ID DCE1_HUMAN Reviewed; 594 AA. AC Q99259; Q49AK1; Q53TQ7; Q9BU91; Q9UHH4; DT 01-FEB-1996, integrated into UniProtKB/Swiss-Prot. DT 01-FEB-1996, sequence version 1. DT 27-MAR-2024, entry version 213. DE RecName: Full=Glutamate decarboxylase 1; DE EC=4.1.1.15 {ECO:0000269|PubMed:10671565, ECO:0000269|PubMed:17384644}; DE AltName: Full=67 kDa glutamic acid decarboxylase; DE Short=GAD-67; DE AltName: Full=Glutamate decarboxylase 67 kDa isoform; GN Name=GAD1 {ECO:0000312|HGNC:HGNC:4092}; Synonyms=GAD, GAD67; OS Homo sapiens (Human). OC Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; OC Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; OC Homo. OX NCBI_TaxID=9606; RN [1] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=1549570; DOI=10.1073/pnas.89.6.2115; RA Bu D.-F., Erlander M.G., Hitz B.C., Tillakaratne N.J., Kaufman D.L., RA Wagner-Mcpherson C.B., Evans G.A., Tobin A.J.; RT "Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each RT encoded by a single gene."; RL Proc. Natl. Acad. Sci. U.S.A. 89:2115-2119(1992). RN [2] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8088791; DOI=10.1006/geno.1994.1246; RA Bu D.-F., Tobin A.J.; RT "The exon-intron organization of the genes (GAD1 and GAD2) encoding two RT human glutamate decarboxylases (GAD67 and GAD65) suggests that they derive RT from a common ancestral GAD."; RL Genomics 21:222-228(1994). RN [3] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=1683462; DOI=10.1016/0140-6736(91)92780-6; RA Kelly C.D., Carter N.D., Johnstone A.P., Nussey S.S.; RT "Cloning of large isoform of human brain glutamic acid decarboxylase."; RL Lancet 338:1468-1469(1991). RN [4] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Brain; RX PubMed=1339255; DOI=10.1111/j.1469-1809.1992.tb01150.x; RA Kelly C.D., Edwards Y., Johnstone A.P., Harfst E., Nogradi A., Nussey S.S., RA Povey S., Carter N.D.; RT "Nucleotide sequence and chromosomal assignment of a cDNA encoding the RT large isoform of human glutamate decarboxylase."; RL Ann. Hum. Genet. 56:255-265(1992). RN [5] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RX PubMed=8507202; DOI=10.1006/bbrc.1993.1564; RA Yamashita K., Cram D.S., Harrison L.C.; RT "Molecular cloning of full-length glutamic acid decarboxylase 67 from human RT pancreas and islets."; RL Biochem. Biophys. Res. Commun. 192:1347-1352(1993). RN [6] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1). RC TISSUE=Pancreatic islet; RX PubMed=8507203; DOI=10.1006/bbrc.1993.1565; RA Kawasaki E., Moriuchi R., Watanabe M., Saitoh K., Brunicardi F.C., RA Watt P.C., Yamaguchi T., Mullen Y., Akazawa S., Miyamoto T.; RT "Cloning and expression of large isoform of glutamic acid decarboxylase RT from human pancreatic islet."; RL Biochem. Biophys. Res. Commun. 