Glutamate decarboxylase 1

NameGlutamate decarboxylase 1
Synonyms
  • 4.1.1.15
  • 67 kDa glutamic acid decarboxylase
  • GAD
  • GAD-67
  • GAD67
  • Glutamate decarboxylase 67 kDa isoform
Gene NameGAD1
OrganismHuman
Amino acid sequence
>lcl|BSEQ0000753|Glutamate decarboxylase 1
MASSTPSSSATSSNAGADPNTTNLRPTTYDTWCGVAHGCTRKLGLKICGFLQRTNSLEEK
SRLVSAFKERQSSKNLLSCENSDRDARFRRTETDFSNLFARDLLPAKNGEEQTVQFLLEV
VDILLNYVRKTFDRSTKVLDFHHPHQLLEGMEGFNLELSDHPESLEQILVDCRDTLKYGV
RTGHPRFFNQLSTGLDIIGLAGEWLTSTANTNMFTYEIAPVFVLMEQITLKKMREIVGWS
SKDGDGIFSPGGAISNMYSIMAARYKYFPEVKTKGMAAVPKLVLFTSEQSHYSIKKAGAA
LGFGTDNVILIKCNERGKIIPADFEAKILEAKQKGYVPFYVNATAGTTVYGAFDPIQEIA
DICEKYNLWLHVDAAWGGGLLMSRKHRHKLNGIERANSVTWNPHKMMGVLLQCSAILVKE
KGILQGCNQMCAGYLFQPDKQYDVSYDTGDKAIQCGRHVDIFKFWLMWKAKGTVGFENQI
NKCLELAEYLYAKIKNREEFEMVFNGEPEHTNVCFWYIPQSLRGVPDSPQRREKLHKVAP
KIKALMMESGTTMVGYQPQGDKANFFRMVISNPAATQSDIDFLIEEIERLGQDL
Number of residues594
Molecular Weight66896.065
Theoretical pI7.67
GO Classification
Functions
  • pyridoxal phosphate binding
  • glutamate decarboxylase activity
Processes
  • synaptic transmission
  • neurotransmitter secretion
  • neurotransmitter biosynthetic process
  • glutamate catabolic process
  • glutamate decarboxylation to succinate
  • protein-pyridoxal-5-phosphate linkage
Components
  • intracellular
  • plasma membrane
  • vesicle membrane
  • clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane
General FunctionPyridoxal phosphate binding
Specific FunctionCatalyzes the production of GABA.
Pfam Domain Function
Transmembrane RegionsNot Available
GenBank Protein ID182936
UniProtKB IDQ99259
UniProtKB Entry NameDCE1_HUMAN
Cellular LocationNot Available
Gene sequence
>lcl|BSEQ0010267|Glutamate decarboxylase 1 (GAD1)
ATGGCGTCTTCGACCCCATCTTCGTCCGCAACCTCCTCGAACGCGGGAGCGGACCCCAAT
ACCACTAACCTGCGCCCCACAACGTACGATACCTGGTGCGGCGTGGCCCATGGATGCACC
AGAAAACTGGGGCTCAAGATCTGCGGCTTCTTGCAAAGGACCAACAGCCTGGAAGAGAAG
AGTCGCCTTGTGAGTGCCTTCAAGGAGAGGCAATCCTCCAAGAACCTGCTTTCCTGTGAA
AACAGCGACCGGGATGCCCGCTTCCGGCGCACAGAGACTGACTTCTCTAATCTGTTTGCT
AGAGATCTGCTTCCGGCTAAGAACGGTGAGGAGCAAACCGTGCAATTCCTCCTGGAAGTG
GTGGACATACTCCTCAACTATGTCCGCAAGACATTTGATCGCTCCACCAAGGTGCTGGAC
TTTCATCACCCACACCAGTTGCTGGAAGGCATGGAGGGCTTCAACTTGGAGCTCTCTGAC
CACCCCGAGTCCCTGGAGCAGATCCTGGTTGACTGCAGAGACACCTTGAAGTATGGGGTT
CGCACAGGTCATCCTCGATTTTTCAACCAGCTCTCCACTGGATTGGATATTATTGGCCTA
GCTGGAGAATGGCTGACATCAACGGCCAATACCAACATGTTTACATATGAAATTGCACCA
GTGTTTGTCCTCATGGAACAAATAACACTTAAGAAGATGAGAGAGATAGTTGGATGGTCA
AGTAAAGATGGTGATGGGATATTTTCTCCTGGGGGCGCCATATCCAACATGTACAGCATC
