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Nac DNA-binding transcriptional dual regulator

Synonyms: Nac
Summary:
Nac, "Nitrogen assimilation control," regulates, without a coeffector, genes involved in nitrogen metabolism under nitrogen-limiting conditions [1] The genes regulated by Nac are transcribed by RNA polymerase σ70. These genes are coupled to the nitrogen regulatory (Ntr) system, which is σ54 dependent, through Nac, whose transcription is activated by NtrC [1] Using DNA microarray analyses, it was shown that Nac could affect the expression of 25 genes [2] This transcriptional regulator is negatively autoregulated [1]and is expressed under nitrogen-limiting conditions [7] Nac belongs to the LysR family [1]and features a helix-turn-helix motif located close to the N terminus [] In contrast with most LysR family members, which are transcribed divergently from the gene they regulate, nac is distant on the genome from its regulated genes [1] In Klebsiella pneumoniae, Nac functions as a dimer, and for some sites it can bind as a tetramer; it recognizes long and short sites in the absence of a coeffector [] Read more >


Transcription factor      
TF conformation(s):
Name Conformation Type TF-Effector Interaction Type Apo/Holo Conformation Evidence (Confirmed, Strong, Weak) References
Nac Functional   [HIFS], [IDA], [IFC] [1], [2]
Evolutionary Family: LysR
Connectivity class: Local Regulator
Gene name: nac
  Genome position: 2061016-2061933
  Length: 918 bp / 305 aa
Operon name: nac
TU(s) encoding the TF:
Transcription unit        Promoter
nac
nacp


Regulon       
Regulated gene(s) asnC, codA, codB, feaR, gabD, gabP, gabT, gdhA, gltB, gltD, gltF, mioC, mnmG, nac, nupC, patD, serA, ydcS, ydcT, ydcU, ydcV
Multifun term(s) of regulated gene(s) MultiFun Term (List of genes associated to the multifun term)
membrane (5)
nitrogen metabolism (4)
Transcription related (3)
activator (3)
nucleotide and nucleoside conversions (3)
Read more >
Regulated operon(s) asnC-mioC-mnmG-rsmG, codBA, csiD-lhgO-gabDTP, feaR, gdhA, gltBDF, nac, nupC, serA, ydcSTUV-patD
First gene in the operon(s) asnC, asnC, asnC, codB, feaR, gabD, gdhA, gltB, nac, nupC, serA, ydcS
Simple and complex regulons AdiY,ArgR,CRP,FNR,Fur,GadE,HdfR,IHF,Lrp,Nac
ArgP,CRP,FNR,Fur,Nac
AsnC,Nac
CRP,CytR,Nac
CRP,Nac,NsrR,PhoB,QseB
Read more >
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[Nac,-](4)
[Nac,+](4)


