UniProt functional annotation for P0AEH1



	UniProt functional annotation for P0AEH1

UniProt code: P0AEH1.

Organism: Escherichia coli (strain K12).

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

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. {ECO:0000269|PubMed:12183368, ECO:0000269|PubMed:12183369, ECO:0000269|PubMed:15496982, ECO:0000269|PubMed:18268014, ECO:0000269|PubMed:18945679, ECO:0000269|PubMed:21810987}.

Cofactor: Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305};

Activity regulation: Inhibited by Zn(2+) chelator 1,10-phenanthroline. {ECO:0000269|PubMed:21810987}.

Subunit: Interacts with RseA; the third transmembrane domain can be cross-linked to the transmembrane domain of RseA. {ECO:0000269|PubMed:14633997, ECO:0000269|PubMed:18268014}.

Subcellular location: Cell inner membrane {ECO:0000269|PubMed:11689431, ECO:0000269|PubMed:11750129, ECO:0000269|PubMed:11867724, ECO:0000269|PubMed:15919996}; Multi-pass membrane protein {ECO:0000269|PubMed:11689431, ECO:0000269|PubMed:11750129, ECO:0000269|PubMed:11867724, ECO:0000269|PubMed:15919996}.

Induction: Part of the sigma-E regulon. Also has a primary sigma-70 factor promoter. {ECO:0000269|PubMed:11274153}.

Domain: The 2 circularly premutated PDZ domains act to negatively regulate protease action on intact RseA; mutations in PDZ 1 (PDZ-N) have a more deleterious effect than similar mutations in PDZ 2 (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. {ECO:0000269|PubMed:11750129, ECO:0000269|PubMed:14633997, ECO:0000269|PubMed:18945679, ECO:0000269|PubMed:19706448, ECO:0000269|PubMed:23016873}.

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. {ECO:0000269|PubMed:11274153, ECO:0000269|PubMed:11689431, ECO:0000269|PubMed:11750129, ECO:0000269|PubMed:12183368, ECO:0000269|PubMed:12183369, ECO:0000269|PubMed:23016873}.

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.

Similarity: Belongs to the peptidase M50B 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-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. {ECO:0000269\|PubMed:12183368, ECO:0000269\|PubMed:12183369, ECO:0000269\|PubMed:15496982, ECO:0000269\|PubMed:18268014, ECO:0000269\|PubMed:18945679, ECO:0000269\|PubMed:21810987}.


Cofactor:		Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000305};
Activity regulation:		Inhibited by Zn(2+) chelator 1,10-phenanthroline. {ECO:0000269\|PubMed:21810987}.
Subunit:		Interacts with RseA; the third transmembrane domain can be cross-linked to the transmembrane domain of RseA. {ECO:0000269\|PubMed:14633997, ECO:0000269\|PubMed:18268014}.
Subcellular location:		Cell inner membrane {ECO:0000269\|PubMed:11689431, ECO:0000269\|PubMed:11750129, ECO:0000269\|PubMed:11867724, ECO:0000269\|PubMed:15919996}; Multi-pass membrane protein {ECO:0000269\|PubMed:11689431, ECO:0000269\|PubMed:11750129, ECO:0000269\|PubMed:11867724, ECO:0000269\|PubMed:15919996}.
Induction:		Part of the sigma-E regulon. Also has a primary sigma-70 factor promoter. {ECO:0000269\|PubMed:11274153}.
Domain:		The 2 circularly premutated PDZ domains act to negatively regulate protease action on intact RseA; mutations in PDZ 1 (PDZ-N) have a more deleterious effect than similar mutations in PDZ 2 (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. {ECO:0000269\|PubMed:11750129, ECO:0000269\|PubMed:14633997, ECO:0000269\|PubMed:18945679, ECO:0000269\|PubMed:19706448, ECO:0000269\|PubMed:23016873}.
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. {ECO:0000269\|PubMed:11274153, ECO:0000269\|PubMed:11689431, ECO:0000269\|PubMed:11750129, ECO:0000269\|PubMed:12183368, ECO:0000269\|PubMed:12183369, ECO:0000269\|PubMed:23016873}.
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.
Similarity:		Belongs to the peptidase M50B family. {ECO:0000305}.