Glutamate decarboxylase 2 - Homo sapiens (Human)

Names and origin

Protein names

Recommended 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

Organism

Homo sapiens (Human)

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Primates › Haplorrhini › Catarrhini › Hominidae › Homo

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Protein attributes

Sequence length	585 AA.
Sequence status	Complete.
Sequence processing	The displayed sequence is not processed.
Protein existence	Evidence at protein level.

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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	Cytoplasm › cytosol. Cytoplasmic vesicle. Cell junction › synapse › presynaptic 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: K_M=2.15 mM for glutamate

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Ontologies

Keywords
Biological process	Neurotransmitter biosynthesis
Cellular component	Cell junction Cell membrane Cytoplasm Cytoplasmic vesicle Golgi apparatus Membrane Synapse
Coding sequence diversity	Polymorphism
Ligand	Pyridoxal phosphate
Molecular function	Decarboxylase Lyase
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	3D-structure
Gene Ontology (GO)
Biological process	glutamate decarboxylation to succinate Ref.2 Traceable author statement. Source: ProtInc neurotransmitter biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW
Cellular component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytoplasmic vesicle Inferred from electronic annotation. Source: UniProtKB-KW synapse Inferred from electronic annotation. Source: UniProtKB-KW
Molecular function	glutamate decarboxylase activity Inferred from electronic annotation. Source: EC protein binding Inferred from physical interaction. Source: UniProtKB pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

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Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 585

585

Glutamate decarboxylase 2

PRO_0000146968

Regions

Region

181 – 183

3

Substrate binding

Sites

Binding site

396

1

Pyridoxal phosphate (covalent)

Binding site

558

1

Substrate

Amino acid modifications

Modified residue

3

1

Phosphoserine

Modified residue

6

1

Phosphoserine

Modified residue

10

1

Phosphoserine

Modified residue

13

1

Phosphoserine

Lipidation

30

1

S-palmitoyl cysteine

Lipidation

45

1

S-palmitoyl cysteine

Natural variations

Natural variant

12

1

G → R: dbSNP rs8190591.

VAR_018821

Natural variant

124

1

K → N: dbSNP rs8190600.

VAR_018822

Natural variant

153

1

P → Q: dbSNP rs2839672.

VAR_029176

Natural variant

232

1

G → E: dbSNP rs2839673.

VAR_029177

Natural variant

286

1

K → R: dbSNP rs8190671.

VAR_018823

Natural variant

326

1

G → A: dbSNP rs2839678.

VAR_029178

Natural variant

375

1

R → Q: dbSNP rs8190730.

VAR_018824

Secondary structure

1

.

585

Helix Strand Turn

Details...

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Sequences

Sequence

Length

Mass (Da)

Tools

Q05329-1 [UniParc].

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

585

65,411

        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

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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.

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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.

PIR

A41292. A41935.

RefSeq

NP_000809.1.
NP_001127838.1.

UniGene

Hs.231829

3D structure databases

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ES0	X-ray	2.60	B	222-235	[»]
2OKK	X-ray	2.30	A	88-584	[»]

ModBase

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PTM databases

PhosphoSite

Q05329.

Polymorphism databases

NIEHS-SNPs

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Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Keywords

Gene Ontology (GO)

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Natural variations

Secondary structure

Sequences

References

Cross-references

Sequence databases

3D structure databases

PTM databases

Polymorphism databases