Escherichia coli K-12 substr. MG1655 Polypeptide: regulator for fimA

Gene: fimB Accession Numbers: EG10309 (EcoCyc), b4312, ECK4303

Synonyms: pil

Regulation Summary Diagram: ?

Regulation summary diagram for fimB

FimB, along with FimE, is a recombinase in Escherichia coli which catalyzes the site-specific recombination required for inversion of a 314-bp invertible DNA element, the fim switch (fimS), to control transcription of the type I fimbrial structural genes--a process known as phase-variation switching. fimS contains the promoter for expression of the fimbrial structural genes. The promoter is positioned to allow expression of fimAICDFGH when fimS is in the ON orientation, but not when it is in the OFF orientation. FimB is responsible for both OFF-to-ON and ON-to-OFF switching at equal rates. FimE is responsible for primarily ON-to-OFF switching.

FimB and FimE share significant homology with the lambda integrase family of site-specific recombinases [Dorman87].

Analyses of fimB and fimE mutants and direct assays indicate that fimB is able to mediate recombination in both directions (on-to-off and off-to-on) while fimE only stimulates recombination in the on-to-off direction [Klemm86, Pallesen89, McClain91, Dove96, McClain93, Gally96]. Extensive analysis of fimS has been performed showing the specificity of FimB and FimE for fimS sequences, the effect of sequence alterations on the ability of FimB and FimE to catalyze inversion, the effects of temperature and media on inversions, and the effects of alterations in the way other accessory proteins like Lrp, IHF, and H-NS are able to interact with this system [Abraham85, Dorman87, Eisenstein87, Schwan92, Dorman92, Blomfield93, Gally93, Olsen94, Gally94, Dove94, Blomfield97, Roesch98, Ogara00, Lahooti05, Kelly06, Holden07, McCusker08].

Protein fusion studies indicate that fimB expression is suppressed by the lysosomal enzyme N-acetyl-B-glucosaminidase [Sohanpal04]. Expression of fimB is regulated by N-acetylglucosamine (GlcNAc) by preventing NagC activation of transcription from two NagC binding sites located upstream of fimB [Sohanpal04]. IHF binds at ibs between the NagC sites and enhances cooperative binding of NagC at the two NagC binding sites [Sohanpal07]. Sialic acid also regulates expression of fimB by preventing NanR and NagC activation of transcription from binding sites upstream of fimB [ElLabany03, Sohanpal04, Sohanpal07]. Mutation of these binding sites reduces fimB expression [Sohanpal07]. Expression of fimB is also controlled by (p)ppGpp, and mutants lacking (p)ppGpp have reduced transcription of the gene [Aberg06]. fimB and fimE are repressed by H-NS [Donato97, Olsen98, Donato99]. RpoS is also involved in negative regulation of fimB. Expression of fimB and fimE are controlled by RcsB during growth at neutral pH by increasing fimB transcription or decreasing fimE transcription depending on salt concentration [Schwan07]. The effects of pH and osmolarity on fimB and fimE expression have also been studied in uropathogenic E. coli [Schwan02].
fimB transcription is regulated by growth phase and its repression require the alternative sigma factor, RpoS during enter stationary phase. Although the mechanism by wich RpoS achieves negative control is unknown it is possible that the effect on fimB is exerted indirectly [Dove97].

By making use of micro arrays analysis, Constantinidou et al [Constantinidou06] concluded that FNR represses fimB gene expression, but it is not know which of the three promoters (fimBp1, fimB2, fimBp3) is affected. They also identified a putative FNR binding site upstream of the gene, but the sequence was not shown.

