Escherichia coli K-12 substr. MG1655 Protein: HF-I, host factor for RNA phage Q β replication

Gene: hfq Accession Numbers: EG10438 (EcoCyc), b4172, ECK4168

Synonyms: HF-I, host factor I

Regulation Summary Diagram: ?

Regulation summary diagram for hfq

Subunit composition of HF-I, host factor for RNA phage Q β replication = [Hfq]6
         RNA-binding protein that affects many cellular processes; homolog of mammalian Sm/Sm-like proteins = Hfq

Hfq is an RNA-binding protein that stimulates RNA-RNA pairing and affects many cellular processes, similar to mammalian Sm/Sm-like proteins [Zhang02, Moller02a]. Hfq interacts with many small RNA species [Wassarman01], and exhibits RNA chaperone activity [Moll03]. The Hfq complex is associated with an ATPase activity [Sukhodolets03].

Hfq is a host factor (HF-I) required for wild-type bacteriophage Q beta replication [Kajitani91, Su97]. Hfq is required for wild-type translation of RpoS [Muffler96]. Hfq interacts with the oxyS RNA to negatively regulate RpoS translation [Zhang98b]. Hfq stimulates binding by oxyS RNA [Zhang02] and spf RNA [Moller02a] to their RNA targets. Hfq binds ompA mRNA and is required for the regulation of its stability by the micA antisense RNA, which also binds to ompA and blocks ribosome binding [Vytvytska98, Vytvytska00, Udekwu05]. Hfq binds to dsrA RNA [Sledjeski01, Brescia03] and is important for its activity [Sledjeski01], and also binds the antisense regulatory ryhB RNA and is necessary for its activity [Masse02]. Hfq is required for protection of ryhB RNA [Masse03, Moll03a], dsrA RNA [Moll03a], and ompA mRNA [Moll03a] from degradation by RNaseE. Hfq binds to sodB mRNA, altering its structure to allow binding of ryhB and leading to the degradation of both ryhB and sodB RNAs [Geissmann04]. The crystal structure of the DsrA-Hfq complex has been solved [Wang11a].

Hfq is required for wild-type regulation of FtsZ abundance and cell division at stationary phase [Takada99]. Hfq interacts with poly(A) RNA [Hajnsdorf00] and increases the processivity of poly(A) polymerase I [Hajnsdorf00, Le03]. Hfq also interacts with RNA polymerase [Sukhodolets03].

A crystal structure of Hfq is presented [Vassilieva03, Sauter03].

Hfq forms a homohexamer [Zhang02, Moller02a, Arluison02, Sauter03]. Hfq is a cytoplasmic [Azam00] ribosome-associated protein [Kajitani94, Azam00]. Hfq exhibits nonspecific DNA interactions [Takada97, Azam99].

An hfq mutant exhibits pleiotropic phenotypes [Tsui94a, Muffler97, Wachi99, Takada99].

hfq is one of a network of 93 genes believed to play a role in promoting the stress-induced mutagenesis (SIM) response of E. coli K-12 [Al12].

Hfq: "host factor for phage Q beta"

Regulation has been described [Tsui94, Kajitani94, Tsui94a, Tsui96, Ali99].

Reviews: [Nogueira00, Lease00, Donahue02, HenggeAronis02, Masse03a, ValentinHansen04, Brennan07, Jousselin09, Sobrero12]

A microarray analysis for Hfq of Escherichia coli was done by [Zhang03d].

Citations: [Ruiz03]

Gene Citations: [Nonaka06, Kitagawa96]

Locations: cytosol

Map Position: [4,398,311 -> 4,398,619] (94.8 centisomes, 341°)
Length: 309 bp / 102 aa

Molecular Weight of Polypeptide: 11.166 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0013659 , CGSC:34450 , DIP:DIP-36047N , EchoBASE:EB0433 , EcoGene:EG10438 , EcoliWiki:b4172 , Mint:MINT-8200668 , OU-Microarray:b4172 , PortEco:hfq , PR:PRO_000022886 , Pride:P0A6X3 , Protein Model Portal:P0A6X3 , RefSeq:NP_418593 , RegulonDB:EG10438 , SMR:P0A6X3 , String:511145.b4172 , UniProt:P0A6X3

