P69908 (DCEA_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Glutamate decarboxylase alpha
Short name=GAD-alpha
EC=4.1.1.15

Gene names

Name:	gadA
Synonyms:	gadS
Ordered Locus Names:	b3517, JW3485

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

Protein attributes

Sequence length	466 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Converts glutamate to gamma-aminobutyrate (GABA), consuming one intracellular proton in the reaction. The gad system helps to maintain a near-neutral intracellular pH when cells are exposed to extremely acidic conditions. The ability to survive transit through the acidic conditions of the stomach is essential for successful colonization of the mammalian host by commensal and pathogenic bacteria.
Catalytic activity	L-glutamate = 4-aminobutanoate + CO2.
Cofactor	Pyridoxal phosphate.
Subunit structure	Homohexamer.
Induction	By acidic conditions. Expression is regulated by a complex system involving RpoS, cAMP, CRP, EvgAS, H-NS, GadE, GadW and GadX. The level of involvement for each regulator varies depending upon the growth phase and the medium. Ref.9 Ref.10 Ref.11 Ref.12 Ref.13 Ref.14 Ref.15
Sequence similarities	Belongs to the group II decarboxylase family.

Ontologies

Keywords
Ligand	Pyridoxal phosphate
Molecular function	Decarboxylase Lyase
Technical term	3D-structure Complete proteome Direct protein sequencing Reference proteome
Gene Ontology (GO)
Biological_process	glutamate metabolic process Inferred from electronic annotation. Source: InterPro intracellular pH elevation Inferred from mutant phenotype PubMed 10348866. Source: EcoCyc
Cellular_component	cytosol Inferred from direct assay PubMed 16858726. Source: UniProtKB membrane Inferred from direct assay PubMed 16858726. Source: UniProtKB
Molecular_function	glutamate decarboxylase activity Inferred from direct assay PubMed 8954890. Source: EcoCyc pyridoxal phosphate binding Inferred from electronic annotation. Source: InterPro
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 466

466

Glutamate decarboxylase alpha

PRO_0000146978

Regions

Region

126 – 127

2

Pyridoxal phosphate binding By similarity

Sites

Binding site

62

1

Substrate By similarity

Binding site

83

1

Substrate By similarity

Binding site

212

1

Pyridoxal phosphate By similarity

Binding site

275

1

Pyridoxal phosphate By similarity

Amino acid modifications

Modified residue

276

1

N6-(pyridoxal phosphate)lysine

Experimental info

Sequence conflict

64

1

C → S AA sequence Ref.2

Sequence conflict

73

1

H → R AA sequence Ref.2

Sequence conflict

153

1

D → N AA sequence Ref.2

Sequence conflict

165

1

C → S in CAA44834. Ref.2

Sequence conflict

208

1

T → N in CAA44834. Ref.2

Sequence conflict

295

1

L → V in CAA44834. Ref.2

Sequence conflict

355

1

D → N AA sequence Ref.2

Secondary structure

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466

Helix Strand Turn

Details...

