Escherichia coli K-12 substr. MG1655 Protein: HdeA dimer, inactive form of acid-resistance protein

Gene: hdeA Accession Numbers: EG11398 (EcoCyc), b3510, ECK3494

Synonyms: yhiB, yhhC

Regulation Summary Diagram: ?

Regulation summary diagram for hdeA

Subunit composition of HdeA dimer, inactive form of acid-resistance protein = [HdeA]2
         acid-resistance protein, possible chaperone = HdeA

HdeA is a periplasmic protein that plays a role in resistance to low pH [Gajiwala00, Masuda03].

HdeA is not required for growth on rich or minimal media [Link97a]. The effects of insertion mutations on cell growth are observed to vary depending on the construction of the mutant allele [Link97a]. A hdeA mutant had severely reduced survival after four hours of growth in fresh or spent LB at pH 2.5 [Mates07].

The crystal structure has been solved at 2.0 Å resolution [Gajiwala00]. A crystal structure is presented [Yang98b]. HdeA dimers dissociate at low pH and the monomer is involved in protecting proteins from acid-induced denaturation and aggregation [Gajiwala00, Tapley09]. HdeA is found in a covalently-bound homomultimeric complex [Link97]. HdeA is found at high abundance in vivo [Link97]. HdeB is predicted to have structural similarity to HdeA and the two proteins may heterodimerize in vivo [Gajiwala00]. HdeA has a signal peptide that is cleaved from the mature protein [Wasinger98].

hdeA is acid inducible (pH 4.5-5.5) [Tucker02]. Addition of HdeA suppresses the aggregation of typical chaperone substrates at pH values below 2.5 [Hong05]. In vitro HdeA forms soluble complexes with denatured substrate proteins at low pH but dissociates upon return to neutral pH [Hong05]. Purified HdeA adopts a disordered conformation at pH values less than 3 [Hong05] and exposes hydrophobic surfaces thaty may be involved in binding denatured substrates [Wu08a].

The periplasmic chaperones SurA and Deg P were identified as HdeA substrates under conditions of low pH [Zhang11b]. In vitro, addition of HdeA suppresses the acid induced aggregation and precipitation of SurA [Zhang11b]. In vivo a large amount of insoluble SurA is recovered from acid treated hdeA deletion strains whilst SurA remains soluble in acid treated cultures of wild-type E. coli [Zhang11b]. SurA or DegP assist HdeA in re-folding acid denatured alkaline phosphatase in vitro leading to the suggestion that HdeA functions to protect chaperones such as DegP and SurA which can then use their chaperoning ability to subsequently enhance refolding of other proteins during pH recovery [Zhang11b].

Transcription is negatively regulated by the TorS-TorR two-component signaling system [Bordi03]. Transcription is induced by overproduction of YdeO [Masuda03]. Crl increases hdeA expression via RpoS [Dudin13].

HdeA: hns-dependent expression [Yoshida93a]

Citations: [Liwo99, Holland99, Spory02, Arnqvist94]

Gene Citations: [Arnqvist94, Yoshida93, Tucker03]

Locations: periplasmic space

Map Position: [3,654,431 <- 3,654,763] (78.76 centisomes, 284°)
Length: 333 bp / 110 aa

Molecular Weight of Polypeptide: 11.858 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0011464 , CGSC:33734 , DIP:DIP-47945N , EchoBASE:EB1370 , EcoGene:EG11398 , EcoliWiki:b3510 , ModBase:P0AES9 , OU-Microarray:b3510 , PortEco:hdeA , PR:PRO_000022868 , Pride:P0AES9 , Protein Model Portal:P0AES9 , RefSeq:NP_417967 , RegulonDB:EG11398 , SMR:P0AES9 , String:511145.b3510 , Swiss-Model:P0AES9 , UniProt:P0AES9

Relationship Links: InterPro:IN-FAMILY:IPR010486 , InterPro:IN-FAMILY:IPR024972 , PDB:Structure:1BG8 , PDB:Structure:1DJ8 , Pfam:IN-FAMILY:PF06411 , ProDom:IN-FAMILY:PD065392

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for hdeA

GO Terms:

Biological Process: GO:0071468 - cellular response to acidic pH Inferred from experiment Inferred by computational analysis [GOA01a, Gajiwala00]
GO:0033554 - cellular response to stress Inferred by computational analysis [GOA06]
Molecular Function: GO:0042803 - protein homodimerization activity Inferred from experiment [Gajiwala00]
GO:0051087 - chaperone binding Inferred from experiment [Zhang11b]
Cellular Component: GO:0030288 - outer membrane-bounded periplasmic space Inferred by computational analysis [GOA01a, Yoshida93, Gajiwala00]
GO:0042597 - periplasmic space Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06]

MultiFun Terms: cell processes adaptations pH
cell processes defense/survival

Essentiality data for hdeA knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 1]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 2]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 1]

Curated 16-Apr-2007 by Johnson A , TIGR
Last-Curated ? 11-Oct-2011 by Mackie A , Macquarie University

Sequence Features

Protein sequence of acid-resistance protein, possible chaperone with features indicated

Feature Class Location Citations Comment
Signal-Sequence 1 -> 21
[Pasquali94, Yoshida93, Wasinger98, Link97, UniProt12]
Chain 22 -> 110
UniProt: Chaperone-like protein hdeA;
Disulfide-Bond-Site 39, 87

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b3510 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG11398; confirmed by SwissProt match.


Arnqvist94: Arnqvist A, Olsen A, Normark S (1994). "Sigma S-dependent growth-phase induction of the csgBA promoter in Escherichia coli can be achieved in vivo by sigma 70 in the absence of the nucleoid-associated protein H-NS." Mol Microbiol 1994;13(6);1021-32. PMID: 7854117

Baba06: Baba T, Ara T, Hasegawa M, Takai Y, Okumura Y, Baba M, Datsenko KA, Tomita M, Wanner BL, Mori H (2006). "Construction of Escherichia coli K-12 in-frame, single-gene knockout mutants: the Keio collection." Mol Syst Biol 2;2006.0008. PMID: 16738554

Bordi03: Bordi C, Theraulaz L, Mejean V, Jourlin-Castelli C (2003). "Anticipating an alkaline stress through the Tor phosphorelay system in Escherichia coli." Mol Microbiol 48(1);211-23. PMID: 12657056

Dudin13: Dudin O, Lacour S, Geiselmann J (2013). "Expression dynamics of RpoS/Crl-dependent genes in Escherichia coli." Res Microbiol 164(8);838-47. PMID: 23867204

Gajiwala00: Gajiwala KS, Burley SK (2000). "HDEA, a periplasmic protein that supports acid resistance in pathogenic enteric bacteria." J Mol Biol 2000;295(3);605-12. PMID: 10623550

GOA01a: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

GOA06: GOA, SIB (2006). "Electronic Gene Ontology annotations created by transferring manual GO annotations between orthologous microbial proteins."

Holland99: Holland RD, Duffy CR, Rafii F, Sutherland JB, Heinze TM, Holder CL, Voorhees KJ, Lay JO (1999). "Identification of bacterial proteins observed in MALDI TOF mass spectra from whole cells." Anal Chem 1999;71(15);3226-30. PMID: 10450164

Hong05: Hong W, Jiao W, Hu J, Zhang J, Liu C, Fu X, Shen D, Xia B, Chang Z (2005). "Periplasmic protein HdeA exhibits chaperone-like activity exclusively within stomach pH range by transforming into disordered conformation." J Biol Chem 280(29);27029-34. PMID: 15911614

Joyce06: Joyce AR, Reed JL, White A, Edwards R, Osterman A, Baba T, Mori H, Lesely SA, Palsson BO, Agarwalla S (2006). "Experimental and computational assessment of conditionally essential genes in Escherichia coli." J Bacteriol 188(23);8259-71. PMID: 17012394

Link97: Link AJ, Robison K, Church GM (1997). "Comparing the predicted and observed properties of proteins encoded in the genome of Escherichia coli K-12." Electrophoresis 18(8);1259-313. PMID: 9298646

Link97a: Link AJ, Phillips D, Church GM (1997). "Methods for generating precise deletions and insertions in the genome of wild-type Escherichia coli: application to open reading frame characterization." J Bacteriol 1997;179(20);6228-37. PMID: 9335267

