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MetJ DNA-binding transcriptional repressor

Synonyms: MetJ-S-adenosylmethionine, MetJ
Summary:
MetJ represses the expression of genes involved in biosynthesis and transport of methionine [4, 12].
MetJ belongs to the ribbon-helix-helix family of regulatory proteins. The typical motif of members of this family, the ribbon-helix-helix motif for DNA binding, has been observed in the crystalline structure of MetJ [13]. This motif is composed of a two-stranded antiparallel β-ribbon that lies along the DNA major groove, two outer α-helices that interact with adjacent proteins along the DNA, and two inner β-helices that form the subunit interface [13].
MetJ as a homodimer [13, 14] recognizes and binds to an 8-bp DNA sequence called the met-box, which varies around a perfect palindromic consensus sequence [15, 16, 17]. MetJ finds its target sites rapidly by facilitated diffusion [18].
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Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
MetJ Non-Functional   Apo [BPP], [IPI] [1], [2]
MetJ-S-adenosylmethionine Functional Allosteric Holo [BPP], [IPI] [1], [2]
Evolutionary Family: MetJ
Sensing class: Using internal synthesized signals
Connectivity class: Local Regulator
Gene name: metJ
  Genome position: 4128078-4128395
  Length: 318 bp / 105 aa
Operon name: metJ
TU(s) encoding the TF:
Transcription unit        Promoter
metJ
metJp1
metJ
metJp2
metJ
metJp3


Regulon       
Regulated gene(s) ahpC, ahpF, folE, metA, metB, metC, metE, metF, metI, metK, metL, metN, metQ, metR, yeiB
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
methionine (5)
detoxification (2)
folic acid (1)
amino acids (1)
threonine catabolism (1)
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Regulated operon(s) ahpCF, folE-yeiB, metA, metBL, metC, metE, metF, metK, metNIQ, metR
First gene in the operon(s) ahpC, folE, metA, metB, metC, metE, metF, metK, metN, metR, metR
Simple and complex regulons CRP,MetJ
HypT,MetJ
HypT,MetJ,PhoP
MetJ
MetJ,MetR
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Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[MetJ,-](10)


