|Gene:||rseP||Accession Numbers: EG12436 (EcoCyc), b0176, ECK0175|
Synonyms: ecfE, yaeL
RseP (formerly YaeL) is a zinc metallo-protease that resides in the inner membrane [Dartigalongue01a]. Upon extracytoplasmic stress, DegS and RseP sequentially catalyze proteolytic cleavage of RseA, thereby relieving repression of σE and activating the σE-mediated stress response [Kanehara02, Alba02]. RseP is involved in the degradation of remnant signal peptides that are left in the inner membrane after their cleavage from preproteins by leader peptidase [Saito11].
RseP cleaves RseA in the cytoplasmic or intramembrane region [Kanehara02]. RseP has also been observed to exhibit proteolytic activity toward RpoE and RpoH [Dartigalongue01a], and a wide range of other membrane proteins [Akiyama04]. RseP can cleave remnant signal peptides from a variety of secretory proteins in vivo including OmpF, LivK, SecM, PhoA and others [Saito11]. RseE can cleave remnant signal peptides from proteins that are processed via the Sec and Tat pathways [Saito11]. RseP cleaves synthetic βlactamase signal peptides within the hydrophobic core region [Saito11].
RseP has an N-terminal domain containing the zinc metalloprotease motif HEXXH, and a C-terminal domain with an LDG sequence [Dartigalongue01a]. The HEXXH and LDG motifs are required [Kanehara01]. RseP also contains two circularly permutated PDZ domains (PDZ-N and PDZ-C) [Inaba08]. Mutational analyses of these two domains in an in vitro reconstitution of RseP catalysed proteolysis suggests that they are involved in ligand binding [Inaba08].
The sequential cleavage of RseA by DegS and RseP has been reconstituted in vitro [Li09]. After cleavage by DegS, the single terminal residue (Val148) of the newly generated C-terminus of RseA binds to the PDZ-C domain of RseP and undergoes a second cleavage. Crystal structures of the PDZ-N and PDZ-C domains of RseP have been obtained suggesting that PDZ-N is in a 'closed' conformation whilst PDZ-C is 'open' to receive a ligand [Li09] The structure of a DegS cleaved RseA peptide (residues 1-148) fused to the PDZ-C domain shows the C-terminal Val148 residue bound to the PDZ-C binding pocket [Li09].
Mutants lacking or depleted of RseP are inviable [Dartigalongue01a, Kanehara01, Baba06]. Overproduction of RseP inhibits transcription directed by σE or σ32-containing polymerase holoenzyme [Dartigalongue01a]. The inviability of an rseP mutant is suppressed by overproduction of RpoE [Kanehara02]. Mutations in the PDZ domain do not appear to be lethal, but render the proteolytic activity of RseP independent of DegS activity, suggesting that the PDZ domain acts as an inhibitor [Bohn04, Kanehara03].
RseP is a member of the site-2 protease (S2P) family [Kinch06] of intra-membrane cleaving proteases (I-CLips) [Kanehara01]. E. coli and mammalian cells exhibit analogous responses to unfolded protein stress [Alba02].
Ecf: "extracytoplasmic function" [Dartigalongue01].
Locations: inner membrane
|Map Position: [196,546 -> 197,898] (4.24 centisomes)||Length: 1353 bp / 450 aa|
Molecular Weight of Polypeptide: 49.071 kD (from nucleotide sequence)
Unification Links: ASAP:ABE-0000603 , DIP:DIP-48061N , EchoBASE:EB2331 , EcoGene:EG12436 , EcoliWiki:b0176 , ModBase:P0AEH1 , OU-Microarray:b0176 , PortEco:rseP , PR:PRO_000023880 , Pride:P0AEH1 , Protein Model Portal:P0AEH1 , RefSeq:NP_414718 , RegulonDB:EG12436 , SMR:P0AEH1 , String:511145.b0176 , UniProt:P0AEH1
Relationship Links: InterPro:IN-FAMILY:IPR001478 , InterPro:IN-FAMILY:IPR004387 , InterPro:IN-FAMILY:IPR008915 , PDB:Structure:2ZPL , PDB:Structure:2ZPM , PDB:Structure:3ID1 , PDB:Structure:3ID2 , PDB:Structure:3ID3 , PDB:Structure:3ID4 , Pfam:IN-FAMILY:PF00595 , Pfam:IN-FAMILY:PF02163 , Prosite:IN-FAMILY:PS00142 , Prosite:IN-FAMILY:PS50106 , Smart:IN-FAMILY:SM00228
|Biological Process:||GO:0006950 - response to stress
GO:0045893 - positive regulation of transcription, DNA-templated [Alba02, Kanehara02]
GO:0006508 - proteolysis [UniProtGOA11a, GOA01a]
