ID   DCE2_RAT                Reviewed;         585 AA.
AC   Q05683;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   27-MAR-2024, entry version 157.
DE   RecName: Full=Glutamate decarboxylase 2 {ECO:0000305};
DE            EC=4.1.1.15 {ECO:0000305|PubMed:8999827};
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   Rattus norvegicus (Rat).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia;
OC   Eutheria; Euarchontoglires; Glires; Rodentia; Myomorpha; Muroidea; Muridae;
OC   Murinae; Rattus.
OX   NCBI_TaxID=10116;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Hippocampus;
RX   PubMed=2069816; DOI=10.1016/0896-6273(91)90077-d;
RA   Erlander M.G., Tillakaratne N.J., Feldblum S., Patel N., Tobin A.J.;
RT   "Two genes encode distinct glutamate decarboxylases.";
RL   Neuron 7:91-100(1991).
RN   [2]
RP   PROTEIN SEQUENCE OF 190-219; 225-266 AND 524-558.
RC   TISSUE=Brain;
RX   PubMed=3385490; DOI=10.1523/jneurosci.08-06-02123.1988;
RA   Chang Y.C., Gottlieb D.I.;
RT   "Characterization of the proteins purified with monoclonal antibodies to
RT   glutamic acid decarboxylase.";
RL   J. Neurosci. 8:2123-2130(1988).
RN   [3]
RP   SUBCELLULAR LOCATION, AND PALMITOYLATION.
RX   PubMed=1321158; DOI=10.1083/jcb.118.2.309;
RA   Christgau S., Aanstoot H.-J., Schierbeck H., Begley K., Tullin S.,
RA   Hejnaes K., Baekkeskov S.;
RT   "Membrane anchoring of the autoantigen GAD65 to microvesicles in pancreatic
RT   beta-cells by palmitoylation in the NH2-terminal domain.";
RL   J. Cell Biol. 118:309-320(1992).
RN   [4]
RP   PALMITOYLATION AT CYS-30 AND CYS-45, AND MUTAGENESIS OF CYS-30; CYS-45;
RP   CYS-73; CYS-75; CYS-80; CYS-82 AND CYS-101.
RX   PubMed=8132714; DOI=10.1083/jcb.124.6.927;
RA   Shi Y., Veit B., Baekkeskov S.;
RT   "Amino acid residues 24-31 but not palmitoylation of cysteines 30 and 45
RT   are required for membrane anchoring of glutamic acid decarboxylase,
RT   GAD65.";
RL   J. Cell Biol. 124:927-934(1994).
RN   [5]
RP   PHOSPHORYLATION AT SER-3; SER-6; SER-10 AND SER-13, BIOPHYSICOCHEMICAL
RP   PROPERTIES, CATALYTIC ACTIVITY, PHOSPHORYLATION AT SER-10; SER-13 AND
RP   SER-17, MUTAGENESIS OF 10-SER--SER-17; CYS-30 AND CYS-45, AND COFACTOR.
RX   PubMed=8999827; DOI=10.1074/jbc.272.3.1548;
RA   Namchuk M., Lindsay L., Turck C.W., Kanaani J., Baekkeskov S.;
RT   "Phosphorylation of serine residues 3, 6, 10, and 13 distinguishes membrane
RT   anchored from soluble glutamic acid decarboxylase 65 and is restricted to
RT   glutamic acid decarboxylase 65alpha.";
RL   J. Biol. Chem. 272:1548-1557(1997).
RN   [6]
RP   PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-3 AND SER-13, AND
RP   IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
RX   PubMed=22673903; DOI=10.1038/ncomms1871;
RA   Lundby A., Secher A., Lage K., Nordsborg N.B., Dmytriyev A., Lundby C.,
RA   Olsen J.V.;
RT   "Quantitative maps of protein phosphorylation sites across 14 different rat
RT   organs and tissues.";
RL   Nat. Commun. 3:876-876(2012).
CC   -!- FUNCTION: Catalyzes the production of GABA.
CC       {ECO:0000305|PubMed:8999827}.
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:0000305|PubMed:8999827};
CC       PhysiologicalDirection=left-to-right; Xref=Rhea:RHEA:17786;
CC         Evidence={ECO:0000305|PubMed:8999827};
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000305|PubMed:8999827};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=1.02 mM for glutamate {ECO:0000269|PubMed:8999827};
CC   -!- SUBUNIT: Homodimer. {ECO:0000250|UniProtKB:Q05329}.
