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Gene Review

CHAT  -  choline O-acetyltransferase

Homo sapiens

Synonyms: CHOACTASE, CHOACTase, CMS1A, CMS1A2, ChAT, ...
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Disease relevance of CHAT


Psychiatry related information on CHAT


High impact information on CHAT


Chemical compound and disease context of CHAT


Biological context of CHAT

  • Vertebrate ChAT mRNAs can contain one or more of three non-coding exons, M, N or R and by RT-PCR we demonstrate, at least, a chicken ChAT mRNA containing exon M [20].
  • Here, we present recent neuroanatomical, developmental, and evolutionary insights into the chemical coding of cholinergic neurotransmission that have been gleaned from the study of the CGL, and its protein products VAChT and ChAT, which comprise a synthesis-sequestration pathway that functionally defines the cholinergic phenotype [21].
  • The cholinergic gene locus (CGL) was first identified in 1994 as the site (human chromosome 10q11.2) at which choline acetyltransferase and a functional vesicular acetylcholine transporter are co-localized [21].
  • The first intron of the ChAT gene encompasses the open reading frame encoding another protein, vesicular acetylcholine transporter (VAChT), which is responsible for the transportation of acetylcholine from the cytoplasm into the synaptic vesicles [22].
  • These data suggest that 69-kDa choline acetyltransferase is a nucleocytoplasmic shuttling protein with a predominantly cytoplasmic localization determined by a functional nuclear localization signal and unidentified putative nuclear export signal [23].

Anatomical context of CHAT


Associations of CHAT with chemical compounds

  • The proportions of neurones containing ChAT and SP were significantly higher in inflamed (11.8%) and non-inflamed (13.9%) areas than in controls (5.0%) [29].
  • The enzyme choline acetyltransferase [EC] (ChAT) synthesizes the neurotransmitter acetylcholine that plays a key morphogenic role in vertebrate retina development [20].
  • To the extent that cholinergic neuron integrity can be inferred from VAChT concentration, our data suggest that methamphetamine does not cause loss of striatal cholinergic neurons, but might damage/downregulate brain ChAT in some high-dose users [26].
  • However, both ACh and mRNA for ChAT are expressed in mononuclear leukocytes and various human leukemic T-cell lines [28].
  • Thus, in HUVEC cultures, ChAT activity amounted to 0.78 +/- 0.15 nmol x mg protein(-1) x h(-1) (n = 3), but was only partially (about 50%) inhibited by the ChAT inhibitor bromoacetylcholine (30 microM) [1].

