Skip Header

You are using a version of Internet Explorer that may not display all features of this website. Please upgrade to a modern browser.
Contribute Send feedback
Read comments (?) or add your own

P0AEH1 (RSEP_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 83. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (4) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended name:
Regulator of sigma-E protease RseP

EC=3.4.24.-
Alternative name(s):
S2P endopeptidase
Site-2 protease RseP
Short name=S2P protease RseP
Site-2-type intramembrane protease
Gene names
Name:rseP
Synonyms:ecfE, yaeL
Ordered Locus Names:b0176, JW0171
OrganismEscherichia coli (strain K12) [Reference proteome] [HAMAP]
Taxonomic identifier83333 [NCBI]
Taxonomic lineageBacteriaProteobacteriaGammaproteobacteriaEnterobacterialesEnterobacteriaceaeEscherichia

Protein attributes

Sequence length450 AA.
Sequence statusComplete.
Protein existenceEvidence at protein level

General annotation (Comments)

Function

A site-2 regulated intramembrane protease (S2P) that cleaves the peptide bond between 'Ala-108' and 'Cys-109' in the transmembrane region of RseA. Part of a regulated intramembrane proteolysis (RIP) cascade. Acts on DegS-cleaved RseA to release the cytoplasmic domain of RseA, residue "Val-148" of RseA may be required for this. This provides the cell with sigma-E (RpoE) activity through the proteolysis of RseA. Can also cleave sequences in transmembrane regions of other proteins (such as LacY) as well as liberated signal peptides of beta-lactamase, OmpF, LivK, SecM, PhoA, LivJ, OmpC, Lpp and TorA, probably within the membrane. Ref.9 Ref.10 Ref.11 Ref.14 Ref.16 Ref.17 Ref.19

Cofactor

Zinc Probable.

Enzyme regulation

Inhibited by Zn2+ chelator 1,10-phenanthroline. Ref.17

Subunit structure

Interacts with RseA; the third transmembrane domain can be cross-linked to the transmembrane domain of RseA. Ref.13 Ref.16

Subcellular location

Cell inner membrane; Multi-pass membrane protein Ref.8 Ref.9 Ref.12 Ref.15.

Induction

Part of the sigma-E regulon. Also has a primary sigma-70 factor promoter. Ref.1 Ref.17

Domain

The 2 circularly premutated PDZ domains act to negatively regulate protease action on intact RseA; mutations in PDZ-N have a more deleterious effect than similar mutations in PDZ-C. A 31 residue insertion in PDZ-C (between Val-261 and Met-262) domain inhibits protease activity, whereas deletion of residues 203-279 alleviates the PDZ-inhibition, allowing cleavage of intact RseA. Ref.9 Ref.13 Ref.18 Ref.19 Ref.20

Disruption phenotype

Essential. Depletion experiments lead to cessation of growth, elongated cells and limited lysis, as well as decreased amounts of sigma-E. Not essential in an rseA deletion strain, when sigma-E is overexpressed or in ompA-ompC deletion strain. In the latter has severely decreased growth at 20 degrees Celsius. Accumulation of an RseA proteolysis intermediate. Ref.1 Ref.8 Ref.9 Ref.10 Ref.11 Ref.18

Miscellaneous

Regulated intramembrane proteolysis (RIP) occurs when an extracytoplasmic signal triggers a concerted proteolytic cascade to transmit information and elicit cellular responses. A membrane-spanning regulatory substrate protein is first cut extracytoplasmically (site-1 protease, S1P), then within the membrane itself (site-2 protease, S2P, this enzyme), while cytoplasmic proteases finish degrading the regulatory protein, liberating the effector protein.

Sequence similarities

Belongs to the peptidase M50B family.

Contains 2 PDZ (DHR) domains.

Caution

Was originally thought to be a negative regulator of sigma-E function and to act directly on sigma-E and RpoH; this may not be physiologically relevant (Ref.8).

