficient mice did not. Here, we investigated the underlying molecular mechanism of the regulation of HNK-1 expression. First, focusing on a major HNK-1 carrier, neural cell adhesion molecule, we found that reduced expression of an N-linked HNK-1 carbohydrate caused by a deficiency of ␤4GalT-II is not likely due to a general loss of the ␤1,4-galactose residue as an acceptor for GlcAT-P. Instead, we demonstrated by co-immunoprecipitation and endoplasmic reticulum-retention analyses using Neuro2a (N2a) cells that ␤4GalT-II physically and specifically associates with GlcAT-P. In addition, we revealed by pulldown assay that Golgi luminal domains of ␤4GalT-II and GlcAT-P are sufficient for the complex to form. With an in vitro assay system, we produced the evidence that the kinetic efficiency k cat /K m of GlcAT-P in the presence of ␤4GalT-II was increased about 2.5-fold compared with that in the absence of ␤4GalT-II. Finally, we showed that co-expression of ␤4GalT-II and GlcAT-P increased HNK-1 expression on various glycoproteins in N2a cells, including neural cell adhesion molecule. These results indicate that the specific enzyme complex of ␤4GalT-II with GlcAT-P plays an important role in the biosynthesis of HNK-1 carbohydrate.

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The expanding beta 4-galactosyltransferase gene family: messages from the databanks

Cited by 186 publications

References 25 publications

Molecular Cloning and Characterization of a Novel Human β1,4-N-Acetylgalactosaminyltransferase, β4GalNAc-T3, Responsible for the Synthesis of N,N′-Diacetyllactosediamine, GalNAcβ1–4GlcNAc

Specific Enzyme Complex of β-1,4-Galactosyltransferase-II and Glucuronyltransferase-P Facilitates Biosynthesis of N-linked Human Natural Killer-1 (HNK-1) Carbohydrate

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