P0C077 (RELE_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
mRNA interferase RelE
EC=3.1.-.-

Alternative name(s):
Endoribonuclease RelE
Toxin RelE

Gene names

Name:	relE
Ordered Locus Names:	b1563, JW1555

Organism

Escherichia coli (strain K12) [Reference proteome] [HAMAP]

Taxonomic identifier

83333 [NCBI]

Taxonomic lineage

cellular organisms › Bacteria › Proteobacteria › Gammaproteobacteria › Enterobacteriales › Enterobacteriaceae › Escherichia › Escherichia coli

Protein attributes

Sequence length	95 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Toxic component of a toxin-antitoxin (TA) module. A sequence-specific, ribosome-dependent mRNA endoribonuclease that inhibits translation during amino acid starvation (the stringent response). 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. 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. Overexpression of RelE results in the inhibition of bacterial growth and a sharp decrease in colony-forming ability which is inhibited by the labile cognate antitoxin RelB. Overexpression also sharply increases persisters (cells that neither grow or die in presence of bactericidal agent and are largely responsible for high levels of biofilm tolerance to antimicrobials). Acts with RelB as a corepressor of relBE transcription. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11 Seems to be a principal mediator of cell death in liquid media. Ref.5 Ref.6 Ref.7 Ref.8 Ref.9 Ref.11
Subunit structure	Binds DNA as a RelE(2)-RelB2 heterotetramer. 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 inhibits its endonuclease activity. Ref.6 Ref.12
Induction	By amino acid starvation, by glucose starvation and by chloramphenicol. Induction is independent of ppGpp. Member of the relBE operon. Ref.7
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. Ref.7 Ref.11
Sequence similarities	Belongs to the RelE toxin family.

Ontologies

Keywords
Biological process	Stress response Transcription Transcription regulation
Ligand	RNA-binding rRNA-binding
Molecular function	Endonuclease Hydrolase Nuclease Repressor Toxin
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cellular response to amino acid starvation Inferred from expression pattern Ref.7. Source: EcoCyc mRNA catabolic process Inferred from direct assay Ref.9. Source: EcoCyc negative regulation of translation Inferred from direct assay Ref.7Ref.8. Source: EcoCyc regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW response to antibiotic Inferred from mutant phenotype Ref.11. Source: EcoCyc transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	SSU rRNA binding Inferred from physical interaction Ref.14. Source: EcoCyc endoribonuclease activity Inferred from direct assay Ref.9PubMed 21324908. Source: EcoCyc ribosome binding Inferred from direct assay Ref.6. Source: EcoCyc
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 95

95

mRNA interferase RelE

PRO_0000097245

Experimental info

Mutagenesis

61

1

R → A: Greatly decreased mRNA cleavage. Ref.14

Mutagenesis

81 – 83

3

RER → AEA: Significant reduction in endonuclease activity, still binds RelB. Ref.8 Ref.14

Mutagenesis

81

1

R → A: Significantly decreased mRNA cleavage, significantly less translation inhibition which is countered by RelB. Almost complete loss of mRNA cleavage; when associated with F-87. Ref.8 Ref.14

Mutagenesis

87

1

Y → A: Significantly decreased mRNA cleavage. Ref.14

Mutagenesis

87

1

Y → F: No effect on mRNA cleavage, almost complete loss; when associated with A-81. Ref.14

Mutagenesis

90 – 95

6

AVKRIL → VTVTVT: Does not inhibit translation. Ref.8

Secondary structure

1

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95

Helix Strand Turn

Details...

