GAD1

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)
End	170,861,151 bp
Gene location (Mouse)
Chr.	Chromosome 2 (mouse)
End	70,432,358 bp
RNA expression pattern
	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
	; ; ; ;
	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
	2571
	14415
	ENSG00000128683
	ENSMUSG00000070880
	Q99259
	P48318
	NM_000817 ; NM_013445
	NM_008077 ; NM_001312900
	NP_000808 ; NP_038473
	NP_001299829 ; NP_032103
	Wikidata
View/Edit Human	View/Edit Mouse

Last updated December 16, 2023

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]

Related Research Articles

Glutamate decarboxylase or glutamic acid decarboxylase (GAD) is an enzyme that catalyzes the decarboxylation of glutamate to gamma-aminobutyric acid (GABA) and carbon dioxide. GAD uses pyridoxal-phosphate (PLP) as a cofactor. The reaction proceeds as follows:

The activin A receptor also known as ACVR1C or ALK-7 is a protein that in humans is encoded by the ACVR1C gene. ACVR1C is a type I receptor for the TGFB family of signaling molecules.

Glycine decarboxylase also known as glycine cleavage system P protein or glycine dehydrogenase is an enzyme that in humans is encoded by the GLDC gene.

Nuclear respiratory factor 1, also known as Nrf1, Nrf-1, NRF1 and NRF-1, encodes a protein that homodimerizes and functions as a transcription factor which activates the expression of some key metabolic genes regulating cellular growth and nuclear genes required for respiration, heme biosynthesis, and mitochondrial DNA transcription and replication. The protein has also been associated with the regulation of neurite outgrowth. Alternate transcriptional splice variants, which encode the same protein, have been characterized. Additional variants encoding different protein isoforms have been described but they have not been fully characterized. Confusion has occurred in bibliographic databases due to the shared symbol of NRF1 for this gene and for "nuclear factor -like 1" which has an official symbol of NFE2L1.

Serine/threonine-protein kinase N1 is an enzyme that in humans is encoded by the PKN1 gene.

Actin-like protein 6A is a protein that in humans is encoded by the ACTL6A gene.

Ran-binding protein 9 is a protein that in humans is encoded by the RANBP9 gene.

Lipoamide acyltransferase component of branched-chain alpha-keto acid dehydrogenase complex, mitochondrial is an enzyme that in humans is encoded by the DBT gene.

Islet cell autoantigen 1 is a protein that in humans is encoded by the ICA1 gene.

FAS-associated factor 1 is a protein that in humans is encoded by the FAF1 gene.

Elongation factor 1-alpha 2 is a protein that in humans is encoded by the EEF1A2 gene.

ATP-binding cassette sub-family D member 3 is a protein that in humans is encoded by the ABCD3 gene.

Ornithine decarboxylase antizyme is an enzyme that in humans is encoded by the OAZ1 gene.

Ubiquitin/ISG15-conjugating enzyme E2 L6 is a protein that in humans is encoded by the UBE2L6 gene.

FK506-binding protein 3 also known as FKBP25 is a protein that in humans is encoded by the FKBP3 gene.

Amyloid beta A4 precursor protein-binding family B member 3 is a protein that in humans is encoded by the APBB3 gene.

Antizyme inhibitor 1 is a protein that in humans is encoded by the AZIN1 gene.

Sodium-dependent phosphate transport protein 1 is a protein that in humans is encoded by the SLC17A1 gene.

Glutamate decarboxylase 2 is an enzyme that in humans is encoded by the GAD2 gene.

Sodium-dependent neutral amino acid transporter B(0)AT1 is a protein that in humans is encoded by the SLC6A19 gene.

References

1 2 3 GRCh38: Ensembl release 89: ENSG00000128683 - Ensembl, May 2017
1 2 3 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.
1 2 "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.

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[refGRCh38Ensembl-1] 1 2 3 GRCh38: Ensembl release 89: ENSG00000128683 - Ensembl, May 2017

[refGRCm38Ensembl-2] 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000070880 - Ensembl, May 2017

[3] "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.

[entrez-5] 1 2 "Entrez Gene: GAD1 glutamate decarboxylase 1 (brain, 67kDa)".

[pmid7836456-6] 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.

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GAD1

Contents

Interactions

See also

Related Research Articles

References

Further reading