UniProt functional annotation for P0AEE3



	UniProt functional annotation for P0AEE3

UniProt code: P0AEE3.

Organism: Escherichia coli (strain K12).

Taxonomy: Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.

Function: A site-1 protease (S1P) that cleaves the peptide bond between 'Val-148' and 'Ser-149' in RseA. Part of a regulated intramembrane proteolysis (RIP) cascade. When heat shock or other environmental stresses disrupt protein folding in the periplasm, DegS senses the accumulation of unassembled outer membrane porins (OMP) and then initiates RseA (anti sigma-E factor) degradation by cleaving its periplasmic domain, making it a substrate for subsequent cleavage by RseP. This cascade ultimately leads to the sigma-E-driven expression of a variety of factors dealing with folding stress in the periplasm and OMP assembly. Required for basal and stress-induced degradation of RseA. {ECO:0000269|PubMed:10500101, ECO:0000269|PubMed:11442831, ECO:0000269|PubMed:12183368, ECO:0000269|PubMed:12183369, ECO:0000269|PubMed:12679035, ECO:0000269|PubMed:17360428, ECO:0000269|PubMed:17938245, ECO:0000269|PubMed:18945679, ECO:0000269|PubMed:19695325, ECO:0000269|PubMed:19706448}.

Catalytic activity: Reaction=Acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-|-Val.; EC=3.4.21.107;

Activity regulation: Allosterically activated by the C-terminus of exposed OMP peptides (consensus Tyr-X-Phe-COOH); cleavage only occurs in the presence of peptides. Inhibited when RseB is bound to RseA. {ECO:0000269|PubMed:12679035, ECO:0000269|PubMed:17360428, ECO:0000269|PubMed:17938245, ECO:0000269|PubMed:19836340, ECO:0000269|PubMed:20739286}.

Biophysicochemical properties: Kinetic parameters: KM=33 uM for RseA-YQF {ECO:0000269|PubMed:17981123, ECO:0000269|PubMed:19836340}; Vmax=0.6 umol/sec/mg enzyme {ECO:0000269|PubMed:17981123, ECO:0000269|PubMed:19836340};

Subunit: Homotrimer. {ECO:0000269|PubMed:12679035, ECO:0000269|PubMed:15137941, ECO:0000269|PubMed:15225661, ECO:0000269|PubMed:17938245, ECO:0000269|PubMed:17981123, ECO:0000269|PubMed:19836340, ECO:0000269|PubMed:20739286}.

Subcellular location: Cell inner membrane {ECO:0000305|PubMed:11442831}; Single-pass membrane protein {ECO:0000305|PubMed:11442831}. Note=It is unclear how this protein is anchored to the inner membrane, programs predict a signal sequence, but replacing the N-terminal 26 residues with a known signal sequence gives a protein unable to fully complement a disruption mutant. {ECO:0000269|PubMed:11442831}.

Domain: The PDZ domain probably binds peptides ending with C-terminal Tyr-X-Phe sequences, which activates proteolysis. In the absence of OMP peptides the PDZ domain inhibits peptidase activity. {ECO:0000269|PubMed:12679035, ECO:0000269|PubMed:17360428}.

Disruption phenotype: Small, slowly growing colonies. 5-fold decrease in basal sigma-E (RpoE) activity, loss of regular growth regulation of sigma-E. No proteolysis of full-length RseA. {ECO:0000269|PubMed:10500101, ECO:0000269|PubMed:11442831, ECO:0000269|PubMed:12183368, ECO:0000269|PubMed:12183369, ECO:0000269|PubMed:8576051}.

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, this enzyme), then within the membrane itself (site-2 protease, S2P), while cytoplasmic proteases finish degrading the regulatory protein, liberating the effector protein.

Similarity: Belongs to the peptidase S1C family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


Organism:		Escherichia coli (strain K12).
Taxonomy:		Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales; Enterobacteriaceae; Escherichia.



Function:		A site-1 protease (S1P) that cleaves the peptide bond between 'Val-148' and 'Ser-149' in RseA. Part of a regulated intramembrane proteolysis (RIP) cascade. When heat shock or other environmental stresses disrupt protein folding in the periplasm, DegS senses the accumulation of unassembled outer membrane porins (OMP) and then initiates RseA (anti sigma-E factor) degradation by cleaving its periplasmic domain, making it a substrate for subsequent cleavage by RseP. This cascade ultimately leads to the sigma-E-driven expression of a variety of factors dealing with folding stress in the periplasm and OMP assembly. Required for basal and stress-induced degradation of RseA. {ECO:0000269\|PubMed:10500101, ECO:0000269\|PubMed:11442831, ECO:0000269\|PubMed:12183368, ECO:0000269\|PubMed:12183369, ECO:0000269\|PubMed:12679035, ECO:0000269\|PubMed:17360428, ECO:0000269\|PubMed:17938245, ECO:0000269\|PubMed:18945679, ECO:0000269\|PubMed:19695325, ECO:0000269\|PubMed:19706448}.


Catalytic activity:		Reaction=Acts on substrates that are at least partially unfolded. The cleavage site P1 residue is normally between a pair of hydrophobic residues, such as Val-\|-Val.; EC=3.4.21.107;
Activity regulation:		Allosterically activated by the C-terminus of exposed OMP peptides (consensus Tyr-X-Phe-COOH); cleavage only occurs in the presence of peptides. Inhibited when RseB is bound to RseA. {ECO:0000269\|PubMed:12679035, ECO:0000269\|PubMed:17360428, ECO:0000269\|PubMed:17938245, ECO:0000269\|PubMed:19836340, ECO:0000269\|PubMed:20739286}.
Biophysicochemical properties:		Kinetic parameters: KM=33 uM for RseA-YQF {ECO:0000269\|PubMed:17981123, ECO:0000269\|PubMed:19836340}; Vmax=0.6 umol/sec/mg enzyme {ECO:0000269\|PubMed:17981123, ECO:0000269\|PubMed:19836340};
Subunit:		Homotrimer. {ECO:0000269\|PubMed:12679035, ECO:0000269\|PubMed:15137941, ECO:0000269\|PubMed:15225661, ECO:0000269\|PubMed:17938245, ECO:0000269\|PubMed:17981123, ECO:0000269\|PubMed:19836340, ECO:0000269\|PubMed:20739286}.
Subcellular location:		Cell inner membrane {ECO:0000305\|PubMed:11442831}; Single-pass membrane protein {ECO:0000305\|PubMed:11442831}. Note=It is unclear how this protein is anchored to the inner membrane, programs predict a signal sequence, but replacing the N-terminal 26 residues with a known signal sequence gives a protein unable to fully complement a disruption mutant. {ECO:0000269\|PubMed:11442831}.
Domain:		The PDZ domain probably binds peptides ending with C-terminal Tyr-X-Phe sequences, which activates proteolysis. In the absence of OMP peptides the PDZ domain inhibits peptidase activity. {ECO:0000269\|PubMed:12679035, ECO:0000269\|PubMed:17360428}.
Disruption phenotype:		Small, slowly growing colonies. 5-fold decrease in basal sigma-E (RpoE) activity, loss of regular growth regulation of sigma-E. No proteolysis of full-length RseA. {ECO:0000269\|PubMed:10500101, ECO:0000269\|PubMed:11442831, ECO:0000269\|PubMed:12183368, ECO:0000269\|PubMed:12183369, ECO:0000269\|PubMed:8576051}.
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, this enzyme), then within the membrane itself (site-2 protease, S2P), while cytoplasmic proteases finish degrading the regulatory protein, liberating the effector protein.
Similarity:		Belongs to the peptidase S1C family. {ECO:0000305}.