192:1353-1359(1993). RN [7] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA]. RA Giorda R., Peakman M., Vergani D., Trucco M.; RT "Sequence of glutamic acid decarboxylase transcripts in human pancreatic RT islets and brain."; RL Submitted (MAR-1992) to the EMBL/GenBank/DDBJ databases. RN [8] RP NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 3), TISSUE SPECIFICITY (ISOFORM 3), RP CATALYTIC ACTIVITY, AND FUNCTION. RC TISSUE=Pancreatic islet, and Testis; RX PubMed=10671565; DOI=10.1074/jbc.275.7.5188; RA Chessler S.D., Lernmark A.; RT "Alternative splicing of GAD67 results in the synthesis of a third form of RT glutamic-acid decarboxylase in human islets and other non-neural tissues."; RL J. Biol. Chem. 275:5188-5192(2000). RN [9] RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS LEU-228 AND GLN-532. RG NIEHS SNPs program; RL Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases. RN [10] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RX PubMed=15815621; DOI=10.1038/nature03466; RA Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., RA Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., RA Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., RA Du H., Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., RA Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., RA Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., RA Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., RA Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., RA Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., RA McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., RA Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., RA Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., RA Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., RA Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., RA Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., RA Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., RA Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., RA Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., RA Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., RA Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., RA Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., RA Wilson R.K.; RT "Generation and annotation of the DNA sequences of human chromosomes 2 and RT 4."; RL Nature 434:724-731(2005). RN [11] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RA Mural R.J., Istrail S., Sutton G.G., Florea L., Halpern A.L., Mobarry C.M., RA Lippert R., Walenz B., Shatkay H., Dew I., Miller J.R., Flanigan M.J., RA Edwards N.J., Bolanos R., Fasulo D., Halldorsson B.V., Hannenhalli S., RA Turner R., Yooseph S., Lu F., Nusskern D.R., Shue B.C., Zheng X.H., RA Zhong F., Delcher A.L., Huson D.H., Kravitz S.A., Mouchard L., Reinert K., RA Remington K.A., Clark A.G., Waterman M.S., Eichler E.E., Adams M.D., RA Hunkapiller M.W., Myers E.W., Venter J.C.; RL Submitted (JUL-2005) to the EMBL/GenBank/DDBJ databases. RN [12] RP NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORMS 1; 3 AND 4). RC TISSUE=Brain; RX PubMed=15489334; DOI=10.1101/gr.2596504; RG The MGC Project Team; RT "The status, quality, and expansion of the NIH full-length cDNA project: RT the Mammalian Gene Collection (MGC)."; RL Genome Res. 14:2121-2127(2004). RN [13] RP NUCLEOTIDE SEQUENCE [MRNA] OF 218-397. RC TISSUE=Brain; RX PubMed=2039509; DOI=10.1016/0006-291x(91)90418-7; RA Cram D.S., Barnett L.D., Joseph J.L., Harrison L.C.; RT "Cloning and partial nucleotide sequence of human glutamic acid RT decarboxylase cDNA from brain and pancreatic islets."; RL Biochem. Biophys. Res. Commun. 