UniProt functional annotation for P0C077



	UniProt functional annotation for P0C077

UniProt code: P0C077.

Organism: Escherichia coli (strain K12).

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

Function: Toxic component of a type II toxin-antitoxin (TA) system (PubMed:9767574). A sequence-specific, ribosome-dependent mRNA endoribonuclease that inhibits translation during amino acid starvation (the stringent response). In vitro acts by cleaving mRNA with high codon specificity in the ribosomal A site between positions 2 and 3. The stop codon UAG is cleaved at a fast rate while UAA and UGA are cleaved with intermediate and slow rates. In vitro mRNA cleavage can also occur in the ribosomal E site after peptide release from peptidyl- tRNA in the P site as well as on free 30S subunits (PubMed:12526800). In vivo cuts frequently in the first 100 codons, most frequently after the second and third base and rarely near the stop codon (PubMed:21324908). Overexpression of RelE results in the inhibition of bacterial growth and a sharp decrease in colony-forming ability which is neutralized by the labile cognate antitoxin RelB. Overexpression also sharply increases persisters (cells that neither grow nor die in the presence of bactericidal agents and are largely responsible for high levels of biofilm tolerance to antimicrobials) (PubMed:15576765). Plays a role in dormancy when expressed in high-density cells in the absence of antitoxin RelB; amino acid starvation and an unidentified extracellular factor promote dormancy, while expression of antitoxin RelB restores cell culturability (PubMed:22210768). Acts with RelB as a corepressor of relBE transcription, considerably increasing the repression of RelB alone. 2 RelB dimers bind to 2 operator sequences; DNA-binding and repression is stronger when complexed with toxin/corepressor RelE by conditional cooperativity (PubMed:9767574, PubMed:19747491, PubMed:18501926, PubMed:22981948). {ECO:0000269|PubMed:11274135, ECO:0000269|PubMed:11717402, ECO:0000269|PubMed:12123459, ECO:0000269|PubMed:12526800, ECO:0000269|PubMed:15576765, ECO:0000269|PubMed:18501926, ECO:0000269|PubMed:18532983, ECO:0000269|PubMed:19747491, ECO:0000269|PubMed:20005802, ECO:0000269|PubMed:21324908, ECO:0000269|PubMed:22210768, ECO:0000269|PubMed:22981948, ECO:0000269|PubMed:24251350, ECO:0000269|PubMed:9767574}.

Function: Seems to be a principal mediator of cell death in liquid media (PubMed:19707553). Implicated in hydroxy radical-mediated cell death induced by hydroxyurea treatment (PubMed:20005847). {ECO:0000269|PubMed:19707553, ECO:0000269|PubMed:20005847}.

Function: Cross-talk can occur between different TA systems. Ectopic expression of this toxin induces transcription of 7 tested TA systems (dinJ/yafQ, hicAB, mazEF, mqsRA, prlF(sohA)/yhaV, relBEF and yefM/yoeB) with specific cleavage of the relBEF mRNA produced immediately upstream and within the relB coding sequence. The cleaved mRNA can be translated into RelE, leading to a positive feedback cycle of RelE expression. The relBEF operon is required for transcription of the mazEF TA system operon during amino acid starvation. {ECO:0000269|PubMed:23432955}.

Subunit: Forms an RelB(2)-RelE(2) heterotetramer (PubMed:18501926, PubMed:22981948). Also forms an RelB(2)-RelE heterotrimer (PubMed:18532983, PubMed:19747491). The RelB(2)-RelE complex is probably the one that binds DNA and represses transcription, possibly as 2 heterotrimers, 1 bound to each of 2 operators (PubMed:22981948, PubMed:19747491). RelE occupies the A site of the 70S ribosome, making extensive contacts with the 16S rRNA. Its presence blocks access of tRNAs and translation factors. RelB bound to RelE prevents RelE from entering the ribosomal A site and thus inhibits its endonuclease activity (PubMed:19297318). {ECO:0000269|PubMed:11274135, ECO:0000269|PubMed:18501926, ECO:0000269|PubMed:18532983, ECO:0000269|PubMed:19297318, ECO:0000269|PubMed:19747491, ECO:0000269|PubMed:22981948}.