Citations: [Teng06, Wolf02, Burns00, Hasman00]

Gene Citations: [Schwan94]

Locations: cytosol

Map Position: [4,538,980 -> 4,539,582] (97.83 centisomes, 352°)
Length: 603 bp / 200 aa

Molecular Weight of Polypeptide: 22.993 kD (from nucleotide sequence), 23.0 kD (experimental) [Klemm85 ]

Unification Links: ASAP:ABE-0014141 , CGSC:18355 , DIP:DIP-47842N , EchoBASE:EB0305 , EcoGene:EG10309 , EcoliWiki:b4312 , Mint:MINT-1221137 , ModBase:P0ADH5 , OU-Microarray:b4312 , PortEco:fimB , PR:PRO_000022617 , Protein Model Portal:P0ADH5 , RefSeq:NP_418732 , RegulonDB:EG10309 , SMR:P0ADH5 , String:511145.b4312 , UniProt:P0ADH5

Relationship Links: InterPro:IN-FAMILY:IPR002104 , InterPro:IN-FAMILY:IPR011010 , InterPro:IN-FAMILY:IPR013762 , Pfam:IN-FAMILY:PF00589

In Paralogous Gene Group: 470 (4 members)

Genetic Regulation Schematic: ?

Genetic regulation schematic for fimB

GO Terms:

Biological Process: GO:0006310 - DNA recombination Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, McClain93]
GO:0006974 - cellular response to DNA damage stimulus Inferred from experiment [Khil02]
GO:0015074 - DNA integration Inferred from experiment Inferred by computational analysis [UniProtGOA11, GOA01, Klemm86]
GO:0006351 - transcription, DNA-templated Inferred by computational analysis [UniProtGOA11]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [UniProtGOA11]
Molecular Function: GO:0003677 - DNA binding Inferred by computational analysis [GOA01]
Cellular Component: GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: cell structure pilus
information transfer DNA related DNA recombination
metabolism biosynthesis of macromolecules (cellular constituents) fimbri, pili
regulation genetic unit regulated operon
regulation type of regulation DNA structure level

Essentiality data for fimB 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 regulator for fimA with features indicated

Feature Class Location Citations Comment
Sequence-Conflict 13
[Schwan94, UniProt10a]
UniProt: (in Ref. 5; AAA23779);
Sequence-Conflict 32
[Schwan94, UniProt10a]
UniProt: (in Ref. 5; AAA23779);
Sequence-Conflict 85
[Klemm86, UniProt10a]
UniProt: (in Ref. 1; CAA27560);
Active-Site 176
UniProt: O-(3'-phospho-DNA)-tyrosine intermediate; Non-Experimental Qualifier: by similarity;

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


10/20/97 Gene b4312 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10309; confirmed by SwissProt match.


Aberg06: Aberg A, Shingler V, Balsalobre C (2006). "(p)ppGpp regulates type 1 fimbriation of Escherichia coli by modulating the expression of the site-specific recombinase FimB." Mol Microbiol 60(6);1520-33. PMID: 16796685

Abraham85: Abraham JM, Freitag CS, Clements JR, Eisenstein BI (1985). "An invertible element of DNA controls phase variation of type 1 fimbriae of Escherichia coli." Proc Natl Acad Sci U S A 82(17);5724-7. PMID: 2863818

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

Blomfield93: Blomfield IC, Calie PJ, Eberhardt KJ, McClain MS, Eisenstein BI (1993). "Lrp stimulates phase variation of type 1 fimbriation in Escherichia coli K-12." J Bacteriol 175(1);27-36. PMID: 8093239

Blomfield97: Blomfield IC, Kulasekara DH, Eisenstein BI (1997). "Integration host factor stimulates both FimB- and FimE-mediated site-specific DNA inversion that controls phase variation of type 1 fimbriae expression in Escherichia coli." Mol Microbiol 23(4);705-17. PMID: 9157242

Burns00: Burns LS, Smith SG, Dorman CJ (2000). "Interaction of the FimB integrase with the fimS invertible DNA element in Escherichia coli in vivo and in vitro." J Bacteriol 182(10);2953-9. PMID: 10781567

