Q05683 (DCE2_RAT) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

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 names

Name:	Gad2
Synonyms:	Gad65

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	585 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Catalyzes the production of GABA.
Catalytic activity	L-glutamate = 4-aminobutanoate + CO2.
Cofactor	Pyridoxal phosphate.
Subunit structure	Homodimer By similarity.
Subcellular location	Cytoplasm › cytosol By similarity. Cytoplasmic vesicle By similarity. Cell junction › synapse › presynaptic cell membrane; Lipid-anchor By similarity. Golgi apparatus membrane; Peripheral membrane protein; Cytoplasmic side By similarity. Note: Associated to cytoplasmic vesicles. In neurons, cytosolic leaflet of Golgi membranes and presynaptic clusters By similarity. Ref.3
Post-translational modification	The N-terminus is blocked. Phosphorylated; which does not affect kinetic parameters or subcellular location. Ref.5 Palmitoylated; which is required for presynaptic clustering By similarity. Ref.3 Ref.4
Sequence similarities	Belongs to the group II decarboxylase family.
Biophysicochemical properties	Kinetic parameters: KM=1.02 mM for glutamate Ref.5

Ontologies

Keywords
Biological process	Neurotransmitter biosynthesis
Cellular component	Cell junction Cell membrane Cytoplasm Cytoplasmic vesicle Golgi apparatus Membrane Synapse
Ligand	Pyridoxal phosphate
Molecular function	Decarboxylase Lyase
PTM	Lipoprotein Palmitate Phosphoprotein
Technical term	Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	glutamate decarboxylation to succinate Inferred from direct assay Ref.5. Source: RGD neurotransmitter biosynthetic process Inferred from electronic annotation. Source: UniProtKB-KW response to drug Inferred from expression pattern PubMed 19359144. Source: RGD synaptic transmission Traceable author statement Ref.5. Source: RGD
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell anchored to membrane Inferred from direct assay Ref.4. Source: RGD axon Inferred from electronic annotation. Source: Compara cell junction Inferred from electronic annotation. Source: UniProtKB-KW cytosol Inferred from direct assay PubMed 17600303. Source: RGD perinuclear region of cytoplasm Inferred from direct assay Ref.4. Source: RGD plasma membrane Inferred from electronic annotation. Source: UniProtKB-KW presynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell synaptic vesicle membrane Inferred from direct assay Ref.5. Source: RGD
Molecular_function	glutamate binding Inferred from direct assay PubMed 10812196. Source: RGD glutamate decarboxylase activity Inferred from direct assay PubMed 10812196Ref.5. Source: RGD protein heterodimerization activity Inferred from direct assay PubMed 7836456. Source: RGD pyridoxal phosphate binding Inferred from direct assay PubMed 1880546. Source: RGD
Complete GO annotation...

Sequence annotation (Features)

	Feature key	Position(s)	Length	Description	Graphical view	Feature identifier
Molecule processing
	Chain	1 – 585	585	Glutamate decarboxylase 2		PRO_0000146971
Regions
	Region	181 – 183	3	Substrate binding By similarity
Sites
	Binding site	558	1	Substrate By similarity
Amino acid modifications
	Modified residue	3	1	Phosphoserine Ref.5
	Modified residue	6	1	Phosphoserine Ref.5
	Modified residue	10	1	Phosphoserine Ref.5
	Modified residue	13	1	Phosphoserine Ref.5
	Modified residue	396	1	N6-(pyridoxal phosphate)lysine By similarity
	Lipidation	30	1	S-palmitoyl cysteine Ref.3 Ref.4
	Lipidation	45	1	S-palmitoyl cysteine Ref.3 Ref.4
Experimental info
	Mutagenesis	30	1	C → A: Abolishes palmitoylation but not membrane-association; when associates with A-45. Ref.4
	Mutagenesis	45	1	C → A: Abolishes palmitoylation but not membrane-association; when associates with A-30. Ref.4
	Mutagenesis	73	1	C → S: No effect on palmitoylation. Ref.4
	Mutagenesis	75	1	C → S: No effect on palmitoylation. Ref.4
	Mutagenesis	80	1	C → S: No effect on palmitoylation. Ref.4
	Mutagenesis	82	1	C → S: No effect on palmitoylation. Ref.4
	Mutagenesis	101	1	C → S: No effect on palmitoylation. Ref.4
	Sequence conflict	190	1	G → V AA sequence Ref.2