ATGGCTGCTCGCTACAAGTACTTCCCGGAAGTTAAGACAAAGGGCATGGCGGCTGTGCCT
AAACTGGTCCTCTTCACCTCAGAACAGAGTCACTATTCCATAAAGAAAGCTGGGGCTGCA
CTTGGCTTTGGAACTGACAATGTGATTTTGATAAAGTGCAATGAAAGGGGGAAAATAATT
CCAGCTGATTTTGAGGCAAAAATTCTTGAAGCCAAACAGAAGGGATATGTTCCCTTTTAT
GTCAATGCAACTGCTGGCACGACTGTTTATGGAGCTTTTGATCCGATACAAGAGATTGCA
GATATATGTGAGAAATATAACCTTTGGTTGCATGTCGATGCTGCCTGGGGAGGTGGGCTG
CTCATGTCCAGGAAGCACCGCCATAAACTCAACGGCATAGAAAGGGCCAACTCAGTCACC
TGGAACCCTCACAAGATGATGGGCGTGCTGTTGCAGTGCTCTGCCATTCTCGTCAAGGAA
AAGGGTATACTCCAAGGATGCAACCAGATGTGTGCAGGATACCTCTTCCAGCCAGACAAG
CAGTATGATGTCTCCTACGACACCGGGGACAAGGCAATTCAGTGTGGCCGCCACGTGGAT
ATCTTCAAGTTCTGGCTGATGTGGAAAGCAAAGGGCACAGTGGGATTTGAAAACCAGATC
AACAAATGCCTGGAACTGGCTGAATACCTCTATGCCAAGATTAAAAACAGAGAAGAATTT
GAGATGGTTTTCAATGGCGAGCCTGAGCACACAAACGTCTGTTTTTGGTATATTCCACAA
AGCCTCAGGGGTGTGCCAGACAGCCCTCAACGACGGGAAAAGCTACACAAGGTGGCTCCA
AAAATCAAAGCCCTGATGATGGAGTCAGGTACGACCATGGTTGGCTACCAGCCCCAAGGG
GACAAGGCCAACTTCTTCCGGATGGTCATCTCCAACCCAGCCGCTACCCAGTCTGACATT
GACTTCCTCATTGAGGAGATAGAAAGACTGGGCCAGGATCTGTAA
GenBank Gene IDM81883
GeneCard IDNot Available
GenAtlas IDGAD1
HGNC IDHGNC:4092
Chromosome Location2
Locus2q31
References
  1. Bu DF, Erlander MG, Hitz BC, Tillakaratne NJ, Kaufman DL, Wagner-McPherson CB, Evans GA, Tobin AJ: 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. 1992 Mar 15;89(6):2115-9. 1549570
  2. Bu DF, Tobin AJ: 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. 1994 May 1;21(1):222-8. 8088791
  3. Kelly C, Carter ND, Johnstone AP, Nussey SS: Cloning of large isoform of human brain glutamic acid decarboxylase. Lancet. 1991 Dec 7;338(8780):1468-9. 1683462
  4. Kelly CD, Edwards Y, Johnstone AP, Harfst E, Nogradi A, Nussey SS, Povey S, Carter ND: Nucleotide sequence and chromosomal assignment of a cDNA encoding the large isoform of human glutamate decarboxylase. Ann Hum Genet. 1992 Jul;56(Pt 3):255-65. 1339255
  5. Yamashita K, Cram DS, Harrison LC: Molecular cloning of full-length glutamic acid decarboxylase 67 from human pancreas and islets. Biochem Biophys Res Commun. 1993 May 14;192(3):1347-52. 8507202
  6. Kawasaki E, Moriuchi R, Watanabe M, Saitoh K, Brunicardi FC, Watt PC, Yamaguchi T, Mullen Y, Akazawa S, Miyamoto T, et al.: Cloning and expression of large isoform of glutamic acid decarboxylase from human pancreatic islet. Biochem Biophys Res Commun. 1993 May 14;192(3):1353-9. 8507203
  7. Chessler SD, Lernmark A: 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. 2000 Feb 18;275(7):5188-92. 10671565