176:1239-1244(1991). RN [14] RP NUCLEOTIDE SEQUENCE [MRNA] OF 527-594. RC TISSUE=Testis; RX PubMed=1697032; DOI=10.1128/mcb.10.9.4701-4711.1990; RA Persson H., Pelto-Huikko M., Metsis M., Soeder O., Brene S., Skog S., RA Hoekfelt T., Ritzen E.M.; RT "Expression of the neurotransmitter-synthesizing enzyme glutamic acid RT decarboxylase in male germ cells."; RL Mol. Cell. Biol. 10:4701-4711(1990). RN [15] RP INVOLVEMENT IN DEE89, VARIANTS DEE89 LYS-232 DEL; LYS-509 AND RP 531-ARG--LEU-594 DEL, AND CHARACTERIZATION OF VARIANT DEE89 LYS-232 DEL. RX PubMed=32282878; DOI=10.1093/brain/awaa085; RG EuroEpinomics-RES consortium AR working group; RA Chatron N., Becker F., Morsy H., Schmidts M., Hardies K., Tuysuz B., RA Roselli S., Najafi M., Alkaya D.U., Ashrafzadeh F., Nabil A., Omar T., RA Maroofian R., Karimiani E.G., Hussien H., Kok F., Ramos L., Gunes N., RA Bilguvar K., Labalme A., Alix E., Sanlaville D., de Bellesciz e J., RA Poulat A.L., Moslemi A.R., Lerche H., May P., Lesca G., Weckhuysen S., RA Tajsharghi H.; RT "Bi-allelic GAD1 variants cause a neonatal onset syndromic developmental RT and epileptic encephalopathy."; RL Brain 143:1447-1461(2020). RN [16] RP X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 93-594 IN COMPLEX WITH SUBSTRATE RP ANALOG, SUBUNIT, COFACTOR, CATALYTIC ACTIVITY, AND FUNCTION. RX PubMed=17384644; DOI=10.1038/nsmb1228; RA Fenalti G., Law R.H.P., Buckle A.M., Langendorf C., Tuck K., Rosado C.J., RA Faux N.G., Mahmood K., Hampe C.S., Banga J.P., Wilce M., Schmidberger J., RA Rossjohn J., El-Kabbani O., Pike R.N., Smith A.I., Mackay I.R., RA Rowley M.J., Whisstock J.C.; RT "GABA production by glutamic acid decarboxylase is regulated by a dynamic RT catalytic loop."; RL Nat. Struct. Mol. Biol. 14:280-286(2007). RN [17] {ECO:0007744|PDB:3VP6} RP X-RAY CRYSTALLOGRAPHY (2.10 ANGSTROMS) OF 90-594. RX PubMed=23126365; DOI=10.1042/bsr20120111; RA Langendorf C.G., Tuck K.L., Key T.L., Fenalti G., Pike R.N., Rosado C.J., RA Wong A.S., Buckle A.M., Law R.H., Whisstock J.C.; RT "Structural characterization of the mechanism through which human glutamic RT acid decarboxylase auto-activates."; RL Biosci. Rep. 33:137-144(2013). RN [18] RP VARIANT CYS-12. RX PubMed=15571623; DOI=10.1186/1471-2377-4-20; RA Lynex C.N., Carr I.M., Leek J.P., Achuthan R., Mitchell S., Maher E.R., RA Woods C.G., Bonthon D.T., Markham A.F.; RT "Homozygosity for a missense mutation in the 67 kDa isoform of glutamate RT decarboxylase in a family with autosomal recessive spastic cerebral palsy: RT parallels with Stiff-Person Syndrome and other movement disorders."; RL BMC Neurol. 4:20-20(2004). RN [19] RP VARIANT CYS-12. RX PubMed=33634263; DOI=10.1093/braincomms/fcab002; RA Morgan N.V., Yngvadottir B., O'Driscoll M., Clark G.R., Walsh D., RA Martin E., Tee L., Reid E., Titheradge H.L., Maher E.R.; RT "Evidence that autosomal recessive spastic cerebral palsy-1 (CPSQ1) is RT caused by a missense variant in HPDL."; RL Brain Commun. 3:fcab002-fcab002(2021). CC -!- FUNCTION: Catalyzes the synthesis of the inhibitory neurotransmitter CC gamma-aminobutyric acid (GABA) with pyridoxal 5'-phosphate as cofactor. CC {ECO:0000269|PubMed:10671565, ECO:0000269|PubMed:17384644}. CC -!