Escherichia coli K-12 substr. MG1655 Polypeptide: anti-sigma factor

Gene: rseA Accession Numbers: EG12341 (EcoCyc), b2572, ECK2570

Synonyms: yfiJ, mclA

Regulation Summary Diagram: ?

Regulation summary diagram for rseA

RseA is an anti-sigma factor that inhibits σE [Missiakas97]. RseA is the major regulator of σE [Ades99]. RseA associates with the region of σE that interacts with DNA and may interfere with promoter binding [Tam02]. Structural studies indicate that RseA interferes with binding of σE to core polymerase [Campbell03]. RseA binding to σE may be regulated by phosphorylation [Klein03].

Upon extracytoplasmic stress, misfolded/unfolded porins interact with the DegS PDZ domain, releasing an inhibitory interaction and activating DegS protease [Walsh03]. DegS and EcfE then sequentially catalyze proteolytic cleavage of RseA, thereby relieving repression of σE and activating the σE-mediated stress response [Kanehara02, Alba02].

The σE system is also involved in the response to hyperosmotic shock [Bianchi99] and in release of nutrients from dead cells during long periods of stationary phase [Nitta00].

A crystal structure of σE in complex with the RseA amino-terminal, cytoplasmic domain is presented at 2 Å resolution [Campbell03].

RseA resides in the inner membrane. The cytoplasmic amino-terminal domain has the anti-sigma activity [Missiakas97, De97]. Residue Y38 is phosphorylated [Klein03].

Mutations cause increased σE activity [Missiakas97, De97]. Overproduction causes decreased σE activity [Missiakas97].

RseA and σE physically interact [Missiakas97, De97]. RseA also interacts with the periplasmic RseB protein [Missiakas97, De97], which acts to stimulate binding of RseA to σE [Collinet00].

E. coli and mammalian cells exhibit analogous responses to unfolded protein stress [Alba02].

RseA: "regulator of sigma E" [De97]

Citations: [Alba01, Ades03]

Gene Citations: [Raina95, Rhodius05]

Locations: inner membrane

Map Position: [2,706,776 <- 2,707,426] (58.34 centisomes, 210°)
Length: 651 bp / 216 aa

Molecular Weight of Polypeptide: 24.321 kD (from nucleotide sequence), 27.7 kD (experimental)

Unification Links: ASAP:ABE-0008462 , CGSC:37241 , DIP:DIP-39581N , DisProt:DP00552 , EchoBASE:EB2245 , EcoGene:EG12341 , EcoliWiki:b2572 , ModBase:P0AFX7 , OU-Microarray:b2572 , PortEco:rseA , PR:PRO_000023877 , Protein Model Portal:P0AFX7 , RefSeq:NP_417067 , RegulonDB:EG12341 , SMR:P0AFX7 , String:511145.b2572 , Swiss-Model:P0AFX7 , UniProt:P0AFX7

Relationship Links: InterPro:IN-FAMILY:IPR005572 , InterPro:IN-FAMILY:IPR005573 , InterPro:IN-FAMILY:IPR026279 , PDB:Structure:1OR7 , PDB:Structure:1YFN , PDB:Structure:3M4W , Pfam:IN-FAMILY:PF03872 , Pfam:IN-FAMILY:PF03873

Genetic Regulation Schematic: ?

Genetic regulation schematic for rseA

GO Terms:

Biological Process: GO:0006950 - response to stress Inferred from experiment Inferred by computational analysis [GOA01a, Ades99]
GO:0006351 - transcription, DNA-templated Inferred by computational analysis [UniProtGOA11a]
GO:0006355 - regulation of transcription, DNA-templated Inferred by computational analysis [UniProtGOA11a]
Molecular Function: GO:0005515 - protein binding Inferred from experiment [Ahuja09, Sohn07]
GO:0016989 - sigma factor antagonist activity Inferred from experiment Inferred by computational analysis [GOA01a, Missiakas97]
Cellular Component: GO:0005886 - plasma membrane Inferred by computational analysis [UniProtGOA11, UniProtGOA11a]
GO:0016020 - membrane Inferred by computational analysis [UniProtGOA11a]
GO:0016021 - integral component of membrane Inferred by computational analysis [UniProtGOA11a]