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
  Nac repressor asnCp Sigma70 -64.0 -92.0 asnC, mioC, mnmG
tttttattgaATGATTATTGCATGTgtgtcggttt
3927088 3927102 [GEA], [HIBSCS] [3]
  Nac repressor asnCp Sigma70 -7.0 -35.0 asnC, mioC, mnmG
attgatgattCATTCTATTTTAGCCttctttttta
3927031 3927045 [GEA], [HIBSCS] [3]
  Nac repressor asnCp Sigma70 16.0 -13.0 asnC, mioC, mnmG
tccataggatTTTCTTATGCGGATTgatgattcat
3927009 3927023 [GEA], [HIBSCS] [3]
  Nac activator codBp Sigma70 -58.0 -96.0 codB, codA
gcactcattcATATAAAAAATATATttccccacga
354819 354833 [AIBSCS], [BPP], [GEA], [SM] [2], [4]
  Nac activator feaRp2 Sigma70 -32.5 -58.0 feaR
tttgtgttgcAATAAACGAAGCTAAtgagcctgac
1447334 1447348 [IHBCE] [5]
  Nac activator gabDp1 Sigma70, Sigma38 -44.0 -145.0 gabD, gabT, gabP
cggcagcgacATCAGCAATTCCTATtggtgcgcat
2791121 2791135 [GEA], [HIBSCS] [2], [6]
  Nac repressor gdhAp1 Sigma70 -81.0 -144.0 gdhA
tcgcatttggTTATGAGATTACTCTcgttattaat
1842220 1842234 [GEA], [HIBSCS] [7]
  Nac repressor gdhAp1 Sigma70 -25.0 -88.0 gdhA
ttcttgcttaCCGTCACATTCTTGAtggtatagtc
1842276 1842290 [GEA], [HIBSCS] [7]
  Nac repressor gdhAp1 Sigma70 25.0 -39.0 gdhA
cacatgacatAAACAACATAAGCACaatcgtatta
1842325 1842339 [GEA], [HIBSCS] [7]
  Nac repressor gdhAp1 Sigma70 45.0 -19.0 gdhA
agcacaatcgTATTAATATATAAGGgttttatatc
1842345 1842359 [GEA], [HIBSCS] [7]
  Nac repressor gltBp Sigma70 nd -3354725.0 gltB, gltD, gltF nd nd [GEA] [2]
  Nac repressor nacp Sigma54 -75.0 -120.0 nac
caactgtcaaATAAGAGATTATGATagattcgtca
2062046 2062060 [BPP], [GEA], [HIBSCS] [1]
  Nac activator nupCp Sigma70 nd -2513042.0 nupC nd nd [GEA] [2]
  Nac repressor serAp1 Sigma70 -30.0 -76.0 serA
tcaaaaaataATATTGCGGCAATATgaacgtttgc
3058479 3058493 [GEA], [HIBSCS] [8]
  Nac repressor serAp1 Sigma70 -19.0 -65.0 serA
ctttcaacatATCAAAAAATAATATtgcggcaata
3058468 3058482 [GEA], [HIBSCS] [8]
  Nac activator ydcSp1 Sigma38 -51.0 -106.0 ydcS, ydcT, ydcU, ydcV, patD
cacaacctgaATAAATTTTCTCAGGggcgaaggtg
1511541 1511555 [GEA], [HIBSCS], [IDA] [9]



High-throughput Transcription factor binding sites (TFBSs)
      