- FUNCTION: [Isoform 3]: Enzymatically inactive as glutamate CC decarboxylase. {ECO:0000269|PubMed:10671565}. CC -!- CATALYTIC ACTIVITY: CC Reaction=H(+) + L-glutamate = 4-aminobutanoate + CO2; CC Xref=Rhea:RHEA:17785, ChEBI:CHEBI:15378, ChEBI:CHEBI:16526, CC ChEBI:CHEBI:29985, ChEBI:CHEBI:59888; EC=4.1.1.15; CC Evidence={ECO:0000269|PubMed:10671565, ECO:0000269|PubMed:17384644}; CC PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17786; CC Evidence={ECO:0000305|PubMed:10671565}; CC -!- COFACTOR: CC Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326; CC Evidence={ECO:0000269|PubMed:17384644}; CC -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:17384644}. CC -!- INTERACTION: CC Q99259; Q6RW13: AGTRAP; NbExp=3; IntAct=EBI-743184, EBI-741181; CC Q99259; Q6RW13-2: AGTRAP; NbExp=6; IntAct=EBI-743184, EBI-11522760; CC Q99259; Q96DZ9: CMTM5; NbExp=4; IntAct=EBI-743184, EBI-2548702; CC Q99259; Q96DZ9-2: CMTM5; NbExp=6; IntAct=EBI-743184, EBI-11522780; CC Q99259; P46952: HAAO; NbExp=8; IntAct=EBI-743184, EBI-743215; CC Q99259; Q969L2: MAL2; NbExp=6; IntAct=EBI-743184, EBI-944295; CC Q99259; P16333: NCK1; NbExp=2; IntAct=EBI-743184, EBI-389883; CC Q99259; Q13188: STK3; NbExp=3; IntAct=EBI-743184, EBI-992580; CC -!- ALTERNATIVE PRODUCTS: CC Event=Alternative splicing; Named isoforms=4; CC Name=1; Synonyms=GAD67; CC IsoId=Q99259-1; Sequence=Displayed; CC Name=2; CC IsoId=Q99259-2; Sequence=Not described; CC Name=3; Synonyms=GAD25 {ECO:0000303|PubMed:10671565}; CC IsoId=Q99259-3; Sequence=VSP_009123, VSP_009124; CC Name=4; CC IsoId=Q99259-4; Sequence=VSP_054473, VSP_054474; CC -!- TISSUE SPECIFICITY: [Isoform 1]: Expressed in brain. CC {ECO:0000269|PubMed:10671565}. CC -!- TISSUE SPECIFICITY: [Isoform 3]: Expressed in pancreatic islets, CC testis, adrenal cortex, and perhaps other endocrine tissues, but not in CC brain. {ECO:0000269|PubMed:10671565}. CC -!- DISEASE: Developmental and epileptic encephalopathy 89 (DEE89) CC [MIM:619124]: A form of epileptic encephalopathy, a heterogeneous group CC of early-onset epilepsies characterized by refractory seizures, CC neurodevelopmental impairment, and poor prognosis. Development is CC normal prior to seizure onset, after which cognitive and motor delays CC become apparent. DEE89 is an autosomal recessive severe form CC characterized by profound global developmental delay with impaired CC intellectual development, absent speech, inability to sit or walk due CC to axial hypotonia and spastic quadriparesis, and onset of seizures in CC the first days or months of life. {ECO:0000269|PubMed:32282878}. CC Note=The disease is caused by variants affecting the gene represented CC in this entry. CC -!- SIMILARITY: Belongs to the group II decarboxylase family. CC {ECO:0000305}. CC -!- WEB RESOURCE: Name=NIEHS-SNPs; CC URL="http://egp.gs.washington.edu/data/gad1/"; CC -!- WEB RESOURCE: Name=Wikipedia; Note=Glutamate decarboxylase entry; CC URL="https://en.wikipedia.org/wiki/Glutamate_decarboxylase"; CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; M81883; AAA62368.1; -; mRNA. DR EMBL; L16888; AAB59427.1; -; mRNA. DR EMBL; Z22750; CAA80435.1; -; mRNA. DR EMBL; S61897; AAB26937.1; -; mRNA. DR EMBL; S61898; AAB26938.1; -; mRNA. DR EMBL; M86522; AAA35900.1; -; Genomic_DNA. DR EMBL; AF178853; AAF18390.2; -; mRNA. DR EMBL; AY337516; AAP88035.1; -; Genomic_DNA. DR EMBL; AC007405; AAY24237.