MultiFun Terms: cell processes adaptations other (mechanical, nutritional, oxidative stress)
cell processes adaptations temperature extremes
information transfer RNA related Transcription related
regulation type of regulation transcriptional level sigma factors, anti-sigmafactors

Essentiality data for rseA 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]

Sequence Features

Protein sequence of anti-sigma factor with features indicated

Feature Class Location Citations Comment
Mutagenesis-Variant 1 -> 28
[Missiakas97, UniProt14]
UniProt: Loss of anti-sigma factor activity.
Protein-Segment 1 -> 97
UniProt: Sufficient to repress sigma-E; Sequence Annotation Type: region of interest.
Mutagenesis-Variant 11
[Missiakas97, UniProt14]
UniProt: Loss of anti-sigma factor activity.
Mutagenesis-Variant 19
[Missiakas97, UniProt14]
UniProt: Loss of anti-sigma factor activity.
Mutagenesis-Variant 33
[Missiakas97, UniProt14]
UniProt: Loss of anti-sigma factor activity.
Mutagenesis-Variant 79
[Levchenko05, UniProt14]
UniProt: No binding of N-terminal fragment to SspB.
Mutagenesis-Variant 85
[Levchenko05, UniProt14]
UniProt: No binding of N-terminal fragment to SspB.
Mutagenesis-Variant 88
[Levchenko05, UniProt14]
UniProt: Reduced binding of N-terminal fragment to SspB.
Transmembrane-Region 101 -> 118
UniProt: Helical;; Non-Experimental Qualifier: potential;
Mutagenesis-Variant 107 -> 108
[Flynn04, UniProt14]
UniProt: Significantly less degradation by ClpX-ClpP when present as a 1-108 peptide fragment.
Amino-Acid-Site 108, 109
UniProt: Cleavage; by RseP; Sequence Annotation Type: site.
Mutagenesis-Variant 146
[Li09, UniProt14]
UniProt: No effect on protein cleavage.
Mutagenesis-Variant 147
[Hizukuri12, Li09, UniProt14]
UniProt: No effect on protein cleavage in vitro and in vivo.
Amino-Acid-Site 148, 149
UniProt: Cleavage; by DegS; Sequence Annotation Type: site.
Mutagenesis-Variant 148
[UniProt14, Hizukuri12, Li09, UniProt14]
[Hizukuri12, Li09, UniProt14]
[Hizukuri12, Li09, UniProt14]
V → H, K, Q, R, S or Y: Cleaved by DegS but not by RseP in vitro (PubMed:19706448), for R-148 and S-148 decreased cleavage by DegS in vivo (PubMed:23016873).
V → A, C, I, L, M, N or T: Normal cleavage by DegS and RseP in vitro (PubMed:19706448), for A-148 decreased cleavage by DegS in vivo (PubMed:23016873).
V → D, E, F, G or P: Not cleaved by DegS nor RseP in vitro (PubMed:19706448).
Mutagenesis-Variant 162 -> 169
[Kanehara03, UniProt14]
UniProt: RseA is degraded by RseP in the absence of DegS.
Protein-Segment 162 -> 169
UniProt: Poly-Gln; Sequence Annotation Type: compositionally biased region;
Protein-Segment 169 -> 186
UniProt: Primary binding site for RseB; Sequence Annotation Type: region of interest.
Mutagenesis-Variant 172
[Kim07, UniProt14]
[Kim07, UniProt14]
R → D: No binding to RseB.
R → A: Still binds RseB. No binding to RseB; when associated with A-185.
Mutagenesis-Variant 185
[Kim07, UniProt14]
[Kim07, UniProt14]
R → E: No binding to RseB.
R → A: Still binds RseB. No binding to RseB; when associated with A-172.
Mutagenesis-Variant 190 -> 200
[Kanehara03, UniProt14]
UniProt: RseA is degraded by RseP in the absence of DegS.
Protein-Segment 190 -> 200
UniProt: Poly-Gln (Q2); Sequence Annotation Type: region of interest.

