HHA_ECOLI
ID HHA_ECOLI Reviewed; 72 AA.
AC P0ACE3; P23870; P77120; Q2MBW7;
DT 22-NOV-2005, integrated into UniProtKB/Swiss-Prot.
DT 22-NOV-2005, sequence version 1.
DT 03-AUG-2022, entry version 119.
DE RecName: Full=Hemolysin expression-modulating protein Hha;
GN Name=hha; OrderedLocusNames=b0460, JW0449;
OS Escherichia coli (strain K12).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Escherichia.
OX NCBI_TaxID=83333;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION IN HEMOLYSIN PRODUCTION, AND
RP DISRUPTION PHENOTYPE.
RC STRAIN=K12 / C600 / CR34 / ATCC 23724 / DSM 3925 / LMG 3041 / NCIB 10222;
RX PubMed=1956303; DOI=10.1111/j.1365-2958.1991.tb01902.x;
RA Nieto J.M., Carmona M., Bolland S., Jubete Y., de la Cruz F., Juarez A.;
RT "The hha gene modulates haemolysin expression in Escherichia coli.";
RL Mol. Microbiol. 5:1285-1293(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RA Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M.,
RA Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D.,
RA Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.;
RT "Sequence of minutes 4-25 of Escherichia coli.";
RL Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases.
RN [3]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=9278503; DOI=10.1126/science.277.5331.1453;
RA Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V.,
RA Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F.,
RA Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B.,
RA Shao Y.;
RT "The complete genome sequence of Escherichia coli K-12.";
RL Science 277:1453-1462(1997).
RN [4]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=16738553; DOI=10.1038/msb4100049;
RA Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S.,
RA Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
RT "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655
RT and W3110.";
RL Mol. Syst. Biol. 2:E1-E5(2006).
RN [5]
RP SIMILARITY TO YMOA.
RX PubMed=1484495; DOI=10.1111/j.1365-2958.1992.tb02214.x;
RA de la Cruz F., Carmona M., Juarez A.;
RT "The Hha protein from Escherichia coli is highly homologous to the YmoA
RT protein from Yersinia enterocolitica.";
RL Mol. Microbiol. 6:3451-3452(1992).
RN [6]
RP FUNCTION, AND FUNCTION IN Y.ENTEROCOLITICA.
RC STRAIN=K12 / C600 / CR34 / ATCC 23724 / DSM 3925 / LMG 3041 / NCIB 10222;
RX PubMed=8145648; DOI=10.1111/j.1365-2958.1994.tb00291.x;
RA Mikulskis A.V., Cornelis G.R.;
RT "A new class of proteins regulating gene expression in enterobacteria.";
RL Mol. Microbiol. 11:77-86(1994).
RN [7]
RP DISRUPTION PHENOTYPE.
RC STRAIN=5K;
RX PubMed=10322001; DOI=10.1128/jb.181.10.3018-3024.1999;
RA Balsalobre C., Johansson J., Uhlin B.E., Juarez A., Munoa F.J.;
RT "Alterations in protein expression caused by the hha mutation in
RT Escherichia coli: influence of growth medium osmolarity.";
RL J. Bacteriol. 181:3018-3024(1999).
RN [8]
RP FUNCTION IN REGULATION OF THE HEMOLYSIN OPERON, DNA-BINDING, AND
RP INTERACTION WITH H-NS.
RX PubMed=10778755; DOI=10.1007/s004380051178;
RA Nieto J.M., Madrid C., Prenafeta A., Miquelay E., Balsalobre C.,
RA Carrascal M., Juarez A.;
RT "Expression of the hemolysin operon in Escherichia coli is modulated by a
RT nucleoid-protein complex that includes the proteins Hha and H-NS.";
RL Mol. Gen. Genet. 263:349-358(2000).
RN [9]
RP FUNCTION, INTERACTION WITH H-NS, DOMAIN, AND MUTAGENESIS OF ARG-16;
RP 44-TYR--ARG-72; ARG-50; 58-LYS--ARG-72; PRO-64 AND ARG-72.
