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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)DescriptionActionsGraphical viewLength
    Binding sitei558Substrate1 Publication1

    GO - Molecular functioni

    GO - Biological processi

    • chemical synaptic transmission Source: ProtInc
    • glutamate decarboxylation to succinate Source: ProtInc
    • neurotransmitter biosynthetic process Source: UniProtKB-KW
    • neurotransmitter secretion Source: Reactome
    • response to drug Source: Ensembl
    Complete GO annotation...

    Keywords - Molecular functioni

    Decarboxylase, Lyase

    Keywords - Biological processi

    Neurotransmitter biosynthesis

    Keywords - Ligandi

    Pyridoxal phosphate

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06208-MONOMER.
    ZFISH:HS06208-MONOMER.
    BRENDAi4.1.1.15. 2681.
    ReactomeiR-HSA-888568. GABA synthesis.
    R-HSA-888590. GABA synthesis, release, reuptake and degradation.
    SABIO-RKQ05329.

    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
    Proteomesi
    • UP000005640 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

    DisGeNETi2572.
    OpenTargetsiENSG00000136750.
    PharmGKBiPA28508.

    Chemistry databases

    ChEMBLiCHEMBL2952.

    Polymorphism and mutation databases

    BioMutaiGAD2.
    DMDMi1352216.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    ChainiPRO_00001469681 – 585Glutamate decarboxylase 2Add BLAST585

    Amino acid modifications

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Modified residuei3Phosphoserine1 Publication1
    Modified residuei6Phosphoserine1 Publication1
    Modified residuei10Phosphoserine1 Publication1
    Modified residuei13Phosphoserine1 Publication1
    Lipidationi30S-palmitoyl cysteine1 Publication1
    Lipidationi45S-palmitoyl cysteine1 Publication1
    Modified residuei396N6-(pyridoxal phosphate)lysine1

    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

    iPTMnetiQ05329.
    PhosphoSitePlusiQ05329.
    SwissPalmiQ05329.

    Expressioni

    Gene expression databases

    BgeeiENSG00000136750.
    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
    ARL6IP1Q150415EBI-9304251,EBI-714543
    CMTM5Q96DZ93EBI-9304251,EBI-2548702
    MAL2Q969L25EBI-9304251,EBI-944295
    TMEM159Q96B963EBI-9304251,EBI-7055862

    Protein-protein interaction databases

    BioGridi108846. 8 interactors.
    DIPiDIP-29293N.
    IntActiQ05329. 6 interactors.
    STRINGi9606.ENSP00000259271.

    Structurei

    Secondary structure

    1585
    Legend: HelixTurnBeta strandPDB Structure known for this area
    Show more details
    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Helixi89 – 91Combined sources3
    Helixi94 – 96Combined sources3
    Helixi104 – 126Combined sources23
    Helixi138 – 144Combined sources7
    Helixi156 – 169Combined sources14
    Beta strandi178 – 183Combined sources6
    Helixi188 – 200Combined sources13
    Turni207 – 209Combined sources3
    Helixi211 – 228Combined sources18
    Helixi231 – 233Combined sources3
    Beta strandi235 – 242Combined sources8
    Helixi243 – 258Combined sources16
    Helixi262 – 265Combined sources4
    Helixi267 – 269Combined sources3
    Beta strandi273 – 278Combined sources6
    Helixi284 – 291Combined sources8
    Helixi296 – 298Combined sources3
    Beta strandi299 – 302Combined sources4
    Helixi312 – 324Combined sources13
    Beta strandi328 – 337Combined sources10
    Turni339 – 341Combined sources3
    Helixi347 – 357Combined sources11
    Beta strandi360 – 365Combined sources6
    Helixi368 – 373Combined sources6
    Turni375 – 377Combined sources3
    Helixi378 – 381Combined sources4
    Helixi384 – 386Combined sources3
    Beta strandi388 – 392Combined sources5
    Beta strandi405 – 411Combined sources7
    Helixi414 – 419Combined sources6
    Helixi435 – 437Combined sources3
    Helixi440 – 442Combined sources3
    Helixi452 – 486Combined sources35
    Beta strandi491 – 497Combined sources7
    Beta strandi500 – 502Combined sources3
    Beta strandi504 – 508Combined sources5
    Turni511 – 515Combined sources5
    Helixi523 – 526Combined sources4
    Helixi529 – 540Combined sources12
    Beta strandi544 – 550Combined sources7
    Beta strandi553 – 559Combined sources7
    Helixi568 – 581Combined sources14

    3D structure databases

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

    Miscellaneous databases

    EvolutionaryTraceiQ05329.