Gene Local Context (not to scale): ?

Gene local context diagram

Transcription Units:

Transcription-unit diagram

Transcription-unit diagram

Transcription-unit diagram


10/20/97 Gene b2572 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12341; confirmed by SwissProt match.


Ades03: Ades SE, Grigorova IL, Gross CA (2003). "Regulation of the alternative sigma factor sigma(E) during initiation, adaptation, and shutoff of the extracytoplasmic heat shock response in Escherichia coli." J Bacteriol 185(8);2512-9. PMID: 12670975

Ades99: Ades SE, Connolly LE, Alba BM, Gross CA (1999). "The Escherichia coli sigma(E)-dependent extracytoplasmic stress response is controlled by the regulated proteolysis of an anti-sigma factor." Genes Dev 13(18);2449-61. PMID: 10500101

Ahuja09: Ahuja N, Korkin D, Chaba R, Cezairliyan BO, Sauer RT, Kim KK, Gross CA (2009). "Analyzing the interaction of RseA and RseB, the two negative regulators of the sigmaE envelope stress response, using a combined bioinformatic and experimental strategy." J Biol Chem 284(8);5403-13. PMID: 19103591

Alba01: Alba BM, Zhong HJ, Pelayo JC, Gross CA (2001). "degS (hhoB) is an essential Escherichia coli gene whose indispensable function is to provide sigma (E) activity." Mol Microbiol 40(6);1323-33. PMID: 11442831

Alba02: Alba BM, Leeds JA, Onufryk C, Lu CZ, Gross CA (2002). "DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response." Genes Dev 16(16);2156-68. PMID: 12183369

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

Bianchi99: Bianchi AA, Baneyx F (1999). "Hyperosmotic shock induces the sigma32 and sigmaE stress regulons of Escherichia coli." Mol Microbiol 34(5);1029-38. PMID: 10594827

Campbell03: Campbell EA, Tupy JL, Gruber TM, Wang S, Sharp MM, Gross CA, Darst SA (2003). "Crystal structure of Escherichia coli sigmaE with the cytoplasmic domain of its anti-sigma RseA." Mol Cell 11(4);1067-78. PMID: 12718891

Collinet00: Collinet B, Yuzawa H, Chen T, Herrera C, Missiakas D (2000). "RseB binding to the periplasmic domain of RseA modulates the RseA:sigmaE interaction in the cytoplasm and the availability of sigmaE.RNA polymerase." J Biol Chem 275(43);33898-904. PMID: 11777003

De97: De Las Penas A, Connolly L, Gross CA (1997). "The sigmaE-mediated response to extracytoplasmic stress in Escherichia coli is transduced by RseA and RseB, two negative regulators of sigmaE." Mol Microbiol 24(2);373-85. PMID: 9159523

Flynn04: Flynn JM, Levchenko I, Sauer RT, Baker TA (2004). "Modulating substrate choice: the SspB adaptor delivers a regulator of the extracytoplasmic-stress response to the AAA+ protease ClpXP for degradation." Genes Dev 18(18);2292-301. PMID: 15371343

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."

Hizukuri12: Hizukuri Y, Akiyama Y (2012). "PDZ domains of RseP are not essential for sequential cleavage of RseA or stress-induced σ(E) activation in vivo." Mol Microbiol 86(5);1232-45. PMID: 23016873

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

Kanehara02: Kanehara K, Ito K, Akiyama Y (2002). "YaeL (EcfE) activates the sigma(E) pathway of stress response through a site-2 cleavage of anti-sigma(E), RseA." Genes Dev 16(16);2147-55. PMID: 12183368

Kanehara03: Kanehara K, Ito K, Akiyama Y (2003). "YaeL proteolysis of RseA is controlled by the PDZ domain of YaeL and a Gln-rich region of RseA." EMBO J 22(23);6389-98. PMID: 14633997

Kim07: Kim DY, Jin KS, Kwon E, Ree M, Kim KK (2007). "Crystal structure of RseB and a model of its binding mode to RseA." Proc Natl Acad Sci U S A 104(21);8779-84. PMID: 17496148