  Functional conformation Function Object name Object type Distance to first Gene Sequence LeftPos RightPos Evidence (Confirmed, Strong, Weak) References
  Nac repressor htrE gene -337.0 155763 155780 nd nd
  Nac repressor yafN gene -244.0 252249 252266 nd nd
  Nac activator argO gene -83.0 3068894 3068910 nd nd
  Nac repressor sbcD gene -82.0 417034 417051 nd nd
  Nac activator bssS gene -80.0 1121035 1121052 nd nd
  Nac activator lysA gene -79.0 2978978 2978995 nd nd
  Nac repressor nanA gene -79.0 3373655 3373672 nd nd
  Nac repressor xapR gene -76.0 2522553 2522570 nd nd
  Nac activator yigI gene -76.0 4004773 4004790 nd nd
  Nac repressor pstS gene -75.0 3911600 3911617 nd nd
  Nac repressor kduI gene -68.0 2984192 2984209 nd nd
  Nac repressor ydcY gene -63.0 1517711 1517728 nd nd
  Nac activator ydiV gene -56.0 1792076 1792093 nd nd
  Nac repressor serA gene -55.0 3058468 3058482 nd nd
  Nac repressor fdhD gene -54.0 4086070 4086087 nd nd
  Nac repressor ydfK gene -53.0 1633125 1633142 nd nd
  Nac repressor nudC gene -48.0 4196951 4196968 nd nd
  Nac activator ytfB gene -45.0 4428762 4428779 nd nd
  Nac activator osmB gene -43.0 1343371 1343388 nd nd
  Nac activator ydaU gene -37.0 1421156 1421173 nd nd
  Nac repressor rnlB gene -37.0 2767021 2767038 nd nd
  Nac repressor mdtG gene -35.0 1115525 1115542 nd nd
  Nac repressor kbl gene -34.0 3792585 3792602 nd [10], [11]
  Nac repressor uspG gene -32.0 641899 641916 nd nd
  Nac repressor tfaR gene -32.0 1432443 1432460 nd nd
  Nac repressor ymjA gene -29.0 1357697 1357714 nd nd
  Nac repressor yeeZ gene -28.0 2089156 2089173 nd nd
  Nac repressor nadC gene -27.0 118672 118689 nd nd
  Nac repressor nudG gene -26.0 1841516 1841533 nd nd
  Nac repressor ygcS gene -23.0 2897893 2897910 nd nd
  Nac repressor uxaC gene -23.0 3244764 3244781 nd nd
  Nac repressor emrK gene -18.0 2483357 2483374 nd nd
  Nac repressor tfaQ gene -17.0 1634902 1634919 nd nd
  Nac repressor yhaI gene -17.0 3252928 3252945 nd nd
  Nac repressor yeiE gene -15.0 2249633 2249650 nd nd
  Nac activator ybjP gene -12.0 904479 904496 nd nd
  Nac repressor cynR gene -9.0 358700 358708 nd nd
  Nac activator yqeJ gene -9.0 2989313 2989330 nd nd
  Nac repressor yajD gene -8.0 430613 430630 nd nd
  Nac activator ybbW gene -6.0 537639 537656 nd nd
  Nac repressor ybhI gene -3.0 801890 801907 nd nd
  Nac repressor lysP gene 2.0 2248530 2248547 nd nd
  Nac repressor gatA gene 2.0 2175047 2175064 nd nd
  Nac activator yidQ gene 4.0 3867724 3867741 nd nd
  Nac activator hupA gene 14.0 4200267 4200284 nd nd
  Nac repressor malY gene 14.0 1700943 1700960 nd nd
  Nac activator pfkB gene 14.0 1806356 1806373 nd nd
  Nac repressor ydiB gene 14.0 1773775 1773792 nd nd
  Nac repressor ubiA gene 14.0 4253002 4253019 nd nd
  Nac activator yigL gene 14.0 4010186 4010203 nd [12]
  Nac repressor pabC gene 14.0 1153286 1153303 nd nd
  Nac repressor ybbC gene 14.0 527567 527584 nd nd
  Nac repressor prfC gene 14.0 4609400 4609417 nd nd
  Nac activator yhjE gene 14.0 3674772 3674789 nd nd
  Nac repressor cdaR gene 14.0 182449 182466 nd nd
  Nac activator ygiL gene 14.0 3185400 3185417 nd nd
  Nac repressor ecnB gene 14.0 4376539 4376556 nd nd
  Nac repressor macA gene 14.0 919221 919238 nd nd
  Nac repressor ycgJ gene 14.0 1226586 1226603 nd nd
  Nac repressor yebQ gene 14.0 1910262 1910279 nd nd