Transcription factor binding sites (TFBSs) arrangements       

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Growth Conditions Evidence (Confirmed, Strong, Weak) References
  MetJ-S-adenosylmethionine repressor ahpCp Sigma70 17.5 -7.5 ahpC, ahpF
catcgaaaacACGGAGGAAGTATAGAtgtccttgat
 638930 638945 nd [AIBSCS] [3]
  MetJ-S-adenosylmethionine repressor ahpCp Sigma70 27.5 2.5 ahpC, ahpF
acggaggaagTATAGATGTCCTTGATtaacaccaaa
 638940 638955 nd [AIBSCS] [3]
  MetJ-S-adenosylmethionine repressor folEp Sigma70 25.5 -171.5 folE, yeiB
tttcacttccGTATTTGCATAACGATgttttaacat
 2243816 2243831 nd [AIBSCS], [BPP], [GEA] [4]
  MetJ-S-adenosylmethionine repressor folEp Sigma70 33.5 -163.5 folE, yeiB
ccgtatttgcATAACGATGTTTTAACatctgctgat
 2243808 2243823 nd [AIBSCS], [BPP], [GEA] [4]
  MetJ-S-adenosylmethionine repressor folEp Sigma70 41.5 -155.5 folE, yeiB
gcataacgatGTTTTAACATCTGCTGatgaaaggca
 2243800 2243815 nd [AIBSCS], [BPP], [GEA] [4]
  MetJ-S-adenosylmethionine repressor folEp Sigma70 49.5 -147.5 folE, yeiB
atgttttaacATCTGCTGATGAAAGGcagcggcaat
 2243792 2243807 nd [AIBSCS], [BPP], [GEA] [4]
  MetJ-S-adenosylmethionine repressor metAp1 Sigma32 4.5 -43.5 metA
ggttatcttcAGCTATCTGGATGTCTaaacgtataa
 4214229 4214244 nd [AIBSCS], [BCE], [BPP], [GEA] [3], [4]
  MetJ-S-adenosylmethionine repressor metAp1 Sigma32 20.5 -27.5 metA
ctggatgtctAAACGTATAAGCGTATgtagtgaggt
 4214245 4214260 nd [AIBSCS], [BCE], [BPP], [GEA] [3], [4]
  MetJ-S-adenosylmethionine repressor metBp Sigma70 -56.5 -92.5 metB, metL
tcaatctataCGCAAAGAAGTTTAGAtgtccagatg
 4128572 4128587 nd [AIBSCS], [GEA] [3], [4], [5]
  MetJ-S-adenosylmethionine repressor metBp Sigma70 -48.5 -84.5 metB, metL
tacgcaaagaAGTTTAGATGTCCAGAtgtattgacg
 4128580 4128595 nd [AIBSCS], [GEA] [3], [4], [5]
  MetJ-S-adenosylmethionine repressor metBp Sigma70 -46.5 -82.5 metB, metL
cgcaaagaagTTTAGATGTCCAGATGtattgacgtc
 4128582 4128597 nd [AIBSCS], [GEA] [3], [4], [5]
  MetJ-S-adenosylmethionine repressor metBp Sigma70 -40.5 -76.5 metB, metL
gaagtttagaTGTCCAGATGTATTGAcgtccattaa
 4128588 4128603 nd [AIBSCS], [GEA] [3], [4], [5]
  MetJ-S-adenosylmethionine repressor metBp Sigma70 -38.5 -74.5 metB, metL
agtttagatgTCCAGATGTATTGACGtccattaaca
 4128590 4128605 nd [AIBSCS], [GEA] [3], [4], [5]
  MetJ-S-adenosylmethionine repressor metBp Sigma70 -30.5 -66.5 metB, metL
tgtccagatgTATTGACGTCCATTAAcacaatgttt
 4128598 4128613 nd [AIBSCS], [GEA] [3], [4], [5]
  MetJ-S-adenosylmethionine repressor metCp Sigma70 nd nd metC
nd
 nd nd nd [BPP] [6], [7]
  MetJ-S-adenosylmethionine repressor metEp nd 1.5 -168.5 metE
aaccgccaatTATGGATGTGTAAACAtctggacggc
 4012877 4012892 [a]
[b] 		[BPP] [8]
  MetJ-S-adenosylmethionine repressor metEp nd 116.5 -53.5 metE
ggatgaataaACTTGCCGCCTTCCCTaaattcaaaa
 4012992 4013007 [a]
[b] 		[BPP] [8]
  MetJ-S-adenosylmethionine repressor metFp Sigma70 -8.5 -78.5 metF
gcccttcggcTTTTCCTTCATCTTTAcatctggacg
 4132530 4132545 [b] [BCE], [SM] [9]
  MetJ-S-adenosylmethionine repressor metFp Sigma70 2.0 -69.5 metF
cttttccttcATCTTTACATCTGGACgtctaaacgg
 4132539 4132554 nd [AIBSCS] [3]
  MetJ-S-adenosylmethionine repressor metFp Sigma70 4.5 -66.5 metF
ttccttcatcTTTACATCTGGACGTCtaaacggata
 4132542 4132557 [b] [BCE], [SM] [9]
  MetJ-S-adenosylmethionine repressor metFp Sigma70 7.5 -63.5 metF
cttcatctttACATCTGGACGTCTAAacggatagat
 4132545 4132560 [b] [AIBSCS] [3]
  MetJ-S-adenosylmethionine repressor metFp Sigma70 9.5 -61.5 metF
tcatctttacATCTGGACGTCTAAACggatagatgt
 4132547 4132562 [b] [AIBSCS] [3]
  MetJ-S-adenosylmethionine repressor metFp Sigma70 17.5 -53.5 metF
acatctggacGTCTAAACGGATAGATgtgcacaaca
 4132555 4132570 [b] [AIBSCS] [3]
  MetJ-S-adenosylmethionine repressor metFp Sigma70 20.5 -50.5 metF
tctggacgtcTAAACGGATAGATGTGcacaacacaa
 4132558 4132573 [b] [BCE], [SM] [9]
  MetJ-S-adenosylmethionine repressor metKp Sigma70 -14.5 -143.5 metK
agaattgaccTAAAATAGCCATCCAGatgttaatcc
 3086555 3086570 nd [AIBSCS] [3]
  MetJ-S-adenosylmethionine repressor metKp Sigma70 -2.5 -131.5 metK
aaatagccatCCAGATGTTAATCCATccataccgat
 3086567 3086582 nd [AIBSCS] [3]
  MetJ-S-adenosylmethionine repressor metNp Sigma70 -25.5 -94.5 metN, metI, metQ
aacctgattgATTTAGACGTCTGGATgccttaacat
 222732 222747 nd [AIBSCS], [HIBSCS] [3], [4], [10], [11]
  MetJ-S-adenosylmethionine repressor metNp Sigma70 -17.5 -86.5 metN, metI, metQ
tgatttagacGTCTGGATGCCTTAACatccatttca
 222724 222739 nd [AIBSCS], [GEA] [3], [4], [10]
  MetJ-S-adenosylmethionine repressor metRp1 nd -144.5 -183.5 metR
ttttgaatttAGGGAAGGCGGCAAGTttattcatcc
 4012992 4013007 [b] [BPP] [8]
  MetJ-S-adenosylmethionine repressor metRp1 nd -29.5 -68.5 metR
gccgtccagaTGTTTACACATCCATAattggcggtt
 4012877 4012892 [b] [BPP] [8]
  MetJ-S-adenosylmethionine repressor metRp2 nd -162.5 -183.5 metR
ttttgaatttAGGGAAGGCGGCAAGTttattcatcc
 4012992 4013007 [b] [BPP] [8]
  MetJ-S-adenosylmethionine repressor metRp2 nd -47.5 -68.5 metR
gccgtccagaTGTTTACACATCCATAattggcggtt
 4012877 4012892 [b] [BPP] [8]


