GAD1

From Wikipedia, the free encyclopedia

Glutamate decarboxylase 1 (brain, 67kDa)

PDB rendering based on 2okj.

Available structures: 2okj

Identifiers

Symbol(s)

GAD1; FLJ45882; GAD; SCP

External IDs

OMIM: 605363 MGI: 95632 HomoloGene: 635

EC number

4.1.1.15

Gene ontology
Molecular Function:	• glutamate decarboxylase activity • protein binding • lyase activity
Cellular Component:	• intracellular • cytoplasm • mitochondrion • vesicle membrane • axon • synapse
Biological Process:	• glutamate decarboxylation to succinate • synaptic transmission • protein-pyridoxal-5-phosphate linkage • carboxylic acid metabolic process • neurotransmitter biosynthetic process

RNA expression pattern

More reference expression data

Orthologs

Human

Mouse

Refseq

NM_000817 (mRNA)
NP_000808 (protein)

NM_008077 (mRNA)
NP_032103 (protein)

Location

Chr 2: 171.38 - 171.43 Mb

Chr 2: 70.36 - 70.4 Mb

Pubmed search

[1]

[2]

Glutamate decarboxylase 1 (brain, 67kDa), also known as GAD1, is a human gene.^[1]

This gene encodes one of several forms of glutamic acid decarboxylase, identified as a major autoantigen in insulin-dependent diabetes. The enzyme encoded is responsible for catalyzing the production of gamma-aminobutyric acid from L-glutamic acid. A pathogenic role for this enzyme has been identified in the human pancreas since it has been identified as an autoantigen and an autoreactive T cell target in insulin-dependent diabetes. This gene may also play a role in the stiff man syndrome. Deficiency in this enzyme has been shown to lead to pyridoxine dependency with seizures. Alternative splicing of this gene results in two products, the predominant 67-kD form and a less-frequent 25-kD form.^[1]

[edit] See also

Glutamate decarboxylase

[edit] References

^ ^a ^b Entrez Gene: GAD1 glutamate decarboxylase 1 (brain, 67kDa).

[edit] Further reading

Kelly CD, Edwards Y, Johnstone AP, et al. (1992). "Nucleotide sequence and chromosomal assignment of a cDNA encoding the large isoform of human glutamate decarboxylase.". Ann. Hum. Genet. 56 (Pt 3): 255–65. PMID 1339255.
Bu DF, Erlander MG, Hitz BC, et al. (1992). "Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene.". Proc. Natl. Acad. Sci. U.S.A. 89 (6): 2115–9. PMID 1549570.
Giorda R, Peakman M, Tan KC, et al. (1991). "Glutamic acid decarboxylase expression in islets and brain.". Lancet 338 (8780): 1469–70. PMID 1683463.
Persson H, Pelto-Huikko M, Metsis M, et al. (1990). "Expression of the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase in male germ cells.". Mol. Cell. Biol. 10 (9): 4701–11. PMID 1697032.
Cram DS, Barnett LD, Joseph JL, Harrison LC (1991). "Cloning and partial nucleotide sequence of human glutamic acid decarboxylase cDNA from brain and pancreatic islets.". Biochem. Biophys. Res. Commun. 176 (3): 1239–44. PMID 2039509.
Dirkx R, Thomas A, Li L, et al. (1995). "Targeting of the 67-kDa isoform of glutamic acid decarboxylase to intracellular organelles is mediated by its interaction with the NH2-terminal region of the 65-kDa isoform of glutamic acid decarboxylase.". J. Biol. Chem. 270 (5): 2241–6. PMID 7836456.
Bu DF, Tobin AJ (1994). "The exon-intron organization of the genes (GAD1 and GAD2) encoding two human glutamate decarboxylases (GAD67 and GAD65) suggests that they derive from a common ancestral GAD.". Genomics 21 (1): 222–8. doi:10.1006/geno.1994.1246. PMID 8088791.
Yamashita K, Cram DS, Harrison LC (1993). "Molecular cloning of full-length glutamic acid decarboxylase 67 from human pancreas and islets.". Biochem. Biophys. Res. Commun. 192 (3): 1347–52. doi:10.1006/bbrc.1993.1564. PMID 8507202.
Kawasaki E, Moriuchi R, Watanabe M, et al. (1993). "Cloning and expression of large isoform of glutamic acid decarboxylase from human pancreatic islet.". Biochem. Biophys. Res. Commun. 192 (3): 1353–9. PMID 8507203.
Asada H, Kawamura Y, Maruyama K, et al. (1997). "Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65) maintain normal levels of GAD67 and GABA in their brains but are susceptible to seizures.". Biochem. Biophys. Res. Commun. 229 (3): 891–5. PMID 8954991.
McHale DP, Mitchell S, Bundey S, et al. (1999). "A gene for autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25.". Am. J. Hum. Genet. 64 (2): 526–32. PMID 9973289.
Chessler SD, Lernmark A (2000). "Alternative splicing of GAD67 results in the synthesis of a third form of glutamic-acid decarboxylase in human islets and other non-neural tissues.". J. Biol. Chem. 275 (7): 5188–92. PMID 10671565.
Luo J, Kaplitt MG, Fitzsimons HL, et al. (2002). "Subthalamic GAD gene therapy in a Parkinson's disease rat model.". Science 298 (5592): 425–9. doi:10.1126/science.1074549. PMID 12376704.
Strausberg RL, Feingold EA, Grouse LH, et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences.". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.
Chessler SD, Hampe CS, Ortqvist E, et al. (2003). "Immune reactivity to GAD25 in type 1 diabetes mellitus.". Autoimmunity 35 (5): 335–41. PMID 12515288.
Demakova EV, Korobov VP, Lemkina LM (2003). "[Determination of gamma-aminobutyric acid concentration and activity of glutamate decarboxylase in blood serum of patients with multiple sclerosis]". Klin. Lab. Diagn. (4): 15–7. PMID 12774663.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs.". Nat. Genet. 36 (1): 40–5. doi:10.1038/ng1285. PMID 14702039.
Flace P, Benagiano V, Lorusso L, et al. (2004). "Glutamic acid decarboxylase immunoreactive large neuron types in the granular layer of the human cerebellar cortex.". Anat. Embryol. 208 (1): 55–64. doi:10.1007/s00429-003-0374-x. PMID 15014985.
De Luca V, Muglia P, Masellis M, et al. (2004). "Polymorphisms in glutamate decarboxylase genes: analysis in schizophrenia.". Psychiatr. Genet. 14 (1): 39–42. PMID 15091314.
Kanno K, Suzuki Y, Yamada A, et al. (2004). "Association between nonsyndromic cleft lip with or without cleft palate and the glutamic acid decarboxylase 67 gene in the Japanese population.". Am. J. Med. Genet. A 127 (1): 11–6. doi:10.1002/ajmg.a.20649. PMID 15103710.