  Nac activator yfeK gene 14.0 2537328 2537345 nd nd
  Nac repressor ygaP gene 14.0 2797506 2797523 nd nd
  Nac repressor ygcP gene 14.0 2894182 2894199 nd nd
  Nac repressor dkgA gene 14.0 3156609 3156626 nd nd
  Nac repressor yhbU gene 14.0 3301471 3301488 nd nd
  Nac repressor gspG gene 14.0 3461009 3461026 nd nd
  Nac repressor feaB gene 14.0 1447505 1447522 nd nd
  Nac repressor hfq gene 17.0 4400271 4400288 nd nd
  Nac activator kbaY gene 17.0 3283126 3283143 nd nd
  Nac repressor nlpE gene 18.0 215251 215268 nd nd
  Nac repressor thrS gene 24.0 1802546 1802563 nd nd
  Nac activator cheA gene 27.0 1975297 1975314 nd nd
  Nac activator rluE gene 27.0 1194924 1194941 nd nd
  Nac repressor ygdR gene 28.0 2971243 2971260 nd nd
  Nac repressor secG gene 32.0 3322473 3322490 nd nd
  Nac repressor yehE gene 35.0 2192761 2192778 nd nd
  Nac repressor lysR gene 43.0 2978978 2978995 nd nd
  Nac activator yfbL gene 46.0 2385814 2385831 nd nd
  Nac activator micC gene 51.0 1437070 1437087 nd nd
  Nac repressor yafO gene 52.0 252249 252266 nd nd
  Nac repressor yfdE gene 53.0 2489115 2489132 nd nd
  Nac repressor ygaM gene 58.0 2800088 2800105 nd nd
  Nac activator allR gene 60.0 532951 532968 nd nd
  Nac repressor ampD gene 61.0 118672 118689 nd nd
  Nac activator ilvL gene 63.0 3950259 3950276 nd nd
  Nac activator ivy gene 76.0 240267 240284 nd nd
  Nac repressor ynfF gene 78.0 1660478 1660495 nd nd
  Nac repressor yadC gene 80.0 150873 150890 nd nd
  Nac activator nrfG gene 80.0 4293463 4293480 nd nd
  Nac repressor yecF gene 81.0 1995737 1995754 nd nd
  Nac repressor spf gene 83.0 4049816 4049833 nd nd
  Nac activator yeiH gene 84.0 2249633 2249650 nd nd
  Nac repressor pldA gene 89.0 4004773 4004790 nd [13]
  Nac repressor ydiO gene 90.0 1777106 1777123 nd nd
  Nac repressor fliD gene 92.0 2003780 2003797 nd nd
  Nac activator wecH gene 92.0 3725795 3725812 nd nd
  Nac repressor thiL gene 92.0 435542 435559 nd nd
  Nac repressor ybfC gene 96.0 735554 735571 nd nd
  Nac activator dadA gene 98.0 1237473 1237490 nd nd
  Nac repressor cynT gene 100.0 358700 358708 nd nd
  Nac repressor codB gene 104.0 354819 354833 nd nd
  Nac activator yafD gene 107.0 231015 231032 nd nd
  Nac repressor phoB gene 108.0 417034 417051 nd nd
  Nac repressor yobB gene 110.0 1925330 1925347 nd nd
  Nac repressor sibE gene 113.0 3195127 3195144 nd nd
  Nac activator ybjQ gene 114.0 904479 904496 nd nd
  Nac repressor yihQ gene 118.0 4069158 4069175 nd nd
  Nac repressor csiD gene 119.0 2788866 2788883 nd [14]
  Nac activator yfgG gene 122.0 2629168 2629185 nd nd
  Nac activator dhaR gene 126.0 1250940 1250957 nd nd
  Nac repressor nupC gene 141.0 2512901 2512918 nd nd
  Nac activator yagU gene 143.0 302848 302865 nd nd
  Nac repressor queD gene 145.0 2892069 2892086 nd nd
  Nac repressor asnV gene 153.0 2062107 2062124 nd nd
  Nac repressor yjbB gene 154.0 4227577 4227594 nd nd
  Nac activator rlmF gene 156.0 842176 842193 nd nd
  Nac repressor yccM gene 156.0 1053206 1053223 nd nd
  Nac repressor yhcD gene 156.0 3362651 3362668 nd nd
  Nac repressor ygiN gene 159.0 3172983 3173000 nd nd
  Nac repressor yfgH gene 159.0 2629633 2629650 nd nd
  Nac repressor yieE gene 161.0 3893720 3893737 nd nd
  Nac activator ycgX gene 166.0 1212941 1212958 nd nd
  Nac repressor yajO gene 168.0 437967 437984 nd nd
  Nac repressor fklB gene 173.0 4428762 4428779 nd nd
