DCE1_HUMAN
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 03-AUG-2022, entry version 204.
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 ARG-531--LEU
RP 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";
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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. [Q99259-3]
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; 26.
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; Q99259; -.
DR PeptideAtlas; Q99259; -.
DR PRIDE; Q99259; -.
DR ProteomicsDB; 62052; -.
DR ProteomicsDB; 78255; -. [Q99259-1]
DR ProteomicsDB; 78256; -. [Q99259-3]
DR ABCD; Q99259; 3 sequenced antibodies.
DR Antibodypedia; 3831; 760 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 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 PhylomeDB; Q99259; -.
DR TreeFam; TF314688; -.
DR BioCyc; MetaCyc:HS05215-MON; -.
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 1080 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 144 other tissues.
DR ExpressionAtlas; Q99259; baseline and differential.
DR Genevisible; Q99259; HS.
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: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:0016831; F:carboxy-lyase activity; IBA:GO_Central.
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; IBA:GO_Central.
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:0042136; P:neurotransmitter biosynthetic process; IDA:UniProtKB.
DR GO; GO:0018352; P:protein-pyridoxal-5-phosphate linkage; IDA:UniProtKB.
DR GO; GO:0035176; P:social behavior; IEA:Ensembl.
DR Gene3D; 3.40.640.10; -; 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 Pfam; PF00282; Pyridoxal_deC; 1.
DR SUPFAM; SSF53383; SSF53383; 1.
DR PROSITE; PS00392; DDC_GAD_HDC_YDC; 1.
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; unknown pathological
FT significance; no effect on protein abundance; no effect on
FT 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; unknown pathological
FT 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