Relationship Links: InterPro:IN-FAMILY:IPR001163 , InterPro:IN-FAMILY:IPR005001 , InterPro:IN-FAMILY:IPR010920 , PDB:Structure:1HK9 , PDB:Structure:1M7C , PDB:Structure:1OOU , PDB:Structure:1OOV , PDB:Structure:2Y90 , PDB:Structure:2YHT , PDB:Structure:3GIB , PDB:Structure:3QHS , PDB:Structure:3QO3 , PDB:Structure:3RER , PDB:Structure:3RES , PDB:Structure:3VU3 , PDB:Structure:4JRI , PDB:Structure:4JRK , PDB:Structure:4JUV , Pfam:IN-FAMILY:PF01423

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for hfq

GO Terms:

Biological Process: GO:0040033 - negative regulation of translation, ncRNA-mediated Inferred from experiment [Pulvermacher09]
GO:0045975 - positive regulation of translation, ncRNA-mediated Inferred from experiment [Muffler96]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [GOA01a]
Molecular Function: GO:0003681 - bent DNA binding Inferred from experiment [Azam99]
GO:0003723 - RNA binding Inferred from experiment Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a, Zhang98b]
GO:0005515 - protein binding Inferred from experiment [Rabhi11, Butland05]
GO:0003677 - DNA binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005829 - cytosol Inferred from experiment [Ishihama08]

MultiFun Terms: extrachromosomal prophage genes and phage related functions
information transfer protein related nucleoproteins, basic proteins
information transfer RNA related antisense RNA
information transfer RNA related RNA degradation
regulation genetic unit regulated global
regulation type of regulation posttranscriptional antisense RNA
regulation type of regulation posttranscriptional translation attenuation and efficiency

Regulated Transcription Units (2 total): ?


Transcription-unit diagram

Transcription-unit diagram

Essentiality data for hfq 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]

Sequence Features

Protein sequence of RNA-binding protein that affects many cellular processes; homolog of mammalian Sm/Sm-like proteins with features indicated

Feature Class Location Citations Comment
Cleavage-of-Initial-Methionine 1
[Carmichael75, Takada97, Kajitani91, UniProt11]
UniProt: Removed.
Chain 2 -> 102
UniProt: Protein hfq;

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b4172 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10438; confirmed by SwissProt match.


Al12: Al Mamun AA, Lombardo MJ, Shee C, Lisewski AM, Gonzalez C, Lin D, Nehring RB, Saint-Ruf C, Gibson JL, Frisch RL, Lichtarge O, Hastings PJ, Rosenberg SM (2012). "Identity and function of a large gene network underlying mutagenic repair of DNA breaks." Science 338(6112);1344-8. PMID: 23224554

Ali99: Ali Azam T, Iwata A, Nishimura A, Ueda S, Ishihama A (1999). "Growth phase-dependent variation in protein composition of the Escherichia coli nucleoid." J Bacteriol 181(20);6361-70. PMID: 10515926

Arluison02: Arluison V, Derreumaux P, Allemand F, Folichon M, Hajnsdorf E, Regnier P (2002). "Structural Modelling of the Sm-like Protein Hfq from Escherichia coli." J Mol Biol 320(4);705-12. PMID: 12095248

Azam00: Azam TA, Hiraga S, Ishihama A (2000). "Two types of localization of the DNA-binding proteins within the Escherichia coli nucleoid." Genes Cells 5(8);613-26. PMID: 10947847

Azam99: Azam TA, Ishihama A (1999). "Twelve species of the nucleoid-associated protein from Escherichia coli. Sequence recognition specificity and DNA binding affinity." J Biol Chem 274(46);33105-13. PMID: 10551881

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

Brennan07: Brennan RG, Link TM (2007). "Hfq structure, function and ligand binding." Curr Opin Microbiol 10(2);125-33. PMID: 17395525

Brescia03: Brescia CC, Mikulecky PJ, Feig AL, Sledjeski DD (2003). "Identification of the Hfq-binding site on DsrA RNA: Hfq binds without altering DsrA secondary structure." RNA 9(1);33-43. PMID: 12554874

Butland05: Butland G, Peregrin-Alvarez JM, Li J, Yang W, Yang X, Canadien V, Starostine A, Richards D, Beattie B, Krogan N, Davey M, Parkinson J, Greenblatt J, Emili A (2005). "Interaction network containing conserved and essential protein complexes in Escherichia coli." Nature 433(7025);531-7. PMID: 15690043

