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Protein

Glutamate decarboxylase 2

Gene

GAD2

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Catalyzes the production of GABA.

Catalytic activityi

L-glutamate = 4-aminobutanoate + CO2.

Cofactori

pyridoxal 5'-phosphate1 Publication

Kineticsi

  1. KM=2.15 mM for glutamate1 Publication

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei558 – 5581Substrate1 Publication

    GO - Molecular functioni

    GO - Biological processi

    Complete GO annotation...

    Keywords - Molecular functioni

    Decarboxylase, Lyase

    Keywords - Biological processi

    Neurotransmitter biosynthesis

    Keywords - Ligandi

    Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06208-MONOMER.
    BRENDAi4.1.1.15. 2681.
    ReactomeiREACT_23947. GABA synthesis, release, reuptake and degradation.
    REACT_24020. GABA synthesis.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    Glutamate decarboxylase 2 (EC:4.1.1.15)
    Alternative name(s):
    65 kDa glutamic acid decarboxylase
    Short name:
    GAD-65
    Glutamate decarboxylase 65 kDa isoform
    Gene namesi
    Name:GAD2
    Synonyms:GAD65
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640 Componenti: Chromosome 10

    Organism-specific databases

    HGNCiHGNC:4093. GAD2.

    Subcellular locationi

    GO - Cellular componenti

    Complete GO annotation...

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Cytoplasm, Cytoplasmic vesicle, Golgi apparatus, Membrane, Synapse

    Pathology & Biotechi

    Organism-specific databases

    PharmGKBiPA28508.

    Polymorphism and mutation databases

    BioMutaiGAD2.
    DMDMi1352216.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 585585Glutamate decarboxylase 2PRO_0000146968Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei3 – 31Phosphoserine1 Publication
    Modified residuei6 – 61Phosphoserine1 Publication
    Modified residuei10 – 101Phosphoserine1 Publication
    Modified residuei13 – 131Phosphoserine1 Publication
    Lipidationi30 – 301S-palmitoyl cysteine1 Publication
    Lipidationi45 – 451S-palmitoyl cysteine1 Publication
    Modified residuei396 – 3961N6-(pyridoxal phosphate)lysine

    Post-translational modificationi

    Phosphorylated; which does not affect kinetic parameters or subcellular location.1 Publication
    Palmitoylated; which is required for presynaptic clustering.1 Publication

    Keywords - PTMi

    Lipoprotein, Palmitate, Phosphoprotein

    Proteomic databases

    PaxDbiQ05329.
    PeptideAtlasiQ05329.
    PRIDEiQ05329.

    PTM databases

    PhosphoSiteiQ05329.

    Expressioni

    Gene expression databases

    BgeeiQ05329.
    CleanExiHS_GAD2.
    ExpressionAtlasiQ05329. baseline and differential.
    GenevisibleiQ05329. HS.

    Organism-specific databases

    HPAiCAB002682.
    HPA044637.

    Interactioni

    Subunit structurei

    Homodimer.2 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    AGTRAPQ6RW133EBI-9304251,EBI-741181
    ARL6IP1Q150413EBI-9304251,EBI-714543
    CMTM5Q96DZ93EBI-9304251,EBI-2548702
    MAL2Q969L23EBI-9304251,EBI-944295
    TMEM159Q96B963EBI-9304251,EBI-7055862

    Protein-protein interaction databases

    BioGridi108846. 8 interactions.
    DIPiDIP-29293N.
    IntActiQ05329. 5 interactions.
    STRINGi9606.ENSP00000259271.

    Structurei

    Secondary structure

    1
    585
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Helixi89 – 913Combined sources
    Helixi94 – 963Combined sources
    Helixi104 – 12623Combined sources
    Helixi138 – 1447Combined sources
    Helixi156 – 16914Combined sources
    Beta strandi178 – 1836Combined sources
    Helixi188 – 20013Combined sources
    Turni207 – 2093Combined sources
    Helixi211 – 22818Combined sources
    Helixi231 – 2333Combined sources
    Beta strandi235 – 2428Combined sources
    Helixi243 – 25816Combined sources
    Helixi262 – 2654Combined sources
    Helixi267 – 2693Combined sources
    Beta strandi273 – 2786Combined sources
    Helixi284 – 2918Combined sources
    Helixi296 – 2983Combined sources
    Beta strandi299 – 3024Combined sources
    Helixi312 – 32413Combined sources
    Beta strandi328 – 33710Combined sources
    Turni339 – 3413Combined sources
    Helixi347 – 35711Combined sources
    Beta strandi360 – 3656Combined sources
    Helixi368 – 3736Combined sources
    Turni375 – 3773Combined sources
    Helixi378 – 3814Combined sources
    Helixi384 – 3863Combined sources
    Beta strandi388 – 3925Combined sources
    Beta strandi405 – 4117Combined sources
    Helixi414 – 4196Combined sources
    Helixi435 – 4373Combined sources
    Helixi440 – 4423Combined sources
    Helixi452 – 48635Combined sources
    Beta strandi491 – 4977Combined sources
    Beta strandi500 – 5023Combined sources
    Beta strandi504 – 5085Combined sources
    Turni511 – 5155Combined sources
    Helixi523 – 5264Combined sources
    Helixi529 – 54012Combined sources
    Beta strandi544 – 5507Combined sources
    Beta strandi553 – 5597Combined sources
    Helixi568 – 58114Combined sources

