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Reviewed, UniProtKB/Swiss-Prot Q05329 (DCE2_HUMAN)

Last modified November 25, 2008. Version 71. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (6) | Third-party data | Customize display text xml rdf/xml gff fasta
Names and origin · Protein attributes · General annotation (Comments) · Ontologies · Sequence annotation (Features) · Sequences · References · Cross-references · Entry information · Relevant documents

Names and origin

Protein namesRecommended name:
    Glutamate decarboxylase 2
    EC=4.1.1.15
Alternative name(s):
    Glutamate decarboxylase 65 kDa isoform
    65 kDa glutamic acid decarboxylase
    GAD-65
Gene names
Name: GAD2
Synonyms: GAD65
OrganismHomo sapiens (Human)
Taxonomic identifier9606 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo

Protein attributes

Sequence length585 AA.
Sequence statusComplete.
Sequence processingThe displayed sequence is not processed.
Protein existenceEvidence at protein level.

General annotation (Comments)

Function

Catalyzes the production of GABA.

Catalytic activity

L-glutamate = 4-aminobutanoate + CO(2).

Cofactor

Pyridoxal phosphate.

Subunit structure

Homodimer.

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.

Post-translational modification

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

Palmitoylated; which is required for presynaptic clustering.

Sequence similarities

Belongs to the group II decarboxylase family.

Biophysicochemical properties

Kinetic parameters:

KM=2.15 mM for glutamate

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 585585Glutamate decarboxylase 2
PRO_0000146968

Regions

Region181 – 1833Substrate binding

Sites

Binding site3961Pyridoxal phosphate (covalent)
Binding site5581Substrate

Amino acid modifications

Modified residue31Phosphoserine
Modified residue61Phosphoserine
Modified residue101Phosphoserine
Modified residue131Phosphoserine
Lipidation301S-palmitoyl cysteine
Lipidation451S-palmitoyl cysteine

Natural variations

Natural variant121G → R: dbSNP rs8190591.
VAR_018821
Natural variant1241K → N: dbSNP rs8190600.
VAR_018822
Natural variant1531P → Q: dbSNP rs2839672.
VAR_029176
Natural variant2321G → E: dbSNP rs2839673.
VAR_029177
Natural variant2861K → R: dbSNP rs8190671.
VAR_018823
Natural variant3261G → A: dbSNP rs2839678.
VAR_029178
Natural variant3751R → Q: dbSNP rs8190730.
VAR_018824

Secondary structure

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

Details...

Sequences

Sequence LengthMass (Da)Tools
Q05329-1 [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: 1924293] [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: 1549570] [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: 8088791] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [MRNA].
[4]"NIEHS-SNPs, environmental genome project, NIEHS ES15478, Department of Genome Sciences, Seattle, WA (URL: http://egp.gs.washington.edu)."
Rieder M.J., Livingston R.J., Daniels M.R., Chung M.-W., Miyamoto K.E., Nguyen C.P., Nguyen D.A., Poel C.L., Robertson P.D., Schackwitz W.S., Sherwood J.K., Witrak L.A., Nickerson D.A.
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: 7680313] [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: 8243826] [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: 8999827] [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: 12356867] [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: 10775108] [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: 17384644] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (2.3 ANGSTROMS) OF 88-584 IN COMPLEX WITH SUBSTRATE, SUBUNIT, COFACTOR.
+Additional computationally mapped references.

Cross-references

Sequence databases

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.
NP_001127838.1.
UniGeneHs.231829

3D structure databases

EntryMethodResolution (Å)ChainPositionsPDBsum
1ES0X-ray2.60B222-235[»]
2OKKX-ray2.30A88-584[»]
ModBaseSearch...

PTM databases

PhosphoSiteQ05329.

Polymorphism databases

NIEHS-SNPsSearch...