Physical interactions of CHAT


Co-localisations of CHAT


Regulatory relationships of CHAT


Other interactions of CHAT


Analytical, diagnostic and therapeutic context of CHAT


  1. The non-neuronal cholinergic system in the endothelium: evidence and possible pathobiological significance. Kirkpatrick, C.J., Bittinger, F., Unger, R.E., Kriegsmann, J., Kilbinger, H., Wessler, I. Jpn. J. Pharmacol. (2001) [Pubmed]
  2. Phosphorylation of 69-kDa choline acetyltransferase at threonine 456 in response to amyloid-beta peptide 1-42. Dobransky, T., Brewer, D., Lajoie, G., Rylett, R.J. J. Biol. Chem. (2003) [Pubmed]
  3. Protein kinase C isoforms differentially phosphorylate human choline acetyltransferase regulating its catalytic activity. Dobransky, T., Doherty-Kirby, A., Kim, A.R., Brewer, D., Lajoie, G., Rylett, R.J. J. Biol. Chem. (2004) [Pubmed]
  4. Expression, purification and characterization of recombinant human choline acetyltransferase: phosphorylation of the enzyme regulates catalytic activity. Dobransky, T., Davis, W.L., Xiao, G.H., Rylett, R.J. Biochem. J. (2000) [Pubmed]
  5. Preservation of nucleus basalis neurons containing choline acetyltransferase and the vesicular acetylcholine transporter in the elderly with mild cognitive impairment and early Alzheimer's disease. Gilmor, M.L., Erickson, J.D., Varoqui, H., Hersh, L.B., Bennett, D.A., Cochran, E.J., Mufson, E.J., Levey, A.I. J. Comp. Neurol. (1999) [Pubmed]
  6. Lewy body disease: thalamic cholinergic activity related to dementia and parkinsonism. Ziabreva, I., Ballard, C.G., Aarsland, D., Larsen, J.P., McKeith, I.G., Perry, R.H., Perry, E.K. Neurobiol. Aging (2006) [Pubmed]
  7. Choline acetyltransferase activity and vesamicol binding in Rett syndrome and in rats with nucleus basalis lesions. Wenk, G.L., Mobley, S.L. Neuroscience (1996) [Pubmed]
  8. Delusions associated with elevated muscarinic binding in dementia with Lewy bodies. Ballard, C., Piggott, M., Johnson, M., Cairns, N., Perry, R., McKeith, I., Jaros, E., O'Brien, J., Holmes, C., Perry, E. Ann. Neurol. (2000) [Pubmed]
  9. Neurochemical alterations in Huntington's chorea: a study of post-mortem brain tissue. Spokes, E.G. Brain (1980) [Pubmed]
  10. Brain neurotransmitters in dystonia musculorum deformans. Hornykiewicz, O., Kish, S.J., Becker, L.E., Farley, I., Shannak, K. N. Engl. J. Med. (1986) [Pubmed]
  11. Biochemical evidence of dysfunction of brain neurotransmitters in the Lesch-Nyhan syndrome. Lloyd, K.G., Hornykiewicz, O., Davidson, L., Shannak, K., Farley, I., Goldstein, M., Shibuya, M., Kelley, W.N., Fox, I.H. N. Engl. J. Med. (1981) [Pubmed]
  12. Huntington's chorea. Changes in neurotransmitter receptors in the brain. Enna, S.J., Bird, E.D., Bennett, J.P., Bylund, D.B., Yamamura, H.I., Iversen, L.L., Snyder, S.H. N. Engl. J. Med. (1976) [Pubmed]
  13. Neurotransmitters in the mammalian circadian system. Rusak, B., Bina, K.G. Annu. Rev. Neurosci. (1990) [Pubmed]
  14. Reciprocal changes in corticotropin-releasing factor (CRF)-like immunoreactivity and CRF receptors in cerebral cortex of Alzheimer's disease. De Souza, E.B., Whitehouse, P.J., Kuhar, M.J., Price, D.L., Vale, W.W. Nature (1986) [Pubmed]
  15. Identification and analysis of the human choline acetyltransferase gene promoter. Bausero, P., Schmitt, M., Toussaint, J.L., Simoni, P., Geoffroy, V., Queuche, D., Duclaud, S., Kempf, J., Quirin-Stricker, C. Neuroreport (1993) [Pubmed]
  16. VIP-sensitive adenylate cyclase, guanylate cyclase, muscarinic receptors, choline acetyltransferase and acetylcholinesterase, in brain tissue afflicted by Alzheimer's disease/senile dementia of the Alzheimer type. Danielsson, E., Eckernäs, S.A., Westlind-Danielsson, A., Nordström, O., Bartfai, T., Gottfries, C.G., Wallin, A. Neurobiol. Aging (1988) [Pubmed]
  17. Overexpression of the high affinity choline transporter in cortical regions affected by Alzheimer's disease. Evidence from rapid autopsy studies. Slotkin, T.A., Nemeroff, C.B., Bissette, G., Seidler, F.J. J. Clin. Invest. (1994) [Pubmed]
  18. Arginine vasopressin and choline acetyltransferase in brains of patients with Alzheimer type senile dementia. Rossor, M.N., Iversen, L.L., Mountjoy, C.Q., Roth, M., Hawthorn, J., Ang, V.Y., Jenkins, J.S. Lancet (1980) [Pubmed]
  19. Circumscribed changes of the cerebral cortex in neuropsychiatric disorders of later life. Bowen, D.M., Najlerahim, A., Procter, A.W., Francis, P.T., Murphy, E. Proc. Natl. Acad. Sci. U.S.A. (1989) [Pubmed]
  20. Cloning of chicken choline acetyltransferase and its expression in early embryonic retina. Mukherjee, R.S., Hausman, R.E. Brain Res. Mol. Brain Res. (2004) [Pubmed]
  21. From the cholinergic gene locus to the cholinergic neuron. Weihe, E., Schäfer, M.K., Schütz, B., Anlauf, M., Depboylu, C., Brett, C., Chen, L., Eiden, L.E. J. Physiol. Paris (1998) [Pubmed]
  22. Choline acetyltransferase: the structure, distribution and pathologic changes in the central nervous system. Oda, Y. Pathol. Int. (1999) [Pubmed]