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol {ECO:0000269|PubMed:8999827}.
CC       Cytoplasmic vesicle {ECO:0000250|UniProtKB:Q05329}. Presynaptic cell
CC       membrane {ECO:0000250|UniProtKB:Q05329}; Lipid-anchor
CC       {ECO:0000250|UniProtKB:Q05329}. Golgi apparatus membrane
CC       {ECO:0000250|UniProtKB:Q05329}; Peripheral membrane protein
CC       {ECO:0000250|UniProtKB:Q05329}; Cytoplasmic side
CC       {ECO:0000250|UniProtKB:Q05329}. Note=Associated to cytoplasmic
CC       vesicles. In neurons, cytosolic leaflet of Golgi membranes and
CC       presynaptic clusters. {ECO:0000250|UniProtKB:Q05329}.
CC   -!- PTM: The N-terminus is blocked.
CC   -!- PTM: Phosphorylated; which does not affect kinetic parameters or
CC       subcellular location. {ECO:0000269|PubMed:8999827}.
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; M72422; AAA63488.1; -; mRNA.
DR   PIR; JH0423; JH0423.
DR   RefSeq; NP_036695.1; NM_012563.1.
DR   PDB; 3CUP; X-ray; 3.09 A; B=221-235.
DR   PDBsum; 3CUP; -.
DR   AlphaFoldDB; Q05683; -.
DR   SMR; Q05683; -.
DR   BioGRID; 246551; 2.
DR   ComplexPortal; CPX-3063; Glutamate decarboxylase 1/2 complex.
DR   ComplexPortal; CPX-3067; Glutamate decarboxylase 2 complex.
DR   IntAct; Q05683; 1.
DR   STRING; 10116.ENSRNOP00000024901; -.
DR   BindingDB; Q05683; -.
DR   iPTMnet; Q05683; -.
DR   PhosphoSitePlus; Q05683; -.
DR   SwissPalm; Q05683; -.
DR   PaxDb; 10116-ENSRNOP00000024901; -.
DR   ABCD; Q05683; 1 sequenced antibody.
DR   Ensembl; ENSRNOT00000024901.5; ENSRNOP00000024901.2; ENSRNOG00000018200.5.
DR   Ensembl; ENSRNOT00055001955; ENSRNOP00055001533; ENSRNOG00055001178.
DR   Ensembl; ENSRNOT00060027867; ENSRNOP00060022394; ENSRNOG00060016275.
DR   Ensembl; ENSRNOT00065004444; ENSRNOP00065003170; ENSRNOG00065003157.
DR   GeneID; 24380; -.
DR   KEGG; rno:24380; -.
DR   UCSC; RGD:2653; rat.
DR   AGR; RGD:2653; -.
DR   CTD; 2572; -.
DR   RGD; 2653; Gad2.
DR   eggNOG; KOG0629; Eukaryota.
DR   GeneTree; ENSGT00940000157951; -.
DR   HOGENOM; CLU_011856_0_0_1; -.
DR   InParanoid; Q05683; -.
DR   OMA; AGMVIFK; -.
DR   OrthoDB; 888358at2759; -.
DR   PhylomeDB; Q05683; -.
DR   TreeFam; TF314688; -.
DR   BRENDA; 4.1.1.15; 5301.
DR   Reactome; R-RNO-888568; GABA synthesis.
DR   Reactome; R-RNO-888590; GABA synthesis, release, reuptake and degradation.
DR   SABIO-RK; Q05683; -.
DR   PRO; PR:Q05683; -.
DR   Proteomes; UP000002494; Chromosome 17.
DR   Bgee; ENSRNOG00000018200; Expressed in cerebellum and 4 other cell types or tissues.
DR   GO; GO:0030424; C:axon; ISO:RGD.
DR   GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0098982; C:GABA-ergic synapse; IDA:SynGO.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0060077; C:inhibitory synapse; IDA:MGI.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IDA:RGD.
DR   GO; GO:0098793; C:presynapse; IDA:SynGO.
DR   GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0045202; C:synapse; ISO:RGD.
DR   GO; GO:0030672; C:synaptic vesicle membrane; IDA:RGD.