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ES0X-ray2.60B207-220[»]
    2OKKX-ray2.30A88-584[»]
    ProteinModelPortaliQ05329.
    SMRiQ05329. Positions 88-584.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiQ05329.

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni181 – 1833Substrate binding

    Sequence similaritiesi

    Belongs to the group II decarboxylase family.Curated

    Phylogenomic databases

    eggNOGiCOG0076.
    GeneTreeiENSGT00760000119205.
    HOGENOMiHOG000005382.
    HOVERGENiHBG004980.
    InParanoidiQ05329.
    KOiK01580.
    OMAiWRAKGTT.
    OrthoDBiEOG7H1JM3.
    PhylomeDBiQ05329.
    TreeFamiTF314688.

    Family and domain databases

    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProiIPR002129. PyrdxlP-dep_de-COase.
    IPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    IPR021115. Pyridoxal-P_BS.
    [Graphical view]
    PfamiPF00282. Pyridoxal_deC. 1 hit.
    [Graphical view]
    SUPFAMiSSF53383. SSF53383. 1 hit.
    PROSITEiPS00392. DDC_GAD_HDC_YDC. 1 hit.
    [Graphical view]

    Sequencei

    Sequence statusi: Complete.

    Q05329-1 [UniParc]FASTAAdd to basket

    « Hide

            10         20         30         40         50
    MASPGSGFWS FGSEDGSGDS ENPGTARAWC QVAQKFTGGI GNKLCALLYG
    60 70 80 90 100
    DAEKPAESGG SQPPRAAARK AACACDQKPC SCSKVDVNYA FLHATDLLPA
    110 120 130 140 150
    CDGERPTLAF LQDVMNILLQ YVVKSFDRST KVIDFHYPNE LLQEYNWELA
    160 170 180 190 200
    DQPQNLEEIL MHCQTTLKYA IKTGHPRYFN QLSTGLDMVG LAADWLTSTA
    210 220 230 240 250
    NTNMFTYEIA PVFVLLEYVT LKKMREIIGW PGGSGDGIFS PGGAISNMYA
    260 270 280 290 300
    MMIARFKMFP EVKEKGMAAL PRLIAFTSEH SHFSLKKGAA ALGIGTDSVI
    310 320 330 340 350
    LIKCDERGKM IPSDLERRIL EAKQKGFVPF LVSATAGTTV YGAFDPLLAV
    360 370 380 390 400
    ADICKKYKIW MHVDAAWGGG LLMSRKHKWK LSGVERANSV TWNPHKMMGV
    410 420 430 440 450
    PLQCSALLVR EEGLMQNCNQ MHASYLFQQD KHYDLSYDTG DKALQCGRHV
    460 470 480 490 500
    DVFKLWLMWR AKGTTGFEAH VDKCLELAEY LYNIIKNREG YEMVFDGKPQ
    510 520 530 540 550
    HTNVCFWYIP PSLRTLEDNE ERMSRLSKVA PVIKARMMEY GTTMVSYQPL
    560 570 580
    GDKVNFFRMV ISNPAATHQD IDFLIEEIER LGQDL
    Length:585
    Mass (Da):65,411
    Last modified:February 1, 1996 - v1
    Checksum:i0322509F0E2C32EE
    GO

    Sequence cautioni

    The sequence CAA49554.1 differs from that shown. Reason: Erroneous initiation. Curated

    Natural variant

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Natural varianti12 – 121G → R.1 Publication
    Corresponds to variant rs8190591 [ dbSNP | Ensembl ].
    VAR_018821
    Natural varianti124 – 1241K → N.1 Publication
    Corresponds to variant rs8190600 [ dbSNP | Ensembl ].
    VAR_018822
    Natural varianti153 – 1531P → Q.
    Corresponds to variant rs2839672 [ dbSNP | Ensembl ].
    VAR_029176
    Natural varianti232 – 2321G → E.
    Corresponds to variant rs2839673 [ dbSNP | Ensembl ].
    VAR_029177
    Natural varianti286 – 2861K → R.1 Publication
    Corresponds to variant rs8190671 [ dbSNP | Ensembl ].
    VAR_018823
    Natural varianti326 – 3261G → A.
    Corresponds to variant rs2839678 [ dbSNP | Ensembl ].
    VAR_029178
    Natural varianti375 – 3751R → Q.1 Publication
    Corresponds to variant rs8190730 [ dbSNP | Ensembl ].
    VAR_018824