Induction: By amino acid starvation, by glucose starvation and by chloramphenicol; induction is independent of ppGpp. Autorepressed by RelB, RelE acts as a corepressor (PubMed:9767574, PubMed:19747491, PubMed:18501926, PubMed:22981948). Member of the relBEF operon (PubMed:2990907). Operon induced by ectopic expression of toxins HicA, HipA, MazF, MqsR and itself, but not by YafQ (PubMed:23432955). {ECO:0000269|PubMed:11717402, ECO:0000269|PubMed:18501926, ECO:0000269|PubMed:18532983, ECO:0000269|PubMed:19747491, ECO:0000269|PubMed:22981948, ECO:0000269|PubMed:23432955, ECO:0000269|PubMed:2990907, ECO:0000269|PubMed:9767574}.

Disruption phenotype: Cells missing relBE have a higher steady-state level of translation during amino acid starvation than wild-type cells. They survive antibiotic treatment in log phase better than wild-type cells. Cells missing mazE-mazF survive hydroxyurea treatment better than wild-type; further disruption of relE-relB and tonB yields even better survival (PubMed:20005847). {ECO:0000269|PubMed:11717402, ECO:0000269|PubMed:19707553, ECO:0000269|PubMed:20005847}.

Miscellaneous: There are estimated to be 550-1100 RelB and 50-100 RelE molecules in rapidly growing cells of MG1655; as they have quite high affinity for each other (dissociation constant of 0.33 nM) there is probably less than 1 free RelE molecule per cell. The RelB(2)-RelE complex has a half-life of over 70 minutes. {ECO:0000269|PubMed:19747491}.

Similarity: Belongs to the RelE toxin family. {ECO:0000305}.

Annotations taken from UniProtKB at the EBI.


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



Function:		Toxic component of a type II toxin-antitoxin (TA) system (PubMed:9767574). A sequence-specific, ribosome-dependent mRNA endoribonuclease that inhibits translation during amino acid starvation (the stringent response). In vitro acts by cleaving mRNA with high codon specificity in the ribosomal A site between positions 2 and 3. The stop codon UAG is cleaved at a fast rate while UAA and UGA are cleaved with intermediate and slow rates. In vitro mRNA cleavage can also occur in the ribosomal E site after peptide release from peptidyl- tRNA in the P site as well as on free 30S subunits (PubMed:12526800). In vivo cuts frequently in the first 100 codons, most frequently after the second and third base and rarely near the stop codon (PubMed:21324908). Overexpression of RelE results in the inhibition of bacterial growth and a sharp decrease in colony-forming ability which is neutralized by the labile cognate antitoxin RelB. Overexpression also sharply increases persisters (cells that neither grow nor die in the presence of bactericidal agents and are largely responsible for high levels of biofilm tolerance to antimicrobials) (PubMed:15576765). Plays a role in dormancy when expressed in high-density cells in the absence of antitoxin RelB; amino acid starvation and an unidentified extracellular factor promote dormancy, while expression of antitoxin RelB restores cell culturability (PubMed:22210768). Acts with RelB as a corepressor of relBE transcription, considerably increasing the repression of RelB alone. 2 RelB dimers bind to 2 operator sequences; DNA-binding and repression is stronger when complexed with toxin/corepressor RelE by conditional cooperativity (PubMed:9767574, PubMed:19747491, PubMed:18501926, PubMed:22981948). {ECO:0000269\|PubMed:11274135, ECO:0000269\|PubMed:11717402, ECO:0000269\|PubMed:12123459, ECO:0000269\|PubMed:12526800, ECO:0000269\|PubMed:15576765, ECO:0000269\|PubMed:18501926, ECO:0000269\|PubMed:18532983, ECO:0000269\|PubMed:19747491, ECO:0000269\|PubMed:20005802, ECO:0000269\|PubMed:21324908, ECO:0000269\|PubMed:22210768, ECO:0000269\|PubMed:22981948, ECO:0000269\|PubMed:24251350, ECO:0000269\|PubMed:9767574}.