Constantinidou06: Constantinidou C, Hobman JL, Griffiths L, Patel MD, Penn CW, Cole JA, Overton TW (2006). "A reassessment of the FNR regulon and transcriptomic analysis of the effects of nitrate, nitrite, NarXL, and NarQP as Escherichia coli K12 adapts from aerobic to anaerobic growth." J Biol Chem 281(8);4802-15. PMID: 16377617

DiazMejia09: Diaz-Mejia JJ, Babu M, Emili A (2009). "Computational and experimental approaches to chart the Escherichia coli cell-envelope-associated proteome and interactome." FEMS Microbiol Rev 33(1);66-97. PMID: 19054114

Donato97: Donato GM, Lelivelt MJ, Kawula TH (1997). "Promoter-specific repression of fimB expression by the Escherichia coli nucleoid-associated protein H-NS." J Bacteriol 179(21);6618-25. PMID: 9352908

Donato99: Donato GM, Kawula TH (1999). "Phenotypic analysis of random hns mutations differentiate DNA-binding activity from properties of fimA promoter inversion modulation and bacterial motility." J Bacteriol 181(3);941-8. PMID: 9922259

Dorman87: Dorman CJ, Higgins CF (1987). "Fimbrial phase variation in Escherichia coli: dependence on integration host factor and homologies with other site-specific recombinases." J Bacteriol 169(8);3840-3. PMID: 2886490

Dorman92: Dorman CJ, Bhriain NN (1992). "Thermal regulation of fimA, the Escherichia coli gene coding for the type 1 fimbrial subunit protein." FEMS Microbiol Lett 78(2-3);125-30. PMID: 1362708

Dove94: Dove SL, Dorman CJ (1994). "The site-specific recombination system regulating expression of the type 1 fimbrial subunit gene of Escherichia coli is sensitive to changes in DNA supercoiling." Mol Microbiol 14(5);975-88. PMID: 7715458

Dove96: Dove SL, Dorman CJ (1996). "Multicopy fimB gene expression in Escherichia coli: binding to inverted repeats in vivo, effect on fimA gene transcription and DNA inversion." Mol Microbiol 21(6);1161-73. PMID: 8898385

Dove97: Dove SL, Smith SG, Dorman CJ (1997). "Control of Escherichia coli type 1 fimbrial gene expression in stationary phase: a negative role for RpoS." Mol Gen Genet 254(1);13-20. PMID: 9108285

Eisenstein87: Eisenstein BI, Sweet DS, Vaughn V, Friedman DI (1987). "Integration host factor is required for the DNA inversion that controls phase variation in Escherichia coli." Proc Natl Acad Sci U S A 84(18);6506-10. PMID: 2888114

ElLabany03: El-Labany S, Sohanpal BK, Lahooti M, Akerman R, Blomfield IC (2003). "Distant cis-active sequences and sialic acid control the expression of fimB in Escherichia coli K-12." Mol Microbiol 49(4);1109-18. PMID: 12890032

Gally93: Gally DL, Bogan JA, Eisenstein BI, Blomfield IC (1993). "Environmental regulation of the fim switch controlling type 1 fimbrial phase variation in Escherichia coli K-12: effects of temperature and media." J Bacteriol 175(19);6186-93. PMID: 8104927

Gally94: Gally DL, Rucker TJ, Blomfield IC (1994). "The leucine-responsive regulatory protein binds to the fim switch to control phase variation of type 1 fimbrial expression in Escherichia coli K-12." J Bacteriol 1994;176(18);5665-72. PMID: 7916011

Gally96: Gally DL, Leathart J, Blomfield IC (1996). "Interaction of FimB and FimE with the fim switch that controls the phase variation of type 1 fimbriae in Escherichia coli K-12." Mol Microbiol 21(4);725-38. PMID: 8878036

GOA01: GOA, DDB, FB, MGI, ZFIN (2001). "Gene Ontology annotation through association of InterPro records with GO terms."

