Glutamate Decarboxylase 1, Brain (GAD1)

GAD67; SCP; 67 kDa glutamic acid decarboxylase; Glutamate decarboxylase 67 kDa isoform

SPN	T953
HGNC	4092
MGI	95632
PubMed	15604684
RGD	2652
UniProt	Q99259
Wiki	GAD1

Glutamate decarboxylase 1 (brain, 67kDa) is 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.

Reference

"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. 89:2115-2119(1992) [PubMed] [Europe PMC] [Abstract]

"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 21:222-228(1994) [PubMed] [Europe PMC] [Abstract]

"Cloning of large isoform of human brain glutamic acid decarboxylase."
Lancet 338:1468-1469(1991) [PubMed] [Europe PMC] [Abstract]

"Nucleotide sequence and chromosomal assignment of a cDNA encoding the large isoform of human glutamate decarboxylase."
Ann. Hum. Genet. 56:255-265(1992) [PubMed] [Europe PMC] [Abstract]

"Molecular cloning of full-length glutamic acid decarboxylase 67 from human pancreas and islets."
Biochem. Biophys. Res. Commun. 192:1347-1352(1993) [PubMed] [Europe PMC] [Abstract]

"Cloning and expression of large isoform of glutamic acid decarboxylase from human pancreatic islet."
Biochem. Biophys. Res. Commun. 192:1353-1359(1993) [PubMed] [Europe PMC] [Abstract]

"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. 275:5188-5192(2000) [PubMed] [Europe PMC] [Abstract]

"Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]

"The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]

"Cloning and partial nucleotide sequence of human glutamic acid decarboxylase cDNA from brain and pancreatic islets."
Biochem. Biophys. Res. Commun. 176:1239-1244(1991) [PubMed] [Europe PMC] [Abstract]

"Expression of the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase in male germ cells."
Mol. Cell. Biol. 10:4701-4711(1990) [PubMed] [Europe PMC] [Abstract]

"GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop."
Nat. Struct. Mol. Biol. 14:280-286(2007) [PubMed] [Europe PMC] [Abstract]

"Homozygosity for a missense mutation in the 67 kDa isoform of glutamate decarboxylase in a family with autosomal recessive spastic cerebral palsy: parallels with Stiff-Person Syndrome and other movement disorders."
BMC Neurol. 4:20-20(2004) [PubMed] [Europe PMC] [Abstract]