GenomeNet

Database: UniProt/SWISS-PROT
Entry: DCE2_HUMAN
LinkDB: DCE2_HUMAN
Original site: DCE2_HUMAN 
ID   DCE2_HUMAN              Reviewed;         585 AA.
AC   Q05329; Q9UD87;
DT   01-FEB-1996, integrated into UniProtKB/Swiss-Prot.
DT   01-FEB-1996, sequence version 1.
DT   20-JUN-2018, entry version 157.
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   Homo sapiens (Human).
OC   Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi;
OC   Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini;
OC   Catarrhini; Hominidae; Homo.
OX   NCBI_TaxID=9606;
RN   [1]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RC   TISSUE=Pancreatic islet;
RX   PubMed=1924293; DOI=10.1073/pnas.88.19.8337;
RA   Karlsen A.E., Hagopian W.A., Grubin C.E., Dube S., Disteche C.M.,
RA   Adler D.A., Barmeier H., Mathewes S., Grant F.J., Foster D.,
RA   Lernmark A.;
RT   "Cloning and primary structure of a human islet isoform of glutamic
RT   acid decarboxylase from chromosome 10.";
RL   Proc. Natl. Acad. Sci. U.S.A. 88:8337-8341(1991).
RN   [2]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=1549570; DOI=10.1073/pnas.89.6.2115;
RA   Bu D.-F., Erlander M.G., Hitz B.C., Tillakaratne N.J., Kaufman D.L.,
RA   Wagner-Mcpherson C.B., Evans G.A., Tobin A.J.;
RT   "Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are
RT   each encoded by a single gene.";
RL   Proc. Natl. Acad. Sci. U.S.A. 89:2115-2119(1992).
RN   [3]
RP   NUCLEOTIDE SEQUENCE [MRNA].
RX   PubMed=8088791; DOI=10.1006/geno.1994.1246;
RA   Bu D.-F., Tobin A.J.;
RT   "The exon-intron organization of the genes (GAD1 and GAD2) encoding
RT   two human glutamate decarboxylases (GAD67 and GAD65) suggests that
RT   they derive from a common ancestral GAD.";
RL   Genomics 21:222-228(1994).
RN   [4]
RP   NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND VARIANTS ARG-12; ASN-124;
RP   ARG-286 AND GLN-375.
RG   NIEHS SNPs program;
RL   Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases.
RN   [5]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 6-585.
RC   TISSUE=Pancreas;
RX   PubMed=7680313; DOI=10.1111/j.1432-1033.1993.tb17698.x;
RA   Mauch L., Abney C.C., Berg H., Scherbaum W.A., Liedvogel B.,
RA   Northemann W.;
RT   "Characterization of a linear epitope within the human pancreatic 64-
RT   kDa glutamic acid decarboxylase and its autoimmune recognition by sera
RT   from insulin-dependent diabetes mellitus patients.";
RL   Eur. J. Biochem. 212:597-603(1993).
RN   [6]
RP   NUCLEOTIDE SEQUENCE [MRNA] OF 245-585.
RX   PubMed=8243826; DOI=10.2337/diab.42.12.1799;
RA   Kim J., Richter W., Aanstoot H.-J., Shi Y., Fu Q., Rajotte R.,
RA   Warnock G., Baekkeskov S.;
RT   "Differential expression of GAD65 and GAD67 in human, rat, and mouse
RT   pancreatic islets.";
RL   Diabetes 42:1799-1808(1993).
RN   [7]
RP   PHOSPHORYLATION AT SER-3; SER-6; SER-10 AND SER-13, AND
RP   BIOPHYSICOCHEMICAL PROPERTIES.
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
RT   membrane anchored from soluble glutamic acid decarboxylase 65 and is
RT   restricted to glutamic acid decarboxylase 65alpha.";
RL   J. Biol. Chem. 272:1548-1557(1997).
RN   [8]
RP   SUBCELLULAR LOCATION, AND PALMITOYLATION AT CYS-30 AND CYS-45.
RX   PubMed=12356867; DOI=10.1083/jcb.200205053;
RA   Kanaani J., El-Din El-Husseini A., Aguilera-Moreno A., Diacovo J.M.,
RA   Bredt D.S., Baekkeskov S.;
RT   "A combination of three distinct trafficking signals mediates axonal
RT   targeting and presynaptic clustering of GAD65.";
RL   J. Cell Biol. 158:1229-1238(2002).