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M81882 mRNA. Translation: AAA62367.1.
    M74826 mRNA. Translation: AAA58491.1.
    AY340073 Genomic DNA. Translation: AAP88040.1.
    X69936 mRNA. Translation: CAA49554.1. Different initiation.
    M70435 mRNA. Translation: AAA52513.1.
    CCDSiCCDS7149.1.
    PIRiA41935. A41292.
    RefSeqiNP_000809.1. NM_000818.2.
    NP_001127838.1. NM_001134366.1.
    UniGeneiHs.231829.

    Genome annotation databases

    EnsembliENST00000259271; ENSP00000259271; ENSG00000136750.
    ENST00000376261; ENSP00000365437; ENSG00000136750.
    GeneIDi2572.
    KEGGihsa:2572.
    UCSCiuc001isp.2. human.

    Keywords - Coding sequence diversityi

    Polymorphism

    Cross-referencesi

    Web resourcesi

    NIEHS-SNPs

    Sequence databases

    Select the link destinations:
    EMBLi
    GenBanki
    DDBJi
    Links Updated
    M81882 mRNA. Translation: AAA62367.1.
    M74826 mRNA. Translation: AAA58491.1.
    AY340073 Genomic DNA. Translation: AAP88040.1.
    X69936 mRNA. Translation: CAA49554.1. Different initiation.
    M70435 mRNA. Translation: AAA52513.1.
    CCDSiCCDS7149.1.
    PIRiA41935. A41292.
    RefSeqiNP_000809.1. NM_000818.2.
    NP_001127838.1. NM_001134366.1.
    UniGeneiHs.231829.

    3D structure databases

    Select the link destinations:
    PDBei
    RCSB PDBi
    PDBji
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    1ES0X-ray2.60B207-220[»]
    2OKKX-ray2.30A88-584[»]
    ProteinModelPortaliQ05329.
    SMRiQ05329. Positions 88-584.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108846. 8 interactions.
    DIPiDIP-29293N.
    IntActiQ05329. 5 interactions.
    STRINGi9606.ENSP00000259271.

    Chemistry

    ChEMBLiCHEMBL2952.
    GuidetoPHARMACOLOGYi1273.

    PTM databases

    PhosphoSiteiQ05329.

    Polymorphism and mutation databases

    BioMutaiGAD2.
    DMDMi1352216.

    Proteomic databases

    PaxDbiQ05329.
    PeptideAtlasiQ05329.
    PRIDEiQ05329.

    Protocols and materials databases

    DNASUi2572.
    Structural Biology KnowledgebaseSearch...

    Genome annotation databases

    EnsembliENST00000259271; ENSP00000259271; ENSG00000136750.
    ENST00000376261; ENSP00000365437; ENSG00000136750.
    GeneIDi2572.
    KEGGihsa:2572.
    UCSCiuc001isp.2. human.

    Organism-specific databases

    CTDi2572.
    GeneCardsiGC10P026545.
    HGNCiHGNC:4093. GAD2.
    HPAiCAB002682.
    HPA044637.
    MIMi138275. gene.
    neXtProtiNX_Q05329.
    PharmGKBiPA28508.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiCOG0076.
    GeneTreeiENSGT00760000119205.
    HOGENOMiHOG000005382.
    HOVERGENiHBG004980.
    InParanoidiQ05329.
    KOiK01580.
    OMAiWRAKGTT.
    OrthoDBiEOG7H1JM3.
    PhylomeDBiQ05329.
    TreeFamiTF314688.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06208-MONOMER.
    BRENDAi4.1.1.15. 2681.
    ReactomeiREACT_23947. GABA synthesis, release, reuptake and degradation.
    REACT_24020. GABA synthesis.

    Miscellaneous databases

    EvolutionaryTraceiQ05329.
    GeneWikiiGAD2.
    GenomeRNAii2572.
    NextBioi10175.
    PROiQ05329.
    SOURCEiSearch...

    Gene expression databases

    BgeeiQ05329.
    CleanExiHS_GAD2.
    ExpressionAtlasiQ05329. baseline and differential.
    GenevisibleiQ05329. HS.

