title: Transglutaminase 6: a protein associated with central nervous system development and motor function.
abstract: Transglutaminases (TG) form a family of enzymes that catalyse various post-translational modifications of glutamine residues in proteins and peptides including intra- and intermolecular isopeptide bond formation, esterification and deamidation. We have characterized a novel member of the mammalian TG family, TG6, which is expressed in a human carcinoma cell line with neuronal characteristics and in mouse brain. Besides full-length protein, alternative splicing results in a short variant lacking the second β-barrel domain in man and a variant with truncated β-sandwich domain in mouse. Biochemical data show that TG6 is allosterically regulated by Ca(2+) and guanine nucleotides. Molecular modelling indicates that TG6 could have Ca(2+) and GDP-binding sites related to those of TG3 and TG2, respectively. Localization of mRNA and protein in the mouse identified abundant expression of TG6 in the central nervous system. Analysis of its temporal and spatial pattern of induction in mouse development indicates an association with neurogenesis. Neuronal expression of TG6 was confirmed by double-labelling of mouse forebrain cells with cell type-specific markers. Induction of differentiation in mouse Neuro 2a cells with NGF or dibutyryl cAMP is associated with an upregulation of TG6 expression. Familial ataxia has recently been linked to mutations in the TGM6 gene. Autoantibodies to TG6 were identified in immune-mediated ataxia in patients with gluten sensitivity. These findings suggest a critical role for TG6 in cortical and cerebellar neurons.
authors: Matrix Biology and Tissue Repair Research Unit, School of Dentistry, Cardiff University, Heath Park, Cardiff CF14 4XY, UK.
authors: Helen
authors: H
authors: Thomas
authors: Konrad
authors: K
authors: Beck
authors: Magdalena
authors: M
authors: Adamczyk
authors: Pascale
authors: P
authors: Aeschlimann
authors: Martin
authors: M
authors: Langley
authors: Radu C
authors: RC
authors: Oita
authors: Lars
authors: L
authors: Thiebach
authors: Martin
authors: M
authors: Hils
authors: Daniel
authors: D
authors: Aeschlimann
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D002454:Cell Differentiation; D002460:Cell Line; D002490:Central Nervous System / Q000166:cytology / Q000196:embryology* / Q000502:physiology*; D003067:Coenzymes; D019143:Evolution, Molecular; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007700:Kinetics; D051379:Mice; D008807:Mice, Inbred BALB C; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009474:Neurons / Q000201:enzymology / Q000502:physiology*; D009711:Nucleotides / Q000737:chemistry; D009928:Organ Specificity; D011485:Protein Binding; D017433:Protein Structure, Secondary; D013379:Substrate Specificity; D011503:Transglutaminases / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism
chemical_list: D003067:Coenzymes; D009711:Nucleotides; C532876:TGM6 protein, human; D011503:Transglutaminases