  Nac repressor yhcA gene 176.0 3361936 3361953 nd nd
  Nac repressor fucA gene 177.0 2933511 2933528 nd nd
  Nac activator ackA gene 184.0 2413286 2413303 nd [15]
  Nac repressor ispD gene 186.0 2872304 2872321 nd nd
  Nac repressor aroD gene 189.0 1774497 1774514 nd nd
  Nac repressor oppC gene 189.0 1303645 1303662 nd nd
  Nac repressor ybdR gene 189.0 641899 641916 nd nd
  Nac activator ftnB gene 189.0 1986731 1986745 nd nd
  Nac activator icd gene 199.0 1194924 1194941 nd nd
  Nac activator yecE gene 200.0 1951195 1951212 nd nd
  Nac repressor ydeQ gene 204.0 1587530 1587547 nd nd
  Nac repressor ytfK gene 205.0 4439382 4439399 nd nd
  Nac repressor ynfK gene 207.0 1667012 1667029 nd nd
  Nac repressor eptA gene 217.0 4335373 4335390 nd nd
  Nac repressor ydgH gene 221.0 1678206 1678223 nd nd
  Nac repressor gltP gene 227.0 4294254 4294271 nd [16], [17]
  Nac repressor torA gene 236.0 1059020 1059037 nd nd
  Nac repressor yifB gene 254.0 3949715 3949732 nd nd
  Nac repressor ydiM gene 262.0 1770809 1770826 nd nd
  Nac repressor yjfZ gene 262.0 4427160 4427177 nd nd
  Nac repressor dsbA gene 263.0 4043155 4043172 nd nd
  Nac repressor ykgE gene 268.0 321340 321357 nd nd
  Nac activator ydcS gene 276.0 1511378 1511395 nd nd
  Nac repressor ygdB gene 277.0 2962879 2962896 nd nd
  Nac repressor intD gene 291.0 565687 565704 nd nd
  Nac repressor ansP gene 291.0 1525689 1525706 nd nd
  Nac repressor leuO gene 298.0 84065 84076 nd nd
  Nac activator yjaH gene 299.0 4200267 4200284 nd nd
  Nac repressor amiB gene 307.0 4395758 4395775 nd nd
  Nac repressor yoeB gene 309.0 2089156 2089173 nd nd
  Nac activator bisC gene 315.0 3716079 3716096 nd nd
  Nac repressor rfbB gene 315.0 2112746 2112763 nd nd
  Nac activator rpmH gene 324.0 3884012 3884029 nd nd
  Nac repressor rsmF gene 335.0 1919888 1919905 nd nd
  Nac repressor hofC gene 336.0 115388 115405 nd nd
  Nac activator yghG gene 345.0 3113132 3113149 nd nd
  Nac activator ileY gene 350.0 2785487 2785504 nd nd
  Nac repressor yhfZ gene 354.0 3511990 3512007 nd nd
  Nac activator ydcI gene 359.0 1494712 1494729 nd nd
  Nac activator yegH gene 364.0 2137538 2137555 nd nd
  Nac activator yjcB gene 371.0 4274670 4274687 nd nd
  Nac activator argU gene 375.0 564348 564365 nd nd
  Nac repressor yfiR gene 378.0 2741497 2741514 nd nd
  Nac repressor lrp gene 380.0 932215 932232 nd nd
  Nac repressor yaeF gene 385.0 216618 216635 nd nd
  Nac repressor yqeB gene 386.0 3013853 3013870 nd nd
  Nac repressor evgA gene 398.0 2483357 2483374 nd nd
  Nac repressor yfeS gene 421.0 2537328 2537345 nd nd
  Nac activator shoB gene 429.0 2699768 2699785 nd nd
  Nac activator rfaH gene 437.0 4024384 4024401 nd nd
  Nac repressor phoH gene 439.0 1084553 1084570 nd nd
  Nac activator sdhC gene 442.0 754740 754754 nd nd
  Nac repressor prmB gene 456.0 2447984 2448001 nd nd
  Nac repressor gspH gene 459.0 3461009 3461026 nd nd
  Nac repressor exuT gene 460.0 3244764 3244781 nd nd
  Nac repressor yggP gene 465.0 3076991 3077008 nd nd
  Nac repressor yiaD gene 468.0 3716079 3716096 nd nd
  Nac repressor pinQ gene 497.0 1633125 1633142 nd nd
  Nac repressor mglA gene 498.0 2238791 2238808 nd nd
  Nac repressor bglB gene 499.0 3903202 3903219 nd nd
  Nac repressor metY gene 499.0 3317790 3317807 nd nd
  Nac repressor asnT gene 500.0 2044049 2044066 nd nd