RX PubMed=11790731; DOI=10.1128/jb.184.3.629-635.2002;
RA Nieto J.M., Madrid C., Miquelay E., Parra J.L., Rodriguez S., Juarez A.;
RT "Evidence for direct protein-protein interaction between members of the
RT enterobacterial Hha/YmoA and H-NS families of proteins.";
RL J. Bacteriol. 184:629-635(2002).
RN [10]
RP INDUCTION.
RC STRAIN=K12 / JM109 / ATCC 53323;
RX PubMed=14727089; DOI=10.1007/s00253-003-1517-y;
RA Ren D., Bedzyk L.A., Thomas S.M., Ye R.W., Wood T.K.;
RT "Gene expression in Escherichia coli biofilms.";
RL Appl. Microbiol. Biotechnol. 64:515-524(2004).
RN [11]
RP FUNCTION IN BIOFILM FORMATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / ATCC 25404 / DSM 5698 / NCIMB 11290;
RX PubMed=16317765; DOI=10.1002/bit.20681;
RA Barrios A.F., Zuo R., Ren D., Wood T.K.;
RT "Hha, YbaJ, and OmpA regulate Escherichia coli K12 biofilm formation and
RT conjugation plasmids abolish motility.";
RL Biotechnol. Bioeng. 93:188-200(2006).
RN [12]
RP SUBUNIT.
RX PubMed=16650431; DOI=10.1016/j.jmb.2006.03.059;
RA Garcia J., Madrid C., Juarez A., Pons M.;
RT "New roles for key residues in helices H1 and H2 of the Escherichia coli H-
RT NS N-terminal domain: H-NS dimer stabilization and Hha binding.";
RL J. Mol. Biol. 359:679-689(2006).
RN [13]
RP FUNCTION IN BIOFILM FORMATION, INDUCTION, AND DNA-BINDING.
RC STRAIN=K12 / BW25113;
RX PubMed=18545668; DOI=10.1371/journal.pone.0002394;
RA Garcia-Contreras R., Zhang X.S., Kim Y., Wood T.K.;
RT "Protein translation and cell death: the role of rare tRNAs in biofilm
RT formation and in activating dormant phage killer genes.";
RL PLoS ONE 3:E2394-E2394(2008).
RN [14]
RP FUNCTION IN PERSISTER CELL FORMATION, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / BW25113;
RX PubMed=19909729; DOI=10.1016/j.bbrc.2009.11.033;
RA Kim Y., Wood T.K.;
RT "Toxins Hha and CspD and small RNA regulator Hfq are involved in persister
RT cell formation through MqsR in Escherichia coli.";
RL Biochem. Biophys. Res. Commun. 391:209-213(2010).
RN [15]
RP FUNCTION IN REGULATION OF THE HEMOLYSIN OPERON, INTERACTION WITH H-NS, AND
RP MUTAGENESIS OF ASP-10; ASP-22; GLU-25; GLU-29; GLU-34; ASP-37; GLU-39;
RP ASP-48 AND ASP-61.
RC STRAIN=K12 / MG1655 / ATCC 47076;
RX PubMed=21600204; DOI=10.1016/j.febslet.2011.05.024;
RA de Alba C.F., Solorzano C., Paytubi S., Madrid C., Juarez A., Garcia J.,
RA Pons M.;
RT "Essential residues in the H-NS binding site of Hha, a co-regulator of
RT horizontally acquired genes in Enterobacteria.";
RL FEBS Lett. 585:1765-1770(2011).
RN [16]
RP FUNCTION, REGULON, AND DISRUPTION PHENOTYPE.
RC STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
RX PubMed=23543115; DOI=10.1093/dnares/dst008;
RA Ueda T., Takahashi H., Uyar E., Ishikawa S., Ogasawara N., Oshima T.;
RT "Functions of the Hha and YdgT proteins in transcriptional silencing by the
RT nucleoid proteins, H-NS and StpA, in Escherichia coli.";
RL DNA Res. 20:263-271(2013).