Hasman00: Hasman H, Schembri MA, Klemm P (2000). "Antigen 43 and type 1 fimbriae determine colony morphology of Escherichia coli K-12." J Bacteriol 182(4);1089-95. PMID: 10648536

Holden07: Holden N, Blomfield IC, Uhlin BE, Totsika M, Kulasekara DH, Gally DL (2007). "Comparative analysis of FimB and FimE recombinase activity." Microbiology 153(Pt 12);4138-49. PMID: 18048927

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

Kelly06: Kelly A, Conway C, O Croinin T, Smith SG, Dorman CJ (2006). "DNA supercoiling and the Lrp protein determine the directionality of fim switch DNA inversion in Escherichia coli K-12." J Bacteriol 188(15);5356-63. PMID: 16855224

Khil02: Khil PP, Camerini-Otero RD (2002). "Over 1000 genes are involved in the DNA damage response of Escherichia coli." Mol Microbiol 44(1);89-105. PMID: 11967071

Klemm85: Klemm P, Jorgensen BJ, van Die I, de Ree H, Bergmans H (1985). "The fim genes responsible for synthesis of type 1 fimbriae in Escherichia coli, cloning and genetic organization." Mol Gen Genet 199(3);410-4. PMID: 2863734

Klemm86: Klemm P (1986). "Two regulatory fim genes, fimB and fimE, control the phase variation of type 1 fimbriae in Escherichia coli." EMBO J 5(6);1389-93. PMID: 2874022

Lahooti05: Lahooti M, Roesch PL, Blomfield IC (2005). "Modulation of the sensitivity of FimB recombination to branched-chain amino acids and alanine in Escherichia coli K-12." J Bacteriol 187(18);6273-80. PMID: 16159759

McClain91: McClain MS, Blomfield IC, Eisenstein BI (1991). "Roles of fimB and fimE in site-specific DNA inversion associated with phase variation of type 1 fimbriae in Escherichia coli." J Bacteriol 173(17);5308-14. PMID: 1679430

McClain93: McClain MS, Blomfield IC, Eberhardt KJ, Eisenstein BI (1993). "Inversion-independent phase variation of type 1 fimbriae in Escherichia coli." J Bacteriol 175(14);4335-44. PMID: 8101185

McCusker08: McCusker MP, Turner EC, Dorman CJ (2008). "DNA sequence heterogeneity in Fim tyrosine-integrase recombinase-binding elements and functional motif asymmetries determine the directionality of the fim genetic switch in Escherichia coli K-12." Mol Microbiol 67(1);171-87. PMID: 18034794

Ogara00: O'gara JP, Dorman CJ (2000). "Effects of local transcription and H-NS on inversion of the fim switch of Escherichia coli." Mol Microbiol 36(2);457-66. PMID: 10792731

Olsen94: Olsen PB, Klemm P (1994). "Localization of promoters in the fim gene cluster and the effect of H-NS on the transcription of fimB and fimE." FEMS Microbiol Lett 1994;116(1);95-100. PMID: 7510658

Olsen98: Olsen PB, Schembri MA, Gally DL, Klemm P (1998). "Differential temperature modulation by H-NS of the fimB and fimE recombinase genes which control the orientation of the type 1 fimbrial phase switch." FEMS Microbiol Lett 1998;162(1);17-23. PMID: 9595659

Pallesen89: Pallesen L, Madsen O, Klemm P (1989). "Regulation of the phase switch controlling expression of type 1 fimbriae in Escherichia coli." Mol Microbiol 3(7);925-31. PMID: 2571915

Roesch98: Roesch PL, Blomfield IC (1998). "Leucine alters the interaction of the leucine-responsive regulatory protein (Lrp) with the fim switch to stimulate site-specific recombination in Escherichia coli." Mol Microbiol 1998;27(4);751-61. PMID: 9515701

Schwan02: Schwan WR, Lee JL, Lenard FA, Matthews BT, Beck MT (2002). "Osmolarity and pH growth conditions regulate fim gene transcription and type 1 pilus expression in uropathogenic Escherichia coli." Infect Immun 70(3);1391-402. PMID: 11854225

