P0AE72 (MAZE_ECOLI) Reviewed, UniProtKB/Swiss-Prot

Names and origin

Protein names

Recommended name:
Antitoxin MazE

Gene names

Name:	mazE
Synonyms:	chpAI, chpR
Ordered Locus Names:	b2783, JW2754

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	82 AA.
Sequence status	Complete.
Protein existence	Evidence at protein level

General annotation (Comments)

Function	Antitoxin component of a toxin-antitoxin (TA) module. Labile antitoxin that binds to the MazF mRNA interferase toxin and neutralizes its endoribonuclease activity. Is considered to be an 'addiction' molecule as the cell will die in its absence. The endoribonuclease activity (MazF, a toxin) is inhibited by the labile cognate antitoxin MazE. Toxicity results when the levels of MazE decrease in the cell, leading to mRNA degradation. This effect can be rescued by expression of MazE, but after 6 hours in rich medium the overexpression of MazF leads to programmed cell death. Cell growth and viability are not affected when MazF and MazE are coexpressed. Both MazE and MazEF bind to the promoter region of the mazEF operon to inhibit their transcription. Ref.5 Ref.7 Ref.9 Ref.11 Cell death governed by the mazEF and dinJ-yafQ TA modules seems to play a role in biofilm formation, while mazEF is also implicated in cell death in liquid media. Ref.5 Ref.7 Ref.9 Ref.11
Subunit structure	Forms a heterohexamer composed of alternating toxin and antitoxin homodimers MazF(2)-MazE(2)-MazF2. Ref.6 Ref.14
Induction	Expressed in exponentially growing cells. Induction has been reported to occur after amino acid starvation in a ppGpp-independent fashion and to be Lon protease-dependent (Ref.8), but also to not occur after amino acid starvation and to be regulated by ppGpp (Ref.5). MazE alone and in combination with MazF, represses transcription of the mazEF operon. Fis activates transcription. Part of the relA-mazE-mazF-mazG operon, there is also a second mazE-mazF specific promoter which is negatively autoregulated. Ref.5 Ref.6 Ref.8 Ref.10
Post-translational modification	Degraded by the ClpPA protease during steady state growth and possibly by the Lon protease during amino acid starvation.
Disruption phenotype	Decreased sensitivity to dramatic intracellular increases of ppGpp. Cells missing mazEF survive high temperature, various DNA-damaging agents and H2O2 exposure better than wild-type cells. Cells missing mazEF produce more P1 phage than wild-type cells, while introduction of lysogens into a growing non-lysogenic deletion culture is lethal. Cells missing mazEF show reduced biofilm formation, and survive antibiotic treatment in log phase better than wild-type cells. Ref.8 Ref.11
Sequence similarities	Belongs to the PemI family. Contains 1 AbrB-like domain.

Ontologies

Keywords
Biological process	Transcription Transcription regulation
Ligand	DNA-binding
Molecular function	Repressor
Technical term	3D-structure Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	regulation of transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW transcription, DNA-dependent Inferred from electronic annotation. Source: UniProtKB-KW
Molecular_function	DNA binding Inferred from electronic annotation. Source: UniProtKB-KW
Complete GO annotation...

Sequence annotation (Features)

Feature key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 82

82

Antitoxin MazE

PRO_0000089649

Regions

Domain

7 – 51

45

AbrB-like

Experimental info

Mutagenesis

8

1

R → A: Binds poorly to DNA. Ref.13

Mutagenesis

16

1

R → A: Does not bind to DNA. Ref.13

Secondary structure

1

.

.

.

.

.

.

.

.

.

.

.

82

Helix Strand Turn

Details...

Beta strand

6 – 9

4

Beta strand

12 – 15

4

Helix

19 – 24

6

Helix

55 – 60

6

Turn

64 – 66

3

Sequences

	Sequence		Length	Mass (Da)
	P0AE72 [UniParc]. Last modified December 6, 2005. Version 1. Checksum: CD452A9AA4FB362E	FASTA	82	9,356
	10 20 30 40 50 60 MIHSSVKRWG NSPAVRIPAT LMQALNLNID DEVKIDLVDG KLIIEPVRKE PVFTLAELVN 70 80 DITPENLHEN IDWGEPKDKE VW