Beta strand

4 – 7

4

Helix

9 – 17

9

Helix

20 – 35

16

Helix

40 – 42

3

Beta strand

45 – 47

3

Beta strand

50 – 54

5

Turn

56 – 59

4

Beta strand

60 – 67

8

Helix

68 – 70

3

Beta strand

72 – 80

9

Helix

82 – 84

3

Helix

85 – 94

10

Sequences

	Sequence		Length	Mass (Da)
	P0C077 [UniParc]. Last modified April 1, 1988. Version 1. Checksum: F516B2E7A437CCEC	FASTA	95	11,225
	10 20 30 40 50 60 MAYFLDFDER ALKEWRKLGS TVREQLKKKL VEVLESPRIE ANKLRGMPDC YKIKLRSSGY 70 80 90 RLVYQVIDEK VVVFVISVGK RERSEVYSEA VKRIL

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"Sequence of the relB transcription unit from Escherichia coli and identification of the relB gene." Bech F.W., Joergensen S.T., Diderichsen B., Karlstroem O.H. EMBO J. 4:1059-1066(1985) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12 / CS520.
[2]	"A 570-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 28.0-40.1 min region on the linkage map." Aiba H., Baba T., Fujita K., Hayashi K., Inada T., Isono K., Itoh T., Kasai H., Kashimoto K., Kimura S., Kitakawa M., Kitagawa M., Makino K., Miki T., Mizobuchi K., Mori H., Mori T., Motomura K. , Nakade S., Nakamura Y., Nashimoto H., Nishio Y., Oshima T., Saito N., Sampei G., Seki Y., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Takeuchi Y., Wada C., Yamamoto Y., Horiuchi T. DNA Res. 3:363-377(1996) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / W3110 / ATCC 27325 / DSM 5911.
[3]	"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 277:1453-1474(1997) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. Strain: K12 / MG1655 / ATCC 47076.
[4]	"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.
[5]	"The Escherichia coli relBE genes belong to a new toxin-antitoxin gene family." Gotfredsen M., Gerdes K. Mol. Microbiol. 29:1065-1076(1998) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A TOXIN, FUNCTION AS A TRANSCRIPTIONAL COREPRESSOR.
[6]	"Purification of the RelB and RelE proteins of Escherichia coli: RelE binds to RelB and to ribosomes." Galvani C., Terry J., Ishiguro E.E. J. Bacteriol. 183:2700-2703(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, SUBUNIT, RIBOSOME-BINDING.
[7]	"RelE, a global inhibitor of translation, is activated during nutritional stress." Christensen S.K., Mikkelsen M., Pedersen K., Gerdes K. Proc. Natl. Acad. Sci. U.S.A. 98:14328-14333(2001) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A TRANSLATION INHIBITOR, INDUCTION, DISRUPTION PHENOTYPE.
[8]	"Rapid induction and reversal of a bacteriostatic condition by controlled expression of toxins and antitoxins." Pedersen K., Christensen S.K., Gerdes K. Mol. Microbiol. 45:501-510(2002) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS A TOXIN, MUTAGENESIS OF ARG-81 AND 90-ALA--LEU-95. Strain: K12.
[9]	"The bacterial toxin RelE displays codon-specific cleavage of mRNAs in the ribosomal A site." Pedersen K., Zavialov A.V., Pavlov M.Y., Elf J., Gerdes K., Ehrenberg M. Cell 112:131-140(2003) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION AS AN ENDORIBONUCLEASE ON THE RIBOSOME.
[10]	"Specialized persister cells and the mechanism of multidrug tolerance in Escherichia coli." Keren I., Shah D., Spoering A., Kaldalu N., Lewis K. J. Bacteriol. 186:8172-8180(2004) [PubMed] [Europe PMC] [Abstract] Cited for: RELATION WITH PERSISTERS.
[11]	"A differential effect of E. coli toxin-antitoxin systems on cell death in liquid media and biofilm formation." Kolodkin-Gal I., Verdiger R., Shlosberg-Fedida A., Engelberg-Kulka H. PLoS ONE 4:E6785-E6785(2009) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION IN CELL DEATH, DISRUPTION PHENOTYPE. Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
[12]	"Structural mechanism of transcriptional autorepression of the Escherichia coli RelB/RelE antitoxin/toxin module." Li G.Y., Zhang Y., Inouye M., Ikura M. J. Mol. Biol. 380:107-119(2008) [PubMed] [Europe PMC] [Abstract] Cited for: SUBUNIT.
[13]	"mRNA interferases, sequence-specific endoribonucleases from the toxin-antitoxin systems." Yamaguchi Y., Inouye M. Prog. Mol. Biol. Transl. Sci. 85:467-500(2009) [PubMed] [Europe PMC] [Abstract] Cited for: REVIEW.
[14]	"The structural basis for mRNA recognition and cleavage by the ribosome-dependent endonuclease RelE." Neubauer C., Gao Y.G., Andersen K.R., Dunham C.M., Kelley A.C., Hentschel J., Gerdes K., Ramakrishnan V., Brodersen D.E. Cell 139:1084-1095(2009) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) IN ISOLATION AND BOUND TO RIBOSOMES BEFORE AND AFTER MRNA CLEAVAGE, RIBOSOME-BINDING, RRNA-BINDING, MECHANISM OF CLEAVAGE, MUTAGENESIS OF ARG-61; ARG-81 AND TYR-87.
[15]	"Inhibitory mechanism of Escherichia coli RelE-RelB toxin-antitoxin module involves a helix displacement near an mRNA interferase active site." Li G.Y., Zhang Y., Inouye M., Ikura M. J. Biol. Chem. 284:14628-14636(2009) [PubMed] [Europe PMC] [Abstract] Cited for: STRUCTURE BY NMR OF MUTANT 81-ARG--ARG-83 IN COMPLEX WITH RELB FRAGMENT.
+	Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