Growth Condition    

 [a] Methionine treatment

 [b] S-adenosylmethionine treatment


Alignment and PSSM for MetJ TFBSs    

Position weight matrix (PWM).    
A	3	13	0	7	0	5	1	8	7	14	2	5	1	3	1	5
C	0	0	10	0	0	8	2	0	0	0	10	0	0	12	1	0
G	9	2	0	6	2	1	1	5	7	1	0	8	5	0	2	8
T	3	0	5	2	13	1	11	2	1	0	3	2	9	0	11	2

PWM logo   


 


Evolutionary conservation of regulatory elements    
     Note: Evolutionary conservation of regulatory interactions and promoters is limited to gammaproteobacteria.
TF-target gene evolutionary conservation
Promoter-target gene evolutionary conservation


Evidence    

 [BPP] Binding of purified proteins

 [IPI] Inferred from physical interaction

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [GEA] Gene expression analysis

 [BCE] Binding of cellular extracts

 [SM] Site mutation

 [HIBSCS] Human inference based on similarity to consensus sequences


Reference(s)    

 [1] Parsons ID., Persson B., Mekhalfia A., Blackburn GM., Stockley PG., 1995, Probing the molecular mechanism of action of co-repressor in the E. coli methionine repressor-operator complex using surface plasmon resonance (SPR)., Nucleic Acids Res. 23(2):211-6

 [2] Saint-Girons I, Belfaiza J, Guillou Y, Perrin D, Guiso N, B¿¿¿rzu O, Cohen GN., 1986, Interactions of the Escherichia coli methionine repressor with the metF operator and with its corepressor, S-adenosylmethionine., J Biol Chem.

 [3] Liu R., Blackwell TW., States DJ., 2001, Conformational model for binding site recognition by the E.coli MetJ transcription factor., Bioinformatics. 17(7):622-33

 [4] Marincs F., Manfield IW., Stead JA., McDowall KJ., Stockley PG., 2006, Transcript analysis reveals an extended regulon and the importance of protein-protein co-operativity for the Escherichia coli methionine repressor., Biochem J. 396(2):227-34

 [5] Kirby TW., Hindenach BR., Greene RC., 1986, Regulation of in vivo transcription of the Escherichia coli K-12 metJBLF gene cluster., J Bacteriol. 165(3):671-7