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11228.1; -; Genomic_DNA. DR EMBL; CH471058; EAX11229.1; -; Genomic_DNA. DR EMBL; BC002815; AAH02815.1; -; mRNA. DR EMBL; BC026349; AAH26349.1; -; mRNA. DR EMBL; BC036552; AAH36552.1; -; mRNA. DR EMBL; M70434; AAA52512.1; -; mRNA. DR EMBL; M55574; AAA72938.1; -; mRNA. DR CCDS; CCDS2239.1; -. [Q99259-1] DR CCDS; CCDS2240.1; -. [Q99259-3] DR PIR; B41935; B41935. DR PIR; S48135; S48135. DR PIR; S51775; S51775. DR PIR; S51776; S51776. DR RefSeq; NP_000808.2; NM_000817.2. [Q99259-1] DR RefSeq; NP_038473.2; NM_013445.3. [Q99259-3] DR RefSeq; XP_005246501.1; XM_005246444.2. DR RefSeq; XP_011509224.1; XM_011510922.1. [Q99259-1] DR RefSeq; XP_016859245.1; XM_017003756.1. [Q99259-1] DR RefSeq; XP_016859247.1; XM_017003758.1. [Q99259-3] DR PDB; 2OKJ; X-ray; 2.30 A; A/B=93-594. DR PDB; 3VP6; X-ray; 2.10 A; A/B=90-594. DR PDBsum; 2OKJ; -. DR PDBsum; 3VP6; -. DR AlphaFoldDB; Q99259; -. DR SMR; Q99259; -. DR BioGRID; 108845; 27. DR ComplexPortal; CPX-3032; Glutamate decarboxylase 1 complex. DR ComplexPortal; CPX-3065; Glutamate decarboxylase 1/2 complex. DR DIP; DIP-29292N; -. DR IntAct; Q99259; 11. DR MINT; Q99259; -. DR STRING; 9606.ENSP00000350928; -. DR ChEMBL; CHEMBL2614; -. DR DrugBank; DB00142; Glutamic acid. DR DrugBank; DB00114; Pyridoxal phosphate. DR iPTMnet; Q99259; -. DR PhosphoSitePlus; Q99259; -. DR BioMuta; GAD1; -. DR DMDM; 1352213; -. DR EPD; Q99259; -. DR MassIVE; Q99259; -. DR PaxDb; 9606-ENSP00000350928; -. DR PeptideAtlas; Q99259; -. DR ProteomicsDB; 62052; -. DR ProteomicsDB; 78255; -. [Q99259-1] DR ProteomicsDB; 78256; -. [Q99259-3] DR ABCD; Q99259; 3 sequenced antibodies. DR Antibodypedia; 3831; 852 antibodies from 46 providers. DR DNASU; 2571; -. DR Ensembl; ENST00000344257.9; ENSP00000341167.5; ENSG00000128683.14. [Q99259-3] DR Ensembl; ENST00000358196.8; ENSP00000350928.3; ENSG00000128683.14. [Q99259-1] DR Ensembl; ENST00000375272.5; ENSP00000364421.1; ENSG00000128683.14. [Q99259-3] DR Ensembl; ENST00000493875.5; ENSP00000434696.1; ENSG00000128683.14. [Q99259-4] DR Ensembl; ENST00000625689.2; ENSP00000486612.1; ENSG00000128683.14. [Q99259-4] DR GeneID; 2571; -. DR KEGG; hsa:2571; -. DR MANE-Select; ENST00000358196.8; ENSP00000350928.3; NM_000817.3; NP_000808.2. DR UCSC; uc002ugh.4; human. [Q99259-1] DR AGR; HGNC:4092; -. DR CTD; 2571; -. DR DisGeNET; 2571; -. DR GeneCards; GAD1; -. DR HGNC; HGNC:4092; GAD1. DR HPA; ENSG00000128683; Group enriched (brain, parathyroid gland, retina). DR MalaCards; GAD1; -. DR MIM; 603513; phenotype. DR MIM; 605363; gene. DR MIM; 619124; phenotype. DR neXtProt; NX_Q99259; -. DR OpenTargets; ENSG00000128683; -. DR Orphanet; 210141; Inherited congenital spastic tetraplegia. DR PharmGKB; PA28507; -. DR VEuPathDB; HostDB:ENSG00000128683; -. DR eggNOG; KOG0629; Eukaryota. DR GeneTree; ENSGT00940000155526; -. DR HOGENOM; CLU_011856_0_0_1; -. DR InParanoid; Q99259; -. DR OMA; RHATYHA; -. DR OrthoDB; 888358at2759; -. DR PhylomeDB; Q99259; -. DR TreeFam; TF314688; -. DR BioCyc; MetaCyc:HS05215-MONOMER; -. DR BRENDA; 4.1.1.15; 2681. DR PathwayCommons; Q99259; -. DR