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Protein

Hemolysin expression-modulating protein Hha

Gene

hha

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein leveli

Functioni

Down-regulates hemolysin (hly) expression in complex with H-NS (PubMed:1956303, PubMed:10778755, PubMed:11790731, PubMed:21600204). Stimulates transposition events in vivo (PubMed:8145648). Modifies the set of genes regulated by H-NS; Hha and Cnu (YdgT) increase the number of genes DNA bound by H-NS/StpA and may also modulate the oligomerization of the H-NS/StpA-complex (PubMed:23543115). Binds DNA and influences DNA topology in response to environmental stimuli; does not however interact with DNA in the absence of H-NS (PubMed:23543115). Involved in persister cell formation, acting downstream of mRNA interferase (toxin) MqsR (PubMed:19909729). Decreases biofilm formation by repressing the transcription of fimbrial genes fimA and ihfA, and by repressing the transcription of tRNAs corresponding to rare codons, which are abundant in type 1 fimbrial genes (PubMed:18545668).9 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sitei25 – 251Interacts with H-NS
Sitei48 – 481Interacts with H-NS

GO - Molecular functioni

GO - Biological processi

  • regulation of gene expression Source: EcoCyc
  • regulation of transcription, DNA-templated Source: UniProtKB-KW
  • transcription, DNA-templated Source: UniProtKB-KW
Complete GO annotation...

Keywords - Molecular functioni

Repressor

Keywords - Biological processi

Transcription, Transcription regulation

Enzyme and pathway databases

BioCyciEcoCyc:EG10439-MONOMER.
ECOL316407:JW0449-MONOMER.

Names & Taxonomyi

Protein namesi
Recommended name:
Hemolysin expression-modulating protein Hha
Gene namesi
Name:hha
Ordered Locus Names:b0460, JW0449
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10439. hha.

Subcellular locationi

GO - Cellular componenti

  • cytosol Source: EcoCyc
Complete GO annotation...

Pathology & Biotechi

Disruption phenotypei

Deletion results in a large increase in the production of extracellular and intracellular hemolysin (PubMed:1956303). At low osmolarity minor changes in overall translation, at 0.4 M NaCl expression of about 25 proteins altered, including decreased OmpA, crr and AhpC (in strain 5K, not a K12 derivative) (PubMed:10322001). At 0.3 M NaCl in strain W3110 up-regulation of 113 genes and down-regulation of 8 genes was observed; a double cnu-hha deletion up-regulated 134 and down-regulated 5 genes, most of which are thought to have been acquired horizontally and are also up-regulated in double hns-stpA deletions (PubMed:23543115). However there are only 12 genes that were commonly up-regulated in the hha and cnu-hha deletions (PubMed:23543115). Represses the production of persister cells (PubMed:19909729). Deletion of hha and tomB (ybaJ), in the presence of a conjugative plasmid (R1drd19), decreases biofilm formation, cell aggregation and increases motility via flagella and motility gene expression (PubMed:16317765).5 Publications

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi10 – 101D → N: Does not affect H-NS binding ability. 1 Publication
Mutagenesisi16 – 161R → C: Derepression of the hly operon, impaired H-NS binding. 1 Publication
Mutagenesisi22 – 221D → N: Does not affect H-NS binding ability. 1 Publication
Mutagenesisi25 – 251E → Q: Affects H-NS binding ability. Decrease in the ability to repress the expression of the hly operon. 1 Publication
Mutagenesisi29 – 291E → Q: Does not affect H-NS binding ability. 1 Publication
Mutagenesisi34 – 341E → Q: Does not affect H-NS binding ability. 1 Publication
Mutagenesisi37 – 371D → N: Does not affect H-NS binding ability. 1 Publication
Mutagenesisi39 – 391E → Q: Does not affect H-NS binding ability. 1 Publication
Mutagenesisi44 – 7229Missing : Derepression of the hly operon, impaired H-NS binding. 1 PublicationAdd
BLAST
Mutagenesisi48 – 481D → E or R: Abolishes the interaction with H-NS. 1 Publication
Mutagenesisi48 – 481D → N: Abolishes the interaction with H-NS. Loss of the ability to repress the expression of the hly operon. 1 Publication
Mutagenesisi50 – 501R → H: Derepression of the hly operon, impaired H-NS binding. 1 Publication
Mutagenesisi58 – 7215Missing : Derepression of the hly operon, impaired H-NS binding. 1 PublicationAdd
BLAST
Mutagenesisi61 – 611D → N: Does not affect H-NS binding ability. 1 Publication
Mutagenesisi64 – 641P → L or S: Derepression of the hly operon, impaired H-NS binding. 1 Publication
Mutagenesisi72 – 721R → RHHHHHH: Derepression of the hly operon, impaired H-NS binding. 1 Publication