    Family & Domainsi

    Region

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Regioni181 – 183Substrate binding3

    Sequence similaritiesi

    Belongs to the group II decarboxylase family.Curated

    Phylogenomic databases

    eggNOGiKOG0629. Eukaryota.
    COG0076. LUCA.
    GeneTreeiENSGT00760000119205.
    HOGENOMiHOG000005382.
    HOVERGENiHBG004980.
    InParanoidiQ05329.
    KOiK01580.
    OMAiWRAKGTT.
    OrthoDBiEOG091G07ZU.
    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 differs from that shown. Reason: Erroneous initiation.Curated

    Natural variant

    Feature keyPosition(s)DescriptionActionsGraphical viewLength
    Natural variantiVAR_01882112G → R.1 PublicationCorresponds to variant rs8190591dbSNPEnsembl.1
    Natural variantiVAR_018822124K → N.1 PublicationCorresponds to variant rs8190600dbSNPEnsembl.1
    Natural variantiVAR_029176153P → Q.Corresponds to variant rs2839672dbSNPEnsembl.1
    Natural variantiVAR_029177232G → E.Corresponds to variant rs2839673dbSNPEnsembl.1
    Natural variantiVAR_018823286K → R.1 PublicationCorresponds to variant rs8190671dbSNPEnsembl.1
    Natural variantiVAR_029178326G → A.Corresponds to variant rs2839678dbSNPEnsembl.1
    Natural variantiVAR_018824375R → Q.1 PublicationCorresponds to variant rs8190730dbSNPEnsembl.1

    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.

    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
    PDB entryMethodResolution (Å)ChainPositionsPDBsum
    1ES0X-ray2.60B207-220[»]
    2OKKX-ray2.30A88-584[»]
    ProteinModelPortaliQ05329.
    SMRiQ05329.
    ModBaseiSearch...
    MobiDBiSearch...

    Protein-protein interaction databases

    BioGridi108846. 8 interactors.
    DIPiDIP-29293N.
    IntActiQ05329. 6 interactors.
    STRINGi9606.ENSP00000259271.

    Chemistry databases

    ChEMBLiCHEMBL2952.

    PTM databases

    iPTMnetiQ05329.
    PhosphoSitePlusiQ05329.
    SwissPalmiQ05329.

    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.

    Organism-specific databases

    CTDi2572.
    DisGeNETi2572.
    GeneCardsiGAD2.
    HGNCiHGNC:4093. GAD2.
    HPAiCAB002682.
    HPA044637.
    MIMi138275. gene.
    neXtProtiNX_Q05329.
    OpenTargetsiENSG00000136750.
    PharmGKBiPA28508.
    GenAtlasiSearch...

    Phylogenomic databases

    eggNOGiKOG0629. Eukaryota.
    COG0076. LUCA.
    GeneTreeiENSGT00760000119205.
    HOGENOMiHOG000005382.
    HOVERGENiHBG004980.
    InParanoidiQ05329.
    KOiK01580.
    OMAiWRAKGTT.
    OrthoDBiEOG091G07ZU.
    PhylomeDBiQ05329.
    TreeFamiTF314688.

    Enzyme and pathway databases

    BioCyciMetaCyc:HS06208-MONOMER.
    ZFISH:HS06208-MONOMER.
    BRENDAi4.1.1.15. 2681.
    ReactomeiR-HSA-888568. GABA synthesis.
    R-HSA-888590. GABA synthesis, release, reuptake and degradation.
    SABIO-RKQ05329.

    Miscellaneous databases

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

    Gene expression databases

    BgeeiENSG00000136750.
    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...

    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: November 30, 2016
    This is version 149 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

    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 one 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.