Reactome; R-HSA-888568; GABA synthesis. DR Reactome; R-HSA-888590; GABA synthesis, release, reuptake and degradation. DR Reactome; R-HSA-9022927; MECP2 regulates transcription of genes involved in GABA signaling. DR SignaLink; Q99259; -. DR SIGNOR; Q99259; -. DR BioGRID-ORCS; 2571; 7 hits in 1160 CRISPR screens. DR ChiTaRS; GAD1; human. DR EvolutionaryTrace; Q99259; -. DR GenomeRNAi; 2571; -. DR Pharos; Q99259; Tbio. DR PRO; PR:Q99259; -. DR Proteomes; UP000005640; Chromosome 2. DR RNAct; Q99259; Protein. DR Bgee; ENSG00000128683; Expressed in endothelial cell and 146 other cell types or tissues. DR ExpressionAtlas; Q99259; baseline and differential. DR GO; GO:0043679; C:axon terminus; IEA:Ensembl. DR GO; GO:0005938; C:cell cortex; IEA:Ensembl. DR GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome. DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central. DR GO; GO:0098982; C:GABA-ergic synapse; IEA:Ensembl. DR GO; GO:0060077; C:inhibitory synapse; IEA:Ensembl. DR GO; GO:0005886; C:plasma membrane; TAS:Reactome. DR GO; GO:0048786; C:presynaptic active zone; IBA:GO_Central. DR GO; GO:0012506; C:vesicle membrane; NAS:UniProtKB. DR GO; GO:0004351; F:glutamate decarboxylase activity; IDA:UniProtKB. DR GO; GO:0042802; F:identical protein binding; IDA:UniProtKB. DR GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro. DR GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc. DR GO; GO:0009449; P:gamma-aminobutyric acid biosynthetic process; IDA:UniProtKB. DR GO; GO:0006538; P:glutamate catabolic process; IDA:UniProtKB. DR GO; GO:0006540; P:glutamate decarboxylation to succinate; TAS:ProtInc. DR GO; GO:0035641; P:locomotory exploration behavior; IEA:Ensembl. DR GO; GO:0035176; P:social behavior; IEA:Ensembl. DR CDD; cd06450; DOPA_deC_like; 1. DR Gene3D; 3.90.1150.170; -; 1. DR Gene3D; 3.40.640.10; Type I PLP-dependent aspartate aminotransferase-like (Major domain); 1. DR InterPro; IPR002129; PyrdxlP-dep_de-COase. DR InterPro; IPR015424; PyrdxlP-dep_Trfase. DR InterPro; IPR015421; PyrdxlP-dep_Trfase_major. DR InterPro; IPR021115; Pyridoxal-P_BS. DR PANTHER; PTHR45677:SF5; GLUTAMATE DECARBOXYLASE 1; 1. DR PANTHER; PTHR45677; GLUTAMATE DECARBOXYLASE-RELATED; 1. DR Pfam; PF00282; Pyridoxal_deC; 1. DR SUPFAM; SSF53383; PLP-dependent transferases; 1. DR PROSITE; PS00392; DDC_GAD_HDC_YDC; 1. DR Genevisible; Q99259; HS. PE 1: Evidence at protein level; KW 3D-structure; Alternative splicing; Decarboxylase; Disease variant; KW Epilepsy; Intellectual disability; Lyase; Neurotransmitter biosynthesis; KW Phosphoprotein; Pyridoxal phosphate; Reference proteome. FT CHAIN 1..594 FT /note="Glutamate decarboxylase 1" FT /id="PRO_0000146963" FT REGION 1..23 FT /note="Disordered" FT /evidence="ECO:0000256|SAM:MobiDB-lite" FT BINDING 190..192 FT /ligand="4-aminobutanoate" FT /ligand_id="ChEBI:CHEBI:59888" FT /evidence="ECO:0000269|PubMed:17384644, FT ECO:0007744|PDB:2OKJ" FT BINDING 567 FT /ligand="4-aminobutanoate" FT /ligand_id="ChEBI:CHEBI:59888" FT /evidence="ECO:0000269|PubMed:17384644, FT ECO:0007744|PDB:2OKJ" FT MOD_RES 78 FT /note="Phosphoserine" FT /evidence="ECO:0000250|UniProtKB:P48318" FT MOD_RES 405 FT /note="N6-(pyridoxal phosphate)lysine" FT /evidence="ECO:0000269|PubMed:17384644, FT ECO:0007744|PDB:2OKJ" FT VAR_SEQ 214..224 FT /note="FTYEIAPVFVL -> PSDMRECWLLR (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10671565, FT ECO:0000303|PubMed:15489334" FT /id="VSP_009123" FT VAR_SEQ 225..594 FT /note="Missing (in isoform 3)" FT /evidence="ECO:0000303|PubMed:10671565, FT ECO:0000303|PubMed:15489334" FT /id="VSP_009124" FT VAR_SEQ 374..425 FT /note="AAWGGGLLMSRKHRHKLNGIERANSVTWNPHKMMGVLLQCSAILVKEKGILQ FT -> GFNFSQLANRIICLATELMTNKGCVTWHPNYSVNMHHGCLGRWAAHVQEAPP (in FT isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054473" FT VAR_SEQ 426..594 FT /note="Missing (in isoform 4)" FT /evidence="ECO:0000303|PubMed:15489334" FT /id="VSP_054474" FT VARIANT 12 FT /note="S -> C (in dbSNP:rs121918345)" FT /evidence="ECO:0000269|PubMed:15571623, FT ECO:0000269|PubMed:33634263" FT /id="VAR_031021" FT VARIANT 228 FT /note="I -> L (in dbSNP:rs45566933)" FT /evidence="ECO:0000269|Ref.9" FT /id="VAR_018861" FT VARIANT 232 FT /note="Missing (in DEE89; uncertain significance; no effect FT on protein abundance; no effect on splicing)" FT /evidence="ECO:0000269|PubMed:32282878" FT /id="VAR_085520" FT VARIANT 474 FT /note="V -> G (in dbSNP:rs769403)" FT /id="VAR_011882" FT VARIANT 509 FT /note="E -> K (in DEE89; dbSNP:rs1381723796)" FT /evidence="ECO:0000269|PubMed:32282878" FT /id="VAR_085521" FT VARIANT 531..594 FT /note="Missing (in DEE89; uncertain significance)" FT /evidence="ECO:0000269|PubMed:32282878" FT /id="VAR_085522" FT VARIANT 532 FT /note="R -> Q (in dbSNP:rs769402)" FT /evidence="ECO:0000269|Ref.9" FT /id="VAR_011883" FT VARIANT 565 FT /note="F -> L (in dbSNP:rs1049736)" FT /id="VAR_011884" FT CONFLICT 9 FT /note="Missing (in Ref. 7; AAA35900)" FT /evidence="ECO:0000305" FT CONFLICT 16..17 FT /note="GA -> EP (in Ref. 4; AAB59427/CAA80435)" FT /evidence="ECO:0000305" FT CONFLICT 17 FT /note="A -> Q (in Ref. 7; AAA35900)" FT /evidence="ECO:0000305" FT CONFLICT 18 FT /note="D -> N (in Ref. 6; AAB26938)" FT /evidence="ECO:0000305" FT CONFLICT 31 FT /note="T -> N (in Ref. 6; AAB26938)" FT /evidence="ECO:0000305" FT CONFLICT 68 FT /note="K -> R (in Ref. 2; AAA62368)" FT /evidence="ECO:0000305" FT CONFLICT 116 FT /note="F -> L (in Ref. 6; AAB26938)" FT /evidence="ECO:0000305" FT CONFLICT 136 FT /note="T -> A (in Ref. 7; AAA35900)" FT /evidence="ECO:0000305" FT CONFLICT 140 FT /note="D -> E (in Ref. 7; AAA35900)" FT /evidence="ECO:0000305" FT CONFLICT 142 FT /note="H -> R (in Ref. 7; AAA35900)" FT /evidence="ECO:0000305" FT CONFLICT 155 FT /note="N -> T (in Ref. 6; AAB26938)" FT /evidence="ECO:0000305" FT CONFLICT 206 FT /note="T -> N (in Ref. 4; AAB59427/CAA80435)" FT /evidence="ECO:0000305" FT CONFLICT 302 FT /note="G -> C (in Ref. 6; AAB26938)" FT /evidence="ECO:0000305" FT CONFLICT 436 FT /note="F -> L (in Ref. 5; AAB26937)" FT /evidence="ECO:0000305" FT CONFLICT 477 FT /note="E -> G (in Ref. 6; AAB26938)" FT /evidence="ECO:0000305" FT CONFLICT 492 FT /note="A -> G (in Ref. 6; AAB26938)" FT /evidence="ECO:0000305" FT CONFLICT 512 FT /note="N -> S (in Ref. 5; AAB26937)" FT /evidence="ECO:0000305" FT TURN 94..97 FT /evidence="ECO:0007829|PDB:2OKJ" FT HELIX 100..102 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 110..131 