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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 [11] 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 [12] Review: [13] 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, fecA, fecB, fecC, fecD, fecE, 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 (7)
Fe aquisition (4)
ABC superfamily, membrane component (4)
nitrogen metabolism (4)
Transcription related (3)
Read more >
Regulated operon(s) asnC-mioC-mnmG-rsmG, codBA, feaR, fecABCDE, gdhA, glaH-lhgD-gabDTP, gltBDF, nac, nupC, serA, ydcSTUV-patD
First gene in the operon(s) asnC, asnC, asnC, codB, feaR, fecA, 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,Fur,HypT,Nac,PdhR
Read more >
Simple and complex regulatory phrases Regulatory phrase (List of promoters regulated by the phrase)
[Nac,+](5)
[Nac,-](5)


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
aaaccgacacACATGCAATAATCATtcaataaaaa
3927088 3927102 [GEA], [HIBSCS] [3]
  Nac repressor asnCp Sigma70 -7.0 -35.0 asnC, mioC, mnmG
taaaaaagaaGGCTAAAATAGAATGaatcatcaat
3927031 3927045 [GEA], [HIBSCS] [3]
  Nac repressor asnCp Sigma70 16.0 -13.0 asnC, mioC, mnmG
atgaatcatcAATCCGCATAAGAAAatcctatgga
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
gtcaggctcaTTAGCTTCGTTTATTgcaacacaaa
1447334 1447348 [IHBCE] [5]
  Nac unknown fecAp nd nd nd fecA, fecB, fecC, fecD, fecE nd nd
  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 Sigma38, Sigma70 nd nd gltB, gltD, gltF nd nd [GEA] [2]
  Nac repressor nacp Sigma54 -75.0 -120.0 nac
tgacgaatctATCATAATCTCTTATttgacagttg
2062046 2062060 [BPP], [GEA], [HIBSCS] [1]
  Nac activator nupCp Sigma70 nd nd nupC nd nd [GEA] [2]
  Nac repressor serAp1 Sigma70 -30.0 -76.0 serA
gcaaacgttcATATTGCCGCAATATtattttttga
3058479 3058493 [GEA], [HIBSCS] [8]
  Nac repressor serAp1 Sigma70 -19.0 -65.0 serA
tattgccgcaATATTATTTTTTGATatgttgaaag
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 Growth Condition Evidence (Confirmed, Strong, Weak) References
  Nac activator nd nd nd 2385814 2385831 nd , , [10]
  Nac activator nd nd nd 997510 997527 nd , , [10]
  Nac activator ivy nd nd 240267 240284 nd , , [10]
  Nac activator nd nd nd 4283073 4283090 nd , , [10]
  Nac activator ackA nd nd 2413286 2413303 nd , , [10]
  Nac activator yqeK nd nd 2990733 2990750 nd , , [10]
  Nac activator nd nd nd 820717 820734 nd , , [10]
  Nac activator ybiN nd nd 842176 842193 nd , , [10]
  Nac activator nd nd nd 3674772 3674789 nd , , [10]
  Nac activator yagU nd nd 302848 302865 nd , , [10]
  Nac activator ygjH nd nd 3220903 3220920 nd , , [10]
  Nac activator nd nd nd 569295 569312 nd , , [10]
  Nac activator nd nd nd 3584539 3584556 nd , , [10]
  Nac activator nd nd nd 607381 607398 nd , , [10]
  Nac activator yjaH nd nd 4200267 4200284 nd , , [10]
  Nac activator yaiS nd nd 384977 384994 nd , , [10]
  Nac activator nd nd nd 3609243 3609260 nd , , [10]
  Nac activator nd nd nd 3113132 3113149 nd , , [10]
  Nac activator rfaH nd nd 4024385 4024402 nd , , [10]
  Nac activator ybeQ nd nd 676576 676593 nd , , [10]
  Nac activator rlmM nd nd 2941103 2941120 nd , , [10]
  Nac activator ydeE nd nd 1621597 1621614 nd , , [10]
  Nac activator dcp nd nd 1627407 1627424 nd , , [10]
  Nac activator nd nd nd 1212942 1212959 nd , , [10]
  Nac activator nd nd nd 4436611 4436628 nd , , [10]
  Nac activator ybhD nd nd 800228 800245 nd , , [10]
  Nac activator nd nd nd 1256267 1256284 nd , , [10]
  Nac activator nd nd nd 2249633 2249650 nd , , [10]
  Nac activator nd nd nd 3354195 3354212 nd , , [10]
  Nac activator nd nd nd 2476418 2476435 nd , , [10]
  Nac activator ycaK nd nd 949967 949984 nd , , [10]
  Nac activator nd nd nd 3321211 3321228 nd , , [10]
  Nac activator nd nd nd 2490531 2490548 nd , , [10]
  Nac activator yjgM nd nd 4479689 4479706 nd , , [10]
  Nac activator uspC nd nd 1979632 1979649 nd , , [10]
  Nac activator ycaN nd nd 949968 949985 nd , , [10]
  Nac activator bisC nd nd 3716080 3716097 nd , , [10]