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 7272Hemolysin expression-modulating protein HhaPRO_0000201727Add
BLAST

Proteomic databases

PaxDbiP0ACE3.
PRIDEiP0ACE3.

Expressioni

Inductioni

Expression is autoregulated (Probable). Induced during biofilm formation (PubMed:14727089, PubMed:18545668).Curated2 Publications

Interactioni

Subunit structurei

Forms a heterotrimeric complex with the H-NS dimer in the absence of DNA.5 Publications

Binary interactionsi

WithEntry#Exp.IntActNotes
hnsP0ACF85EBI-1122578,EBI-544934

Protein-protein interaction databases

BioGridi4262034. 9 interactions.
DIPiDIP-9897N.
IntActiP0ACE3. 2 interactions.
MINTiMINT-8175118.
STRINGi511145.b0460.

Structurei

Secondary structure

1
72
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Helixi8 – 169Combined sources
Helixi21 – 3414Combined sources
Helixi37 – 5519Combined sources
Beta strandi56 – 583Combined sources
Helixi65 – 706Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JW2NMR-A1-72[»]
2MW2NMR-A1-72[»]
ProteinModelPortaliP0ACE3.
SMRiP0ACE3. Positions 1-72.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP0ACE3.

Family & Domainsi

Domaini

Histidine-tagging (His-tagging) at the N-terminus does not impair interaction with H-NS, whereas His-tagging at the C-terminus does impair interaction (PubMed:11790731).1 Publication

Sequence similaritiesi

Belongs to the Hha/YmoA/Cnu family.2 Publications

Phylogenomic databases

eggNOGiENOG4105KF5. Bacteria.
ENOG4111U15. LUCA.
HOGENOMiHOG000219358.
KOiK05839.
OMAiRRCQSID.
OrthoDBiEOG6CZQR6.

Family and domain databases

Gene3Di1.20.1280.40. 1 hit.
InterProiIPR007985. Hemolysn_expr_modulating_HHA.
[Graphical view]
PfamiPF05321. HHA. 1 hit.
[Graphical view]
SUPFAMiSSF68989. SSF68989. 1 hit.

Sequencei

Sequence statusi: Complete.

P0ACE3-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MSEKPLTKTD YLMRLRRCQT IDTLERVIEK NKYELSDNEL AVFYSAADHR
60 70
LAELTMNKLY DKIPSSVWKF IR
Length:72
Mass (Da):8,628
Last modified:November 22, 2005 - v1
Checksum:iA77211B87CF0134A
GO

Sequence cautioni

The sequence AAB40215.1 differs from that shown. Reason: Erroneous initiation. Translation N-terminally shortened.Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57977 Genomic DNA. Translation: CAA41043.1.
U82664 Genomic DNA. Translation: AAB40215.1. Different initiation.
U00096 Genomic DNA. Translation: AAC73562.1.
AP009048 Genomic DNA. Translation: BAE76239.1.
PIRiC64776.
RefSeqiNP_414993.1. NC_000913.3.
WP_001291435.1. NZ_LN832404.1.