Carmichael75: Carmichael GG, Weber K, Niveleau A, Wahba AJ (1975). "The host factor required for RNA phage Qbeta RNA replication in vitro. Intracellular location, quantitation, and purification by polyadenylate-cellulose chromatography." J Biol Chem 250(10);3607-612. PMID: 805130

Donahue02: Donahue WF, Jarrell KA (2002). "A BLAST from the past: ancient origin of human Sm proteins." Mol Cell 9(1);7-8. PMID: 11804580

Geissmann04: Geissmann TA, Touati D (2004). "Hfq, a new chaperoning role: binding to messenger RNA determines access for small RNA regulator." EMBO J 23(2);396-405. PMID: 14739933

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."

Hajnsdorf00: Hajnsdorf E, Regnier P (2000). "Host factor Hfq of Escherichia coli stimulates elongation of poly(A) tails by poly(A) polymerase I." Proc Natl Acad Sci U S A 97(4);1501-5. PMID: 10677490

HenggeAronis02: Hengge-Aronis R (2002). "Signal transduction and regulatory mechanisms involved in control of the sigma(S) (RpoS) subunit of RNA polymerase." Microbiol Mol Biol Rev 66(3);373-95, table of contents. PMID: 12208995

Ishihama08: Ishihama Y, Schmidt T, Rappsilber J, Mann M, Hartl FU, Kerner MJ, Frishman D (2008). "Protein abundance profiling of the Escherichia coli cytosol." BMC Genomics 9;102. PMID: 18304323

Jousselin09: Jousselin A, Metzinger L, Felden B (2009). "On the facultative requirement of the bacterial RNA chaperone, Hfq." Trends Microbiol 17(9);399-405. PMID: 19733080

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

Kajitani91: Kajitani M, Ishihama A (1991). "Identification and sequence determination of the host factor gene for bacteriophage Q beta." Nucleic Acids Res 19(5);1063-6. PMID: 2020545

Kajitani94: Kajitani M, Kato A, Wada A, Inokuchi Y, Ishihama A (1994). "Regulation of the Escherichia coli hfq gene encoding the host factor for phage Q beta." J Bacteriol 176(2);531-4. PMID: 8288550

Kitagawa96: Kitagawa R, Mitsuki H, Okazaki T, Ogawa T (1996). "A novel DnaA protein-binding site at 94.7 min on the Escherichia coli chromosome." Mol Microbiol 1996;19(5);1137-47. PMID: 8830270

Le03: Le Derout J, Folichon M, Briani F, Deho G, Regnier P, Hajnsdorf E (2003). "Hfq affects the length and the frequency of short oligo(A) tails at the 3' end of Escherichia coli rpsO mRNAs." Nucleic Acids Res 31(14);4017-23. PMID: 12853618

Lease00: Lease RA, Belfort M (2000). "Riboregulation by DsrA RNA: trans-actions for global economy." Mol Microbiol 38(4);667-72. PMID: 11115103

Masse02: Masse E, Gottesman S (2002). "A small RNA regulates the expression of genes involved in iron metabolism in Escherichia coli." Proc Natl Acad Sci U S A 99(7);4620-5. PMID: 11917098

Masse03: Masse E, Escorcia FE, Gottesman S (2003). "Coupled degradation of a small regulatory RNA and its mRNA targets in Escherichia coli." Genes Dev 17(19);2374-83. PMID: 12975324

Masse03a: Masse E, Majdalani N, Gottesman S (2003). "Regulatory roles for small RNAs in bacteria." Curr Opin Microbiol 6(2);120-4. PMID: 12732300

Moll03: Moll I, Leitsch D, Steinhauser T, Blasi U (2003). "RNA chaperone activity of the Sm-like Hfq protein." EMBO Rep 4(3);284-9. PMID: 12634847

Moll03a: Moll I, Afonyushkin T, Vytvytska O, Kaberdin VR, Blasi U (2003). "Coincident Hfq binding and RNase E cleavage sites on mRNA and small regulatory RNAs." RNA 9(11);1308-14. PMID: 14561880

Moller02a: Moller T, Franch T, Hojrup P, Keene DR, Bachinger HP, Brennan RG, Valentin-Hansen P (2002). "Hfq: a bacterial Sm-like protein that mediates RNA-RNA interaction." Mol Cell 9(1);23-30. PMID: 11804583