X02405 Genomic DNA. Translation: CAA26251.1.
U00096 Genomic DNA. Translation: AAC74636.1.
AP009048 Genomic DNA. Translation: BAA15262.1.

PIR

QQECR1. B22830.

RefSeq

NP_416081.1. NC_000913.2.
YP_489827.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
2KC8	NMR	-	A	1-95	[»]
2KC9	NMR	-	A	1-95	[»]
3KIQ	X-ray	3.30	y	1-95	[»]
3KIS	X-ray	3.30	y	1-95	[»]
3KIU	X-ray	3.60	y	1-95	[»]
3KIX	X-ray	3.60	y	1-95	[»]
4FXE	X-ray	2.75	D/E/F	1-95	[»]
4FXH	X-ray	2.40	A/B	1-95	[»]
4FXI	X-ray	2.50	A/B/C	1-95	[»]

ProteinModelPortal

P0C077.

SMR

P0C077. Positions 2-95.

ModBase

Search...

Protein-protein interaction databases

DIP

DIP-35978N.

IntAct

P0C077. 11 interactions.

MINT

MINT-1282331.

STRING

511145.b1563.

Proteomic databases

PaxDb

P0C077.

PRIDE

P0C077.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC74636; AAC74636; b1563.
BAA15262; BAA15262; BAA15262.

GeneID

12931249.
947549.

KEGG

ecj:Y75_p1539.
eco:b1563.

PATRIC

32118432. VBIEscCol129921_1636.

Organism-specific databases

EchoBASE

EB1121.

EcoGene

EG11131. relE.

Phylogenomic databases

eggNOG

COG2026.

HOGENOM

HOG000219994.

KO

K06218.

OMA

RRALKEW.

ProtClustDB

CLSK891757.

Enzyme and pathway databases

BioCyc

EcoCyc:EG11131-MONOMER.
ECOL316407:JW1555-MONOMER.
MetaCyc:EG11131-MONOMER.

Gene expression databases

Genevestigator

P0C077.

Family and domain databases

InterPro

IPR007712. RelE/ParE_toxin.
[Graphical view]

Pfam

PF05016. Plasmid_stabil. 1 hit.
[Graphical view]

TIGRFAMs

TIGR02385. RelE_StbE. 1 hit.

ProtoNet

Search...

Other

EvolutionaryTrace

P0C077.

Entry information

Entry name

RELE_ECOLI

Accession

Primary (citable) accession number: P0C077
Secondary accession number(s): P07008

Entry history

Integrated into UniProtKB/Swiss-Prot:	April 1, 1988
Last sequence update:	April 1, 1988
Last modified:	May 1, 2013
This is version 68 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program