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MetJ DNA-binding transcriptional repressor

Synonyms: MetJ-S-adenosyl-L-methionine, MetJ-adenine, MetJ-MTA, MetJ
Summary:
MetJ represses the expression of genes involved in biosynthesis and transport of methionine [7, 13]. 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 []. 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 []. MetJ as a homodimer [5] recognizes and binds to an 8-bp DNA sequence called the met-box, which varies around a perfect palindromic consensus sequence [4]. MetJ finds its target sites rapidly by facilitated diffusion [].
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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]
MetJ-S-adenosyl-L-methionine Functional Allosteric Holo [APPHINH], [BPP], [HIFS], [IPI] [1], [2], [3], [4], [5]
MetJ-MTA Non-Functional   nd nd
MetJ-adenine Non-Functional   [IPI] [6]
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
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-S-adenosylmethionine,-](12)


Transcription factor regulation    


Transcription factor binding sites (TFBSs) arrangements
      

  Functional conformation Function Promoter Sigma factor Central Rel-Pos Distance to first Gene Genes Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  MetJ-S-adenosyl-L-methionine repressor ahpCp Sigma70 17.5 -7.5 ahpC, ahpF
catcgaaaacACGGAGGAAGTATAGATgtccttgatt
638930 638945 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor ahpCp Sigma70 27.5 3.5 ahpC, ahpF
acggaggaagTATAGATGTCCTTGATTaacaccaaaa
638940 638955 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor folEp Sigma70 25.5 -171.5 folE, yeiB
ctttcacttcCGTATTTGCATAACGATgttttaacat
2243816 2243831 [AIBSCS], [BPP], [GEA] [7]
  MetJ-S-adenosyl-L-methionine repressor folEp Sigma70 33.5 -163.5 folE, yeiB
tccgtatttgCATAACGATGTTTTAACatctgctgat
2243808 2243823 [AIBSCS], [BPP], [GEA] [7]
  MetJ-S-adenosyl-L-methionine repressor folEp Sigma70 41.5 -155.5 folE, yeiB
tgcataacgaTGTTTTAACATCTGCTGatgaaaggca
2243800 2243815 [AIBSCS], [BPP], [GEA] [7]
  MetJ-S-adenosyl-L-methionine repressor folEp Sigma70 49.5 -147.5 folE, yeiB
gatgttttaaCATCTGCTGATGAAAGGcagcggcaat
2243792 2243807 [AIBSCS], [BPP], [GEA] [7]
  MetJ-S-adenosyl-L-methionine repressor metAp1 Sigma32 4.5 -43.5 metA
ggttatcttcAGCTATCTGGATGTCTAaacgtataag
4214229 4214244 [AIBSCS], [BCE], [BPP], [GEA] [3], [7]
  MetJ-S-adenosyl-L-methionine repressor metAp1 Sigma32 20.5 -27.5 metA
ctggatgtctAAACGTATAAGCGTATGtagtgaggta
4214245 4214260 [AIBSCS], [BCE], [BPP], [GEA] [3], [7]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -56.5 -92.5 metB, metL
tcaatctataCGCAAAGAAGTTTAGATgtccagatgt
4128572 4128587 [AIBSCS], [GEA] [3], [7], [8]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -48.5 -84.5 metB, metL
tacgcaaagaAGTTTAGATGTCCAGATgtattgacgt
4128580 4128595 [AIBSCS], [GEA] [3], [7], [8]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -46.5 -82.5 metB, metL
cgcaaagaagTTTAGATGTCCAGATGTattgacgtcc
4128582 4128597 [AIBSCS], [GEA] [3], [7], [8]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -40.5 -76.5 metB, metL
gaagtttagaTGTCCAGATGTATTGACgtccattaac
4128588 4128603 [AIBSCS], [GEA] [3], [7], [8]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -38.5 -74.5 metB, metL
agtttagatgTCCAGATGTATTGACGTccattaacac
4128590 4128605 [AIBSCS], [GEA] [3], [7], [8]
  MetJ-S-adenosyl-L-methionine repressor metBp Sigma70 -30.5 -66.5 metB, metL
tgtccagatgTATTGACGTCCATTAACacaatgttta
4128598 4128613 [AIBSCS], [GEA] [3], [7], [8]
  MetJ-S-adenosyl-L-methionine repressor metCp Sigma70 nd nd metC nd nd [BPP], [GEA], [IGI] [9], [10]
  MetJ-S-adenosyl-L-methionine repressor metEp nd 1.5 -168.5 metE
aaccgccaatTATGGATGTGTAAACATctggacggct
4012877 4012892 [BPP] [2]
  MetJ-S-adenosyl-L-methionine repressor metEp nd 116.5 -53.5 metE
ggatgaataaACTTGCCGCCTTCCCTAaattcaaaat
4012992 4013007 [BPP] [2]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 -8.5 -78.5 metF
gcccttcggcTTTTCCTTCATCTTTACatctggacgt
4132530 4132545 [BCE], [SM]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 2.0 -69.0 metF
cttttccttcATCTTTACATCTGGACGtctaaacgga
4132539 4132554 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 4.5 -66.5 metF
ttccttcatcTTTACATCTGGACGTCTaaacggatag
4132542 4132557 [BCE], [SM]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 7.5 -63.5 metF
cttcatctttACATCTGGACGTCTAAAcggatagatg
4132545 4132560 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 9.5 -61.5 metF
tcatctttacATCTGGACGTCTAAACGgatagatgtg
4132547 4132562 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 17.5 -53.5 metF
acatctggacGTCTAAACGGATAGATGtgcacaacac
4132555 4132570 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor metFp Sigma70 20.5 -50.5 metF
tctggacgtcTAAACGGATAGATGTGCacaacacaac
4132558 4132573 [BCE], [SM]
  MetJ-S-adenosyl-L-methionine repressor metKp Sigma70 -14.5 -143.5 metK
agaattgaccTAAAATAGCCATCCAGAtgttaatcca
3086555 3086570 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor metKp Sigma70 -2.5 -131.5 metK
aaatagccatCCAGATGTTAATCCATCcataccgatt
3086567 3086582 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor metKp2 Sigma38 -14.5 -143.5 metK
agaattgaccTAAAATAGCCATCCAGAtgttaatcca
3086555 3086570 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor metKp2 Sigma38 -2.5 -131.5 metK
aaatagccatCCAGATGTTAATCCATCcataccgatt
3086567 3086582 [AIBSCS] [3]
  MetJ-S-adenosyl-L-methionine repressor metNp Sigma70 -25.5 -94.5 metN, metI, metQ
aaacctgattGATTTAGACGTCTGGATgccttaacat
222732 222747 [AIBSCS], [APIORCISFBSCS] [7], [11], [12]
  MetJ-S-adenosyl-L-methionine repressor metNp Sigma70 -17.5 -86.5 metN, metI, metQ
ttgatttagaCGTCTGGATGCCTTAACatccatttca
222724 222739 [AIBSCS], [GEA] [7], [11]
  MetJ-S-adenosyl-L-methionine repressor metRp1 nd -144.5 -183.5 metR
attttgaattTAGGGAAGGCGGCAAGTttattcatcc
4012992 4013007 [BPP] [2]
  MetJ-S-adenosyl-L-methionine repressor metRp1 nd -29.5 -68.5 metR
agccgtccagATGTTTACACATCCATAattggcggtt
4012877 4012892 [BPP] [2]
  MetJ-S-adenosyl-L-methionine repressor metRp2 nd -162.5 -183.5 metR
attttgaattTAGGGAAGGCGGCAAGTttattcatcc
4012992 4013007 [BPP] [2]
  MetJ-S-adenosyl-L-methionine repressor metRp2 nd -47.5 -68.5 metR
agccgtccagATGTTTACACATCCATAattggcggtt
4012877 4012892 [BPP] [2]