RN   [9]
RP   X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 222-235 IN COMPLEX WITH MHC.
RX   PubMed=10775108; DOI=10.1126/science.288.5465.505;
RA   Corper A.L., Stratmann T., Apostolopoulos V., Scott C.A., Garcia K.C.,
RA   Kang A.S., Wilson I.A., Teyton L.;
RT   "A structural framework for deciphering the link between I-Ag7 and
RT   autoimmune diabetes.";
RL   Science 288:505-511(2000).
RN   [10]
RP   X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 88-584 IN COMPLEX WITH
RP   SUBSTRATE, SUBUNIT, AND COFACTOR.
RX   PubMed=17384644; DOI=10.1038/nsmb1228;
RA   Fenalti G., Law R.H.P., Buckle A.M., Langendorf C., Tuck K.,
RA   Rosado C.J., Faux N.G., Mahmood K., Hampe C.S., Banga J.P., Wilce M.,
RA   Schmidberger J., Rossjohn J., El-Kabbani O., Pike R.N., Smith A.I.,
RA   Mackay I.R., Rowley M.J., Whisstock J.C.;
RT   "GABA production by glutamic acid decarboxylase is regulated by a
RT   dynamic catalytic loop.";
RL   Nat. Struct. Mol. Biol. 14:280-286(2007).
CC   -!- FUNCTION: Catalyzes the production of GABA.
CC   -!- CATALYTIC ACTIVITY: L-glutamate = 4-aminobutanoate + CO(2).
CC   -!- COFACTOR:
CC       Name=pyridoxal 5'-phosphate; Xref=ChEBI:CHEBI:597326;
CC         Evidence={ECO:0000269|PubMed:17384644};
CC   -!- BIOPHYSICOCHEMICAL PROPERTIES:
CC       Kinetic parameters:
CC         KM=2.15 mM for glutamate {ECO:0000269|PubMed:8999827};
CC   -!- SUBUNIT: Homodimer. {ECO:0000269|PubMed:10775108,
CC       ECO:0000269|PubMed:17384644}.
CC   -!- INTERACTION:
CC       Q6RW13:AGTRAP; NbExp=3; IntAct=EBI-9304251, EBI-741181;
CC       Q15041:ARL6IP1; NbExp=5; IntAct=EBI-9304251, EBI-714543;
CC       Q96DZ9:CMTM5; NbExp=3; IntAct=EBI-9304251, EBI-2548702;
CC       Q969L2:MAL2; NbExp=5; IntAct=EBI-9304251, EBI-944295;
CC       Q96B96:TMEM159; NbExp=5; IntAct=EBI-9304251, EBI-7055862;
CC   -!- SUBCELLULAR LOCATION: Cytoplasm, cytosol
CC       {ECO:0000269|PubMed:12356867}. Cytoplasmic vesicle
CC       {ECO:0000269|PubMed:12356867}. Cell junction, synapse, presynaptic
CC       cell membrane {ECO:0000269|PubMed:12356867}; Lipid-anchor
CC       {ECO:0000269|PubMed:12356867}. Golgi apparatus membrane
CC       {ECO:0000269|PubMed:12356867}; Peripheral membrane protein
CC       {ECO:0000269|PubMed:12356867}; Cytoplasmic side
CC       {ECO:0000269|PubMed:12356867}. Note=Associated to cytoplasmic
CC       vesicles. In neurons, cytosolic leaflet of Golgi membranes and
CC       presynaptic clusters.
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:0000269|PubMed:12356867}.
CC   -!- SIMILARITY: Belongs to the group II decarboxylase family.
CC       {ECO:0000305}.
CC   -!- SEQUENCE CAUTION:
CC       Sequence=CAA49554.1; Type=Erroneous initiation; Evidence={ECO:0000305};
CC   -!- WEB RESOURCE: Name=NIEHS-SNPs;
CC       URL="http://egp.gs.washington.edu/data/gad2/";
DR   EMBL; M81882; AAA62367.1; -; mRNA.
DR   EMBL; M74826; AAA58491.1; -; mRNA.
DR   EMBL; AY340073; AAP88040.1; -; Genomic_DNA.