Genome annotation databases

EnsemblBacteriaiAAC73562; AAC73562; b0460.
BAE76239; BAE76239; BAE76239.
GeneIDi945098.
KEGGiecj:JW0449.
eco:b0460.
PATRICi32116073. VBIEscCol129921_0478.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
X57977 Genomic DNA. Translation: CAA41043.1.
U82664 Genomic DNA. Translation: AAB40215.1. Different initiation.
U00096 Genomic DNA. Translation: AAC73562.1.
AP009048 Genomic DNA. Translation: BAE76239.1.
PIRiC64776.
RefSeqiNP_414993.1. NC_000913.3.
WP_001291435.1. NZ_LN832404.1.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
1JW2NMR-A1-72[»]
2MW2NMR-A1-72[»]
ProteinModelPortaliP0ACE3.
SMRiP0ACE3. Positions 1-72.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4262034. 9 interactions.
DIPiDIP-9897N.
IntActiP0ACE3. 2 interactions.
MINTiMINT-8175118.
STRINGi511145.b0460.

Proteomic databases

PaxDbiP0ACE3.
PRIDEiP0ACE3.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC73562; AAC73562; b0460.
BAE76239; BAE76239; BAE76239.
GeneIDi945098.
KEGGiecj:JW0449.
eco:b0460.
PATRICi32116073. VBIEscCol129921_0478.

Organism-specific databases

EchoBASEiEB0434.
EcoGeneiEG10439. hha.

Phylogenomic databases

eggNOGiENOG4105KF5. Bacteria.
ENOG4111U15. LUCA.
HOGENOMiHOG000219358.
KOiK05839.
OMAiRRCQSID.
OrthoDBiEOG6CZQR6.

Enzyme and pathway databases

BioCyciEcoCyc:EG10439-MONOMER.
ECOL316407:JW0449-MONOMER.

Miscellaneous databases

EvolutionaryTraceiP0ACE3.
PROiP0ACE3.

Family and domain databases

Gene3Di1.20.1280.40. 1 hit.
InterProiIPR007985. Hemolysn_expr_modulating_HHA.
[Graphical view]
PfamiPF05321. HHA. 1 hit.
[Graphical view]
SUPFAMiSSF68989. SSF68989. 1 hit.
ProtoNetiSearch...