RN [17]
RP STRUCTURE BY NMR.
RX PubMed=11854485; DOI=10.1073/pnas.042684599;
RA Yee A., Chang X., Pineda-Lucena A., Wu B., Semesi A., Le B., Ramelot T.,
RA Lee G.M., Bhattacharyya S., Gutierrez P., Denisov A., Lee C.-H., Cort J.R.,
RA Kozlov G., Liao J., Finak G., Chen L., Wishart D., Lee W., McIntosh L.P.,
RA Gehring K., Kennedy M.A., Edwards A.M., Arrowsmith C.H.;
RT "An NMR approach to structural proteomics.";
RL Proc. Natl. Acad. Sci. U.S.A. 99:1825-1830(2002).
RN [18]
RP STRUCTURE BY NMR IN COMPLEX WITH H-NS, AND SUBUNIT.
RX PubMed=26085102; DOI=10.1074/jbc.m114.630400;
RA Cordeiro T.N., Garcia J., Bernado P., Millet O., Pons M.;
RT "A three-protein charge zipper stabilizes a complex modulating bacterial
RT gene silencing.";
RL J. Biol. Chem. 290:21200-21212(2015).
CC -!- FUNCTION: Down-regulates hemolysin (hly) expression in complex with H-
CC NS (PubMed:1956303, PubMed:10778755, PubMed:11790731, PubMed:21600204).
CC Stimulates transposition events in vivo (PubMed:8145648). Modifies the
CC set of genes regulated by H-NS; Hha and Cnu (YdgT) increase the number
CC of genes DNA bound by H-NS/StpA and may also modulate the
CC oligomerization of the H-NS/StpA-complex (PubMed:23543115). Binds DNA
CC and influences DNA topology in response to environmental stimuli; does
CC not however interact with DNA in the absence of H-NS (PubMed:23543115).
CC Involved in persister cell formation, acting downstream of mRNA
CC interferase (toxin) MqsR (PubMed:19909729). Decreases biofilm formation
CC by repressing the transcription of fimbrial genes fimA and ihfA, and by
CC repressing the transcription of tRNAs corresponding to rare codons,
CC which are abundant in type 1 fimbrial genes (PubMed:18545668).
CC {ECO:0000269|PubMed:10778755, ECO:0000269|PubMed:11790731,
CC ECO:0000269|PubMed:16317765, ECO:0000269|PubMed:18545668,
CC ECO:0000269|PubMed:1956303, ECO:0000269|PubMed:19909729,
CC ECO:0000269|PubMed:21600204, ECO:0000269|PubMed:23543115,
CC ECO:0000269|PubMed:8145648}.
CC -!- SUBUNIT: Forms a heterotrimeric complex with the H-NS dimer in the
CC absence of DNA. {ECO:0000269|PubMed:10778755,
CC ECO:0000269|PubMed:11790731, ECO:0000269|PubMed:16650431,
CC ECO:0000269|PubMed:21600204, ECO:0000269|PubMed:26085102}.
CC -!- INTERACTION:
CC P0ACE3; P0ACF8: hns; NbExp=5; IntAct=EBI-1122578, EBI-544934;
CC -!- INDUCTION: Expression is autoregulated (Probable). Induced during
CC biofilm formation (PubMed:14727089, PubMed:18545668).
CC {ECO:0000269|PubMed:14727089, ECO:0000269|PubMed:18545668,
CC ECO:0000305}.
CC -!- DOMAIN: Histidine-tagging (His-tagging) at the N-terminus does not
CC impair interaction with H-NS, whereas His-tagging at the C-terminus
CC does impair interaction (PubMed:11790731).
CC {ECO:0000269|PubMed:11790731}.