DR   EMBL; X69936; CAA49554.1; ALT_INIT; mRNA.
DR   EMBL; M70435; AAA52513.1; -; mRNA.
DR   CCDS; CCDS7149.1; -.
DR   PIR; A41935; A41292.
DR   RefSeq; NP_000809.1; NM_000818.2.
DR   RefSeq; NP_001127838.1; NM_001134366.1.
DR   UniGene; Hs.231829; -.
DR   PDB; 1ES0; X-ray; 2.60 A; B=207-220.
DR   PDB; 2OKK; X-ray; 2.30 A; A=88-584.
DR   PDBsum; 1ES0; -.
DR   PDBsum; 2OKK; -.
DR   ProteinModelPortal; Q05329; -.
DR   SMR; Q05329; -.
DR   BioGrid; 108846; 8.
DR   ComplexPortal; CPX-3033; Glutamate decarboxylase 2 complex.
DR   ComplexPortal; CPX-3065; Glutamate decarboxylase 1/2 complex.
DR   DIP; DIP-29293N; -.
DR   IntAct; Q05329; 19.
DR   STRING; 9606.ENSP00000259271; -.
DR   ChEMBL; CHEMBL2952; -.
DR   DrugBank; DB00142; L-Glutamic Acid.
DR   iPTMnet; Q05329; -.
DR   PhosphoSitePlus; Q05329; -.
DR   SwissPalm; Q05329; -.
DR   BioMuta; GAD2; -.
DR   DMDM; 1352216; -.
DR   PaxDb; Q05329; -.
DR   PeptideAtlas; Q05329; -.
DR   PRIDE; Q05329; -.
DR   ProteomicsDB; 58319; -.
DR   DNASU; 2572; -.
DR   Ensembl; ENST00000259271; ENSP00000259271; ENSG00000136750.
DR   Ensembl; ENST00000376261; ENSP00000365437; ENSG00000136750.
DR   GeneID; 2572; -.
DR   KEGG; hsa:2572; -.
DR   CTD; 2572; -.
DR   DisGeNET; 2572; -.
DR   EuPathDB; HostDB:ENSG00000136750.11; -.
DR   GeneCards; GAD2; -.
DR   HGNC; HGNC:4093; GAD2.
DR   HPA; CAB078177; -.
DR   HPA; HPA044637; -.
DR   MIM; 138275; gene.
DR   neXtProt; NX_Q05329; -.
DR   OpenTargets; ENSG00000136750; -.
DR   PharmGKB; PA28508; -.
DR   eggNOG; KOG0629; Eukaryota.
DR   eggNOG; COG0076; LUCA.
DR   GeneTree; ENSGT00760000119205; -.
DR   HOGENOM; HOG000005382; -.
DR   HOVERGEN; HBG004980; -.
DR   InParanoid; Q05329; -.
DR   KO; K01580; -.
DR   OMA; WRAKGTT; -.
DR   OrthoDB; EOG091G07ZU; -.
DR   PhylomeDB; Q05329; -.
DR   TreeFam; TF314688; -.
DR   BioCyc; MetaCyc:HS06208-MONOMER; -.
DR   BRENDA; 4.1.1.15; 2681.
DR   Reactome; R-HSA-888568; GABA synthesis.
DR   Reactome; R-HSA-888590; GABA synthesis, release, reuptake and degradation.
DR   SABIO-RK; Q05329; -.
DR   EvolutionaryTrace; Q05329; -.
DR   GeneWiki; GAD2; -.
DR   GenomeRNAi; 2572; -.
DR   PRO; PR:Q05329; -.
DR   Proteomes; UP000005640; Chromosome 10.
DR   Bgee; ENSG00000136750; -.
DR   CleanEx; HS_GAD2; -.
DR   ExpressionAtlas; Q05329; baseline and differential.
DR   Genevisible; Q05329; HS.
DR   GO; GO:0031225; C:anchored component of membrane; IEA:Ensembl.
DR   GO; GO:0030424; C:axon; IEA:Ensembl.
DR   GO; GO:0030054; C:cell junction; IEA:UniProtKB-KW.
DR   GO; GO:0061202; C:clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane; TAS:Reactome.
DR   GO; GO:0005829; C:cytosol; IEA:UniProtKB-SubCell.