Alignment and PSSM for MetJ TFBSs    

Aligned TFBS of MetJ   
  Sequence
  GGACGTCAATACATCTGGA
  GGACGTCTAAACGGATAGA
  AGACGTCTGGATGCCTTAA
  GGACATCTAAACTTCTTTG
  AGACATCCAGATAGCTGAA
  AGATGTTAAAACATCGTTA
  AGACGTCCAGATGTAAAGA
  AGATGTTTACACATCCATA
  GGATGGATTAACATCTGGA
  GGACATCTATACTTCCTCC
  AGATGTAAAGATGAAGGAA
  AAACGTATAAGCGTATGTA
  GGATGGCTATTTTAGGTCA
  GGAAGGCGGCAAGTTTATT
  TTTCATCAGCAGATGTTAA

Position weight matrix (PWM). MetJ matrix-quality result   
A	7	1	14	1	4	0	3	4	11	5	13	1	6	2	4	1	4	4	12
C	0	0	0	9	0	0	10	2	0	3	0	8	0	1	8	2	0	2	1
G	7	13	0	0	11	3	0	1	3	4	1	1	6	2	2	3	5	4	1
T	1	1	1	5	0	12	2	8	1	3	1	5	3	10	1	9	6	5	1

Consensus   
;	consensus.strict             	gGACGtCtagAcgtctgga
;	consensus.strict.rc          	TCCAGACGTCTAGACGTCC
;	consensus.IUPAC              	rGAYGtCtarAyrtctkka
;	consensus.IUPAC.rc           	TMMAGAYRTYTAGACRTCY
;	consensus.regexp             	[ag]GA[CT]GtCta[ag]A[ct][ag]tct[gt][gt]a
;	consensus.regexp.rc          	T[AC][AC]AGA[CT][AG]T[CT]TAGAC[AG]TC[CT]

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




Reference(s)    

 [1] 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.

 [2] 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

 [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] 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

 [5] 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

 [6] 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

 [7] 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

 [8] 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

 [9] 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

 [10] 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

 [11] 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

 [12] 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

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



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