  8. Hillier LW, Graves TA, Fulton RS, Fulton LA, Pepin KH, Minx P, Wagner-McPherson C, Layman D, Wylie K, Sekhon M, Becker MC, Fewell GA, Delehaunty KD, Miner TL, Nash WE, Kremitzki C, Oddy L, Du H, Sun H, Bradshaw-Cordum H, Ali J, Carter J, Cordes M, Harris A, Isak A, van Brunt A, Nguyen C, Du F, Courtney L, Kalicki J, Ozersky P, Abbott S, Armstrong J, Belter EA, Caruso L, Cedroni M, Cotton M, Davidson T, Desai A, Elliott G, Erb T, Fronick C, Gaige T, Haakenson W, Haglund K, Holmes A, Harkins R, Kim K, Kruchowski SS, Strong CM, Grewal N, Goyea E, Hou S, Levy A, Martinka S, Mead K, McLellan MD, Meyer R, Randall-Maher J, Tomlinson C, Dauphin-Kohlberg S, Kozlowicz-Reilly A, Shah N, Swearengen-Shahid S, Snider J, Strong JT, Thompson J, Yoakum M, Leonard S, Pearman C, Trani L, Radionenko M, Waligorski JE, Wang C, Rock SM, Tin-Wollam AM, Maupin R, Latreille P, Wendl MC, Yang SP, Pohl C, Wallis JW, Spieth J, Bieri TA, Berkowicz N, Nelson JO, Osborne J, Ding L, Meyer R, Sabo A, Shotland Y, Sinha P, Wohldmann PE, Cook LL, Hickenbotham MT, Eldred J, Williams D, Jones TA, She X, Ciccarelli FD, Izaurralde E, Taylor J, Schmutz J, Myers RM, Cox DR, Huang X, McPherson JD, Mardis ER, Clifton SW, Warren WC, Chinwalla AT, Eddy SR, Marra MA, Ovcharenko I, Furey TS, Miller W, Eichler EE, Bork P, Suyama M, Torrents D, Waterston RH, Wilson RK: Generation and annotation of the DNA sequences of human chromosomes 2 and 4. Nature. 2005 Apr 7;434(7034):724-31. 15815621
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  10. Cram DS, Barnett LD, Joseph JL, Harrison LC: Cloning and partial nucleotide sequence of human glutamic acid decarboxylase cDNA from brain and pancreatic islets. Biochem Biophys Res Commun. 1991 May 15;176(3):1239-44. 2039509
  11. Persson H, Pelto-Huikko M, Metsis M, Soder O, Brene S, Skog S, Hokfelt T, Ritzen EM: Expression of the neurotransmitter-synthesizing enzyme glutamic acid decarboxylase in male germ cells. Mol Cell Biol. 1990 Sep;10(9):4701-11. 1697032
  12. Fenalti G, Law RH, Buckle AM, Langendorf C, Tuck K, Rosado CJ, Faux NG, Mahmood K, Hampe CS, Banga JP, Wilce M, Schmidberger J, Rossjohn J, El-Kabbani O, Pike RN, Smith AI, Mackay IR, Rowley MJ, Whisstock JC: GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop. Nat Struct Mol Biol. 2007 Apr;14(4):280-6. Epub 2007 Mar 25. 17384644
  13. Lynex CN, Carr IM, Leek JP, Achuthan R, Mitchell S, Maher ER, Woods CG, Bonthon DT, Markham AF: 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. 2004 Nov 30;4(1):20. 15571623