DR   GO; GO:0016595; F:glutamate binding; IDA:RGD.
DR   GO; GO:0004351; F:glutamate decarboxylase activity; IDA:RGD.
DR   GO; GO:0044877; F:protein-containing complex binding; IDA:RGD.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IDA:RGD.
DR   GO; GO:0007268; P:chemical synaptic transmission; TAS:RGD.
DR   GO; GO:0009449; P:gamma-aminobutyric acid biosynthetic process; IBA:GO_Central.
DR   GO; GO:0006540; P:glutamate decarboxylation to succinate; IDA:RGD.
DR   GO; GO:0042220; P:response to cocaine; IEP:RGD.
DR   GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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; Q05683; RN.
PE   1: Evidence at protein level;
KW   3D-structure; Cell membrane; Cell projection; Cytoplasm;
KW   Cytoplasmic vesicle; Decarboxylase; Direct protein sequencing;
KW   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_0000146971"
FT   REGION          1..25
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:0000269|PubMed:8999827,
FT                   ECO:0007744|PubMed:22673903"
FT   MOD_RES         6
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:8999827"
FT   MOD_RES         10
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:8999827"
FT   MOD_RES         13
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:8999827,
FT                   ECO:0007744|PubMed:22673903"
FT   MOD_RES         17
FT                   /note="Phosphoserine"
FT                   /evidence="ECO:0000269|PubMed:8999827"
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:0000269|PubMed:8132714"
FT   LIPID           45
FT                   /note="S-palmitoyl cysteine"
FT                   /evidence="ECO:0000269|PubMed:8132714"
FT   MUTAGEN         10..17
FT                   /note="SFGSEDGS->AFGAEDGA: No effect on glutamate
FT                   decarboxylase activity."
FT                   /evidence="ECO:0000269|PubMed:8999827"
FT   MUTAGEN         30
FT                   /note="C->A: Abolishes palmitoylation but not
FT                   membrane-association; when associates with A-45. No effect
FT                   on glutamate decarboxylase activity; when associated with
FT                   A-45."
FT                   /evidence="ECO:0000269|PubMed:8132714,
FT                   ECO:0000269|PubMed:8999827"
FT   MUTAGEN         45
FT                   /note="C->A: Abolishes palmitoylation but not
FT                   membrane-association; when associates with A-30. No effect
FT                   on glutamate decarboxylase activity; when associated with
FT                   A-30."
FT                   /evidence="ECO:0000269|PubMed:8132714,
FT                   ECO:0000269|PubMed:8999827"
FT   MUTAGEN         73
FT                   /note="C->S: No effect on palmitoylation."
FT                   /evidence="ECO:0000269|PubMed:8132714"
FT   MUTAGEN         75
FT                   /note="C->S: No effect on palmitoylation."
FT                   /evidence="ECO:0000269|PubMed:8132714"
FT   MUTAGEN         80
FT                   /note="C->S: No effect on palmitoylation."
FT                   /evidence="ECO:0000269|PubMed:8132714"
FT   MUTAGEN         82
FT                   /note="C->S: No effect on palmitoylation."
FT                   /evidence="ECO:0000269|PubMed:8132714"
FT   MUTAGEN         101
FT                   /note="C->S: No effect on palmitoylation."
FT                   /evidence="ECO:0000269|PubMed:8132714"
FT   CONFLICT        190
FT                   /note="G -> V (in Ref. 2; AA sequence)"
FT                   /evidence="ECO:0000305"
SQ   SEQUENCE   585 AA;  65402 MW;  C04040B7BA7B37D1 CRC64;
     MASPGSGFWS FGSEDGSGDP ENPGTARAWC QVAQKFTGGI GNKLCALLYG DSEKPAESGG
     SVTSRAATRK VACTCDQKPC SCPKGDVNYA LLHATDLLPA CEGERPTLAF 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 LNGVERANSV TWNPHKMMGV PLQCSALLVR EEGLMQSCNQ
     MHASYLFQQD KHYDLSYDTG DKALQCGRHV DVFKLWLMWR AKGTTGFEAH IDKCLELAEY
     LYNIIKNREG YEMVFDGKPQ HTNVCFWFVP PSLRVLEDNE ERMSRLSKVA PVIKARMMEY
     GTTMVSYQPL GDKVNFFRMV ISNPAATHQD IDFLIEEIER LGQDL
//