DR   GO; GO:0000139; C:Golgi membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0060077; C:inhibitory synapse; IEA:Ensembl.
DR   GO; GO:0048471; C:perinuclear region of cytoplasm; IEA:Ensembl.
DR   GO; GO:0005886; C:plasma membrane; TAS:Reactome.
DR   GO; GO:0042734; C:presynaptic membrane; IEA:UniProtKB-SubCell.
DR   GO; GO:0030672; C:synaptic vesicle membrane; IEA:Ensembl.
DR   GO; GO:0016595; F:glutamate binding; IEA:Ensembl.
DR   GO; GO:0004351; F:glutamate decarboxylase activity; TAS:Reactome.
DR   GO; GO:0046982; F:protein heterodimerization activity; IEA:Ensembl.
DR   GO; GO:0030170; F:pyridoxal phosphate binding; IEA:Ensembl.
DR   GO; GO:0007268; P:chemical synaptic transmission; TAS:ProtInc.
DR   GO; GO:0006540; P:glutamate decarboxylation to succinate; TAS:ProtInc.
DR   GO; GO:0042136; P:neurotransmitter biosynthetic process; IEA:UniProtKB-KW.
DR   GO; GO:0042493; P:response to drug; IEA:Ensembl.
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 junction; Cell membrane; Complete proteome;
KW   Cytoplasm; Cytoplasmic vesicle; Decarboxylase; Golgi apparatus;
KW   Lipoprotein; Lyase; Membrane; Neurotransmitter biosynthesis;
KW   Palmitate; Phosphoprotein; Polymorphism; Pyridoxal phosphate;
KW   Reference proteome; Synapse.
FT   CHAIN         1    585       Glutamate decarboxylase 2.
FT                                /FTId=PRO_0000146968.
FT   REGION      181    183       Substrate binding.
FT   BINDING     558    558       Substrate. {ECO:0000269|PubMed:17384644}.
FT   MOD_RES       3      3       Phosphoserine.
FT                                {ECO:0000269|PubMed:8999827}.
FT   MOD_RES       6      6       Phosphoserine.
FT                                {ECO:0000269|PubMed:8999827}.
FT   MOD_RES      10     10       Phosphoserine.
FT                                {ECO:0000269|PubMed:8999827}.
FT   MOD_RES      13     13       Phosphoserine.
FT                                {ECO:0000269|PubMed:8999827}.
FT   MOD_RES     396    396       N6-(pyridoxal phosphate)lysine.
FT   LIPID        30     30       S-palmitoyl cysteine.
FT                                {ECO:0000269|PubMed:12356867}.
FT   LIPID        45     45       S-palmitoyl cysteine.
FT                                {ECO:0000269|PubMed:12356867}.
FT   VARIANT      12     12       G -> R (in dbSNP:rs8190591).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_018821.
FT   VARIANT     124    124       K -> N (in dbSNP:rs8190600).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_018822.
FT   VARIANT     153    153       P -> Q (in dbSNP:rs2839672).
FT                                /FTId=VAR_029176.
FT   VARIANT     232    232       G -> E (in dbSNP:rs2839673).
FT                                /FTId=VAR_029177.
FT   VARIANT     286    286       K -> R (in dbSNP:rs8190671).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_018823.
FT   VARIANT     326    326       G -> A (in dbSNP:rs2839678).
FT                                /FTId=VAR_029178.
FT   VARIANT     375    375       R -> Q (in dbSNP:rs8190730).
FT                                {ECO:0000269|Ref.4}.
FT                                /FTId=VAR_018824.
FT   HELIX        89     91       {ECO:0000244|PDB:2OKK}.
FT   HELIX        94     96       {ECO:0000244|PDB:2OKK}.
FT   HELIX       104    126       {ECO:0000244|PDB:2OKK}.
FT   HELIX       138    144       {ECO:0000244|PDB:2OKK}.
FT   HELIX       156    169       {ECO:0000244|PDB:2OKK}.
FT   STRAND      178    183       {ECO:0000244|PDB:2OKK}.
FT   HELIX       188    200       {ECO:0000244|PDB:2OKK}.
FT   TURN        207    209       {ECO:0000244|PDB:2OKK}.
FT   HELIX       211    228       {ECO:0000244|PDB:2OKK}.