Sequences

	Sequence		Length	Mass (Da)
	Q05683 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: C04040B7BA7B37D1	FASTA	585	65,402
	10 20 30 40 50 60 MASPGSGFWS FGSEDGSGDP ENPGTARAWC QVAQKFTGGI GNKLCALLYG DSEKPAESGG 70 80 90 100 110 120 SVTSRAATRK VACTCDQKPC SCPKGDVNYA LLHATDLLPA CEGERPTLAF LQDVMNILLQ 130 140 150 160 170 180 YVVKSFDRST KVIDFHYPNE LLQEYNWELA DQPQNLEEIL THCQTTLKYA IKTGHPRYFN 190 200 210 220 230 240 QLSTGLDMVG LAADWLTSTA NTNMFTYEIA PVFVLLEYVT LKKMREIIGW PGGSGDGIFS 250 260 270 280 290 300 PGGAISNMYA MLIARYKMFP EVKEKGMAAV PRLIAFTSEH SHFSLKKGAA ALGIGTDSVI 310 320 330 340 350 360 LIKCDERGKM IPSDLERRIL EVKQKGFVPF LVSATAGTTV YGAFDPLLAV ADICKKYKIW 370 380 390 400 410 420 MHVDAAWGGG LLMSRKHKWK LNGVERANSV TWNPHKMMGV PLQCSALLVR EEGLMQSCNQ 430 440 450 460 470 480 MHASYLFQQD KHYDLSYDTG DKALQCGRHV DVFKLWLMWR AKGTTGFEAH IDKCLELAEY 490 500 510 520 530 540 LYNIIKNREG YEMVFDGKPQ HTNVCFWFVP PSLRVLEDNE ERMSRLSKVA PVIKARMMEY 550 560 570 580 GTTMVSYQPL GDKVNFFRMV ISNPAATHQD IDFLIEEIER LGQDL

References

[1]	"Two genes encode distinct glutamate decarboxylases." Erlander M.G., Tillakaratne N.J., Feldblum S., Patel N., Tobin A.J. Neuron 7:91-100(1991) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [MRNA]. Tissue: Hippocampus.
[2]	"Characterization of the proteins purified with monoclonal antibodies to glutamic acid decarboxylase." Chang Y.C., Gottlieb D.I. J. Neurosci. 8:2123-2130(1988) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 190-219; 225-266 AND 524-558. Tissue: Brain.
[3]	"Membrane anchoring of the autoantigen GAD65 to microvesicles in pancreatic beta-cells by palmitoylation in the NH2-terminal domain." Christgau S., Aanstoot H.-J., Schierbeck H., Begley K., Tullin S., Hejnaes K., Baekkeskov S. J. Cell Biol. 118:309-320(1992) [PubMed] [Europe PMC] [Abstract] Cited for: SUBCELLULAR LOCATION, PALMITOYLATION.
[4]	"Amino acid residues 24-31 but not palmitoylation of cysteines 30 and 45 are required for membrane anchoring of glutamic acid decarboxylase, GAD65." Shi Y., Veit B., Baekkeskov S. J. Cell Biol. 124:927-934(1994) [PubMed] [Europe PMC] [Abstract] Cited for: PALMITOYLATION AT CYS-30 AND CYS-45, MUTAGENESIS OF CYS-30; CYS-45; CYS-73; CYS-75; CYS-80; CYS-82 AND CYS-101.
[5]	"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.
+	Additional computationally mapped references.

Cross-references

Sequence databases
EMBL GenBank DDBJ	M72422 mRNA. Translation: AAA63488.1.
IPI	IPI00191733.
PIR	JH0423.
RefSeq	NP_036695.1. NM_012563.1.
UniGene	Rn.29951.
3D structure databases
ProteinModelPortal	Q05683.
SMR	Q05683. Positions 88-584.
ModBase	Search...
Protein-protein interaction databases
STRING	10116.ENSRNOP00000024901.
PTM databases
PhosphoSite	Q05683.
Proteomic databases
PRIDE	Q05683.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
Ensembl	ENSRNOT00000024901; ENSRNOP00000024901; ENSRNOG00000018200.
GeneID	24380.
KEGG	rno:24380.
UCSC	RGD:2653. rat.
Organism-specific databases
CTD	2572.
RGD	2653. Gad2.
Phylogenomic databases
eggNOG	COG0076.
GeneTree	ENSGT00550000074275.
HOGENOM	HOG000005382.
HOVERGEN	HBG004980.
InParanoid	Q05683.
KO	K01580.
OMA	HQDIDFL.
OrthoDB	EOG408N7N.
Enzyme and pathway databases
SABIO-RK	Q05683.
Gene expression databases
ArrayExpress	Q05683.
Genevestigator	Q05683.
GermOnline	ENSRNOG00000018200. Rattus norvegicus.
Family and domain databases
Gene3D	3.40.640.10. 1 hit. 3.90.1150.10. 1 hit.
InterPro	IPR002129. 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]
Pfam	PF00282. Pyridoxal_deC. 1 hit. [Graphical view]
SUPFAM	SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.
PROSITE	PS00392. DDC_GAD_HDC_YDC. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	Q05683.
NextBio	603141.

Entry information

Entry name

DCE2_RAT

Accession

Primary (citable) accession number: Q05683

Entry history

Integrated into UniProtKB/Swiss-Prot:	February 1, 1996
Last sequence update:	February 1, 1996
Last modified:	April 3, 2013
This is version 97 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program