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 450450Regulator of sigma-E protease RseP
PRO_0000088417

Regions

Transmembrane1 – 2121Helical; Potential
Topological domain22 – 10382Periplasmic Probable
Transmembrane104 – 12421Helical; Potential
Topological domain125 – 375251Cytoplasmic Probable
Transmembrane376 – 39621Helical; Potential
Topological domain397 – 42933Periplasmic Probable
Transmembrane430 – 45021Helical; Potential
Domain127 – 22094PDZ 1 (PDZ-N)
Domain222 – 30988PDZ 2 (PDZ-C)

Sites

Active site231 Probable
Metal binding221Zinc; catalytic Probable
Metal binding261Zinc; catalytic Potential

Experimental info

Mutagenesis221H → A: Loss of protease activity. Ref.8 Ref.9 Ref.10 Ref.14 Ref.16 Ref.17
Mutagenesis221H → F: Loss of protease activity of RseA and signal peptides, does not complement deletion mutant. Binds substrate. Ref.8 Ref.9 Ref.10 Ref.14 Ref.16 Ref.17
Mutagenesis231E → A: Low basal sigma-E activity, sigma-E not induced. No proteolysis of RseA. Ref.9 Ref.11 Ref.16
Mutagenesis231E → D: Behaves like wild-type in vivo, slight reduction in RseA cleavage in vitro. Ref.9 Ref.11 Ref.16
Mutagenesis231E → Q: Does not complement deletion mutant. Ref.9 Ref.11 Ref.16
Mutagenesis231E → S: Loss of protease activity. Ref.9 Ref.11 Ref.16
Mutagenesis261H → F: Does not complement deletion mutant. Ref.9
Mutagenesis1151A → V: No effect. Cleaves RseA without previous DegS cleavage; when associated with R-214. Ref.19
Mutagenesis1451I → N: Cuts RseA without previous DegS cleavage. Ref.19
Mutagenesis1511L → P: Cuts RseA without previous DegS cleavage. Ref.19
Mutagenesis1621W → R: Cuts RseA without previous DegS cleavage. Ref.19
Mutagenesis1691L → S: Cuts RseA without previous DegS cleavage. Ref.19
Mutagenesis2131L → P: Cuts RseA without previous DegS cleavage. Ref.19
Mutagenesis2141G → E or Q: Cuts RseA without previous DegS cleavage. Ref.13 Ref.19
Mutagenesis2141G → R: Weakly cuts RseA without previous DegS cleavage. Stronger cleavage; when associated with V-115. Ref.13 Ref.19
Mutagenesis2151I → A: No cleavage of RseA in vitro (PubMed:19706448), cleavage of RseA (PubMed:23016873) in vivo. Ref.18 Ref.20
Mutagenesis234 – 2352AA → KK: Cuts RseA without previous DegS cleavage.
Mutagenesis2431G → Q: Cuts RseA without previous DegS cleavage. Ref.13
Mutagenesis2441D → K: Cuts RseA without previous DegS cleavage. Ref.13
Mutagenesis2461I → Y: Cuts RseA without previous DegS cleavage. Ref.13
Mutagenesis2611V → VTDSYTQVASWTEPFPFSIQ GDPRSDQETAFV: Does not complement deletion mutant. Ref.9
Mutagenesis3041I → A: No cleavage of RseA in vitro (PubMed:19706448), cleavage of RseA (PubMed:23016873) in vivo. Ref.18 Ref.20
Mutagenesis3891N → C, G or L: Decreased substrate binding, retains some proteolytic activity. Ref.16
Mutagenesis3891N → Q: No effect. Ref.16
Mutagenesis3941N → C: Decreased substrate binding, retains some proteolytic activity. Ref.16
Mutagenesis3971P → C: Decreased substrate binding, retains some proteolytic activity. Ref.16
Mutagenesis3991P → C: Decreased substrate binding, retains some proteolytic activity. Ref.16
Mutagenesis4021D → N: Does not complement deletion mutant, loss of protease activity. Ref.9 Ref.10

Secondary structure

......................................... 450
Helix Strand Turn

Details...

Sequences

Sequence LengthMass (Da)Tools
P0AEH1 [UniParc].