References

	« Hide 'large scale' referencesShow 'large scale' references »
[1]	"The nucleotide sequence and characterization of the relA gene of Escherichia coli." Metzger S., Dror I.B., Aizenman E., Schreiber G., Toone M., Friesen J.D., Cashel M., Glaser G. J. Biol. Chem. 263:15699-15704(1988) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA], OPERON STRUCTURE. Strain: K12.
[2]	"chpA and chpB, Escherichia coli chromosomal homologs of the pem locus responsible for stable maintenance of plasmid R100." Masuda Y., Miyakawa K., Nishimura Y., Ohtsubo E. J. Bacteriol. 175:6850-6856(1993) [PubMed] [Europe PMC] [Abstract] Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA]. Strain: K12 / MC1000 / ATCC 39531.
[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]	"An Escherichia coli chromosomal 'addiction module' regulated by guanosine 3',5'-bispyrophosphate: a model for programmed bacterial cell death." Aizenman E., Engelberg-Kulka H., Glaser G. Proc. Natl. Acad. Sci. U.S.A. 93:6059-6063(1996) [PubMed] [Europe PMC] [Abstract] Cited for: FUNCTION, CLEAVAGE BY THE CLPPA PROTEASE, INTERACTION WITH MAZF, INDUCTION, OPERON STRUCTURE. Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
[6]	"The regulation of the Escherichia coli mazEF promoter involves an unusual alternating palindrome." Marianovsky I., Aizenman E., Engelberg-Kulka H., Glaser G. J. Biol. Chem. 276:5975-5984(2001) [PubMed] [Europe PMC] [Abstract] Cited for: TRANSCRIPTION REGULATION, DNA-BINDING, SUBUNIT. Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
[7]	"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 AN ANTITOXIN. Strain: K12.
[8]	"Toxin-antitoxin loci as stress-response-elements: ChpAK/MazF and ChpBK cleave translated RNAs and are counteracted by tmRNA." Christensen S.K., Pedersen K., Hansen F.G., Gerdes K. J. Mol. Biol. 332:809-819(2003) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION, POSSIBLE CLEAVAGE BY THE LON PROTEASE, DISRUPTION PHENOTYPE. Strain: K12 / MG1655 / ATCC 47076.
[9]	"MazF-mediated cell death in Escherichia coli: a point of no return." Amitai S., Yassin Y., Engelberg-Kulka H. J. Bacteriol. 186:8295-8300(2004) [PubMed] [Europe PMC] [Abstract] Cited for: ROLE IN PROGRAMMED CELL DEATH. Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
[10]	"MazG -- a regulator of programmed cell death in Escherichia coli." Gross M., Marianovsky I., Glaser G. Mol. Microbiol. 59:590-601(2006) [PubMed] [Europe PMC] [Abstract] Cited for: INDUCTION, OPERON STRUCTURE. Strain: K12 / MC4100 / ATCC 35695 / DSM 6574 and K12 / W3110 / ATCC 27325 / DSM 5911.
[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, FUNCTION IN BIOFILM FORMATION, DISRUPTION PHENOTYPE. Strain: K12 / MC4100 / ATCC 35695 / DSM 6574.
[12]	"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.
[13]	"Crystal structure of the intrinsically flexible addiction antidote MazE." Loris R., Marianovsky I., Lah J., Laeremans T., Engelberg-Kulka H., Glaser G., Muyldermans S., Wyns L. J. Biol. Chem. 278:28252-28257(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.65 ANGSTROMS) IN COMPLEX WITH AN ANTIBODY FRAGMENT, DNA-BINDING, MUTAGENESIS OF ARG-8 AND ARG-16.
[14]	"Crystal structure of the MazE/MazF complex: molecular bases of antidote-toxin recognition." Kamada K., Hanaoka F., Burley S.K. Mol. Cell 11:875-884(2003) [PubMed] [Europe PMC] [Abstract] Cited for: X-RAY CRYSTALLOGRAPHY (1.7 ANGSTROMS), SUBUNIT.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ

D16450 Genomic DNA. Translation: BAA41177.1.
J04039 Unassigned DNA. Translation: AAA03238.1.
U29580 Genomic DNA. Translation: AAA69293.1.
U00096 Genomic DNA. Translation: AAC75825.1.
AP009048 Genomic DNA. Translation: BAE76857.1.

PIR

BVECZE. B31996.

RefSeq

NP_417263.1. NC_000913.2.
YP_490991.1. NC_007779.1.

3D structure databases

PDBe
RCSB PDB
PDBj

Entry	Method	Resolution (Å)	Chain	Positions	PDBsum
1MVF	X-ray	1.65	D/E	1-82	[»]
1UB4	X-ray	1.70	C	1-82	[»]

ProteinModelPortal

P0AE72.

SMR

P0AE72. Positions 2-76.

ModBase

Search...

Protein-protein interaction databases

IntAct

P0AE72. 10 interactions.

STRING

511145.b2783.

Protocols and materials databases

StructuralBiologyKnowledgebase

Search...

Genome annotation databases

EnsemblBacteria

AAC75825; AAC75825; b2783.
BAE76857; BAE76857; BAE76857.

GeneID

12933307.
947245.

KEGG

ecj:Y75_p2720.
eco:b2783.

PATRIC

32120982. VBIEscCol129921_2883.

Organism-specific databases

EchoBASE

EB0566.

EcoGene

EG10571. mazE.

Phylogenomic databases

eggNOG

COG2336.

HOGENOM

HOG000289070.

KO

K07172.

OMA

PENRHEE.

ProtClustDB

PRK09798.

Enzyme and pathway databases

BioCyc

EcoCyc:EG10571-MONOMER.
ECOL316407:JW2754-MONOMER.

Gene expression databases

Genevestigator

P0AE72.

Family and domain databases

InterPro

IPR007159. AbrB-like_dom.
[Graphical view]

Pfam

PF04014. Antitoxin-MazE. 1 hit.
[Graphical view]

SMART

SM00966. SpoVT_AbrB. 1 hit.
[Graphical view]

ProtoNet

Search...

Other

EvolutionaryTrace

P0AE72.

Entry information

Entry name

MAZE_ECOLI

Accession

Primary (citable) accession number: P0AE72
Secondary accession number(s): P18534, Q2MA49

Entry history

Integrated into UniProtKB/Swiss-Prot:	December 6, 2005
Last sequence update:	December 6, 2005
Last modified:	May 1, 2013
This is version 67 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Prokaryotic Protein Annotation Program