Alignment and PSSM for Nac TFBSs    

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

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    

 [HIFS] Human inference of function from sequence

 [IDA] Inferred from direct assay

 [IFC] Inferred by functional complementation

 [GEA] Gene expression analysis

 [HIBSCS] Human inference based on similarity to consensus sequences

 [AIBSCS] Automated inference based on similarity to consensus sequences

 [BPP] Binding of purified proteins

 [SM] Site mutation

 [IHBCE] Inferred by a human based on computational evidence



Reference(s)    

 [1] Muse WB., Bender RA., 1998, The nac (nitrogen assimilation control) gene from Escherichia coli., J Bacteriol 180(5):1166-73

 [2] Zimmer DP., Soupene E., Lee HL., Wendisch VF., Khodursky AB., Peter BJ., Bender RA., Kustu S., 2000, Nitrogen regulatory protein C-controlled genes of Escherichia coli: scavenging as a defense against nitrogen limitation., Proc Natl Acad Sci U S A 97(26):14674-9

 [3] Poggio S., Domeinzain C., Osorio A., Camarena L., 2002, The nitrogen assimilation control (Nac) protein represses asnC and asnA transcription in Escherichia coli., FEMS Microbiol Lett 206(2):151-6

 [4] Muse WB., Rosario CJ., Bender RA., 2003, Nitrogen regulation of the codBA (cytosine deaminase) operon from Escherichia coli by the nitrogen assimilation control protein, NAC., J Bacteriol 185(9):2920-6

 [5] Zeng J., Spiro S., 2013, Finely tuned regulation of the aromatic amine degradation pathway in Escherichia coli., J Bacteriol 195(22):5141-50

 [6] Schneider BL., Ruback S., Kiupakis AK., Kasbarian H., Pybus C., Reitzer L., 2002, The Escherichia coli gabDTPC operon: specific gamma-aminobutyrate catabolism and nonspecific induction., J Bacteriol 184(24):6976-86

 [7] Camarena L., Poggio S., Garcia N., Osorio A., 1998, Transcriptional repression of gdhA in Escherichia coli is mediated by the Nac protein., FEMS Microbiol Lett 167(1):51-6

 [8] Blauwkamp TA., Ninfa AJ., 2002, Nac-mediated repression of the serA promoter of Escherichia coli., Mol Microbiol 45(2):351-63

 [9] Schneider BL., Hernandez VJ., Reitzer L., 2013, Putrescine catabolism is a metabolic response to several stresses in Escherichia coli., Mol Microbiol 88(3):537-50

 [10] Aronson BD., Ravnikar PD., Somerville RL., 1988, Nucleotide sequence of the 2-amino-3-ketobutyrate coenzyme A ligase (kbl) gene of E. coli., Nucleic Acids Res 16(8):3586

 [11] Rex JH., Aronson BD., Somerville RL., 1991, The tdh and serA operons of Escherichia coli: mutational analysis of the regulatory elements of leucine-responsive genes., J Bacteriol 173(19):5944-53

 [12] Talukder AA., Yanai S., Yamada M., 2005, Analysis of reading frame and expressional regulation of randomly selected promoter-proximal genes in Escherichia coli., J Gen Appl Microbiol 51(2):93-103

 [13] de Geus P., van Die I., Bergmans H., Tommassen J., de Haas G., 1983, Molecular cloning of pldA, the structural gene for outer membrane phospholipase of E. coli K12., Mol Gen Genet 190(1):150-5

 [14] Marschall C., Labrousse V., Kreimer M., Weichart D., Kolb A., Hengge-Aronis R., 1998, Molecular analysis of the regulation of csiD, a carbon starvation-inducible gene in Escherichia coli that is exclusively dependent on sigma s and requires activation by cAMP-CRP., J Mol Biol 276(2):339-53

 [15] Matsuyama A., Yamamoto H., Nakano E., 1989, Cloning, expression, and nucleotide sequence of the Escherichia coli K-12 ackA gene., J Bacteriol 171(1):577-80

 [16] Tolner B., Poolman B., Wallace B., Konings WN., 1992, Revised nucleotide sequence of the gltP gene, which encodes the proton-glutamate-aspartate transport protein of Escherichia coli K-12., J Bacteriol 174(7):2391-3

 [17] Wallace B., Yang YJ., Hong JS., Lum D., 1990, Cloning and sequencing of a gene encoding a glutamate and aspartate carrier of Escherichia coli K-12., J Bacteriol 172(6):3214-20



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