CC -!- DISRUPTION PHENOTYPE: Deletion results in a large increase in the
CC production of extracellular and intracellular hemolysin
CC (PubMed:1956303). At low osmolarity minor changes in overall
CC translation, at 0.4 M NaCl expression of about 25 proteins altered,
CC including decreased OmpA, crr and AhpC (in strain 5K, not a K12
CC derivative) (PubMed:10322001). At 0.3 M NaCl in strain W3110 up-
CC regulation of 113 genes and down-regulation of 8 genes was observed; a
CC double cnu-hha deletion up-regulated 134 and down-regulated 5 genes,
CC most of which are thought to have been acquired horizontally and are
CC also up-regulated in double hns-stpA deletions (PubMed:23543115).
CC However there are only 12 genes that were commonly up-regulated in the
CC hha and cnu-hha deletions (PubMed:23543115). Represses the production
CC of persister cells (PubMed:19909729). Deletion of hha and tomB (ybaJ),
CC in the presence of a conjugative plasmid (R1drd19), decreases biofilm
CC formation, cell aggregation and increases motility via flagella and
CC motility gene expression (PubMed:16317765).
CC {ECO:0000269|PubMed:10322001, ECO:0000269|PubMed:16317765,
CC ECO:0000269|PubMed:1956303, ECO:0000269|PubMed:19909729,
CC ECO:0000269|PubMed:23543115}.
CC -!- MISCELLANEOUS: Hha and TomB may form a type II toxin-antitoxin (TA)
CC system (PubMed:18545668). {ECO:0000305|PubMed:18545668}.
CC -!- SIMILARITY: Belongs to the Hha/YmoA/Cnu family.
CC {ECO:0000305|PubMed:1484495, ECO:0000305|PubMed:8145648}.
CC -!- SEQUENCE CAUTION:
CC Sequence=AAB40215.1; Type=Erroneous initiation; Note=Extended N-terminus.; Evidence={ECO:0000305};
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DR EMBL; X57977; CAA41043.1; -; Genomic_DNA.
DR EMBL; U82664; AAB40215.1; ALT_INIT; Genomic_DNA.
DR EMBL; U00096; AAC73562.1; -; Genomic_DNA.
DR EMBL; AP009048; BAE76239.1; -; Genomic_DNA.
DR PIR; C64776; C64776.
DR RefSeq; NP_414993.1; NC_000913.3.
DR RefSeq; WP_001291435.1; NZ_STEB01000007.1.
DR PDB; 1JW2; NMR; -; A=1-72.
DR PDB; 2MW2; NMR; -; A=1-72.
DR PDBsum; 1JW2; -.
DR PDBsum; 2MW2; -.
DR AlphaFoldDB; P0ACE3; -.
DR BMRB; P0ACE3; -.
DR SMR; P0ACE3; -.
DR BioGRID; 4262034; 9.
DR ComplexPortal; CPX-1979; H-NS-Hha transcription factor complex.
DR DIP; DIP-9897N; -.
DR IntAct; P0ACE3; 2.
DR MINT; P0ACE3; -.
DR STRING; 511145.b0460; -.
DR PaxDb; P0ACE3; -.
DR PRIDE; P0ACE3; -.
DR EnsemblBacteria; AAC73562; AAC73562; b0460.
DR EnsemblBacteria; BAE76239; BAE76239; BAE76239.
DR GeneID; 66671238; -.
DR GeneID; 945098; -.
DR KEGG; ecj:JW0449; -.
DR KEGG; eco:b0460; -.
DR PATRIC; fig|511145.12.peg.478; -.
DR EchoBASE; EB0434; -.
DR eggNOG; ENOG5032SGA; Bacteria.
DR HOGENOM; CLU_190629_0_0_6; -.
DR OMA; RRCQSID; -.
DR PhylomeDB; P0ACE3; -.
DR BioCyc; EcoCyc:EG10439-MON; -.
DR EvolutionaryTrace; P0ACE3; -.
DR PRO; PR:P0ACE3; -.
DR Proteomes; UP000000318; Chromosome.
DR Proteomes; UP000000625; Chromosome.