  23. Identification of a novel nuclear localization signal common to 69- and 82-kDa human choline acetyltransferase. Gill, S.K., Bhattacharya, M., Ferguson, S.S., Rylett, R.J. J. Biol. Chem. (2003) [Pubmed]
  24. The neurochemical coding and projections of circular muscle motor neurons in the human colon. Porter, A.J., Wattchow, D.A., Brookes, S.J., Costa, M. Gastroenterology (1997) [Pubmed]
  25. Comparative study of gene expression of cholinergic system-related molecules in the human spinal cord and term placenta. Oda, Y., Muroishi, Y., Misawa, H., Suzuki, S. Neuroscience (2004) [Pubmed]
  26. Brain vesicular acetylcholine transporter in human users of drugs of abuse. Siegal, D., Erickson, J., Varoqui, H., Ang, L., Kalasinsky, K.S., Peretti, F.J., Aiken, S.S., Wickham, D.J., Kish, S.J. Synapse (2004) [Pubmed]
  27. Quantification of subclasses of human colonic myenteric neurons by immunoreactivity to Hu, choline acetyltransferase and nitric oxide synthase. Murphy, E.M., Defontgalland, D., Costa, M., Brookes, S.J., Wattchow, D.A. Neurogastroenterol. Motil. (2007) [Pubmed]
  28. Expression of multiple mRNA species for choline acetyltransferase in human T-lymphocytes. Ogawa, H., Fujii, T., Watanabe, Y., Kawashima, K. Life Sci. (2003) [Pubmed]
  29. Changes in chemical coding of myenteric neurones in ulcerative colitis. Neunlist, M., Aubert, P., Toquet, C., Oreshkova, T., Barouk, J., Lehur, P.A., Schemann, M., Galmiche, J.P. Gut (2003) [Pubmed]
  30. Galanin receptor binding sites in the temporal and occipital cortex are minimally affected in Alzheimer's disease. Ikeda, M., Dewar, D., McCulloch, J. Neurosci. Lett. (1995) [Pubmed]
  31. Calbindin D-28k and choline acetyltransferase are expressed by different neuronal populations in pedunculopontine nucleus but not in nucleus basalis in squirrel monkeys. Côté, P.Y., Parent, A. Brain Res. (1992) [Pubmed]
  32. Pituitary adenylyl cyclase-activating polypeptide (PACAP) and its receptor (PAC1-R) are positioned to modulate afferent signaling in the cochlea. Drescher, M.J., Drescher, D.G., Khan, K.M., Hatfield, J.S., Ramakrishnan, N.A., Abu-Hamdan, M.D., Lemonnier, L.A. Neuroscience (2006) [Pubmed]
  33. Nerve growth factor receptor immunoreactivity within the nucleus basalis (Ch4) in Parkinson's disease: reduced cell numbers and co-localization with cholinergic neurons. Mufson, E.J., Presley, L.N., Kordower, J.H. Brain Res. (1991) [Pubmed]
  34. More than one way to toy with ChAT and VAChT. Castell, X., Diebler, M.F., Tomasi, M., Bigari, C., De Gois, S., Berrard, S., Mallet, J., Israël, M., Dolezal, V. J. Physiol. Paris (2002) [Pubmed]
  35. Regulation of tyrosine hydroxylase gene expression in IMR-32 neuroblastoma cells by basic fibroblast growth factor and ciliary neurotrophic factor. Rabinovsky, E.D., Ramchatesingh, J., McManaman, J.L. J. Neurochem. (1995) [Pubmed]
  36. Polysialic acid limits choline acetyltransferase activity induced by brain-derived neurotrophic factor. Burgess, A., Aubert, I. J. Neurochem. (2006) [Pubmed]
  37. Activation of the MAP kinase cascade by histone deacetylase inhibitors is required for the stimulation of choline acetyltransferase gene promoter. Espinos, E., Weber, M.J. Brain Res. Mol. Brain Res. (1998) [Pubmed]
  38. Long-term cultivation of cryopreserved human fetal brain cells in a chemically defined medium. Haselbacher, G., Groscurth, P., Otten, U., Vedder, H., Lutz, U., Sonderegger, P., Bulatko, A., Greeff, N., Humbel, R. J. Neurosci. Methods (1989) [Pubmed]
  39. Correlation of vasoactive intestinal peptide and nitric oxide synthase with choline acetyltransferase in the airway innervation. Fischer, A., Canning, B.J., Kummer, W. Ann. N. Y. Acad. Sci. (1996) [Pubmed]
  40. Identification of a single nucleotide polymorphism in the choline acetyltransferase gene associated with Alzheimer's disease. Mubumbila, V., Sutter, A., Ptok, U., Heun, R., Quirin-Stricker, C. Neurosci. Lett. (2002) [Pubmed]
  41. Hypothalamic proopiomelanocortin (POMC) neurons have a cholinergic phenotype. Meister, B., G??m????, B., Suarez, E., Ishii, Y., D??rr, K., Gillberg, L. Eur. J. Neurosci. (2006) [Pubmed]
  42. The cholinergic gene locus. Eiden, L.E. J. Neurochem. (1998) [Pubmed]
  43. Localization of a 900-bp-long fragment of the human choline acetyltransferase gene to 10q11.2 by nonradioactive in situ hybridization. Viegas-Péquignot, E., Berrard, S., Brice, A., Apiou, F., Mallet, J. Genomics (1991) [Pubmed]
  44. Isolation and sub-chromosomal localization of a DNA fragment of the human choline acetyltransferase gene. Cervini, R., Rocchi, M., DiDonato, S., Finocchiaro, G. Neurosci. Lett. (1991) [Pubmed]
  45. Two mRNAs are transcribed from the human gene for choline acetyltransferase. Lorenzi, M.V., Trinidad, A.C., Zhang, R., Strauss, W.L. DNA Cell Biol. (1992) [Pubmed]
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