|Molecular Function:||GO:0004222 - metalloendopeptidase activity
GO:0043856 - anti-sigma factor antagonist activity [Kanehara02, Alba02]
GO:0045152 - antisigma factor binding [Li09]
GO:0008233 - peptidase activity [UniProtGOA11a]
GO:0008237 - metallopeptidase activity [UniProtGOA11a]
GO:0016787 - hydrolase activity [UniProtGOA11a]
GO:0046872 - metal ion binding [UniProtGOA11a]
|Cellular Component:||GO:0005886 - plasma membrane
[UniProtGOA11, UniProtGOA11a, DiazMejia09, Zhang07, Daley05, Dartigalongue01a]
GO:0005887 - integral component of plasma membrane [Drew02]
GO:0016020 - membrane [UniProtGOA11a]
GO:0016021 - integral component of membrane [UniProtGOA11a, GOA01a]
|MultiFun Terms:||cell processes → adaptations → other (mechanical, nutritional, oxidative stress)|
|cell processes → adaptations → temperature extremes|
|information transfer → protein related → turnover, degradation|
|metabolism → degradation of macromolecules → proteins/peptides/glycopeptides|
|regulation → type of regulation → posttranscriptional → proteases, cleavage of compounds|
|regulation → type of regulation → transcriptional level → sigma factors, anti-sigmafactors|
|Growth Medium||Growth?||T (°C)||O2||pH||Osm/L||Growth Observations|
|LB enriched||Yes||37||Aerobic||6.95||Yes [Gerdes03, Comment 1]|
|LB Lennox||No||37||Aerobic||7||No [Baba06, Comment 2]|
|Feature Class||Location||Common Name||Citations||Comment|
|Transmembrane-Region||107 -> 127|
|Conserved-Region||127 -> 220||PDZ-N|
|Conserved-Region||199 -> 291|
|Conserved-Region||222 -> 309||PDZ-C|
|Transmembrane-Region||376 -> 396|
|Transmembrane-Region||430 -> 450|
10/20/97 Gene b0176 from Blattner lab Genbank (v. M52) entry merged into EcoCyc gene EG12436; confirmed by SwissProt match.
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
Dartigalongue01a: Dartigalongue C, Loferer H, Raina S (2001). "EcfE, a new essential inner membrane protease: its role in the regulation of heat shock response in Escherichia coli." EMBO J 20(21);5908-18. PMID: 11689431
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
Drew02: Drew D, Sjostrand D, Nilsson J, Urbig T, Chin CN, de Gier JW, von Heijne G (2002). "Rapid topology mapping of Escherichia coli inner-membrane proteins by prediction and PhoA/GFP fusion analysis." Proc Natl Acad Sci U S A 99(5);2690-5. PMID: 11867724
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
Inaba08: Inaba K, Suzuki M, Maegawa KI, Akiyama S, Ito K, Akiyama Y (2008). "A pair of circularly permutated PDZ domains control RseP, the S2P family intramembrane protease of E. coli." J Biol Chem 283(50):35042-52. PMID: 18945679
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
Kinch06: Kinch LN, Ginalski K, Grishin NV (2006). "Site-2 protease regulated intramembrane proteolysis: sequence homologs suggest an ancient signaling cascade." Protein Sci 15(1);84-93. PMID: 16322567
Koide07: Koide K, Maegawa S, Ito K, Akiyama Y (2007). "Environment of the active site region of RseP, an Escherichia coli regulated intramembrane proteolysis protease, assessed by site-directed cysteine alkylation." J Biol Chem 282(7);4553-60. PMID: 17179147
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
Saito11: Saito A, Hizukuri Y, Matsuo E, Chiba S, Mori H, Nishimura O, Ito K, Akiyama Y (2011). "Post-liberation cleavage of signal peptides is catalyzed by the site-2 protease (S2P) in bacteria." Proc Natl Acad Sci U S A 108(33);13740-5. PMID: 21810987
Zhang07: Zhang N, Chen R, Young N, Wishart D, Winter P, Weiner JH, Li L (2007). "Comparison of SDS- and methanol-assisted protein solubilization and digestion methods for Escherichia coli membrane proteome analysis by 2-D LC-MS/MS." Proteomics 7(4);484-93. PMID: 17309111
Viveiros07: Viveiros M, Dupont M, Rodrigues L, Couto I, Davin-Regli A, Martins M, Pages JM, Amaral L (2007). "Antibiotic stress, genetic response and altered permeability of E. coli." PLoS ONE 2;e365. PMID: 17426813
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