 [6] Otsuka J., Watanabe H., Mori KT., 1996, Evolution of transcriptional regulation system through promiscuous coupling of regulatory proteins with operons; suggestion from protein sequence similarities in Escherichia coli., J Theor Biol. 178(2):183-204

 [7] Wild CM., McNally T., Phillips SE., Stockley PG., 1996, Effects of systematic variation of the minimal Escherichia coli met consensus operator site: in vivo and in vitro met repressor binding., Mol Microbiol. 21(6):1125-35

 [8] Cai XY., Maxon ME., Redfield B., Glass R., Brot N., Weissbach H., 1989, Methionine synthesis in Escherichia coli: effect of the MetR protein on metE and metH expression., Proc Natl Acad Sci U S A. 86(12):4407-11

 [9] Stauffer GV., Stauffer LT., 1988, Salmonella typhimurium LT2 metF operator mutations., Mol Gen Genet. 214(1):32-6

 [10] Gal J., Szvetnik A., Schnell R., Kalman M., 2002, The metD D-methionine transporter locus of Escherichia coli is an ABC transporter gene cluster., J Bacteriol. 184(17):4930-2

 [11] Merlin C., Gardiner G., Durand S., Masters M., 2002, The Escherichia coli metD locus encodes an ABC transporter which includes Abc (MetN), YaeE (MetI), and YaeC (MetQ)., J Bacteriol. 184(19):5513-7

 [12] Weissbach H., Brot N., 1991, Regulation of methionine synthesis in Escherichia coli., Mol Microbiol. 5(7):1593-7

 [13] Somers WS., Phillips SE., 1992, Crystal structure of the met repressor-operator complex at 2.8 A resolution reveals DNA recognition by beta-strands., Nature. 359(6394):387-93

 [14] Smith AA., Greene RC., Kirby TW., Hindenach BR., 1985, Isolation and characterization of the product of the methionine-regulatory gene metJ of Escherichia coli K-12., Proc Natl Acad Sci U S A. 82(18):6104-8

 [15] Saint-Girons I., Duchange N., Cohen GN., Zakin MM., 1984, Structure and autoregulation of the metJ regulatory gene in Escherichia coli., J Biol Chem. 259(22):14282-5

 [16] Phillips SE., Manfield I., Parsons I., Davidson BE., Rafferty JB., Somers WS., Margarita D., Cohen GN., Saint-Girons I., Stockley PG., 1989, Cooperative tandem binding of met repressor of Escherichia coli., Nature. 341(6244):711-5

 [17] Belfaiza J., Parsot C., Martel A., de la Tour CB., Margarita D., Cohen GN., Saint-Girons I., 1986, Evolution in biosynthetic pathways: two enzymes catalyzing consecutive steps in methionine biosynthesis originate from a common ancestor and possess a similar regulatory region., Proc Natl Acad Sci U S A. 83(4):867-71

 [18] Augustus AM., Reardon PN., Spicer LD., 2009, MetJ repressor interactions with DNA probed by in-cell NMR., Proc Natl Acad Sci U S A. 106(13):5065-9

 [19] Hyre DE., Spicer LD., 1995, Thermodynamic evaluation of binding interactions in the methionine repressor system of Escherichia coli using isothermal titration calorimetry., Biochemistry. 34(10):3212-21

 [20] LaMonte BL., Hughes JA., 2006, In vivo hydrolysis of S-adenosylmethionine induces the met regulon of Escherichia coli., Microbiology. 152(Pt 5):1451-9

 [21] Phillips K., Phillips SE., 1994, Electrostatic activation of Escherichia coli methionine repressor., Structure. 2(4):309-16

 [22] Marti-Arbona R., Teshima M., Anderson PS., Nowak-Lovato KL., Hong-Geller E., Unkefer CJ., Unkefer PJ., 2012, Identification of new ligands for the methionine biosynthesis transcriptional regulator (MetJ) by FAC-MS., J Mol Microbiol Biotechnol. 22(4):205-14

 [23] Old IG., Phillips SE., Stockley PG., Saint Girons I., 1991, Regulation of methionine biosynthesis in the Enterobacteriaceae., Prog Biophys Mol Biol. 56(3):145-85


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