ID   DCE2_MOUSE              Reviewed;         585 AA.
AC   P48320; O35519;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 179.
DE   RecName: Full=Glutamate decarboxylase 2;
DE            EC=4.1.1.15;
DE   AltName: Full=65 kDa glutamic acid decarboxylase;
DE            Short=GAD-65;
DE   AltName: Full=Glutamate decarboxylase 65 kDa isoform;
GN   Name=Gad2; Synonyms=Gad65;
OS   Mus musculus (Mouse).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Mus; Mus.
OX   NCBI_TaxID=10090;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RX   PubMed=8218409; DOI=10.1016/0167-4781(93)90056-j;
RA   Lee D.S., Tian J., Phan T., Kaufman D.L.;
RT   "Cloning and sequence analysis of a murine cDNA encoding glutamate
RT   decarboxylase (GAD65).";
RL   Biochim. Biophys. Acta 1216:157-160(1993).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   STRAIN=C57BL/6J; TISSUE=Brain;
RX   PubMed=8954991; DOI=10.1006/bbrc.1996.1898;
RA   Asada H., Kawamura Y., Maruyama K., Kume H., Ding R.G., Ji F.Y.,
RA   Kanbara N., Kuzume H., Sanbo M., Yagi T., Obata K.;
RT   "Mice lacking the 65 kDa isoform of glutamic acid decarboxylase (GAD65)
RT   maintain normal levels of GAD67 and GABA in their brains but are
RT   susceptible to seizures.";
RL   Biochem. Biophys. Res. Commun. 229:891-895(1996).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA].
RC   TISSUE=Eye;
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   [4]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 175-379.
RC   TISSUE=Brain;
RX   PubMed=8243324; DOI=10.1210/endo.133.6.8243324;
RA   Faulkner-Jones B.E., Cram D.S., Kun J., Harrison L.C.;
RT   "Localization and quantitation of expression of two glutamate decarboxylase
RT   genes in pancreatic beta-cells and other peripheral tissues of mouse and
RT   rat.";
RL   Endocrinology 133:2962-2972(1993).
RN   [5]
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RC   TISSUE=Brain;
RX   PubMed=21183079; DOI=10.1016/j.cell.2010.12.001;
RA   Huttlin E.L., Jedrychowski M.P., Elias J.E., Goswami T., Rad R.,
RA   Beausoleil S.A., Villen J., Haas W., Sowa M.E., Gygi S.P.;
RT   "A tissue-specific atlas of mouse protein phosphorylation and expression.";
RL   Cell 143:1174-1189(2010).
CC   -!- FUNCTION: Catalyzes the production of GABA.
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}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000250}. Cytoplasmic
CC       vesicle {ECO:0000250}. Presynaptic cell membrane {ECO:0000250}; Lipid-
CC       anchor {ECO:0000250}. Golgi apparatus membrane {ECO:0000250};
CC       Peripheral membrane protein {ECO:0000250}; Cytoplasmic side
CC       {ECO:0000250}. Note=Associated to cytoplasmic vesicles. In neurons,
CC       cytosolic leaflet of Golgi membranes and presynaptic clusters (By
CC       similarity). {ECO:0000250}.
CC   -!- PTM: Phosphorylated; which does not affect kinetic parameters or
CC       subcellular location. {ECO:0000250}.
CC   -!- PTM: Palmitoylated; which is required for presynaptic clustering.
CC       {ECO:0000250}.
CC   -!- SIMILARITY: Belongs to the group II decarboxylase family.
CC       {ECO:0000305}.
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DR   EMBL; L16980; AAA93049.1; -; mRNA.
DR   EMBL; D42051; BAA22893.1; -; mRNA.
DR   EMBL; BC018380; AAH18380.1; -; mRNA.
DR   EMBL; S67454; -; NOT_ANNOTATED_CDS; mRNA.
DR   CCDS; CCDS15724.1; -.
DR   PIR; S38533; S38533.
DR   RefSeq; NP_032104.2; NM_008078.2.
DR   AlphaFoldDB; P48320; -.
DR   SMR; P48320; -.
DR   BioGRID; 199815; 8.
DR   ComplexPortal; CPX-3062; Glutamate decarboxylase 2 complex.
DR   ComplexPortal; CPX-3064; Glutamate decarboxylase 1/2 complex.
DR   IntAct; P48320; 1.
DR   STRING; 10090.ENSMUSP00000028123; -.
DR   GlyGen; P48320; 1 site, 1 O-linked glycan (1 site).
DR   iPTMnet; P48320; -.
DR   PhosphoSitePlus; P48320; -.
DR   SwissPalm; P48320; -.
DR   PaxDb; 10090-ENSMUSP00000028123; -.
DR   PeptideAtlas; P48320; -.
DR   ProteomicsDB; 279885; -.
DR   ABCD; P48320; 1 sequenced antibody.
DR   Antibodypedia; 3635; 871 antibodies from 44 providers.
DR   DNASU; 14417; -.
DR   Ensembl; ENSMUST00000028123.4; ENSMUSP00000028123.4; ENSMUSG00000026787.4.
DR   GeneID; 14417; -.
DR   KEGG; mmu:14417; -.
DR   UCSC; uc008inj.1; mouse.
DR   AGR; MGI:95634; -.
DR   CTD; 2572; -.
DR   MGI; MGI:95634; Gad2.