Liwo99: Liwo A, Lee J, Ripoll DR, Pillardy J, Scheraga HA (1999). "Protein structure prediction by global optimization of a potential energy function." Proc Natl Acad Sci U S A 1999;96(10);5482-5. PMID: 10318909

Masuda03: Masuda N, Church GM (2003). "Regulatory network of acid resistance genes in Escherichia coli." Mol Microbiol 48(3);699-712. PMID: 12694615

Mates07: Mates AK, Sayad AK, Foster JW (2007). "Products of the Escherichia coli Acid Fitness Island Attenuate Metabolite Stress at Extreme Low pH and Mediate a Cell Density-Dependent Acid Resistance." J Bacteriol 189(7):2759-68. PMID: 17259322

Pasquali94: Pasquali C., Sanchez J.-C., Ravier F., Golaz O., Hughes G.J., Frutiger S., Paquet N., Wilkins M., Appel R.D., Bairoch A., Hochstrasser D.F. (1994). Data submission to UniProtKB on 1994-09.

Spory02: Spory A, Bosserhoff A, von Rhein C, Goebel W, Ludwig A (2002). "Differential regulation of multiple proteins of Escherichia coli and Salmonella enterica serovar Typhimurium by the transcriptional regulator SlyA." J Bacteriol 2002;184(13);3549-59. PMID: 12057949

Tapley09: Tapley TL, Korner JL, Barge MT, Hupfeld J, Schauerte JA, Gafni A, Jakob U, Bardwell JC (2009). "Structural plasticity of an acid-activated chaperone allows promiscuous substrate binding." Proc Natl Acad Sci U S A 106(14);5557-62. PMID: 19321422

Tucker02: Tucker DL, Tucker N, Conway T (2002). "Gene expression profiling of the pH response in Escherichia coli." J Bacteriol 184(23);6551-8. PMID: 12426343

Tucker03: Tucker DL, Tucker N, Ma Z, Foster JW, Miranda RL, Cohen PS, Conway T (2003). "Genes of the GadX-GadW regulon in Escherichia coli." J Bacteriol 185(10);3190-201. PMID: 12730179

UniProt09: UniProt Consortium (2009). "UniProt version 15.8 released on 2009-10-01 00:00:00." Database.

UniProt12: UniProt Consortium (2012). "UniProt version 2012-02 released on 2012-02-29 00:00:00." Database.

UniProt15: UniProt Consortium (2015). "UniProt version 2015-01 released on 2015-01-16 00:00:00." Database.

UniProtGOA11: UniProt-GOA (2011). "Gene Ontology annotation based on the manual assignment of UniProtKB Subcellular Location terms in UniProtKB/Swiss-Prot entries."

UniProtGOA11a: UniProt-GOA (2011). "Gene Ontology annotation based on manual assignment of UniProtKB keywords in UniProtKB/Swiss-Prot entries."

Wasinger98: Wasinger VC, Humphery-Smith I (1998). "Small genes/gene-products in Escherichia coli K-12." FEMS Microbiol Lett 169(2);375-82. PMID: 9868784

Wu08a: Wu YE, Hong W, Liu C, Zhang L, Chang Z (2008). "Conserved amphiphilic feature is essential for periplasmic chaperone HdeA to support acid resistance in enteric bacteria." Biochem J 412(2);389-97. PMID: 18271752

Yang98b: Yang F, Gustafson KR, Boyd MR, Wlodawer A (1998). "Crystal structure of Escherichia coli HdeA." Nat Struct Biol 1998;5(9);763-4. PMID: 9731767

Yoshida93: Yoshida T, Ueguchi C, Yamada H, Mizuno T (1993). "Function of the Escherichia coli nucleoid protein, H-NS: molecular analysis of a subset of proteins whose expression is enhanced in a hns deletion mutant." Mol Gen Genet 237(1-2);113-22. PMID: 8455549

Yoshida93a: Yoshida T, Ueguchi C, Mizuno T (1993). "Physical map location of a set of Escherichia coli genes (hde) whose expression is affected by the nucleoid protein H-NS." J Bacteriol 1993;175(23);7747-8. PMID: 8244952

Zhang11b: Zhang M, Lin S, Song X, Liu J, Fu Y, Ge X, Fu X, Chang Z, Chen PR (2011). "A genetically incorporated crosslinker reveals chaperone cooperation in acid resistance." Nat Chem Biol 7(10);671-7. PMID: 21892184