Helix

6 – 14

9

Turn

17 – 19

3

Helix

21 – 24

4

Helix

39 – 49

11

Helix

50 – 53

4

Helix

56 – 58

3

Helix

70 – 78

9

Turn

79 – 81

3

Turn

87 – 89

3

Helix

91 – 107

17

Beta strand

119 – 125

7

Helix

126 – 147

22

Beta strand

156 – 161

6

Helix

165 – 172

8

Beta strand

176 – 179

4

Helix

191 – 197

7

Beta strand

202 – 206

5

Beta strand

208 – 210

3

Turn

212 – 214

3

Helix

220 – 234

15

Beta strand

240 – 243

4

Helix

247 – 249

3

Helix

251 – 254

4

Beta strand

267 – 273

7

Turn

274 – 278

5

Beta strand

285 – 291

7

Helix

292 – 294

3

Helix

297 – 299

3

Beta strand

301 – 305

5

Beta strand

308 – 312

5

Helix

322 – 357

36

Beta strand

360 – 368

9

Turn

371 – 373

3

Beta strand

374 – 382

9

Helix

392 – 400

9

Turn

401 – 403

3

Beta strand

408 – 410

3

Helix

413 – 415

3

Beta strand

419 – 424

6

Helix

431 – 449

19

Sequences

	Sequence		Length	Mass (Da)
	P69908 [UniParc]. Last modified January 4, 2005. Version 1. Checksum: 86F963E710553E22	FASTA	466	52,685
	10 20 30 40 50 60 MDQKLLTDFR SELLDSRFGA KAISTIAESK RFPLHEMRDD VAFQIINDEL YLDGNARQNL 70 80 90 100 110 120 ATFCQTWDDE NVHKLMDLSI NKNWIDKEEY PQSAAIDLRC VNMVADLWHA PAPKNGQAVG 130 140 150 160 170 180 TNTIGSSEAC MLGGMAMKWR WRKRMEAAGK PTDKPNLVCG PVQICWHKFA RYWDVELREI 190 200 210 220 230 240 PMRPGQLFMD PKRMIEACDE NTIGVVPTFG VTYTGNYEFP QPLHDALDKF QADTGIDIDM 250 260 270 280 290 300 HIDAASGGFL APFVAPDIVW DFRLPRVKSI SASGHKFGLA PLGCGWVIWR DEEALPQELV 310 320 330 340 350 360 FNVDYLGGQI GTFAINFSRP AGQVIAQYYE FLRLGREGYT KVQNASYQVA AYLADEIAKL 370 380 390 400 410 420 GPYEFICTGR PDEGIPAVCF KLKDGEDPGY TLYDLSERLR LRGWQVPAFT LGGEATDIVV 430 440 450 460 MRIMCRRGFE MDFAELLLED YKASLKYLSD HPKLQGIAQQ NSFKHT

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Escherichia coli has two homologous glutamate decarboxylase genes that map to distinct loci." Smith D.K., Kassam T., Singh B., Elliott J.F. J. Bacteriol. 174:5820-5826(1992) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12.
[2]	"The amino acid sequence of glutamate decarboxylase from Escherichia coli. Evolutionary relationship between mammalian and bacterial enzymes." Maras B., Sweeney G., Barra D., Bossa F., John R.A. Eur. J. Biochem. 204:93-98(1992) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE, NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 148-466. Strain: ATCC 11246.
[3]	"Analysis of the Escherichia coli genome. V. DNA sequence of the region from 76.0 to 81.5 minutes." Sofia H.J., Burland V., Daniels D.L., Plunkett G. III, Blattner F.R. Nucleic Acids Res. 22:2576-2586(1994) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"The complete genome sequence of Escherichia coli K-12." Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y. Science 277:1453-1474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[5]	"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T. Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]	"Expression of the Escherichia coli dimorphic glutamic acid decarboxylases is regulated by the nucleoid protein H-NS." Yoshida T., Yamashino T., Ueguchi C., Mizuno T. Biosci. Biotechnol. Biochem. 57:1568-1569(1993) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 1-22.
[7]	"Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Link A.J., Robison K., Church G.M. Electrophoresis 18:1259-1313(1997) [PubMed] [Europe PMC] [Abstract] Cited for: PROTEIN SEQUENCE OF 382-392. Strain: K12 / EMG2.
[8]	"Escherichia coli proteome analysis using the gene-protein database." VanBogelen R.A., Abshire K.Z., Moldover B., Olson E.R., Neidhardt F.C. Electrophoresis 18:1243-1251(1997) [PubMed] [Europe PMC] [Abstract] Cited for: IDENTIFICATION BY 2D-GEL.
[9]	"The response to stationary-phase stress conditions in Escherichia coli: role and regulation of the glutamic acid decarboxylase system." De Biase D., Tramonti A., Bossa F., Visca P. Mol. Microbiol. 32:1198-1211(1999) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSCRIPTIONAL REGULATION. Strain: ATCC 11246.
[10]	"Functional characterization and regulation of gadX, a gene encoding an AraC/XylS-like transcriptional activator of the Escherichia coli glutamic acid decarboxylase system." Tramonti A., Visca P., De Canio M., Falconi M., De Biase D. J. Bacteriol. 184:2603-2613(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSCRIPTIONAL REGULATION. Strain: ATCC 11246.
[11]	"Escherichia coli gene expression responsive to levels of the response regulator EvgA." Masuda N., Church G.M. J. Bacteriol. 184:6225-6234(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSCRIPTIONAL REGULATION. Strain: K12 / MG1655 / ATCC 47076.
[12]	"Collaborative regulation of Escherichia coli glutamate-dependent acid resistance by two AraC-like regulators, GadX and GadW (YhiW)." Ma Z., Richard H., Tucker D.L., Conway T., Foster J.W. J. Bacteriol. 184:7001-7012(2002) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSCRIPTIONAL REGULATION. Strain: K12.
[13]	"Transcriptional expression of Escherichia coli glutamate-dependent acid resistance genes gadA and gadBC in an hns rpoS mutant." Waterman S.R., Small P.L.C. J. Bacteriol. 185:4644-4647(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSCRIPTIONAL REGULATION.
[14]	"Regulatory network of acid resistance genes in Escherichia coli." Masuda N., Church G.M. Mol. Microbiol. 48:699-712(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSCRIPTIONAL REGULATION. Strain: K12 / MG1655 / ATCC 47076.
[15]	"GadE (YhiE) activates glutamate decarboxylase-dependent acid resistance in Escherichia coli K-12." Ma Z., Gong S., Richard H., Tucker D.L., Conway T., Foster J.W. Mol. Microbiol. 49:1309-1320(2003) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSCRIPTIONAL REGULATION. Strain: K12.
[16]	"Structure of the complex of Escherichia coli glutamate decarboxylase (gadA) with glutarate at 2.05 A resolution." Dutyshev D.I., Darii E.L., Fomenkova N.P., Pechik I.V., Polyakov K.M., Nikonov S.V., Andreeva N.S., Sukhareva B.S. Submitted (SEP-2004) to the PDB data bank Cited for: X-RAY CRYSTALLOGRAPHY (2.05 ANGSTROMS).
+	Additional computationally mapped references.

