GAD1

Protein-coding gene in the species Homo sapiens

GAD1

Available structures

PDB

Ortholog search: PDBe RCSB

List of PDB id codes
2OKJ, 3VP6

Identifiers

Aliases

GAD1, CPSQ1, GAD, SCP, glutamate decarboxylase 1, DEE89

External IDs

OMIM: 605363 MGI: 95632 HomoloGene: 635 GeneCards: GAD1

Gene location (Human)

Chr.	Chromosome 2 (human)^[1]

Band	2q31.1	Start	170,813,213 bp^[1]
Band	2q31.1	End	170,861,151 bp^[1]

Gene location (Mouse)

Chr.	Chromosome 2 (mouse)^[2]

Band	2 C2\|2 41.63 cM	Start	70,383,416 bp^[2]
Band	2 C2\|2 41.63 cM	End	70,432,358 bp^[2]

RNA expression pattern

Bgee

Human

Mouse (ortholog)

Top expressed in

endothelial cell

middle temporal gyrus

Brodmann area 23

Brodmann area 10

external globus pallidus

frontal pole

orbitofrontal cortex

superior frontal gyrus

Brodmann area 46

secondary oocyte

Top expressed in

globus pallidus

dorsal tegmental nucleus

cerebellar vermis

lateral geniculate nucleus

olfactory tubercle

nucleus accumbens

dorsomedial hypothalamic nucleus

lateral hypothalamus

superior colliculus

medial vestibular nucleus

More reference expression data

BioGPS


More reference expression data

Gene ontology
Molecular function	protein binding catalytic activity lyase activity protein heterodimerization activity pyridoxal phosphate binding carboxy-lyase activity glutamate binding glutamate decarboxylase activity protein N-terminus binding
Cellular component	vesicle membrane plasma membrane clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane intracellular anatomical structure presynaptic active zone cytoplasm cell cortex axon axon terminus neuron projection terminus synapse inhibitory synapse
Biological process	gamma-aminobutyric acid biosynthetic process glutamate catabolic process carboxylic acid metabolic process neurotransmitter biosynthetic process protein-pyridoxal-5-phosphate linkage glutamate decarboxylation to succinate chemical synaptic transmission social behavior locomotory exploration behavior neurotransmitter secretion
Sources:Amigo / QuickGO

Orthologs

Species

Human

Mouse

Entrez


2571


14415

Ensembl


ENSG00000128683


ENSMUSG00000070880

UniProt


Q99259


P48318

RefSeq (mRNA)


NM_000817 NM_013445


NM_008077 NM_001312900

RefSeq (protein)


NP_000808 NP_038473


NP_001299829 NP_032103

Location (UCSC)

Chr 2: 170.81 – 170.86 Mb

Chr 2: 70.38 – 70.43 Mb

PubMed search

^[3]

^[4]

Wikidata

View/Edit Human

View/Edit Mouse

Glutamate decarboxylase 1 (brain, 67kDa) (GAD67), also known as GAD1, is a human gene.^[5]

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.^[5]

Interactions

GAD1 has been shown to interact with GAD2.^[6]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000128683 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000070880 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ ^a ^b "Entrez Gene: GAD1 glutamate decarboxylase 1 (brain, 67kDa)".
^ Dirkx R, Thomas A, Li L, Lernmark A, Sherwin RS, De Camilli P, Solimena M (February 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. doi:10.1074/jbc.270.5.2241. PMID 7836456.

Kelly CD, Edwards Y, Johnstone AP, Harfst E, Nógrádi A, Nussey SS, Povey S, Carter ND (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. doi:10.1111/j.1469-1809.1992.tb01150.x. PMID 1339255. S2CID 35482098.
Bu DF, Erlander MG, Hitz BC, Tillakaratne NJ, Kaufman DL, Wagner-McPherson CB, Evans GA, Tobin AJ (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. Bibcode:1992PNAS...89.2115B. doi:10.1073/pnas.89.6.2115. PMC 48607. PMID 1549570.
Giorda R, Peakman M, Tan KC, Vergani D, Trucco M (1991). "Glutamic acid decarboxylase expression in islets and brain". Lancet. 338 (8780): 1469–70. doi:10.1016/0140-6736(91)92781-V. PMID 1683463. S2CID 32944832.
Persson H, Pelto-Huikko M, Metsis M, Söder O, Brene S, Skog S, Hökfelt T, Ritzén EM (1990). "Expression of the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase in male germ cells". Mol. Cell. Biol. 10 (9): 4701–11. doi:10.1128/mcb.10.9.4701. PMC 361065. 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. doi:10.1016/0006-291X(91)90418-7. PMID 2039509.
Dirkx R, Thomas A, Li L, Lernmark A, Sherwin RS, De Camilli P, Solimena M (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. doi:10.1074/jbc.270.5.2241. 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, Saitoh K, Brunicardi FC, Watt PC, Yamaguchi T, Mullen Y, Akazawa S, Miyamoto T (1993). "Cloning and expression of large isoform of glutamic acid decarboxylase from human pancreatic islet". Biochem. Biophys. Res. Commun. 192 (3): 1353–9. doi:10.1006/bbrc.1993.1565. PMID 8507203.
Asada H, Kawamura Y, Maruyama K, Kume H, Ding R, Ji FY, Kanbara N, Kuzume H, Sanbo M, Yagi T, Obata K (1996). "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. doi:10.1006/bbrc.1996.1898. PMID 8954991.
McHale DP, Mitchell S, Bundey S, Moynihan L, Campbell DA, Woods CG, Lench NJ, Mueller RF, Markham AF (1999). "A gene for autosomal recessive symmetrical spastic cerebral palsy maps to chromosome 2q24-25". Am. J. Hum. Genet. 64 (2): 526–32. doi:10.1086/302237. PMC 1377761. 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. doi:10.1074/jbc.275.7.5188. PMID 10671565.
Luo J, Kaplitt MG, Fitzsimons HL, Zuzga DS, Liu Y, Oshinsky ML, During MJ (2002). "Subthalamic GAD gene therapy in a Parkinson's disease rat model". Science. 298 (5592): 425–9. doi:10.1126/science.1074549. PMID 12376704. S2CID 11538987.
Chessler SD, Hampe CS, Ortqvist E, Simonson WT, Bekris L (2002). "Immune reactivity to GAD25 in type 1 diabetes mellitus". Autoimmunity. 35 (5): 335–41. doi:10.1080/0891693021000005402. PMID 12515288. S2CID 29584474.
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.
Flace P, Benagiano V, Lorusso L, Girolamo F, Rizzi A, Virgintino D, Roncali L, Ambrosi G (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. S2CID 12464664.
De Luca V, Muglia P, Masellis M, Jane Dalton E, Wong GW, Kennedy JL (2004). "Polymorphisms in glutamate decarboxylase genes: analysis in schizophrenia". Psychiatr. Genet. 14 (1): 39–42. doi:10.1097/00041444-200403000-00006. PMID 15091314. S2CID 40410463.
Kanno K, Suzuki Y, Yamada A, Aoki Y, Kure S, Matsubara Y (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. 127A (1): 11–6. doi:10.1002/ajmg.a.20649. PMID 15103710. S2CID 30016360.