Function:		Seems to be a principal mediator of cell death in liquid media (PubMed:19707553). Implicated in hydroxy radical-mediated cell death induced by hydroxyurea treatment (PubMed:20005847). {ECO:0000269\|PubMed:19707553, ECO:0000269\|PubMed:20005847}.



Function:		Cross-talk can occur between different TA systems. Ectopic expression of this toxin induces transcription of 7 tested TA systems (dinJ/yafQ, hicAB, mazEF, mqsRA, prlF(sohA)/yhaV, relBEF and yefM/yoeB) with specific cleavage of the relBEF mRNA produced immediately upstream and within the relB coding sequence. The cleaved mRNA can be translated into RelE, leading to a positive feedback cycle of RelE expression. The relBEF operon is required for transcription of the mazEF TA system operon during amino acid starvation. {ECO:0000269\|PubMed:23432955}.


Subunit:		Forms an RelB(2)-RelE(2) heterotetramer (PubMed:18501926, PubMed:22981948). Also forms an RelB(2)-RelE heterotrimer (PubMed:18532983, PubMed:19747491). The RelB(2)-RelE complex is probably the one that binds DNA and represses transcription, possibly as 2 heterotrimers, 1 bound to each of 2 operators (PubMed:22981948, PubMed:19747491). RelE occupies the A site of the 70S ribosome, making extensive contacts with the 16S rRNA. Its presence blocks access of tRNAs and translation factors. RelB bound to RelE prevents RelE from entering the ribosomal A site and thus inhibits its endonuclease activity (PubMed:19297318). {ECO:0000269\|PubMed:11274135, ECO:0000269\|PubMed:18501926, ECO:0000269\|PubMed:18532983, ECO:0000269\|PubMed:19297318, ECO:0000269\|PubMed:19747491, ECO:0000269\|PubMed:22981948}.
Induction:		By amino acid starvation, by glucose starvation and by chloramphenicol; induction is independent of ppGpp. Autorepressed by RelB, RelE acts as a corepressor (PubMed:9767574, PubMed:19747491, PubMed:18501926, PubMed:22981948). Member of the relBEF operon (PubMed:2990907). Operon induced by ectopic expression of toxins HicA, HipA, MazF, MqsR and itself, but not by YafQ (PubMed:23432955). {ECO:0000269\|PubMed:11717402, ECO:0000269\|PubMed:18501926, ECO:0000269\|PubMed:18532983, ECO:0000269\|PubMed:19747491, ECO:0000269\|PubMed:22981948, ECO:0000269\|PubMed:23432955, ECO:0000269\|PubMed:2990907, ECO:0000269\|PubMed:9767574}.
Disruption phenotype:		Cells missing relBE have a higher steady-state level of translation during amino acid starvation than wild-type cells. They survive antibiotic treatment in log phase better than wild-type cells. Cells missing mazE-mazF survive hydroxyurea treatment better than wild-type; further disruption of relE-relB and tonB yields even better survival (PubMed:20005847). {ECO:0000269\|PubMed:11717402, ECO:0000269\|PubMed:19707553, ECO:0000269\|PubMed:20005847}.
Miscellaneous:		There are estimated to be 550-1100 RelB and 50-100 RelE molecules in rapidly growing cells of MG1655; as they have quite high affinity for each other (dissociation constant of 0.33 nM) there is probably less than 1 free RelE molecule per cell. The RelB(2)-RelE complex has a half-life of over 70 minutes. {ECO:0000269\|PubMed:19747491}.
Similarity:		Belongs to the RelE toxin family. {ECO:0000305}.