DCE_DROME
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 03-AUG-2022, entry version 162.
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; Hexapoda; Insecta; Pterygota;
OC Neoptera; Endopterygota; 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=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 -!- 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 IntAct; P20228; 1.
DR STRING; 7227.FBpp0073131; -.
DR PaxDb; P20228; -.
DR PRIDE; 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 CTD; 2571; -.
DR FlyBase; FBgn0004516; Gad1.
DR VEuPathDB; VectorBase:FBgn0004516; -.
DR eggNOG; KOG0629; Eukaryota.
DR GeneTree; ENSGT00940000170473; -.
DR HOGENOM; CLU_011856_0_0_1; -.
DR InParanoid; P20228; -.
DR OMA; RHATYHA; -.
DR OrthoDB; 810772at2759; -.
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 ChiTaRS; Gad1; fly.
DR GenomeRNAi; 38484; -.
DR PRO; PR:P20228; -.
DR Proteomes; UP000000803; Chromosome 3L.
DR Bgee; FBgn0004516; Expressed in brain and 14 other tissues.
DR ExpressionAtlas; P20228; baseline and differential.
DR Genevisible; P20228; DM.
DR GO; GO:0005737; C:cytoplasm; IBA:GO_Central.
DR GO; GO:0005829; C:cytosol; HDA:FlyBase.
DR GO; GO:0016831; F:carboxy-lyase activity; IBA:GO_Central.
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:gamma-aminobutyric acid biosynthetic process; IMP:FlyBase.
DR GO; GO:0006538; P: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:0042136; P:neurotransmitter biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0045213; P:neurotransmitter receptor metabolic process; 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 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 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