Muffler96: Muffler A, Fischer D, Hengge-Aronis R (1996). "The RNA-binding protein HF-I, known as a host factor for phage Qbeta RNA replication, is essential for rpoS translation in Escherichia coli." Genes Dev 10(9);1143-51. PMID: 8654929

Muffler97: Muffler A, Traulsen DD, Fischer D, Lange R, Hengge-Aronis R (1997). "The RNA-binding protein HF-I plays a global regulatory role which is largely, but not exclusively, due to its role in expression of the sigmaS subunit of RNA polymerase in Escherichia coli." J Bacteriol 179(1);297-300. PMID: 8982015

Nogueira00: Nogueira T, Springer M (2000). "Post-transcriptional control by global regulators of gene expression in bacteria." Curr Opin Microbiol 3(2);154-8. PMID: 10744991

Nonaka06: Nonaka G, Blankschien M, Herman C, Gross CA, Rhodius VA (2006). "Regulon and promoter analysis of the E. coli heat-shock factor, sigma32, reveals a multifaceted cellular response to heat stress." Genes Dev 20(13);1776-89. PMID: 16818608

Pulvermacher09: Pulvermacher SC, Stauffer LT, Stauffer GV (2009). "Role of the sRNA GcvB in regulation of cycA in Escherichia coli." Microbiology 155(Pt 1);106-14. PMID: 19118351

Rabhi11: Rabhi M, Espeli O, Schwartz A, Cayrol B, Rahmouni AR, Arluison V, Boudvillain M (2011). "The Sm-like RNA chaperone Hfq mediates transcription antitermination at Rho-dependent terminators." EMBO J 30(14);2805-16. PMID: 21673658

Ruiz03: Ruiz N, Silhavy TJ (2003). "Constitutive activation of the Escherichia coli Pho regulon upregulates rpoS translation in an Hfq-dependent fashion." J Bacteriol 185(20);5984-92. PMID: 14526009

Sauter03: Sauter C, Basquin J, Suck D (2003). "Sm-like proteins in Eubacteria: the crystal structure of the Hfq protein from Escherichia coli." Nucleic Acids Res 31(14);4091-8. PMID: 12853626

Sledjeski01: Sledjeski DD, Whitman C, Zhang A (2001). "Hfq is necessary for regulation by the untranslated RNA DsrA." J Bacteriol 183(6);1997-2005. PMID: 11222598

Sobrero12: Sobrero P, Valverde C (2012). "The bacterial protein Hfq: much more than a mere RNA-binding factor." Crit Rev Microbiol. PMID: 22435753

Su97: Su Q, Schuppli D, Tsui HcT , Winkler ME, Weber H (1997). "Strongly reduced phage Qbeta replication, but normal phage MS2 replication in an Escherichia coli K12 mutant with inactivated Qbeta host factor (hfq) gene." Virology 227(1);211-4. PMID: 9007075

Sukhodolets03: Sukhodolets MV, Garges S (2003). "Interaction of Escherichia coli RNA polymerase with the ribosomal protein S1 and the Sm-like ATPase Hfq." Biochemistry 42(26);8022-34. PMID: 12834354

Takada97: Takada A, Wachi M, Kaidow A, Takamura M, Nagai K (1997). "DNA binding properties of the hfq gene product of Escherichia coli." Biochem Biophys Res Commun 236(3);576-9. PMID: 9245691

Takada99: Takada A, Wachi M, Nagai K (1999). "Negative regulatory role of the Escherichia coli hfq gene in cell division." Biochem Biophys Res Commun 266(2);579-83. PMID: 10600545

Tsui94: Tsui HC, Winkler ME (1994). "Transcriptional patterns of the mutL-miaA superoperon of Escherichia coli K-12 suggest a model for posttranscriptional regulation." Biochimie 76(12);1168-77. PMID: 7748952

Tsui94a: Tsui HC, Leung HC, Winkler ME (1994). "Characterization of broadly pleiotropic phenotypes caused by an hfq insertion mutation in Escherichia coli K-12." Mol Microbiol 13(1);35-49. PMID: 7984093

Tsui96: Tsui HC, Feng G, Winkler ME (1996). "Transcription of the mutL repair, miaA tRNA modification, hfq pleiotropic regulator, and hflA region protease genes of Escherichia coli K-12 from clustered Esigma32-specific promoters during heat shock." J Bacteriol 178(19);5719-31. PMID: 8824618

Udekwu05: Udekwu KI, Darfeuille F, Vogel J, Reimegard J, Holmqvist E, Wagner EG (2005). "Hfq-dependent regulation of OmpA synthesis is mediated by an antisense RNA." Genes Dev 19(19);2355-66. PMID: 16204185

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

UniProt11: UniProt Consortium (2011). "UniProt version 2011-06 released on 2011-06-30 00:00:00." Database.