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 144..149 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 165..177 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 187..192 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 197..209 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 212..214 FT /evidence="ECO:0007829|PDB:2OKJ" FT TURN 216..218 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 220..237 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 241..243 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 245..251 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 252..267 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 270..274 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 276..278 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 282..287 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 293..300 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 305..307 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 308..311 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 321..333 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 337..346 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 348..350 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 356..366 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 369..374 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 377..382 FT /evidence="ECO:0007829|PDB:3VP6" FT TURN 384..386 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 387..390 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 393..395 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 397..401 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 414..420 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 423..428 FT /evidence="ECO:0007829|PDB:3VP6" FT TURN 433..435 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 444..446 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 449..451 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 461..495 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 500..506 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 509..511 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 513..517 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 520..522 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 529..549 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 553..559 FT /evidence="ECO:0007829|PDB:3VP6" FT STRAND 562..568 FT /evidence="ECO:0007829|PDB:3VP6" FT HELIX 577..591 FT /evidence="ECO:0007829|PDB:3VP6" SQ SEQUENCE 594 AA; 66897 MW; 6D761C471C81FDAE CRC64; MASSTPSSSA TSSNAGADPN TTNLRPTTYD TWCGVAHGCT RKLGLKICGF LQRTNSLEEK SRLVSAFKER QSSKNLLSCE NSDRDARFRR TETDFSNLFA RDLLPAKNGE EQTVQFLLEV VDILLNYVRK TFDRSTKVLD FHHPHQLLEG MEGFNLELSD HPESLEQILV DCRDTLKYGV RTGHPRFFNQ LSTGLDIIGL AGEWLTSTAN TNMFTYEIAP VFVLMEQITL KKMREIVGWS SKDGDGIFSP GGAISNMYSI MAARYKYFPE VKTKGMAAVP KLVLFTSEQS HYSIKKAGAA LGFGTDNVIL IKCNERGKII PADFEAKILE AKQKGYVPFY VNATAGTTVY GAFDPIQEIA DICEKYNLWL HVDAAWGGGL LMSRKHRHKL NGIERANSVT WNPHKMMGVL LQCSAILVKE KGILQGCNQM CAGYLFQPDK QYDVSYDTGD KAIQCGRHVD IFKFWLMWKA KGTVGFENQI NKCLELAEYL YAKIKNREEF EMVFNGEPEH TNVCFWYIPQ SLRGVPDSPQ RREKLHKVAP KIKALMMESG TTMVGYQPQG DKANFFRMVI SNPAATQSDI DFLIEEIERL GQDL //