ID   DCE_DROME               Reviewed;         510 AA.
AC   P20228; A4V1G1; Q9VZI7;
DT   01-FEB-1991, integrated into UniProtKB/Swiss-Prot.
DT   21-JUN-2005, sequence version 2.
DT   04-NOV-2026, entry version 176.
DE   RecName: Full=Glutamate decarboxylase;
DE            Short=GAD;
DE            EC=4.1.1.15;
GN   Name=Gad1; Synonyms=Gad, Glb; ORFNames=CG14994;
OS   Drosophila melanogaster (Fruit fly).
OC   Eukaryota; Metazoa; Ecdysozoa; Arthropoda; Altocrustacea; Allotriocarida;
OC   Hexapoda; Insecta; Pterygota; Neoptera; Eumetabola; Endopterygota;
OC   Aparaglossata; Panorpida; Diptera; Brachycera; Muscomorpha; Ephydroidea;
OC   Drosophilidae; Drosophila; Sophophora.
OX   NCBI_TaxID=7227;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA], TISSUE SPECIFICITY, AND DEVELOPMENTAL STAGE.
RX   PubMed=1689376; DOI=10.1111/j.1471-4159.1990.tb02359.x;
RA   Jackson F.R., Newby L.M., Kulkarni S.J.;
RT   "Drosophila GABAergic systems: sequence and expression of glutamic acid
RT   decarboxylase.";
RL   J. Neurochem. 54:1068-1078(1990).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC   STRAIN=Berkeley;
RX   PubMed=10731132; DOI=10.1126/science.287.5461.2185;
RA   Adams M.D., Celniker S.E., Holt R.A., Evans C.A., Gocayne J.D.,
RA   Amanatides P.G., Scherer S.E., Li P.W., Hoskins R.A., Galle R.F.,
RA   George R.A., Lewis S.E., Richards S., Ashburner M., Henderson S.N.,
RA   Sutton G.G., Wortman J.R., Yandell M.D., Zhang Q., Chen L.X., Brandon R.C.,
RA   Rogers Y.-H.C., Blazej R.G., Champe M., Pfeiffer B.D., Wan K.H., Doyle C.,
RA   Baxter E.G., Helt G., Nelson C.R., Miklos G.L.G., Abril J.F., Agbayani A.,
RA   An H.-J., Andrews-Pfannkoch C., Baldwin D., Ballew R.M., Basu A.,
RA   Baxendale J., Bayraktaroglu L., Beasley E.M., Beeson K.Y., Benos P.V.,
RA   Berman B.P., Bhandari D., Bolshakov S., Borkova D., Botchan M.R., Bouck J.,
RA   Brokstein P., Brottier P., Burtis K.C., Busam D.A., Butler H., Cadieu E.,
RA   Center A., Chandra I., Cherry J.M., Cawley S., Dahlke C., Davenport L.B.,
RA   Davies P., de Pablos B., Delcher A., Deng Z., Mays A.D., Dew I.,
RA   Dietz S.M., Dodson K., Doup L.E., Downes M., Dugan-Rocha S., Dunkov B.C.,
RA   Dunn P., Durbin K.J., Evangelista C.C., Ferraz C., Ferriera S.,
RA   Fleischmann W., Fosler C., Gabrielian A.E., Garg N.S., Gelbart W.M.,
RA   Glasser K., Glodek A., Gong F., Gorrell J.H., Gu Z., Guan P., Harris M.,
RA   Harris N.L., Harvey D.A., Heiman T.J., Hernandez J.R., Houck J., Hostin D.,
RA   Houston K.A., Howland T.J., Wei M.-H., Ibegwam C., Jalali M., Kalush F.,
RA   Karpen G.H., Ke Z., Kennison J.A., Ketchum K.A., Kimmel B.E., Kodira C.D.,
RA   Kraft C.L., Kravitz S., Kulp D., Lai Z., Lasko P., Lei Y., Levitsky A.A.,
RA   Li J.H., Li Z., Liang Y., Lin X., Liu X., Mattei B., McIntosh T.C.,
RA   McLeod M.P., McPherson D., Merkulov G., Milshina N.V., Mobarry C.,
RA   Morris J., Moshrefi A., Mount S.M., Moy M., Murphy B., Murphy L.,
RA   Muzny D.M., Nelson D.L., Nelson D.R., Nelson K.A., Nixon K., Nusskern D.R.,
RA   Pacleb J.M., Palazzolo M., Pittman G.S., Pan S., Pollard J., Puri V.,
RA   Reese M.G., Reinert K., Remington K., Saunders R.D.C., Scheeler F.,
RA   Shen H., Shue B.C., Siden-Kiamos I., Simpson M., Skupski M.P., Smith T.J.,
RA   Spier E., Spradling A.C., Stapleton M., Strong R., Sun E., Svirskas R.,
RA   Tector C., Turner R., Venter E., Wang A.H., Wang X., Wang Z.-Y.,
RA   Wassarman D.A., Weinstock G.M., Weissenbach J., Williams S.M., Woodage T.,
RA   Worley K.C., Wu D., Yang S., Yao Q.A., Ye J., Yeh R.-F., Zaveri J.S.,
RA   Zhan M., Zhang G., Zhao Q., Zheng L., Zheng X.H., Zhong F.N., Zhong W.,
RA   Zhou X., Zhu S.C., Zhu X., Smith H.O., Gibbs R.A., Myers E.W., Rubin G.M.,
RA   Venter J.C.;
RT   "The genome sequence of Drosophila melanogaster.";
RL   Science 287:2185-2195(2000).