Klein03: Klein G, Dartigalongue C, Raina S (2003). "Phosphorylation-mediated regulation of heat shock response in Escherichia coli." Mol Microbiol 48(1);269-85. PMID: 12657060

Levchenko05: Levchenko I, Grant RA, Flynn JM, Sauer RT, Baker TA (2005). "Versatile modes of peptide recognition by the AAA+ adaptor protein SspB." Nat Struct Mol Biol 12(6);520-5. PMID: 15880122

Li09: Li X, Wang B, Feng L, Kang H, Qi Y, Wang J, Shi Y (2009). "Cleavage of RseA by RseP requires a carboxyl-terminal hydrophobic amino acid following DegS cleavage." Proc Natl Acad Sci U S A 106(35);14837-42. PMID: 19706448

Missiakas97: Missiakas D, Mayer MP, Lemaire M, Georgopoulos C, Raina S (1997). "Modulation of the Escherichia coli sigmaE (RpoE) heat-shock transcription-factor activity by the RseA, RseB and RseC proteins." Mol Microbiol 24(2);355-71. PMID: 9159522

Nitta00: Nitta T, Nagamitsu H, Murata M, Izu H, Yamada M (2000). "Function of the sigma(E) regulon in dead-cell lysis in stationary-phase Escherichia coli." J Bacteriol 182(18);5231-7. PMID: 10960110

Raina95: Raina S, Missiakas D, Georgopoulos C (1995). "The rpoE gene encoding the sigma E (sigma 24) heat shock sigma factor of Escherichia coli." EMBO J 14(5);1043-55. PMID: 7889935

Rhodius05: Rhodius VA, Suh WC, Nonaka G, West J, Gross CA (2005). "Conserved and variable functions of the sigmaE stress response in related genomes." PLoS Biol 4(1);e2. PMID: 16336047

Sohn07: Sohn J, Grant RA, Sauer RT (2007). "Allosteric activation of DegS, a stress sensor PDZ protease." Cell 131(3);572-83. PMID: 17981123

Tam02: Tam C, Collinet B, Lau G, Raina S, Missiakas D (2002). "Interaction of the conserved region 4.2 of sigma(E) with the RseA anti-sigma factor." J Biol Chem 277(30);27282-7. PMID: 12016219

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

UniProt10a: UniProt Consortium (2010). "UniProt version 2010-07 released on 2010-06-15 00:00:00." Database.

UniProt14: UniProt Consortium (2014). "UniProt version 2014-08 released on 2014-08-01 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."

Walsh03: Walsh NP, Alba BM, Bose B, Gross CA, Sauer RT (2003). "OMP peptide signals initiate the envelope-stress response by activating DegS protease via relief of inhibition mediated by its PDZ domain." Cell 113(1);61-71. PMID: 12679035

Other References Related to Gene Regulation

BuryMone09: Bury-Mone S, Nomane Y, Reymond N, Barbet R, Jacquet E, Imbeaud S, Jacq A, Bouloc P (2009). "Global analysis of extracytoplasmic stress signaling in Escherichia coli." PLoS Genet 5(9);e1000651. PMID: 19763168

De02: De Wulf P, McGuire AM, Liu X, Lin EC (2002). "Genome-wide profiling of promoter recognition by the two-component response regulator CpxR-P in Escherichia coli." J Biol Chem 277(29);26652-61. PMID: 11953442

Rouviere95: Rouviere PE, De Las Penas A, Mecsas J, Lu CZ, Rudd KE, Gross CA (1995). "rpoE, the gene encoding the second heat-shock sigma factor, sigma E, in Escherichia coli." EMBO J 14(5);1032-42. PMID: 7889934

Thompson07: Thompson KM, Rhodius VA, Gottesman S (2007). "{sigma}E Regulates and Is Regulated by a Small RNA in Escherichia coli." J Bacteriol 189(11);4243-56. PMID: 17416652

Yamamoto05b: Yamamoto K, Ishihama A (2005). "Transcriptional response of Escherichia coli to external zinc." J Bacteriol 187(18);6333-40. PMID: 16159766

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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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