Schwan07: Schwan WR, Shibata S, Aizawa S, Wolfe AJ (2007). "The two-component response regulator RcsB regulates type 1 piliation in Escherichia coli." J Bacteriol 189(19);7159-63. PMID: 17644608

Schwan92: Schwan WR, Seifert HS, Duncan JL (1992). "Growth conditions mediate differential transcription of fim genes involved in phase variation of type 1 pili." J Bacteriol 174(7);2367-75. PMID: 1348054

Schwan94: Schwan WR, Seifert HS, Duncan JL (1994). "Analysis of the fimB promoter region involved in type 1 pilus phase variation in Escherichia coli." Mol Gen Genet 1994;242(5);623-30. PMID: 8121417

Sohanpal04: Sohanpal BK, El-Labany S, Lahooti M, Plumbridge JA, Blomfield IC (2004). "Integrated regulatory responses of fimB to N-acetylneuraminic (sialic) acid and GlcNAc in Escherichia coli K-12." Proc Natl Acad Sci U S A 101(46);16322-7. PMID: 15534208

Sohanpal07: Sohanpal BK, Friar S, Roobol J, Plumbridge JA, Blomfield IC (2007). "Multiple co-regulatory elements and IHF are necessary for the control of fimB expression in response to sialic acid and N-acetylglucosamine in Escherichia coli K-12." Mol Microbiol 63(4);1223-36. PMID: 17238917

Teng06: Teng CH, Xie Y, Shin S, Di Cello F, Paul-Satyaseela M, Cai M, Kim KS (2006). "Effects of ompA deletion on expression of type 1 fimbriae in Escherichia coli K1 strain RS218 and on the association of E. coli with human brain microvascular endothelial cells." Infect Immun 74(10);5609-16. PMID: 16988236

UniProt10: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-11 released on 2010-11-02 00:00:00." Database.

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

Wolf02: Wolf DM, Arkin AP (2002). "Fifteen minutes of fim: control of type 1 pili expression in E. coli." OMICS 6(1);91-114. PMID: 11881836

Other References Related to Gene Regulation

Aberg08: Aberg A, Shingler V, Balsalobre C (2008). "Regulation of the fimB promoter: a case of differential regulation by ppGpp and DksA in vivo." Mol Microbiol 67(6);1223-41. PMID: 18284577

Condemine05: Condemine G, Berrier C, Plumbridge J, Ghazi A (2005). "Function and expression of an N-acetylneuraminic acid-inducible outer membrane channel in Escherichia coli." J Bacteriol 187(6);1959-65. PMID: 15743943

Gogol11: Gogol EB, Rhodius VA, Papenfort K, Vogel J, Gross CA (2011). "Small RNAs endow a transcriptional activator with essential repressor functions for single-tier control of a global stress regulon." Proc Natl Acad Sci U S A 108(31);12875-80. PMID: 21768388

Kalivoda13: Kalivoda KA, Steenbergen SM, Vimr ER (2013). "Control of the Escherichia coli sialoregulon by transcriptional repressor NanR." J Bacteriol 195(20);4689-701. PMID: 23935044

Oberto10: Oberto J (2010). "FITBAR: a web tool for the robust prediction of prokaryotic regulons." BMC Bioinformatics 11;554. PMID: 21070640

Ogasawara12: Ogasawara H, Shinohara S, Yamamoto K, Ishihama A (2012). "Novel regulation targets of the metal-response BasS-BasR two-component system of Escherichia coli." Microbiology 158(Pt 6);1482-92. PMID: 22442305

Wade06: Wade JT, Roa DC, Grainger DC, Hurd D, Busby SJ, Struhl K, Nudler E (2006). "Extensive functional overlap between sigma factors in Escherichia coli." Nat Struct Mol Biol 13(9);806-14. PMID: 16892065

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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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