FT   HELIX       231    233       {ECO:0000244|PDB:2OKK}.
FT   STRAND      235    242       {ECO:0000244|PDB:2OKK}.
FT   HELIX       243    258       {ECO:0000244|PDB:2OKK}.
FT   HELIX       262    265       {ECO:0000244|PDB:2OKK}.
FT   HELIX       267    269       {ECO:0000244|PDB:2OKK}.
FT   STRAND      273    278       {ECO:0000244|PDB:2OKK}.
FT   HELIX       284    291       {ECO:0000244|PDB:2OKK}.
FT   HELIX       296    298       {ECO:0000244|PDB:2OKK}.
FT   STRAND      299    302       {ECO:0000244|PDB:2OKK}.
FT   HELIX       312    324       {ECO:0000244|PDB:2OKK}.
FT   STRAND      328    337       {ECO:0000244|PDB:2OKK}.
FT   TURN        339    341       {ECO:0000244|PDB:2OKK}.
FT   HELIX       347    357       {ECO:0000244|PDB:2OKK}.
FT   STRAND      360    365       {ECO:0000244|PDB:2OKK}.
FT   HELIX       368    373       {ECO:0000244|PDB:2OKK}.
FT   TURN        375    377       {ECO:0000244|PDB:2OKK}.
FT   HELIX       378    381       {ECO:0000244|PDB:2OKK}.
FT   HELIX       384    386       {ECO:0000244|PDB:2OKK}.
FT   STRAND      388    392       {ECO:0000244|PDB:2OKK}.
FT   STRAND      405    411       {ECO:0000244|PDB:2OKK}.
FT   HELIX       414    419       {ECO:0000244|PDB:2OKK}.
FT   HELIX       435    437       {ECO:0000244|PDB:2OKK}.
FT   HELIX       440    442       {ECO:0000244|PDB:2OKK}.
FT   HELIX       452    486       {ECO:0000244|PDB:2OKK}.
FT   STRAND      491    497       {ECO:0000244|PDB:2OKK}.
FT   STRAND      500    502       {ECO:0000244|PDB:2OKK}.
FT   STRAND      504    508       {ECO:0000244|PDB:2OKK}.
FT   TURN        511    515       {ECO:0000244|PDB:2OKK}.
FT   HELIX       523    526       {ECO:0000244|PDB:2OKK}.
FT   HELIX       529    540       {ECO:0000244|PDB:2OKK}.
FT   STRAND      544    550       {ECO:0000244|PDB:2OKK}.
FT   STRAND      553    559       {ECO:0000244|PDB:2OKK}.
FT   HELIX       568    581       {ECO:0000244|PDB:2OKK}.
SQ   SEQUENCE   585 AA;  65411 MW;  0322509F0E2C32EE CRC64;
     MASPGSGFWS FGSEDGSGDS ENPGTARAWC QVAQKFTGGI GNKLCALLYG DAEKPAESGG
     SQPPRAAARK AACACDQKPC SCSKVDVNYA FLHATDLLPA CDGERPTLAF LQDVMNILLQ
     YVVKSFDRST KVIDFHYPNE LLQEYNWELA DQPQNLEEIL MHCQTTLKYA IKTGHPRYFN
     QLSTGLDMVG LAADWLTSTA NTNMFTYEIA PVFVLLEYVT LKKMREIIGW PGGSGDGIFS
     PGGAISNMYA MMIARFKMFP EVKEKGMAAL PRLIAFTSEH SHFSLKKGAA ALGIGTDSVI
     LIKCDERGKM IPSDLERRIL EAKQKGFVPF LVSATAGTTV YGAFDPLLAV ADICKKYKIW
     MHVDAAWGGG LLMSRKHKWK LSGVERANSV TWNPHKMMGV PLQCSALLVR EEGLMQNCNQ
     MHASYLFQQD KHYDLSYDTG DKALQCGRHV DVFKLWLMWR AKGTTGFEAH VDKCLELAEY
     LYNIIKNREG YEMVFDGKPQ HTNVCFWYIP PSLRTLEDNE ERMSRLSKVA PVIKARMMEY
     GTTMVSYQPL GDKVNFFRMV ISNPAATHQD IDFLIEEIER LGQDL
//
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