Escherichia coli K-12 substr. MG1655 Polypeptide: anti-sigma factor for FliA (σ28)

Gene: flgM Accession Numbers: G369 (EcoCyc), b1071, ECK1056

Regulation Summary Diagram: ?

Regulation summary diagram for flgM

FlgM is an anti-sigma factor that protects its corresponding sigma factor, σ28 (FliA), against degradation by the Lon protease [Barembruch07].

FlgM is an intrinsically disordered protein that exists in a pre-molten globule-like conformation [Ma13].

FlgM function has been extensively studied in Salmonella typhimurium. FlgM is an intrinsically disordered protein that becomes structured on binding to the transcription factor σ28, regulating flagellar synthesis [Daughdrill97]. FlgM is produced from both the class 2 transcript of flgAMN and the class 3 transcript of flgMN. FlgM is initially translated from its class 2, FlhDC-activated, σ70-dependent transcript. FlgM is the anti-σ28 factor responsible for regulation of σ28 activity and functions in coupling of flagellar assembly to gene expression. FlgM prevents σ28 from binding to DNA by interacting with its promoter -binding domain. Once the hook-basal body structure of the flagellum is complete, the cell becomes capable of flagellum-specific type III secretion of FlgM, and it is secreted. This reduces the FlgM in the cytoplasm and derepresses σ28, which is responsible for expression of class 3 transcripts involved in the third and final phase of flagellar development. The purpose of expressing FlgM from the class 3 promoter only to be secreted is predicted to be to improve motility by reducing the number and length of flagella [Chilcott00].

Unfortunately the source of FlgM protein used in various publications, e.g. [Daughdrill97, Daughdrill98, Dedmon02], was not reported.

A complex between σ28 and the C-terminal σ28-binding fragment of FlgM has been crystallized [Okada07].

Temporal expression of flgM compared to other genes in the flagellar pathway has been measured [Kalir01, Barembruch07]. Increasing expression of flgM increases chemotaxis efficiency [Kollmann05]; a Δ flgM mutant has larger chemotaxis receptor clusters than wild type [Schulmeister08, Thiem08].

Reviews: [Brown95, Hughes98, Chilcott00, Soutourina03, TrevinoQuintani13]

Citations: [Heel13, Dudin13]

Gene Citations: [Macnab92]

Locations: cytosol

Map Position: [1,129,058 <- 1,129,351] (24.33 centisomes, 88°)
Length: 294 bp / 97 aa

Molecular Weight of Polypeptide: 10.341 kD (from nucleotide sequence)

Unification Links: ASAP:ABE-0003634 , EchoBASE:EB2530 , EcoGene:EG12664 , EcoliWiki:b1071 , OU-Microarray:b1071 , PortEco:flgM , PR:PRO_000022648 , Pride:P0AEM4 , Protein Model Portal:P0AEM4 , RefSeq:NP_415589 , RegulonDB:G369 , String:511145.b1071 , UniProt:P0AEM4

Relationship Links: InterPro:IN-FAMILY:IPR007412 , Pfam:IN-FAMILY:PF04316

Genetic Regulation Schematic: ?

Genetic regulation schematic for flgM

GO Terms:

Biological Process: GO:0045861 - negative regulation of proteolysis Inferred from experiment [Barembruch07]
GO:0006351 - transcription, DNA-templated Inferred by computational analysis [UniProtGOA11]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [UniProtGOA11]
GO:0044781 - bacterial-type flagellum organization Inferred by computational analysis [UniProtGOA11]
GO:0045892 - negative regulation of transcription, DNA-templated Inferred by computational analysis [GOA01]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Rajagopala14, Arifuzzaman06, Rajagopala09]
GO:0016989 - sigma factor antagonist activity Inferred from experiment [Barembruch07]
Cellular Component: GO:0005737 - cytoplasm

MultiFun Terms: cell processes motility, chemotaxis, energytaxis (aerotaxis, redoxtaxis etc)
cell structure flagella
information transfer RNA related Transcription related
regulation type of regulation transcriptional level sigma factors, anti-sigmafactors

Essentiality data for flgM 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]

Last-Curated ? 07-Jul-2014 by Keseler I , SRI International

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b1071 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene G369.


Arifuzzaman06: Arifuzzaman M, Maeda M, Itoh A, Nishikata K, Takita C, Saito R, Ara T, Nakahigashi K, Huang HC, Hirai A, Tsuzuki K, Nakamura S, Altaf-Ul-Amin M, Oshima T, Baba T, Yamamoto N, Kawamura T, Ioka-Nakamichi T, Kitagawa M, Tomita M, Kanaya S, Wada C, Mori H (2006). "Large-scale identification of protein-protein interaction of Escherichia coli K-12." Genome Res 16(5);686-91. PMID: 16606699

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

Barembruch07: Barembruch C, Hengge R (2007). "Cellular levels and activity of the flagellar sigma factor FliA of Escherichia coli are controlled by FlgM-modulated proteolysis." Mol Microbiol 65(1);76-89. PMID: 17537210

Brown95: Brown KL, Hughes KT (1995). "The role of anti-sigma factors in gene regulation." Mol Microbiol 16(3);397-404. PMID: 7565101

Chilcott00: Chilcott GS, Hughes KT (2000). "Coupling of flagellar gene expression to flagellar assembly in Salmonella enterica serovar typhimurium and Escherichia coli." Microbiol Mol Biol Rev 64(4);694-708. PMID: 11104815

Daughdrill97: Daughdrill GW, Chadsey MS, Karlinsey JE, Hughes KT, Dahlquist FW (1997). "The C-terminal half of the anti-sigma factor, FlgM, becomes structured when bound to its target, sigma 28." Nat Struct Biol 4(4);285-91. PMID: 9095196

