Escherichia coli K-12 substr. MG1655 Polypeptide: FlhC

Gene: flhC Accession Numbers: EG10319 (EcoCyc), b1891, ECK1892

Synonyms: flaI

Regulation Summary Diagram: ?

Regulation summary diagram for flhC

Component of: FlhDC DNA-binding transcriptional dual regulator (extended summary available)

Citations: [Claret02]

Gene Citations: [Shin95, Bertin94, Lehti12]

Locations: cytosol

Map Position: [1,975,290 <- 1,975,868] (42.57 centisomes, 153°)
Length: 579 bp / 192 aa

Molecular Weight of Polypeptide: 21.566 kD (from nucleotide sequence), 22 kD (experimental) [Liu94 ]

Unification Links: ASAP:ABE-0006301 , CGSC:767 , DIP:DIP-9645N , EchoBASE:EB0315 , EcoGene:EG10319 , EcoliWiki:b1891 , OU-Microarray:b1891 , PortEco:flhC , PR:PRO_000022652 , Pride:P0ABY7 , Protein Model Portal:P0ABY7 , RefSeq:NP_416405 , RegulonDB:EG10319 , SMR:P0ABY7 , String:511145.b1891 , Swiss-Model:P0ABY7 , UniProt:P0ABY7

Relationship Links: InterPro:IN-FAMILY:IPR007944 , PDB:Structure:2AVU , Pfam:IN-FAMILY:PF05280 , ProDom:IN-FAMILY:PD016592

Gene-Reaction Schematic: ?

Gene-Reaction Schematic

Genetic Regulation Schematic: ?

Genetic regulation schematic for flhC

GO Terms:

Biological Process: GO:0006351 - transcription, DNA-templated Inferred from experiment Inferred by computational analysis [UniProtGOA11a, Liu94]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [UniProtGOA11a, GOA06]
GO:0044781 - bacterial-type flagellum organization Inferred by computational analysis [UniProtGOA11a]
GO:0045893 - positive regulation of transcription, DNA-templated Inferred by computational analysis [GOA01a]
GO:1902208 - regulation of bacterial-type flagellum assembly Inferred by computational analysis [GOA06, GOA01a]
Molecular Function: GO:0003677 - DNA binding Inferred by computational analysis [UniProtGOA11a, GOA06, GOA01a]
GO:0008270 - zinc ion binding Inferred by computational analysis [GOA06]
GO:0046872 - metal ion binding Inferred by computational analysis [UniProtGOA11a]
Cellular Component: GO:0005737 - cytoplasm Inferred by computational analysis [UniProtGOA11, UniProtGOA11a, GOA06]
GO:0005829 - cytosol Inferred by computational analysis [DiazMejia09]

MultiFun Terms: cell processes motility, chemotaxis, energytaxis (aerotaxis, redoxtaxis etc)
cell structure flagella
information transfer RNA related Transcription related
metabolism biosynthesis of macromolecules (cellular constituents) flagellum
regulation genetic unit regulated operon
regulation type of regulation transcriptional level activator
regulation type of regulation transcriptional level repressor

Essentiality data for flhC knockouts: ?

Growth Medium Growth? T (°C) O2 pH Osm/L Growth Observations
LB enriched Yes 37 Aerobic 6.95   Yes [Gerdes03, Comment 1]
LB Lennox Yes 37 Aerobic 7   Yes [Baba06, Comment 2]
M9 medium with 1% glycerol Yes 37 Aerobic 7.2 0.35 Yes [Joyce06, Comment 3]
MOPS medium with 0.4% glucose Yes 37 Aerobic 7.2 0.22 Yes [Baba06, Comment 2]

Subunit of: FlhDC DNA-binding transcriptional dual regulator

Synonyms: FlhDC

Subunit composition of FlhDC DNA-binding transcriptional dual regulator = [FlhD]4[FlhC]2