Other References Related to Gene Regulation

De99: De Biase D, Tramonti A, Bossa F, Visca P (1999). "The response to stationary-phase stress conditions in Escherichia coli: role and regulation of the glutamic acid decarboxylase system." Mol Microbiol 32(6);1198-211. PMID: 10383761

Hayes06: Hayes ET, Wilks JC, Sanfilippo P, Yohannes E, Tate DP, Jones BD, Radmacher MD, BonDurant SS, Slonczewski JL (2006). "Oxygen limitation modulates pH regulation of catabolism and hydrogenases, multidrug transporters, and envelope composition in Escherichia coli K-12." BMC Microbiol 6;89. PMID: 17026754

Hirakawa10: Hirakawa H, Hayashi-Nishino M, Yamaguchi A, Nishino K (2010). "Indole enhances acid resistance in Escherichia coli." Microb Pathog 49(3);90-4. PMID: 20470880

Hommais04: Hommais F, Krin E, Coppee JY, Lacroix C, Yeramian E, Danchin A, Bertin P (2004). "GadE (YhiE): a novel activator involved in the response to acid environment in Escherichia coli." Microbiology 150(Pt 1);61-72. PMID: 14702398

Itou09: Itou J, Eguchi Y, Utsumi R (2009). "Molecular mechanism of transcriptional cascade initiated by the EvgS/EvgA system in Escherichia coli K-12." Biosci Biotechnol Biochem 73(4);870-8. PMID: 19352034

Johnson11: Johnson MD, Burton NA, Gutierrez B, Painter K, Lund PA (2011). "RcsB Is Required for Inducible Acid Resistance in Escherichia coli and Acts at gadE-Dependent and -Independent Promoters." J Bacteriol 193(14);3653-6. PMID: 21571995

Marzan13: Marzan LW, Hasan CM, Shimizu K (2013). "Effect of acidic condition on the metabolic regulation of Escherichia coli and its phoB mutant." Arch Microbiol 195(3);161-71. PMID: 23274360

Pesavento12: Pesavento C, Hengge R (2012). "The global repressor FliZ antagonizes gene expression by σS-containing RNA polymerase due to overlapping DNA binding specificity." Nucleic Acids Res 40(11);4783-93. PMID: 22323519

Ruiz08: Ruiz C, McMurry LM, Levy SB (2008). "Role of the multidrug resistance regulator MarA in global regulation of the hdeAB acid resistance operon in Escherichia coli." J Bacteriol 190(4);1290-7. PMID: 18083817

Schneiders04: Schneiders T, Barbosa TM, McMurry LM, Levy SB (2004). "The Escherichia coli transcriptional regulator MarA directly represses transcription of purA and hdeA." J Biol Chem 279(10);9037-42. PMID: 14701822

Shin05: Shin M, Song M, Rhee JH, Hong Y, Kim YJ, Seok YJ, Ha KS, Jung SH, Choy HE (2005). "DNA looping-mediated repression by histone-like protein H-NS: specific requirement of Esigma70 as a cofactor for looping." Genes Dev 19(19);2388-98. PMID: 16204188

Tramonti08: Tramonti A, De Canio M, De Biase D (2008). "GadX/GadW-dependent regulation of the Escherichia coli acid fitness island: transcriptional control at the gadY-gadW divergent promoters and identification of four novel 42 bp GadX/GadW-specific binding sites." Mol Microbiol 70(4);965-82. PMID: 18808381

Weber05: Weber H, Polen T, Heuveling J, Wendisch VF, Hengge R (2005). "Genome-wide analysis of the general stress response network in Escherichia coli: sigmaS-dependent genes, promoters, and sigma factor selectivity." J Bacteriol 187(5);1591-603. PMID: 15716429

Zwir05: Zwir I, Shin D, Kato A, Nishino K, Latifi T, Solomon F, Hare JM, Huang H, Groisman EA (2005). "Dissecting the PhoP regulatory network of Escherichia coli and Salmonella enterica." Proc Natl Acad Sci U S A 102(8);2862-7. PMID: 15703297

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Please cite the following article in publications resulting from the use of EcoCyc: Nucleic Acids Research 41:D605-12 2013
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