Last modified December 6, 2005. Version 1.
Checksum: 81A93BC113FBB66C

FASTA45049,071
        10         20         30         40         50         60 
MLSFLWDLAS FIVALGVLIT VHEFGHFWVA RRCGVRVERF SIGFGKALWR RTDKLGTEYV 

        70         80         90        100        110        120 
IALIPLGGYV KMLDERAEPV VPELRHHAFN NKSVGQRAAI IAAGPVANFI FAIFAYWLVF 

       130        140        150        160        170        180 
IIGVPGVRPV VGEIAANSIA AEAQIAPGTE LKAVDGIETP DWDAVRLQLV DKIGDESTTI 

       190        200        210        220        230        240 
TVAPFGSDQR RDVKLDLRHW AFEPDKEDPV SSLGIRPRGP QIEPVLENVQ PNSAASKAGL 

       250        260        270        280        290        300 
QAGDRIVKVD GQPLTQWVTF VMLVRDNPGK SLALEIERQG SPLSLTLIPE SKPGNGKAIG 

       310        320        330        340        350        360 
FVGIEPKVIP LPDEYKVVRQ YGPFNAIVEA TDKTWQLMKL TVSMLGKLIT GDVKLNNLSG 

       370        380        390        400        410        420 
PISIAKGAGM TAELGVVYYL PFLALISVNL GIINLFPLPV LDGGHLLFLA IEKIKGGPVS 