Daughdrill98: Daughdrill GW, Hanely LJ, Dahlquist FW (1998). "The C-terminal half of the anti-sigma factor FlgM contains a dynamic equilibrium solution structure favoring helical conformations." Biochemistry 37(4);1076-82. PMID: 9454599

Dedmon02: Dedmon MM, Patel CN, Young GB, Pielak GJ (2002). "FlgM gains structure in living cells." Proc Natl Acad Sci U S A 99(20);12681-4. PMID: 12271132

Dudin13: Dudin O, Lacour S, Geiselmann J (2013). "Expression dynamics of RpoS/Crl-dependent genes in Escherichia coli." Res Microbiol 164(8);838-47. PMID: 23867204

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

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

Heel13: Heel T, Vogel GF, Lammirato A, Schneider R, Auer B (2013). "FlgM as a secretion moiety for the development of an inducible type III secretion system." PLoS One 8(3);e59034. PMID: 23554966

Hughes98: Hughes KT, Mathee K (1998). "The anti-sigma factors." Annu Rev Microbiol 52;231-86. PMID: 9891799

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

Kalir01: Kalir S, McClure J, Pabbaraju K, Southward C, Ronen M, Leibler S, Surette MG, Alon U (2001). "Ordering genes in a flagella pathway by analysis of expression kinetics from living bacteria." Science 292(5524);2080-3. PMID: 11408658

Kollmann05: Kollmann M, Lovdok L, Bartholome K, Timmer J, Sourjik V (2005). "Design principles of a bacterial signalling network." Nature 438(7067);504-7. PMID: 16306993

Ma13: Ma WK, Hendrix R, Stewart C, Campbell EV, Lavarias M, Morris K, Nichol S, Gage MJ (2013). "FlgM proteins from different bacteria exhibit different structural characteristics." Biochim Biophys Acta 1834(4);808-16. PMID: 23352839

Macnab92: Macnab RM (1992). "Genetics and biogenesis of bacterial flagella." Annu Rev Genet 1992;26;131-58. PMID: 1482109

Okada07: Okada K, Ichihara H, Takahashi H, Fujita N, Ishihama A, Hakoshima T (2007). "Preparation and preliminary X-ray diffraction analysis of crystals of bacterial flagellar sigma factor sigma 28 in complex with the sigma 28-binding region of its antisigma factor, FlgM." Acta Crystallogr Sect F Struct Biol Cryst Commun 63(Pt 3);196-9. PMID: 17329813

Rajagopala09: Rajagopala SV, Hughes KT, Uetz P (2009). "Benchmarking yeast two-hybrid systems using the interactions of bacterial motility proteins." Proteomics 9(23);5296-302. PMID: 19834901

Rajagopala14: Rajagopala SV, Sikorski P, Kumar A, Mosca R, Vlasblom J, Arnold R, Franca-Koh J, Pakala SB, Phanse S, Ceol A, Hauser R, Siszler G, Wuchty S, Emili A, Babu M, Aloy P, Pieper R, Uetz P (2014). "The binary protein-protein interaction landscape of Escherichia coli." Nat Biotechnol 32(3);285-90. PMID: 24561554

Schulmeister08: Schulmeister S, Ruttorf M, Thiem S, Kentner D, Lebiedz D, Sourjik V (2008). "Protein exchange dynamics at chemoreceptor clusters in Escherichia coli." Proc Natl Acad Sci U S A 105(17);6403-8. PMID: 18427119

Soutourina03: Soutourina OA, Bertin PN (2003). "Regulation cascade of flagellar expression in Gram-negative bacteria." FEMS Microbiol Rev 27(4);505-23. PMID: 14550943

Thiem08: Thiem S, Sourjik V (2008). "Stochastic assembly of chemoreceptor clusters in Escherichia coli." Mol Microbiol 68(5);1228-36. PMID: 18476921

TrevinoQuintani13: Trevino-Quintanilla LG, Freyre-Gonzalez JA, Martinez-Flores I (2013). "Anti-Sigma Factors in E. coli: Common Regulatory Mechanisms Controlling Sigma Factors Availability." Curr Genomics 14(6);378-87. PMID: 24396271

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

Other References Related to Gene Regulation

Dudin14: Dudin O, Geiselmann J, Ogasawara H, Ishihama A, Lacour S (2014). "Repression of flagellar genes in exponential phase by CsgD and CpxR, two crucial modulators of Escherichia coli biofilm formation." J Bacteriol 196(3);707-15. PMID: 24272779

Ide99: Ide N, Ikebe T, Kutsukake K (1999). "Reevaluation of the promoter structure of the class 3 flagellar operons of Escherichia coli and Salmonella." Genes Genet Syst 74(3);113-6. PMID: 10586520

Ko00a: Ko M, Park C (2000). "Two novel flagellar components and H-NS are involved in the motor function of Escherichia coli." J Mol Biol 303(3);371-82. PMID: 11031114

Park01: Park K, Choi S, Ko M, Park C (2001). "Novel sigmaF-dependent genes of Escherichia coli found using a specified promoter consensus." FEMS Microbiol Lett 2001;202(2);243-50. PMID: 11520622

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

Yu06a: Yu HH, Di Russo EG, Rounds MA, Tan M (2006). "Mutational analysis of the promoter recognized by Chlamydia and Escherichia coli sigma(28) RNA polymerase." J Bacteriol 188(15);5524-31. PMID: 16855242

Yu06b: Yu HH, Kibler D, Tan M (2006). "In Silico Prediction and Functional Validation of {sigma}28-Regulated Genes in Chlamydia and Escherichia coli." J Bacteriol 188(23);8206-8212. PMID: 16997971

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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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