Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

Q05329 (DCE2_HUMAN) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 125. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Web links·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:GAD2
Synonyms:GAD65
OrganismHomo sapiens (Human) [Reference proteome]
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length585 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

Catalyzes the production of GABA.

Catalytic activity

L-glutamate = 4-aminobutanoate + CO2.

Cofactor

Pyridoxal phosphate. Ref.10

Subunit structure

Homodimer. Ref.10

Subcellular location

Cytoplasmcytosol. Cytoplasmic vesicle. Cell junctionsynapsepresynaptic cell membrane; Lipid-anchor. Golgi apparatus membrane; Peripheral membrane protein; Cytoplasmic side. Note: Associated to cytoplasmic vesicles. In neurons, cytosolic leaflet of Golgi membranes and presynaptic clusters. Ref.8

Post-translational modification

Phosphorylated; which does not affect kinetic parameters or subcellular location. Ref.7

Palmitoylated; which is required for presynaptic clustering. Ref.8

Sequence similarities

Belongs to the group II decarboxylase family.

Biophysicochemical properties

Kinetic parameters:

KM=2.15 mM for glutamate Ref.7

Sequence caution

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

Ontologies

Keywords
   Biological processNeurotransmitter biosynthesis
   Cellular componentCell junction
Cell membrane
Cytoplasm
Cytoplasmic vesicle
Golgi apparatus
Membrane
Synapse
   Coding sequence diversityPolymorphism
   LigandPyridoxal phosphate
   Molecular functionDecarboxylase
Lyase
   PTMLipoprotein
Palmitate
Phosphoprotein
   Technical term3D-structure
Complete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processglutamate decarboxylation to succinate

Traceable author statement Ref.2. Source: ProtInc

neurotransmitter biosynthetic process

Inferred from electronic annotation. Source: UniProtKB-KW

neurotransmitter secretion

Traceable author statement. Source: Reactome

response to drug

Inferred from electronic annotation. Source: Ensembl

synaptic transmission

Traceable author statement. Source: Reactome

   Cellular_componentGolgi membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

anchored component of membrane

Inferred from electronic annotation. Source: Ensembl

axon

Inferred from electronic annotation. Source: Ensembl

cell junction

Inferred from electronic annotation. Source: UniProtKB-KW

clathrin-sculpted gamma-aminobutyric acid transport vesicle membrane

Traceable author statement. Source: Reactome

cytosol

Inferred from electronic annotation. Source: UniProtKB-SubCell

perinuclear region of cytoplasm

Inferred from electronic annotation. Source: Ensembl

plasma membrane

Traceable author statement. Source: Reactome

presynaptic membrane

Inferred from electronic annotation. Source: UniProtKB-SubCell

synaptic vesicle membrane

Inferred from electronic annotation. Source: Ensembl

   Molecular_functionglutamate binding

Inferred from electronic annotation. Source: Ensembl

glutamate decarboxylase activity

Inferred from electronic annotation. Source: UniProtKB-EC

pyridoxal phosphate binding

Inferred from electronic annotation. Source: Ensembl

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 585585Glutamate decarboxylase 2
PRO_0000146968

Regions

Region181 – 1833Substrate binding

Sites

Binding site5581Substrate

Amino acid modifications

Modified residue31Phosphoserine Ref.7
Modified residue61Phosphoserine Ref.7
Modified residue101Phosphoserine Ref.7
Modified residue131Phosphoserine Ref.7
Modified residue3961N6-(pyridoxal phosphate)lysine
Lipidation301S-palmitoyl cysteine Ref.8
Lipidation451S-palmitoyl cysteine Ref.8

Natural variations

Natural variant121G → R. Ref.4
Corresponds to variant rs8190591 [ dbSNP | Ensembl ].
VAR_018821
Natural variant1241K → N. Ref.4
Corresponds to variant rs8190600 [ dbSNP | Ensembl ].
VAR_018822
Natural variant1531P → Q.
Corresponds to variant rs2839672 [ dbSNP | Ensembl ].
VAR_029176
Natural variant2321G → E.
Corresponds to variant rs2839673 [ dbSNP | Ensembl ].
VAR_029177
Natural variant2861K → R. Ref.4
Corresponds to variant rs8190671 [ dbSNP | Ensembl ].
VAR_018823
Natural variant3261G → A.
Corresponds to variant rs2839678 [ dbSNP | Ensembl ].
VAR_029178
Natural variant3751R → Q. Ref.4
Corresponds to variant rs8190730 [ dbSNP | Ensembl ].
VAR_018824

Secondary structure

.................................................................................. 585
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
Q05329 [UniParc].