       430        440        450 
ERVQDFCYRI GSILLVLLMG LALFNDFSRL 

« Hide

References

« Hide 'large scale' references
[1]"Characterization of the Escherichia coli sigma E regulon."
Dartigalongue C., Missiakas D., Raina S.
J. Biol. Chem. 276:20866-20875(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], INDUCTION, DISRUPTION PHENOTYPE.
[2]"Systematic sequencing of the Escherichia coli genome: analysis of the 4.0 - 6.0 min (189,987 - 281,416bp) region."
Takemoto K., Mori H., Murayama N., Kataoka K., Yano M., Itoh T., Yamamoto Y., Inokuchi H., Miki T., Hatada E., Fukuda R., Ichihara S., Mizuno T., Makino K., Nakata A., Yura T., Sampei G., Mizobuchi K.
Submitted (FEB-1996) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[3]"Sequence of minutes 4-25 of Escherichia coli."
Chung E., Allen E., Araujo R., Aparicio A.M., Davis K., Duncan M., Federspiel N., Hyman R., Kalman S., Komp C., Kurdi O., Lew H., Lin D., Namath A., Oefner P., Roberts D., Schramm S., Davis R.W.
Submitted (JAN-1997) to the EMBL/GenBank/DDBJ databases
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[4]"The complete genome sequence of Escherichia coli K-12."
Blattner F.R., Plunkett G. III, Bloch C.A., Perna N.T., Burland V., Riley M., Collado-Vides J., Glasner J.D., Rode C.K., Mayhew G.F., Gregor J., Davis N.W., Kirkpatrick H.A., Goeden M.A., Rose D.J., Mau B., Shao Y.
Science 277:1453-1462(1997) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / MG1655 / ATCC 47076.
[5]"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110."
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.
Mol. Syst. Biol. 2:E1-E5(2006) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[6]"Molecular cloning and sequencing of the gene for CDP-diglyceride synthetase of Escherichia coli."
Icho T., Sparrow C.P., Raetz C.R.H.
J. Biol. Chem. 260:12078-12083(1985) [PubMed] [Europe PMC] [Abstract]
Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-103.
[7]"Intrinsic and extrinsic approaches for detecting genes in a bacterial genome."
Borodovsky M., Rudd K.E., Koonin E.V.
Nucleic Acids Res. 22:4756-4767(1994) [PubMed] [Europe PMC] [Abstract]
Cited for: IDENTIFICATION.
[8]"EcfE, a new essential inner membrane protease: its role in the regulation of heat shock response in Escherichia coli."
Dartigalongue C., Loferer H., Raina S.
EMBO J. 20:5908-5918(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION, DISRUPTION PHENOTYPE, MUTAGENESIS OF HIS-22.
[9]"Characterization of the yaeL gene product and its S2P-protease motifs in Escherichia coli."
Kanehara K., Akiyama Y., Ito K.
Gene 281:71-79(2001) [PubMed] [Europe PMC] [Abstract]
Cited for: DISCUSSION OF FUNCTION, SUBCELLULAR LOCATION, TOPOLOGY, DOMAIN, DISRUPTION PHENOTYPE, MUTAGENESIS OF HIS-22; GLU-23; HIS-26; VAL-261 AND ASP-402.
Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[10]"YaeL (EcfE) activates the sigma(E) pathway of stress response through a site-2 cleavage of anti-sigma(E), RseA."
Kanehara K., Ito K., Akiyama Y.
Genes Dev. 16:2147-2155(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CLEAVAGE OF RSEA, DISRUPTION PHENOTYPE, MUTAGENESIS OF HIS-22 AND ASP-402.
Strain: K12.
[11]"DegS and YaeL participate sequentially in the cleavage of RseA to activate the sigma(E)-dependent extracytoplasmic stress response."
Alba B.M., Leeds J.A., Onufryk C., Lu C.Z., Gross C.A.
Genes Dev. 16:2156-2168(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE CLEAVAGE OF RSEA, POSSIBLE ACTIVE SITE, DISRUPTION PHENOTYPE, MUTAGENESIS OF GLU-23.
Strain: K12.
[12]"Rapid topology mapping of Escherichia coli inner-membrane proteins by prediction and PhoA/GFP fusion analysis."
Drew D., Sjoestrand D., Nilsson J., Urbig T., Chin C.-N., de Gier J.-W., von Heijne G.
Proc. Natl. Acad. Sci. U.S.A. 99:2690-2695(2002) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
Strain: K12 / JM109 / ATCC 53323.
[13]"YaeL proteolysis of RseA is controlled by the PDZ domain of YaeL and a Gln-rich region of RseA."
Kanehara K., Ito K., Akiyama Y.
EMBO J. 22:6389-6398(2003) [PubMed] [Europe PMC] [Abstract]
Cited for: INTERACTION WITH RSEA, DOMAIN, MUTAGENESIS OF GLY-214; 234-ALA-ALA-235; GLY-243; ASP-244 AND ILE-246.
Strain: K12 / AD16.
[14]"RseP (YaeL), an Escherichia coli RIP protease, cleaves transmembrane sequences."
Akiyama Y., Kanehara K., Ito K.
EMBO J. 23:4434-4442(2004) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN THE CLEAVAGE OF RSEA, MUTAGENESIS OF HIS-22.
[15]"Global topology analysis of the Escherichia coli inner membrane proteome."
Daley D.O., Rapp M., Granseth E., Melen K., Drew D., von Heijne G.
Science 308:1321-1323(2005) [PubMed] [Europe PMC] [Abstract]
Cited for: SUBCELLULAR LOCATION.
Strain: K12 / MG1655 / ATCC 47076.
[16]"Substrate recognition and binding by RseP, an Escherichia coli intramembrane protease."
Koide K., Ito K., Akiyama Y.
J. Biol. Chem. 283:9562-9570(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CLEAVAGE OF RSEA, INTERACTION WITH RSEA, SUBSTRATE RECOGNITION, MUTAGENESIS OF HIS-22; GLU-23; ASN-389; ASN-394; PRO-397 AND PRO-399.
Strain: K12 / AD16.
[17]"Post-liberation cleavage of signal peptides is catalyzed by the site-2 protease (S2P) in bacteria."
Saito A., Hizukuri Y., Matsuo E., Chiba S., Mori H., Nishimura O., Ito K., Akiyama Y.
Proc. Natl. Acad. Sci. U.S.A. 108:13740-13745(2011) [PubMed] [Europe PMC] [Abstract]
Cited for: FUNCTION IN CLEAVAGE OF SIGNAL PEPTIDES, ENZYME REGULATION, MUTAGENESIS OF HIS-22.
Strain: K12.
[18]"PDZ domains of RseP are not essential for sequential cleavage of RseA or stress-induced sigma(E) activation in vivo."
Hizukuri Y., Akiyama Y.
Mol. Microbiol. 86:1232-1245(2012) [PubMed] [Europe PMC] [Abstract]
Cited for: DOMAIN, DISRUPTION PHENOTYPE, MUTAGENESIS OF ILE-215 AND ILE-304.
Strain: K12.
[19]"A pair of circularly permutated PDZ domains control RseP, the S2P family intramembrane protease of Escherichia coli."
Inaba K., Suzuki M., Maegawa K., Akiyama S., Ito K., Akiyama Y.
J. Biol. Chem. 283:35042-35052(2008) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.70 ANGSTROMS) OF 127-221, X-RAY CRYSTALLOGRAPHY (0.98 ANGSTROMS) OF 222-309, FUNCTION IN CLEAVAGE OF RSEA, DOMAIN, MUTAGENESIS OF ALA-115; ILE-145; LEU-151; TRP-162; LEU-169; LEU-213 AND GLY-214.
Strain: K12.
[20]"Cleavage of RseA by RseP requires a carboxyl-terminal hydrophobic amino acid following DegS cleavage."
Li X., Wang B., Feng L., Kang H., Qi Y., Wang J., Shi Y.
Proc. Natl. Acad. Sci. U.S.A. 106:14837-14842(2009) [PubMed] [Europe PMC] [Abstract]
Cited for: X-RAY CRYSTALLOGRAPHY (1.67 ANGSTROMS) OF 127-220, X-RAY CRYSTALLOGRAPHY (1.60 ANGSTROMS) OF 222-307, DOMAIN, MUTAGENESIS OF ILE-215 AND ILE-304.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
AF407012 Genomic DNA. Translation: AAL01378.1.
U70214 Genomic DNA. Translation: AAB08605.1.
U00096 Genomic DNA. Translation: AAC73287.1.
AP009048 Genomic DNA. Translation: BAA77851.1.
M11330 Genomic DNA. No translation available.
PIRH64741.
RefSeqNP_414718.1. NC_000913.3.
YP_488478.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj
EntryMethodResolution (Å)ChainPositionsPDBsum
2ZPLX-ray1.70A/B/C127-221[»]
2ZPMX-ray0.98A222-309[»]
3ID1X-ray1.67A127-220[»]
3ID2X-ray3.09A/B222-309[»]
3ID3X-ray2.01A/B222-309[»]
3ID4X-ray1.60A222-307[»]
ProteinModelPortalP0AEH1.
SMRP0AEH1. Positions 13-116, 127-307.
ModBaseSearch...
MobiDBSearch...

