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 Genevisible; P48320; MM.
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.
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
//