RN   [3]
RP   GENOME REANNOTATION.
RC   STRAIN=Berkeley;
RX   PubMed=12537572; DOI=10.1186/gb-2002-3-12-research0083;
RA   Misra S., Crosby M.A., Mungall C.J., Matthews B.B., Campbell K.S.,
RA   Hradecky P., Huang Y., Kaminker J.S., Millburn G.H., Prochnik S.E.,
RA   Smith C.D., Tupy J.L., Whitfield E.J., Bayraktaroglu L., Berman B.P.,
RA   Bettencourt B.R., Celniker S.E., de Grey A.D.N.J., Drysdale R.A.,
RA   Harris N.L., Richter J., Russo S., Schroeder A.J., Shu S.Q., Stapleton M.,
RA   Yamada C., Ashburner M., Gelbart W.M., Rubin G.M., Lewis S.E.;
RT   "Annotation of the Drosophila melanogaster euchromatic genome: a systematic
RT   review.";
RL   Genome Biol. 3:RESEARCH0083.1-RESEARCH0083.22(2002).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   STRAIN=Berkeley; TISSUE=Head;
RX   PubMed=12537569; DOI=10.1186/gb-2002-3-12-research0080;
RA   Stapleton M., Carlson J.W., Brokstein P., Yu C., Champe M., George R.A.,
RA   Guarin H., Kronmiller B., Pacleb J.M., Park S., Wan K.H., Rubin G.M.,
RA   Celniker S.E.;
RT   "A Drosophila full-length cDNA resource.";
RL   Genome Biol. 3:RESEARCH0080.1-RESEARCH0080.8(2002).
RN   [5]
RP   DISRUPTION PHENOTYPE.
RX   PubMed=24241395; DOI=10.1038/nn.3581;
RA   Yuan Q., Song Y., Yang C.H., Jan L.Y., Jan Y.N.;
RT   "Female contact modulates male aggression via a sexually dimorphic
RT   GABAergic circuit in Drosophila.";
RL   Nat. Neurosci. 17:81-88(2014).
CC   -!- FUNCTION: Catalyzes the production of GABA.
CC       {ECO:0000305|PubMed:1689376}.
CC   -!- CATALYTIC ACTIVITY:
CC       Reaction=L-glutamate + H(+) = 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   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q99259}.
CC   -!- TISSUE SPECIFICITY: Expressed in the head (at protein level).
CC       {ECO:0000269|PubMed:1689376}.
CC   -!- DEVELOPMENTAL STAGE: Expressed in early embryonic development (4-8 h)
CC       and in all later developmental stages. {ECO:0000269|PubMed:1689376}.
CC   -!- DISRUPTION PHENOTYPE: RNAi-mediated knockdown in 5-HT1B+ neurons leads
CC       to dis-inhibition of male aggressive behavior.
CC       {ECO:0000269|PubMed:24241395}.
CC   -!- SIMILARITY: Belongs to the group II decarboxylase family.
CC       {ECO:0000305}.
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DR   EMBL; X76198; CAA53791.1; -; mRNA.
DR   EMBL; AE014296; AAF47834.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAN11581.1; -; Genomic_DNA.
DR   EMBL; AE014296; AAN11582.1; -; Genomic_DNA.
DR   EMBL; AY089526; AAL90264.1; -; mRNA.
DR   PIR; JH0192; A30999.
DR   RefSeq; NP_001261396.1; NM_001274467.1.
DR   RefSeq; NP_523914.2; NM_079190.3.
DR   RefSeq; NP_728930.1; NM_168055.2.
DR   RefSeq; NP_728931.1; NM_168056.2.
DR   AlphaFoldDB; P20228; -.
DR   SMR; P20228; -.
DR   BioGRID; 63964; 5.
DR   FunCoup; P20228; 362.
DR   IntAct; P20228; 1.
DR   STRING; 7227.FBpp0073131; -.
DR   PaxDb; 7227-FBpp0073131; -.