Protein-protein interaction databases

DIPDIP-48061N.
IntActP0AEH1. 1 interaction.
STRING511145.b0176.

Protein family/group databases

MEROPSM50.004.

Proteomic databases

PRIDEP0AEH1.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaAAC73287; AAC73287; b0176.
BAA77851; BAA77851; BAA77851.
GeneID12932742.
944871.
KEGGecj:Y75_p0172.
eco:b0176.
PATRIC32115463. VBIEscCol129921_0183.

Organism-specific databases

EchoBASEEB2331.
EcoGeneEG12436. rseP.

Phylogenomic databases

eggNOGCOG0750.
HOGENOMHOG000006281.
KOK11749.
OMAPDEYKTV.
OrthoDBEOG66F07W.
PhylomeDBP0AEH1.
ProtClustDBPRK10779.

Enzyme and pathway databases

BioCycEcoCyc:EG12436-MONOMER.
ECOL316407:JW0171-MONOMER.
BRENDA3.4.24.85. 2026.

Gene expression databases

GenevestigatorP0AEH1.

Family and domain databases

Gene3D2.30.42.10. 2 hits.
InterProIPR001478. PDZ.
IPR004387. Pept_M50_Zn.
IPR008915. Peptidase_M50.
[Graphical view]
PfamPF00595. PDZ. 1 hit.
PF02163. Peptidase_M50. 1 hit.
[Graphical view]
SMARTSM00228. PDZ. 2 hits.
[Graphical view]
SUPFAMSSF50156. SSF50156. 2 hits.
TIGRFAMsTIGR00054. TIGR00054. 1 hit.
PROSITEPS50106. PDZ. 1 hit.
PS00142. ZINC_PROTEASE. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

EvolutionaryTraceP0AEH1.
PROP0AEH1.

Entry information

Entry nameRSEP_ECOLI
AccessionPrimary (citable) accession number: P0AEH1
Secondary accession number(s): P37764
Entry history
Integrated into UniProtKB/Swiss-Prot: December 6, 2005
Last sequence update: December 6, 2005
Last modified: April 16, 2014
This is version 83 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Peptidase families

Classification of peptidase families and list of entries

PDB cross-references

Index of Protein Data Bank (PDB) cross-references

Escherichia coli

Escherichia coli (strain K12): entries and cross-references to EcoGene