Q05329 (DCE2_HUMAN) 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

Homo sapiens (Human) [Reference proteome]

Taxonomic identifier

9606 [NCBI]

Taxonomic lineage

cellular organisms › Eukaryota › Opisthokonta › Metazoa › Eumetazoa › Bilateria › Deuterostomia › Chordata › Craniata › Vertebrata › Gnathostomata › Teleostomi › Euteleostomi › Sarcopterygii › Tetrapoda › Amniota › Mammalia › Theria › Eutheria › Euarchontoglires › Primates › Haplorrhini › Simiiformes › Catarrhini › Hominoidea › Hominidae › Homininae › Homo

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. Ref.10
Subunit structure	Homodimer. Ref.10
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. 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 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 Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	glutamate 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: Compara
Cellular_component	Golgi membrane Inferred from electronic annotation. Source: UniProtKB-SubCell anchored to membrane Inferred from electronic annotation. Source: Compara axon Inferred from electronic annotation. Source: Compara 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: Compara plasma membrane Traceable author statement. Source: Reactome presynaptic membrane Inferred from electronic annotation. Source: UniProtKB-SubCell synaptic vesicle membrane Inferred from electronic annotation. Source: Compara
Molecular_function	glutamate binding Inferred from electronic annotation. Source: Compara glutamate decarboxylase activity Inferred from electronic annotation. Source: EC pyridoxal phosphate binding Inferred from electronic annotation. Source: Compara
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_0000146968

Regions

Region

181 – 183

3

Substrate binding

Sites

Binding site

558

1

Substrate

Amino acid modifications

Modified residue

3

1

Phosphoserine Ref.7

Modified residue

6

1

Phosphoserine Ref.7

Modified residue

10

1

Phosphoserine Ref.7

Modified residue

13

1

Phosphoserine Ref.7

Modified residue

396

1

N6-(pyridoxal phosphate)lysine

Lipidation

30

1

S-palmitoyl cysteine Ref.8

Lipidation

45

1

S-palmitoyl cysteine Ref.8

Natural variations

Natural variant

12

1

G → R. Ref.4
Corresponds to variant rs8190591 [ dbSNP | Ensembl ].

VAR_018821

Natural variant

124

1

K → N. Ref.4
Corresponds to variant rs8190600 [ dbSNP | Ensembl ].

VAR_018822

Natural variant

153

1

P → Q.
Corresponds to variant rs2839672 [ dbSNP | Ensembl ].

VAR_029176

Natural variant

232

1

G → E.
Corresponds to variant rs2839673 [ dbSNP | Ensembl ].

VAR_029177

Natural variant

286

1

K → R. Ref.4
Corresponds to variant rs8190671 [ dbSNP | Ensembl ].

VAR_018823

Natural variant

326

1

G → A.
Corresponds to variant rs2839678 [ dbSNP | Ensembl ].

VAR_029178

Natural variant

375

1

R → Q. Ref.4
Corresponds to variant rs8190730 [ dbSNP | Ensembl ].

VAR_018824

Secondary structure

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585

Helix Strand Turn

Details...

Helix

89 – 91

3

Helix

94 – 96

3

Helix

104 – 126

23

Helix

138 – 144

7

Helix

156 – 169

14

Beta strand

178 – 183

6

Helix

188 – 200

13

Turn

207 – 209

3

Helix

211 – 228

18

Helix

231 – 233

3

Beta strand

235 – 242

8

Helix

243 – 258

16

Helix

262 – 265

4

Helix

267 – 269

3

Beta strand

273 – 278

6

Helix

284 – 291

8

Helix

296 – 298

3

Beta strand

299 – 302

4

Helix

312 – 324

13

Beta strand

328 – 337

10

Turn

339 – 341

3

Helix

347 – 357

11

Beta strand

360 – 365

6

Helix

368 – 373

6

Turn

375 – 377

3

Helix

378 – 381

4

Helix

384 – 386

3

Beta strand

388 – 392

5

Beta strand

405 – 411

7

Helix

414 – 419

6

Helix

435 – 437

3

Helix

440 – 442

3

Helix

452 – 486

35

Beta strand

491 – 497

7

Beta strand

500 – 502

3

Beta strand

504 – 508

5

Turn

511 – 515

5

Helix

523 – 526

4

Helix

529 – 540

12

Beta strand

544 – 550

7

Beta strand

553 – 559

7

Helix

568 – 581

14

Sequences

	Sequence		Length	Mass (Da)
	Q05329 [UniParc]. Last modified February 1, 1996. Version 1. Checksum: 0322509F0E2C32EE	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

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

NIEHS-SNPs

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.

IPI

IPI00012796.

PIR

A41292. A41935.

RefSeq

NP_000809.1. NM_000818.2.
NP_001127838.1. NM_001134366.1.

UniGene

Hs.231829.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1ES0	X-ray	2.60	B	207-220	[»]
2OKK	X-ray	2.30	A	88-584	[»]

ProteinModelPortal

Q05329.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-29293N.

STRING

9606.ENSP00000259271.

PTM databases

PhosphoSite

Q05329.

Polymorphism databases

DMDM

1352216.

Proteomic databases

PaxDb

Q05329.

PeptideAtlas

Q05329.

PRIDE

Q05329.

Protocols and materials databases

DNASU

2572.

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

Ensembl

ENST00000259271; ENSP00000259271; ENSG00000136750.
ENST00000376261; ENSP00000365437; ENSG00000136750.

GeneID

2572.

KEGG

hsa:2572.

UCSC

uc001isp.2. human.

Organism-specific databases

CTD

2572.

GeneCards

GC10P026545.

HGNC

HGNC:4093. GAD2.

HPA

CAB002682.
HPA044637.

MIM

138275. gene.

neXtProt

NX_Q05329.

PharmGKB

PA28508.

GenAtlas

Search...

Phylogenomic databases

eggNOG

COG0076.

HOGENOM

HOG000005382.

HOVERGEN

HBG004980.

InParanoid

Q05329.

KO

K01580.

OMA

HQDIDFL.

OrthoDB

EOG408N7N.

PhylomeDB

Q05329.

Enzyme and pathway databases

BioCyc

MetaCyc:HS06208-MONOMER.

Reactome

REACT_13685. Neuronal System.

Gene expression databases

ArrayExpress

Q05329.

Bgee

Q05329.

CleanEx

HS_GAD2.

Genevestigator

Q05329.

GermOnline

ENSG00000136750. Homo sapiens.

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

Q05329.

ChEMBL

CHEMBL2952.

DrugBank

DB00142. L-Glutamic Acid.

EvolutionaryTrace

Q05329.

GenomeRNAi

2572.

NextBio

10175.

SOURCE

Search...

Entry information

Entry name

DCE2_HUMAN

Accession

Primary (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:	May 1, 2013
This is version 118 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Disclaimer

Any 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.