DCE2_RAT
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 03-AUG-2022, entry version 149.
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; Q05683; -.
DR PRIDE; Q05683; -.
DR ABCD; Q05683; 1 sequenced antibody.
DR Ensembl; ENSRNOT00000024901; ENSRNOP00000024901; ENSRNOG00000018200.
DR GeneID; 24380; -.
DR KEGG; rno:24380; -.
DR UCSC; RGD:2653; rat.
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; VACTCDQ; -.
DR OrthoDB; 810772at2759; -.
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 tissues.
DR Genevisible; Q05683; RN.
DR GO; GO:0031225; C:anchored component of membrane; IDA:RGD.
DR GO; GO:0070161; C:anchoring junction; IEA:UniProtKB-KW.
DR GO; GO:0030424; C:axon; ISO:RGD.
DR GO; GO:0005737; C:cytoplasm; ISO:RGD.
DR GO; GO:0031410; C:cytoplasmic vesicle; IDA:RGD.
DR GO; GO:0005829; C:cytosol; IDA:RGD.
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: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:0016831; F:carboxy-lyase activity; IBA:GO_Central.
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:0042136; P:neurotransmitter biosynthetic process; IEA:UniProtKB-KW.
DR GO; GO:0009410; P:response to xenobiotic stimulus; IEP:RGD.
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 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 membrane-
FT association; when associates with A-45. No effect on
FT glutamate decarboxylase activity; when associated with A-
FT 45."
FT /evidence="ECO:0000269|PubMed:8132714,
FT ECO:0000269|PubMed:8999827"
FT MUTAGEN 45
FT /note="C->A: Abolishes palmitoylation but not membrane-
FT association; when associates with A-30. No effect on
FT glutamate decarboxylase activity; when associated with A-
FT 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