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

ValentinHansen04: Valentin-Hansen P, Eriksen M, Udesen C (2004). "The bacterial Sm-like protein Hfq: a key player in RNA transactions." Mol Microbiol 51(6);1525-33. PMID: 15009882

Vassilieva03: Vassilieva IM, Nikulin AD, Blasi U, Moll I, Garber MB (2003). "Crystallization of Hfq protein: a bacterial gene-expression regulator." Acta Crystallogr D Biol Crystallogr 59(Pt 6);1061-3. PMID: 12777774

Vytvytska00: Vytvytska O, Moll I, Kaberdin VR, von Gabain A, Blasi U (2000). "Hfq (HF1) stimulates ompA mRNA decay by interfering with ribosome binding." Genes Dev 14(9);1109-18. PMID: 10809669

Vytvytska98: Vytvytska O, Jakobsen JS, Balcunaite G, Andersen JS, Baccarini M, von Gabain A (1998). "Host factor I, Hfq, binds to Escherichia coli ompA mRNA in a growth rate-dependent fashion and regulates its stability." Proc Natl Acad Sci U S A 95(24);14118-23. PMID: 9826663

Wachi99: Wachi M, Takada A, Nagai K (1999). "Overproduction of the outer-membrane proteins FepA and FhuE responsible for iron transport in Escherichia coli hfq::cat mutant." Biochem Biophys Res Commun 264(2);525-9. PMID: 10529396

Wang11a: Wang W, Wang L, Zou Y, Zhang J, Gong Q, Wu J, Shi Y (2011). "Cooperation of Escherichia coli Hfq hexamers in DsrA binding." Genes Dev 25(19);2106-17. PMID: 21979921

Wassarman01: Wassarman KM, Repoila F, Rosenow C, Storz G, Gottesman S (2001). "Identification of novel small RNAs using comparative genomics and microarrays." Genes Dev 15(13);1637-51. PMID: 11445539

Zhang02: Zhang A, Wassarman KM, Ortega J, Steven AC, Storz G (2002). "The Sm-like Hfq protein increases OxyS RNA interaction with target mRNAs." Mol Cell 9(1);11-22. PMID: 11804582

Zhang03d: Zhang A, Wassarman KM, Rosenow C, Tjaden BC, Storz G, Gottesman S (2003). "Global analysis of small RNA and mRNA targets of Hfq." Mol Microbiol 50(4);1111-24. PMID: 14622403

Zhang98b: Zhang A, Altuvia S, Tiwari A, Argaman L, Hengge-Aronis R, Storz G (1998). "The OxyS regulatory RNA represses rpoS translation and binds the Hfq (HF-I) protein." EMBO J 17(20);6061-8. PMID: 9774349

Other References Related to Gene Regulation

Lin11: Lin HH, Hsu CC, Yang CD, Ju YW, Chen YP, Tseng CP (2011). "Negative Effect of Glucose on ompA mRNA Stability: a Potential Role of Cyclic AMP in the Repression of hfq in Escherichia coli." J Bacteriol 193(20);5833-40. PMID: 21840983

Maciag11: Maciag A, Peano C, Pietrelli A, Egli T, De Bellis G, Landini P (2011). "In vitro transcription profiling of the {sigma}S subunit of bacterial RNA polymerase: re-definition of the {sigma}S regulon and identification of {sigma}S-specific promoter sequence elements." Nucleic Acids Res 39(13);5338-55. PMID: 21398637

Mangat08: Mangat CS, Brown ED (2008). "Known bioactive small molecules probe the function of a widely conserved but enigmatic bacterial ATPase, YjeE." Chem Biol 15(12);1287-95. PMID: 19101473

Zaslaver06: Zaslaver A, Bren A, Ronen M, Itzkovitz S, Kikoin I, Shavit S, Liebermeister W, Surette MG, Alon U (2006). "A comprehensive library of fluorescent transcriptional reporters for Escherichia coli." Nat Methods 3(8);623-8. PMID: 16862137

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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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