DR GO; GO:0005829; C:cytosol; IDA:EcoCyc.
DR GO; GO:0097495; C:H-NS-Hha complex; IPI:ComplexPortal.
DR GO; GO:0005667; C:transcription regulator complex; IC:ComplexPortal.
DR GO; GO:0003677; F:DNA binding; IDA:EcoCyc.
DR GO; GO:0010468; P:regulation of gene expression; IMP:EcoCyc.
DR GO; GO:0006355; P:regulation of transcription, DNA-templated; IC:ComplexPortal.
DR Gene3D; 1.20.1280.40; -; 1.
DR InterPro; IPR007985; Hemolysn_expr_modulating_HHA.
DR InterPro; IPR036666; HHA_sf.
DR Pfam; PF05321; HHA; 1.
DR SUPFAM; SSF68989; SSF68989; 1.
PE 1: Evidence at protein level;
KW 3D-structure; Reference proteome; Repressor; Transcription;
KW Transcription regulation.
FT CHAIN 1..72
FT /note="Hemolysin expression-modulating protein Hha"
FT /id="PRO_0000201727"
FT SITE 25
FT /note="Interacts with H-NS"
FT SITE 48
FT /note="Interacts with H-NS"
FT MUTAGEN 10
FT /note="D->N: Does not affect H-NS binding ability."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 16
FT /note="R->C: Derepression of the hly operon, impaired H-NS
FT binding."
FT /evidence="ECO:0000269|PubMed:11790731"
FT MUTAGEN 22
FT /note="D->N: Does not affect H-NS binding ability."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 25
FT /note="E->Q: Affects H-NS binding ability. Decrease in the
FT ability to repress the expression of the hly operon."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 29
FT /note="E->Q: Does not affect H-NS binding ability."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 34
FT /note="E->Q: Does not affect H-NS binding ability."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 37
FT /note="D->N: Does not affect H-NS binding ability."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 39
FT /note="E->Q: Does not affect H-NS binding ability."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 44..72
FT /note="Missing: Derepression of the hly operon, impaired H-
FT NS binding."
FT /evidence="ECO:0000269|PubMed:11790731"
FT MUTAGEN 48
FT /note="D->E,R: Abolishes the interaction with H-NS."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 48
FT /note="D->N: Abolishes the interaction with H-NS. Loss of
FT the ability to repress the expression of the hly operon."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 50
FT /note="R->H: Derepression of the hly operon, impaired H-NS
FT binding."
FT /evidence="ECO:0000269|PubMed:11790731"
FT MUTAGEN 58..72
FT /note="Missing: Derepression of the hly operon, impaired H-
FT NS binding."
FT /evidence="ECO:0000269|PubMed:11790731"
FT MUTAGEN 61
FT /note="D->N: Does not affect H-NS binding ability."
FT /evidence="ECO:0000269|PubMed:21600204"
FT MUTAGEN 64
FT /note="P->L,S: Derepression of the hly operon, impaired H-
FT NS binding."
FT /evidence="ECO:0000269|PubMed:11790731"
FT MUTAGEN 72
FT /note="R->RHHHHHH: Derepression of the hly operon, impaired
FT H-NS binding."
FT /evidence="ECO:0000269|PubMed:11790731"
FT HELIX 8..16
FT /evidence="ECO:0007829|PDB:1JW2"
FT HELIX 21..34
FT /evidence="ECO:0007829|PDB:1JW2"
FT HELIX 37..55
FT /evidence="ECO:0007829|PDB:1JW2"
FT STRAND 56..58
FT /evidence="ECO:0007829|PDB:1JW2"
FT HELIX 65..70
FT /evidence="ECO:0007829|PDB:1JW2"
SQ SEQUENCE 72 AA; 8628 MW; A77211B87CF0134A CRC64;
MSEKPLTKTD YLMRLRRCQT IDTLERVIEK NKYELSDNEL AVFYSAADHR LAELTMNKLY
DKIPSSVWKF IR