The FlhD and FlhC proteins are transcriptional factors and can form homodimers independently (FlhD2 and FlhC2) [Liu94], and the assembly of these homodimers results in the formation of heterotetramers (FlhD2C2) [Liu94, Claret02, Stafford05]. The complex transcription factor FlhD2C2 is the principal regulator of bacterial flagellum biogenesis and swarming migration [Claret02, Stafford05]. This heterotetrameric regulator activates class II genes involved in the flagellar basal body [Claret02, Stafford05, Liu94, Ikebe99], proteins of the export machinery, the flagellar σ subunit (FliA), and its anti-σ factor, FlgM [Claret02, Stafford05, Barker04]. Currently, no inducer for this regulator has been reported in the literature. A microarray analysis showed that the master regulator, FlhD2C2, regulates several nonflagellar genes, but the direct effect has not been determined.

FlhD and FlhC are part of the unusual flhDC operon that encodes two transcriptional regulators [Liu94, Bartlett88]. The expression of the flhDC master operon is multirregulated by several systems including those that respond to high osmolarity [Shin95], catabolic repression [Soutourina99], quorum sensing [Sperandio02], synthesis of type 1 fimbriae [Lehnen02], the histone-like nucleoid protein [Bertin94, Soutourina99], heat shock, etc.

The flagellar regulator activates transcription of class II genes by overlapping the -35 box of the promoters [Stafford05, Claret02, Liu94]. The binding targets for FlhD2C2 consist of two repeat sequences that possess conserved motifs; each heterodimer (FlhDC) binds to one of these conserved sequences, which are separated by a 10- to 11-bp spacer [Stafford05, Claret02].

The flagellar regulator is conformed by two FlhD subunits and two FlhC subunits, as a heterotetramer [Wang06], while FlhD is constituted by two domains: the N-terminal domain is responsible for dimerization and the C terminal is a highly flexible domain contain the DNA-binding (helix-turn-helix motif) region [Wang06, Campos01]. FlhC is constituted by two domains; arrangement of the domains is unique in the FlhC family [Wang06]. The crystal structure of FlhDC has been solved to 3 Å resolution [Wang06] .

Molecular Weight: 68 kD (experimental) [Liu94]

Relationship Links: PDB:Structure:2AVU

GO Terms:

Biological Process: GO:0006355 - regulation of transcription, DNA-templated Inferred from experiment [Stafford05]
Molecular Function: GO:0000987 - core promoter proximal region sequence-specific DNA binding Inferred from experiment [Liu94]
GO:0042803 - protein homodimerization activity Inferred from experiment [Liu94]
GO:0046982 - protein heterodimerization activity Inferred from experiment [Liu94]

DNA binding site length: 17 base-pairs

Symmetry: Asymmetric

Consensus DNA Binding Sequence: CAATGGCAgAAATAGCG

Regulated Transcription Units (21 total): ?


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

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

Sequence Features

Protein sequence of FlhC with features indicated

Feature Class Location Citations Comment
Metal-Binding-Site 137
UniProt: Zinc.
Metal-Binding-Site 140
UniProt: Zinc.
Sequence-Conflict 149
[Bartlett88, UniProt10a]
UniProt: (in Ref. 1; AAA23788);
Metal-Binding-Site 157
UniProt: Zinc.
Metal-Binding-Site 160
UniProt: Zinc.

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b1891 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG10319; confirmed by SwissProt match.


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

Barker04: Barker CS, Pruss BM, Matsumura P (2004). "Increased motility of Escherichia coli by insertion sequence element integration into the regulatory region of the flhD operon." J Bacteriol 186(22);7529-37. PMID: 15516564

Bartlett88: Bartlett DH, Frantz BB, Matsumura P (1988). "Flagellar transcriptional activators FlbB and FlaI: gene sequences and 5' consensus sequences of operons under FlbB and FlaI control." J Bacteriol 170(4);1575-81. PMID: 2832369