DR   PeptideAtlas; P20228; -.
DR   DNASU; 38484; -.
DR   EnsemblMetazoa; FBtr0073275; FBpp0073131; FBgn0004516.
DR   EnsemblMetazoa; FBtr0073276; FBpp0073132; FBgn0004516.
DR   EnsemblMetazoa; FBtr0073277; FBpp0073133; FBgn0004516.
DR   EnsemblMetazoa; FBtr0332980; FBpp0305196; FBgn0004516.
DR   GeneID; 38484; -.
DR   KEGG; dme:Dmel_CG14994; -.
DR   AGR; FB:FBgn0004516; -.
DR   CTD; 2571; -.
DR   FlyBase; FBgn0004516; Gad1.
DR   VEuPathDB; VectorBase:FBgn0004516; -.
DR   eggNOG; KOG0629; Eukaryota.
DR   HOGENOM; CLU_011856_0_0_1; -.
DR   InParanoid; P20228; -.
DR   OMA; AADHMLD; -.
DR   OrthoDB; 392571at2759; -.
DR   PhylomeDB; P20228; -.
DR   BRENDA; 4.1.1.15; 1994.
DR   Reactome; R-DME-888568; GABA synthesis.
DR   Reactome; R-DME-888590; GABA synthesis, release, reuptake and degradation.
DR   BioGRID-ORCS; 38484; 0 hits in 3 CRISPR screens.
DR   GenomeRNAi; 38484; -.
DR   PRO; PR:P20228; -.
DR   Proteomes; UP000000803; Chromosome 3L.
DR   Bgee; FBgn0004516; Expressed in proximal medullary amacrine neuron Pm4 in brain and 93 other cell types or tissues.
DR   ExpressionAtlas; P20228; baseline and differential.
DR   GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR   GO; GO:0005829; C:cytosol; HDA:FlyBase.
DR   GO; GO:0004351; F:glutamate decarboxylase activity; IDA:FlyBase.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:InterPro.
DR   GO; GO:0009449; P:GABA biosynthetic process; IMP:FlyBase.
DR   GO; GO:0006540; P:GABA shunt; ISS:FlyBase.
DR   GO; GO:0006538; P:L-glutamate catabolic process; IMP:FlyBase.
DR   GO; GO:0008345; P:larval locomotory behavior; IMP:FlyBase.
DR   GO; GO:0007528; P:neuromuscular junction development; IMP:FlyBase.
DR   GO; GO:0008355; P:olfactory learning; IMP:FlyBase.
DR   GO; GO:0009612; P:response to mechanical stimulus; IGI:FlyBase.
DR   GO; GO:0007416; P:synapse assembly; IMP:FlyBase.
DR   CDD; cd06450; DOPA_deC_like; 1.
DR   FunFam; 3.40.640.10:FF:000016; Glutamate decarboxylase like 1; 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:SF10; GLUTAMATE DECARBOXYLASE; 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.
PE   1: Evidence at protein level;
KW   Decarboxylase; Lyase; Neurotransmitter biosynthesis; Pyridoxal phosphate;
KW   Reference proteome.
FT   CHAIN           1..510
FT                   /note="Glutamate decarboxylase"
FT                   /id="PRO_0000146972"
FT   BINDING         107..109
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         483
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         322
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        201
FT                   /note="F -> L (in Ref. 1; CAA53791)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        301
FT                   /note="K -> T (in Ref. 1; CAA53791)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   510 AA;  57819 MW;  AAEBFC6FDC662001 CRC64;
     MSLNPNGYKL SERTGKLTAY DLMPTTVTAG PETREFLLKV IDVLLDFVKA TNDRNEKVLD
     FHHPEDMKRL LDLDVPDRAL PLQQLIEDCA TTLKYQVKTG HPHFFNQLSN GLDLISMAGE
     WLTATANTNM FTYEIAPVFI LMENVVLTKM REIIGWSGGD SILAPGGSIS NLYAFLAARH
     KMFPNYKEHG SVGLPGTLVM FTSDQCHYSI KSCAAVCGLG TDHCIVVPSD EHGKMITSEL
     ERLILERKAK GDIPFFVNAT AGTTVLGAFD DINTIADICQ KYNCWMHIDA AWGGGLLMSR
     KHRHPRFTGV ERADSVTWNP HKLMGALLQC STIHFKEDGL LISCNQMSAE YLFMTDKQYD
     ISYDTGDKVI QCGRHNDIFK LWLQWRAKGT EGFEQQQDRL MELVQYQLKR IREQSDRFHL
     ILEPECVNVS FWYVPKRLRG VPHDAKKEVE LGKICPIIKG RMMQKGTLMV GYQPDDRRPN
     FFRSIISSAA VNEADVDFML DEIHRLGDDL
//