    Family and domain databases

    Gene3Di3.40.640.10. 1 hit.
    3.90.1150.10. 1 hit.
    InterProiIPR002129. PyrdxlP-dep_de-COase.
    IPR015424. PyrdxlP-dep_Trfase.
    IPR015421. PyrdxlP-dep_Trfase_major_sub1.
    IPR015422. PyrdxlP-dep_Trfase_major_sub2.
    IPR021115. Pyridoxal-P_BS.
    [Graphical view]
    PfamiPF00282. Pyridoxal_deC. 1 hit.
    [Graphical view]
    SUPFAMiSSF53383. SSF53383. 1 hit.
    PROSITEiPS00392. DDC_GAD_HDC_YDC. 1 hit.
    [Graphical view]
    ProtoNetiSearch...

    Publicationsi

    1. "Cloning and primary structure of a human islet isoform of glutamic acid decarboxylase from chromosome 10."
      Karlsen A.E., Hagopian W.A., Grubin C.E., Dube S., Disteche C.M., Adler D.A., Barmeier H., Mathewes S., Grant F.J., Foster D., Lernmark A.
      Proc. Natl. Acad. Sci. U.S.A. 88:8337-8341(1991) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Tissue: Pancreatic islet.
    2. "Two human glutamate decarboxylases, 65-kDa GAD and 67-kDa GAD, are each encoded by a single gene."
      Bu D.-F., Erlander M.G., Hitz B.C., Tillakaratne N.J., Kaufman D.L., Wagner-Mcpherson C.B., Evans G.A., Tobin A.J.
      Proc. Natl. Acad. Sci. U.S.A. 89:2115-2119(1992) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    3. "The exon-intron organization of the genes (GAD1 and GAD2) encoding two human glutamate decarboxylases (GAD67 and GAD65) suggests that they derive from a common ancestral GAD."
      Bu D.-F., Tobin A.J.
      Genomics 21:222-228(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    4. NIEHS SNPs program
      Submitted (JUL-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], VARIANTS ARG-12; ASN-124; ARG-286 AND GLN-375.
    5. "Characterization of a linear epitope within the human pancreatic 64-kDa glutamic acid decarboxylase and its autoimmune recognition by sera from insulin-dependent diabetes mellitus patients."
      Mauch L., Abney C.C., Berg H., Scherbaum W.A., Liedvogel B., Northemann W.
      Eur. J. Biochem. 212:597-603(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 6-585.
      Tissue: Pancreas.
    6. "Differential expression of GAD65 and GAD67 in human, rat, and mouse pancreatic islets."
      Kim J., Richter W., Aanstoot H.-J., Shi Y., Fu Q., Rajotte R., Warnock G., Baekkeskov S.
      Diabetes 42:1799-1808(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] OF 245-585.
    7. "Phosphorylation of serine residues 3, 6, 10, and 13 distinguishes membrane anchored from soluble glutamic acid decarboxylase 65 and is restricted to glutamic acid decarboxylase 65alpha."
      Namchuk M., Lindsay L., Turck C.W., Kanaani J., Baekkeskov S.
      J. Biol. Chem. 272:1548-1557(1997) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-3; SER-6; SER-10 AND SER-13, BIOPHYSICOCHEMICAL PROPERTIES.
    8. "A combination of three distinct trafficking signals mediates axonal targeting and presynaptic clustering of GAD65."
      Kanaani J., El-Din El-Husseini A., Aguilera-Moreno A., Diacovo J.M., Bredt D.S., Baekkeskov S.
      J. Cell Biol. 158:1229-1238(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION, PALMITOYLATION AT CYS-30 AND CYS-45.
    9. "A structural framework for deciphering the link between I-Ag7 and autoimmune diabetes."
      Corper A.L., Stratmann T., Apostolopoulos V., Scott C.A., Garcia K.C., Kang A.S., Wilson I.A., Teyton L.
      Science 288:505-511(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.6 ANGSTROMS) OF 222-235 IN COMPLEX WITH MHC.
    10. Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 88-584 IN COMPLEX WITH SUBSTRATE, SUBUNIT, COFACTOR.

    Entry informationi

    Entry nameiDCE2_HUMAN
    AccessioniPrimary (citable) accession number: Q05329
    Secondary accession number(s): Q9UD87
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: February 1, 1996
    Last sequence update: February 1, 1996
    Last modified: July 22, 2015
    This is version 137 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. Human chromosome 10
      Human chromosome 10: entries, gene names and cross-references to MIM
    2. Human entries with polymorphisms or disease mutations
      List of human entries with polymorphisms or disease mutations
    3. Human polymorphisms and disease mutations
      Index of human polymorphisms and disease mutations
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3

    Similar proteinsi

    Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
    100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into Uniref entry.
    90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
    50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.