Bertin94: Bertin P, Terao E, Lee EH, Lejeune P, Colson C, Danchin A, Collatz E (1994). "The H-NS protein is involved in the biogenesis of flagella in Escherichia coli." J Bacteriol 1994;176(17);5537-40. PMID: 8071234

Campos01: Campos A, Zhang RG, Alkire RW, Matsumura P, Westbrook EM (2001). "Crystal structure of the global regulator FlhD from Escherichia coli at 1.8 A resolution." Mol Microbiol 39(3);567-80. PMID: 11169099

Claret02: Claret L, Hughes C (2002). "Interaction of the atypical prokaryotic transcription activator FlhD2C2 with early promoters of the flagellar gene hierarchy." J Mol Biol 321(2);185-99. PMID: 12144778

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

Gerdes03: Gerdes SY, Scholle MD, Campbell JW, Balazsi G, Ravasz E, Daugherty MD, Somera AL, Kyrpides NC, Anderson I, Gelfand MS, Bhattacharya A, Kapatral V, D'Souza M, Baev MV, Grechkin Y, Mseeh F, Fonstein MY, Overbeek R, Barabasi AL, Oltvai ZN, Osterman AL (2003). "Experimental determination and system level analysis of essential genes in Escherichia coli MG1655." J Bacteriol 185(19);5673-84. PMID: 13129938

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."

Ikebe99: Ikebe T, Iyoda S, Kutsukake K (1999). "Promoter analysis of the class 2 flagellar operons of Salmonella." Genes Genet Syst 74(4);179-83. PMID: 10650844

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

Lehnen02: Lehnen D, Blumer C, Polen T, Wackwitz B, Wendisch VF, Unden G (2002). "LrhA as a new transcriptional key regulator of flagella, motility and chemotaxis genes in Escherichia coli." Mol Microbiol 2002;45(2);521-32. PMID: 12123461

Lehti12: Lehti TA, Bauchart P, Dobrindt U, Korhonen TK, Westerlund-Wikstrom B (2012). "The fimbriae activator MatA switches off motility in Escherichia coli by repression of the flagellar master operon flhDC." Microbiology 158(Pt 6);1444-55. PMID: 22422754

Liu94: Liu X, Matsumura P (1994). "The FlhD/FlhC complex, a transcriptional activator of the Escherichia coli flagellar class II operons." J Bacteriol 176(23);7345-51. PMID: 7961507

Shin95: Shin S, Park C (1995). "Modulation of flagellar expression in Escherichia coli by acetyl phosphate and the osmoregulator OmpR." J Bacteriol 1995;177(16);4696-702. PMID: 7642497

Soutourina99: Soutourina O, Kolb A, Krin E, Laurent-Winter C, Rimsky S, Danchin A, Bertin P (1999). "Multiple control of flagellum biosynthesis in Escherichia coli: role of H-NS protein and the cyclic AMP-catabolite activator protein complex in transcription of the flhDC master operon." J Bacteriol 1999;181(24);7500-8. PMID: 10601207

Sperandio02: Sperandio V, Torres AG, Kaper JB (2002). "Quorum sensing Escherichia coli regulators B and C (QseBC): a novel two-component regulatory system involved in the regulation of flagella and motility by quorum sensing in E. coli." Mol Microbiol 43(3);809-21. PMID: 11929534

Stafford05: Stafford GP, Ogi T, Hughes C (2005). "Binding and transcriptional activation of non-flagellar genes by the Escherichia coli flagellar master regulator FlhD2C2." Microbiology 151(Pt 6);1779-88. PMID: 15941987

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

Wang06: Wang S, Fleming RT, Westbrook EM, Matsumura P, McKay DB (2006). "Structure of the Escherichia coli FlhDC complex, a prokaryotic heteromeric regulator of transcription." J Mol Biol 355(4);798-808. PMID: 16337229

Other References Related to Gene Regulation

Barrios99: Barrios H, Valderrama B, Morett E (1999). "Compilation and analysis of sigma(54)-dependent promoter sequences." Nucleic Acids Res 27(22);4305-13. PMID: 10536136