DR   VEuPathDB; HostDB:ENSMUSG00000026787; -.
DR   eggNOG; KOG0629; Eukaryota.
DR   GeneTree; ENSGT00940000157951; -.
DR   HOGENOM; CLU_011856_0_0_1; -.
DR   InParanoid; P48320; -.
DR   OMA; AGMVIFK; -.
DR   OrthoDB; 888358at2759; -.
DR   PhylomeDB; P48320; -.
DR   TreeFam; TF314688; -.
DR   BRENDA; 4.1.1.15; 3474.
DR   Reactome; R-MMU-888568; GABA synthesis.
DR   Reactome; R-MMU-888590; GABA synthesis, release, reuptake and degradation.
DR   BioGRID-ORCS; 14417; 1 hit in 76 CRISPR screens.
DR   ChiTaRS; Gad2; mouse.
DR   PRO; PR:P48320; -.
DR   Proteomes; UP000000589; Chromosome 2.
DR   RNAct; P48320; Protein.
DR   Bgee; ENSMUSG00000026787; Expressed in olfactory tubercle and 128 other cell types or tissues.
DR   ExpressionAtlas; P48320; baseline and differential.
DR   GO; GO:0030424; C:axon; IDA:MGI.
DR   GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome.
DR   GO; GO:0005737; C:cytoplasm; IDA:MGI.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0098982; C:GABA-ergic synapse; ISO:MGI.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0060077; C:inhibitory synapse; ISO:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; ISO:MGI.
DR   GO; GO:0098793; C:presynapse; ISO:MGI.
DR   GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; IDA:MGI.
DR   GO; GO:0030672; C:synaptic vesicle membrane; ISO:MGI.
DR   GO; GO:0016595; F:glutamate binding; ISO:MGI.
DR   GO; GO:0004351; F:glutamate decarboxylase activity; ISO:MGI.
DR   GO; GO:0044877; F:protein-containing complex binding; ISO:MGI.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; ISO:MGI.
DR   GO; GO:0009449; P:gamma-aminobutyric acid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0006540; P:glutamate decarboxylation to succinate; ISO:MGI.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; 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:SF11; GLUTAMATE DECARBOXYLASE 2; 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; P48320; MM.
PE   1: Evidence at protein level;
KW   Cell membrane; Cell projection; Cytoplasm; Cytoplasmic vesicle;
KW   Decarboxylase; Golgi apparatus; Lipoprotein; Lyase; Membrane;
KW   Neurotransmitter biosynthesis; Palmitate; Phosphoprotein;
KW   Pyridoxal phosphate; Reference proteome; Synapse.
FT   CHAIN           1..585
FT                   /note="Glutamate decarboxylase 2"
FT                   /id="PRO_0000146969"
FT   REGION          1..24
FT                   /note="Disordered"
FT                   /evidence="ECO:0000256|SAM:MobiDB-lite"
FT   BINDING         181..183
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   BINDING         558
FT                   /ligand="substrate"
FT                   /evidence="ECO:0000250"
FT   MOD_RES         3
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05329"
FT   MOD_RES         6
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05329"
FT   MOD_RES         10
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05329"
FT   MOD_RES         13
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000250|UniProtKB:Q05329"
FT   MOD_RES         396
FT                   /note="N6-(pyridoxal phosphate)lysine"
FT                   /evidence="ECO:0000250"
FT   LIPID           30
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   LIPID           45
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000250"
FT   CONFLICT        259
FT                   /note="F -> S (in Ref. 2; BAA22893)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        319
FT                   /note="I -> S (in Ref. 4; S67454)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        325
FT                   /note="K -> E (in Ref. 2; BAA22893)"
FT                   /evidence="ECO:0000305"
FT   CONFLICT        499
FT                   /note="P -> S (in Ref. 2; BAA22893)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   585 AA;  65224 MW;  C2F486E85123B057 CRC64;
     MASPGSGFWS FGSEDGSADP ENPGTARAWC QVAQKFTGGI GNKLCALLYG DSGKPAEGGG
     SVTSRAATGK VACTCDQKPC NCPKGDVNYA FLHATDLLPA CDGERPTLAF LQDVMNILLQ
     YVVKSFDRST KVIDFHYPNE LLQEYNWELA DQPQNLEEIL THCQTTLKYA IKTGHPRYFN
     QLSTGLDMVG LAADWLTSTA NTNMFTYEIA PVFVLLEYVT LKKMREIIGW PGGSGDGIFS
     PGGAISNMYA MLIARYKMFP EVKEKGMAAV PRLIAFTSEH SHFSLKKGAA ALGIGTDSVI
     LIKCDERGKM IPSDLERRIL EVKQKGFVPF LVSATAGTTV YGAFDPLLAV ADICKKYKIW
     MHVDAAWGGG LLMSRKHKWK LSGVERANSV TWNPHKMMGV PLQCSALLVR EEGLMQSCNQ
     MHASYLFQQD KHYDLSYDTG DKALQCGRHV DVFKLWLMWR AKGTTGFEAH IDKCLELAEY
     LYTIIKNREG YEMVFDGKPQ HTNVCFWFVP PSLRTLEDNE ERMSRLSKVA PVIKARMMEY
     GTTMVSYQPL GDKVNFFRMV ISNPAATHQD IDFLIEEIER LGQDL
//