Last modified February 1, 1996. Version 1.
Checksum: 0322509F0E2C32EE

FASTA58565,411
        10         20         30         40         50         60 
MASPGSGFWS FGSEDGSGDS ENPGTARAWC QVAQKFTGGI GNKLCALLYG DAEKPAESGG 

        70         80         90        100        110        120 
SQPPRAAARK AACACDQKPC SCSKVDVNYA FLHATDLLPA CDGERPTLAF LQDVMNILLQ 

       130        140        150        160        170        180 
YVVKSFDRST KVIDFHYPNE LLQEYNWELA DQPQNLEEIL MHCQTTLKYA IKTGHPRYFN 

       190        200        210        220        230        240 
QLSTGLDMVG LAADWLTSTA NTNMFTYEIA PVFVLLEYVT LKKMREIIGW PGGSGDGIFS 

       250        260        270        280        290        300 
PGGAISNMYA MMIARFKMFP EVKEKGMAAL PRLIAFTSEH SHFSLKKGAA ALGIGTDSVI 

       310        320        330        340        350        360 
LIKCDERGKM IPSDLERRIL EAKQKGFVPF LVSATAGTTV YGAFDPLLAV ADICKKYKIW 

       370        380        390        400        410        420 
MHVDAAWGGG LLMSRKHKWK LSGVERANSV TWNPHKMMGV PLQCSALLVR EEGLMQNCNQ 

       430        440        450        460        470        480 
MHASYLFQQD KHYDLSYDTG DKALQCGRHV DVFKLWLMWR AKGTTGFEAH VDKCLELAEY 

       490        500        510        520        530        540 
LYNIIKNREG YEMVFDGKPQ HTNVCFWYIP PSLRTLEDNE ERMSRLSKVA PVIKARMMEY 

       550        560        570        580 
GTTMVSYQPL GDKVNFFRMV ISNPAATHQD IDFLIEEIER LGQDL 

« Hide

References

[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]"GABA production by glutamic acid decarboxylase is regulated by a dynamic catalytic loop."
Fenalti G., Law R.H.P., Buckle A.M., Langendorf C., Tuck K., Rosado C.J., Faux N.G., Mahmood K., Hampe C.S., Banga J.P., Wilce M., Schmidberger J., Rossjohn J., El-Kabbani O., Pike R.N., Smith A.I., Mackay I.R., Rowley M.J., Whisstock J.C.
Nat. Struct. Mol. Biol. 14:280-286(2007) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 88-584 IN COMPLEX WITH SUBSTRATE, SUBUNIT, COFACTOR.
+Additional computationally mapped references.

Web resources

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
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.
PIRA41292. A41935.
RefSeqNP_000809.1. NM_000818.2.
NP_001127838.1. NM_001134366.1.
UniGeneHs.231829.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
1ES0X-ray2.60B207-220[»]
2OKKX-ray2.30A88-584[»]
ProteinModelPortalQ05329.
SMRQ05329. Positions 88-584.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

BioGrid108846. 3 interactions.
DIPDIP-29293N.
STRING9606.ENSP00000259271.

Chemistry

BindingDBQ05329.
ChEMBLCHEMBL2952.
DrugBankDB00142. L-Glutamic Acid.

PTM databases

PhosphoSiteQ05329.

Polymorphism databases

DMDM1352216.

Proteomic databases

PaxDbQ05329.
PeptideAtlasQ05329.
PRIDEQ05329.

Protocols and materials databases

DNASU2572.
StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblENST00000259271; ENSP00000259271; ENSG00000136750.
ENST00000376261; ENSP00000365437; ENSG00000136750.
GeneID2572.
KEGGhsa:2572.
UCSCuc001isp.2. human.

Organism-specific databases

CTD2572.
GeneCardsGC10P026545.
HGNCHGNC:4093. GAD2.
HPACAB002682.
HPA044637.
MIM138275. gene.
neXtProtNX_Q05329.
PharmGKBPA28508.
GenAtlasSearch...

Phylogenomic databases

eggNOGCOG0076.
HOGENOMHOG000005382.
HOVERGENHBG004980.
InParanoidQ05329.
KOK01580.
OMAWRAKGTT.
OrthoDBEOG7H1JM3.
PhylomeDBQ05329.
TreeFamTF314688.

Enzyme and pathway databases

BioCycMetaCyc:HS06208-MONOMER.
ReactomeREACT_13685. Neuronal System.

Gene expression databases

ArrayExpressQ05329.
BgeeQ05329.
CleanExHS_GAD2.
GenevestigatorQ05329.

Family and domain databases

Gene3D3.40.640.10. 1 hit.
3.90.1150.10. 1 hit.
InterProIPR002129. 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]
PfamPF00282. Pyridoxal_deC. 1 hit.
[Graphical view]
SUPFAMSSF53383. SSF53383. 1 hit.
PROSITEPS00392. DDC_GAD_HDC_YDC. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceQ05329.
GeneWikiGAD2.
GenomeRNAi2572.
NextBio10175.
PROQ05329.
SOURCESearch...

Entry information

Entry nameDCE2_HUMAN
AccessionPrimary (citable) accession number: Q05329
Secondary accession number(s): Q9UD87
Entry history
Integrated into UniProtKB/Swiss-Prot: February 1, 1996
Last sequence update: February 1, 1996
Last modified: April 16, 2014
This is version 125 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (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.

Relevant documents

SIMILARITY comments

Index of protein domains and families

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

MIM cross-references

Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot

Human polymorphisms and disease mutations

Index of human polymorphisms and disease mutations

Human entries with polymorphisms or disease mutations

List of human entries with polymorphisms or disease mutations

Human chromosome 10

Human chromosome 10: entries, gene names and cross-references to MIM