Publicationsi

« Hide 'large scale' publications
  1. "The hha gene modulates haemolysin expression in Escherichia coli."
    Nieto J.M., Carmona M., Bolland S., Jubete Y., de la Cruz F., Juarez A.
    Mol. Microbiol. 5:1285-1293(1991) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], FUNCTION IN HEMOLYSIN PRODUCTION, DISRUPTION PHENOTYPE.
    Strain: K12 / C600 / ATCC 23724 / DSM 3925 / LMG 3041 / NCIB 10222.
  2. "Sequence of minutes 4-25 of Escherichia coli."
    Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.
    Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  3. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    Strain: K12 / MG1655 / ATCC 47076.
  4. "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.
  5. "The Hha protein from Escherichia coli is highly homologous to the YmoA protein from Yersinia enterocolitica."
    de la Cruz F., Carmona M., Juarez A.
    Mol. Microbiol. 6:3451-3452(1992) [PubMed] [Europe PMC] [Abstract]
    Cited for: SIMILARITY TO YMOA.
  6. "A new class of proteins regulating gene expression in enterobacteria."
    Mikulskis A.V., Cornelis G.R.
    Mol. Microbiol. 11:77-86(1994) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, FUNCTION IN Y.ENTEROCOLITICA.
    Strain: K12 / C600 / ATCC 23724 / DSM 3925 / LMG 3041 / NCIB 10222.
  7. "Alterations in protein expression caused by the hha mutation in Escherichia coli: influence of growth medium osmolarity."
    Balsalobre C., Johansson J., Uhlin B.E., Juarez A., Munoa F.J.
    J. Bacteriol. 181:3018-3024(1999) [PubMed] [Europe PMC] [Abstract]
    Cited for: DISRUPTION PHENOTYPE.
    Strain: 5K.
  8. "Expression of the hemolysin operon in Escherichia coli is modulated by a nucleoid-protein complex that includes the proteins Hha and H-NS."
    Nieto J.M., Madrid C., Prenafeta A., Miquelay E., Balsalobre C., Carrascal M., Juarez A.
    Mol. Gen. Genet. 263:349-358(2000) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN REGULATION OF THE HEMOLYSIN OPERON, DNA-BINDING, INTERACTION WITH H-NS.
  9. "Evidence for direct protein-protein interaction between members of the enterobacterial Hha/YmoA and H-NS families of proteins."
    Nieto J.M., Madrid C., Miquelay E., Parra J.L., Rodriguez S., Juarez A.
    J. Bacteriol. 184:629-635(2002) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, INTERACTION WITH H-NS, DOMAIN, MUTAGENESIS OF ARG-16; 44-TYR--ARG-72; ARG-50; 58-LYS--ARG-72; PRO-64 AND ARG-72.
  10. Cited for: INDUCTION.
    Strain: K12 / JM109 / ATCC 53323.
  11. "Hha, YbaJ, and OmpA regulate Escherichia coli K12 biofilm formation and conjugation plasmids abolish motility."
    Barrios A.F., Zuo R., Ren D., Wood T.K.
    Biotechnol. Bioeng. 93:188-200(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BIOFILM FORMATION, DISRUPTION PHENOTYPE.
    Strain: K12 / ATCC 25404 / DSM 5698 / NCIMB 11290.
  12. "New roles for key residues in helices H1 and H2 of the Escherichia coli H-NS N-terminal domain: H-NS dimer stabilization and Hha binding."
    Garcia J., Madrid C., Juarez A., Pons M.
    J. Mol. Biol. 359:679-689(2006) [PubMed] [Europe PMC] [Abstract]
    Cited for: SUBUNIT.
  13. "Protein translation and cell death: the role of rare tRNAs in biofilm formation and in activating dormant phage killer genes."
    Garcia-Contreras R., Zhang X.S., Kim Y., Wood T.K.
    PLoS ONE 3:E2394-E2394(2008) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN BIOFILM FORMATION, INDUCTION, DNA-BINDING.
    Strain: K12 / BW25113.
  14. "Toxins Hha and CspD and small RNA regulator Hfq are involved in persister cell formation through MqsR in Escherichia coli."
    Kim Y., Wood T.K.
    Biochem. Biophys. Res. Commun. 391:209-213(2010) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN PERSISTER CELL FORMATION, DISRUPTION PHENOTYPE.
    Strain: K12 / BW25113.
  15. "Essential residues in the H-NS binding site of Hha, a co-regulator of horizontally acquired genes in Enterobacteria."
    de Alba C.F., Solorzano C., Paytubi S., Madrid C., Juarez A., Garcia J., Pons M.
    FEBS Lett. 585:1765-1770(2011) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION IN REGULATION OF THE HEMOLYSIN OPERON, INTERACTION WITH H-NS, MUTAGENESIS OF ASP-10; ASP-22; GLU-25; GLU-29; GLU-34; ASP-37; GLU-39; ASP-48 AND ASP-61.
    Strain: K12 / MG1655 / ATCC 47076.
  16. "Functions of the Hha and YdgT proteins in transcriptional silencing by the nucleoid proteins, H-NS and StpA, in Escherichia coli."
    Ueda T., Takahashi H., Uyar E., Ishikawa S., Ogasawara N., Oshima T.
    DNA Res. 20:263-271(2013) [PubMed] [Europe PMC] [Abstract]
    Cited for: FUNCTION, REGULON, DISRUPTION PHENOTYPE.
    Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
  17. Cited for: STRUCTURE BY NMR.
  18. "A three-protein charge zipper stabilizes a complex modulating bacterial gene silencing."
    Cordeiro T.N., Garcia J., Bernado P., Millet O., Pons M.
    J. Biol. Chem. 290:21200-21212(2015) [PubMed] [Europe PMC] [Abstract]
    Cited for: STRUCTURE BY NMR IN COMPLEX WITH H-NS, SUBUNIT.

Entry informationi

Entry nameiHHA_ECOLI
AccessioniPrimary (citable) accession number: P0ACE3
Secondary accession number(s): P23870, P77120, Q2MBW7
Entry historyi
Integrated into UniProtKB/Swiss-Prot: November 22, 2005
Last sequence update: November 22, 2005
Last modified: July 6, 2016
This is version 86 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Miscellaneous

Hha and TomB may form a toxin-antitoxin (TA) module (PubMed:18545668).1 Publication

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.