Web resources

Worthington enzyme manual

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

M84024 Genomic DNA. Translation: AAA23833.1.
X63123 Genomic DNA. Translation: CAA44834.1.
U00039 Genomic DNA. Translation: AAB18493.1.
U00096 Genomic DNA. Translation: AAC76542.1.
AP009048 Genomic DNA. Translation: BAE77777.1.

PIR

S24234. S47737.

RefSeq

NP_417974.1. NC_000913.2.
YP_491918.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1XEY	X-ray	2.05	A/B	1-466	[»]

ProteinModelPortal

P69908.

SMR

P69908. Positions 4-452.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-36201N.

IntAct

P69908. 13 interactions.

MINT

MINT-1224142.

STRING

511145.b3517.

Proteomic databases

PRIDE

P69908.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC76542; AAC76542; b3517.
BAE77777; BAE77777; BAE77777.

GeneID

12932603.
948027.

KEGG

ecj:Y75_p3660.
eco:b3517.

PATRIC

32122496. VBIEscCol129921_3626.

Organism-specific databases

EchoBASE

EB4302.

EcoGene

EG50009. gadA.

Phylogenomic databases

HOGENOM

HOG000070228.

KO

K01580.

OMA

IELREVP.

ProtClustDB

CLSK880040.

Enzyme and pathway databases

BioCyc

EcoCyc:GLUTDECARBOXA-MONOMER.
ECOL316407:JW3485-MONOMER.
MetaCyc:GLUTDECARBOXA-MONOMER.

Gene expression databases

Genevestigator

P69908.

Family and domain databases

Gene3D

3.40.640.10. 1 hit.

InterPro

IPR010107. Glutamate_decarboxylase.
IPR002129. PyrdxlP-dep_de-COase.
IPR015424. PyrdxlP-dep_Trfase.
IPR015421. PyrdxlP-dep_Trfase_major_sub1.
IPR021115. Pyridoxal-P_BS.
[Graphical view]

PANTHER

PTHR11999:SF1. PTHR11999:SF1. 1 hit.

Pfam

PF00282. Pyridoxal_deC. 1 hit.
[Graphical view]

SUPFAM

SSF53383. PyrdxlP-dep_Trfase_major. 1 hit.

TIGRFAMs

TIGR01788. Glu-decarb-GAD. 1 hit.

PROSITE

PS00392. DDC_GAD_HDC_YDC. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P69908.

Entry information

Entry name

DCEA_ECOLI

Accession

Primary (citable) accession number: P69908
Secondary accession number(s): P80063, Q2M7H9

Entry history

Integrated into UniProtKB/Swiss-Prot:	January 4, 2005
Last sequence update:	January 4, 2005
Last modified:	May 1, 2013
This is version 80 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program