De12: De Lay N, Gottesman S (2012). "A complex network of small non-coding RNAs regulate motility in Escherichia coli." Mol Microbiol 86(3);524-38. PMID: 22925049

FrancezCharlot03: Francez-Charlot A, Laugel B, Van Gemert A, Dubarry N, Wiorowski F, Castani?-Cornet MP, Gutierrez C, Cam K (2003). "RcsCDB His-Asp phosphorelay system negatively regulates the flhDC operon in Escherichia coli." Mol Microbiol 49(3);823-32. PMID: 12864862

Ko00: Ko M, Park C (2000). "H-NS-Dependent regulation of flagellar synthesis is mediated by a LysR family protein." J Bacteriol 182(16);4670-2. PMID: 10913108

Lee13: Lee C, Park C (2013). "Mutations upregulating the flhDC operon of Escherichia coli K-12." J Microbiol 51(1);140-4. PMID: 23456724

Otsuka96: Otsuka J, Watanabe H, Mori KT (1996). "Evolution of transcriptional regulation system through promiscuous coupling of regulatory proteins with operons; suggestion from protein sequence similarities in Escherichia coli." J Theor Biol 1996;178(2);183-204. PMID: 8729576

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

Raivio13: Raivio TL, Leblanc SK, Price NL (2013). "The Escherichia coli Cpx envelope stress response regulates genes of diverse function that impact antibiotic resistance and membrane integrity." J Bacteriol 195(12);2755-67. PMID: 23564175

Samanta13: Samanta P, Clark ER, Knutson K, Horne SM, Pruß BM (2013). "OmpR and RcsB abolish temporal and spatial changes in expression of flhD in Escherichia coli Biofilm." BMC Microbiol 13(1);182. PMID: 23914787

Stojiljkovic94: Stojiljkovic I, Baumler AJ, Hantke K (1994). "Fur regulon in gram-negative bacteria. Identification and characterization of new iron-regulated Escherichia coli genes by a fur titration assay." J Mol Biol 236(2);531-45. PMID: 8107138

Theodorou12: Theodorou MC, Theodorou EC, Kyriakidis DA (2012). "Involvement of AtoSC two-component system in Escherichia coli flagellar regulon." Amino Acids 43(2);833-44. PMID: 22083893

Thomason12: Thomason MK, Fontaine F, De Lay N, Storz G (2012). "A small RNA that regulates motility and biofilm formation in response to changes in nutrient availability in Escherichia coli." Mol Microbiol 84(1);17-35. PMID: 22289118

Uchiyama10: Uchiyama J, Nobue Y, Zhao H, Matsuzaki H, Nagahama H, Matsuoka S, Matsumoto K, Hara H (2010). "Involvement of sigmaS accumulation in repression of the flhDC operon in acidic phospholipid-deficient mutants of Escherichia coli." Microbiology 156(Pt 6);1650-60. PMID: 20185506

Wang11b: Wang X, Wood TK (2011). "IS5 inserts upstream of the master motility operon flhDC in a quasi-Lamarckian way." ISME J 5(9);1517-25. PMID: 21390082

Wei01: Wei BL, Brun-Zinkernagel AM, Simecka JW, Pruss BM, Babitzke P, Romeo T (2001). "Positive regulation of motility and flhDC expression by the RNA-binding protein CsrA of Escherichia coli." Mol Microbiol 40(1);245-56. PMID: 11298291

Zhao07: Zhao K, Liu M, Burgess RR (2007). "Adaptation in bacterial flagellar and motility systems: from regulon members to 'foraging'-like behavior in E. coli." Nucleic Acids Res 35(13);4441-52. PMID: 17576668

Zhao10a: Zhao K, Liu M, Burgess RR (2010). "Promoter and regulon analysis of nitrogen assimilation factor, sigma54, reveal alternative strategy for E. coli MG1655 flagellar biosynthesis." Nucleic Acids Res 38(4);1273-83. PMID: 19969540

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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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