  Nac activator wecH nd nd 3725795 3725812 nd , , [10]
  Nac activator nd nd nd 246141 246158 nd , , [10]
  Nac activator nd nd nd 1770808 1770825 nd , , [10]
  Nac activator ybeT nd nd 679645 679662 nd , , [10]
  Nac repressor nd nd nd 2990733 2990750 nd , , [10]
  Nac repressor nd nd nd 3716079 3716096 nd , , [10]
  Nac repressor ddlA nd nd 401177 401194 nd , , [10]
  Nac repressor eptA nd nd 4335374 4335391 nd , , [10]
  Nac repressor nd nd nd 801889 801906 nd , , [10]
  Nac repressor nd nd nd 3066865 3066882 nd , , [10]
  Nac repressor nd nd nd 3896693 3896710 nd , , [10]
  Nac repressor yafC nd nd 231015 231032 nd , , [10]
  Nac repressor nd nd nd 2192762 2192779 nd , , [10]
  Nac repressor nd nd nd 3897634 3897651 nd , , [10]
  Nac repressor nd nd nd 2044048 2044065 nd , , [GEA] [10]
  Nac repressor nd nd nd 1678206 1678223 nd , , [10]
  Nac repressor nd nd nd 234215 234232 nd , , [10]
  Nac repressor abgR nd nd 1404611 1404628 nd , , [10]
  Nac repressor yebQ nd nd 1910262 1910279 nd , , [10]
  Nac repressor nd nd nd 3674084 3674101 nd , , [10]
  Nac repressor eamA nd nd 1621597 1621614 nd , , [10]
  Nac repressor nd nd nd 3287383 3287400 nd , , [10]
  Nac repressor nd nd nd 1115525 1115542 nd , , [10]
  Nac repressor nd nd nd 2010188 2010205 nd , , [10]
  Nac repressor nd nd nd 2926293 2926310 nd , , [10]
  Nac repressor yghT nd nd 3133888 3133905 nd , , [10]
  Nac repressor nd nd nd 4086069 4086086 nd , , [10]
  Nac repressor nd nd nd 2892069 2892086 nd , , [10]
  Nac repressor nd nd nd 641899 641916 nd , , [10]
  Nac repressor nd nd nd 4294254 4294271 nd , , [10]
  Nac repressor nd nd nd 4428762 4428779 nd , , [10]
  Nac repressor nd nd nd 3632989 3633006 nd , , [10]
  Nac repressor nd nd nd 3172983 3173000 nd , , [10]
  Nac repressor nd nd nd 2215642 2215659 nd , , [10]
  Nac repressor nd nd nd 2859653 2859670 nd , [10]
  Nac repressor nd nd nd 2249633 2249650 nd , , [10]
  Nac repressor nd nd nd 3252928 3252945 nd , , [10]
  Nac repressor nd nd nd 1996895 1996912 nd , , [10]
  Nac repressor nd nd nd 3226582 3226599 nd , , [10]
  Nac repressor yfbK nd nd 2385814 2385831 nd , , [10]
  Nac repressor nd nd nd 3333499 3333516 nd , , [10]
  Nac repressor nd nd nd 1633125 1633142 nd , , [10]
  Nac repressor nd nd nd 1357697 1357714 nd , , [10]
  Nac repressor nd nd nd 1517710 1517727 nd , , [10]
  Nac repressor nd nd nd 216619 216636 nd , , [10]
  Nac repressor nd nd nd 1434155 1434172 nd , , [10]
  Nac repressor nd nd nd 4297158 4297175 nd , , [10]
  Nac repressor nd nd nd 3267262 3267279 nd , , [10]
  Nac repressor nd nd nd 1655690 1655707 nd , , [10]
  Nac repressor nd nd nd 3418272 3418289 nd , , [10]
  Nac repressor nd nd nd 1919888 1919905 nd , , [10]
  Nac repressor ycaC nd nd 945739 945756 nd , , [10]
  Nac repressor yjgN nd nd 4479689 4479706 nd , , [10]
  Nac repressor nd nd nd 3499134 3499151 nd , , [10]
  Nac repressor nd nd nd 1770809 1770826 nd , , [10]
  Nac repressor nd nd nd 945739 945756 nd , , [10]
  Nac repressor nd nd nd 850405 850422 nd , , [10]
  Nac repressor nd nd nd 2897893 2897910 nd , , [10]
  Nac repressor nd nd nd 4609400 4609417 nd , , [10]
  Nac repressor nd nd nd 2759168 2759185 nd , , [10]
  Nac repressor nudG nd nd 1841515 1841532 nd , , [10]
  Nac repressor nd nd nd 2099737 2099754 nd , , [10]
  Nac repressor nd nd nd 1517710 1517727 nd , , [10]
  Nac repressor yaiY nd nd 399494 399511 nd , , [10]
  Nac repressor nd nd nd 1806356 1806373 nd [AIBSCS], , [10]
  Nac repressor ykgL nd nd 311568 311585 nd , , [10]
  Nac repressor ligB nd nd 3821374 3821391 nd , , [10]
  Nac repressor nd nd nd 1518792 1518809 nd , , [10]
  Nac repressor nd nd nd 4374417 4374434 nd , , [10]
  Nac repressor nd nd nd 1755139 1755156 nd , , [10]
  Nac repressor ycgJ nd nd 1226586 1226603 nd , , [10]
  Nac repressor nd nd nd 430612 430629 nd , , [10]
  Nac repressor dld nd nd 2221976 2221993 nd , , [10]
  Nac repressor nd nd nd 2984192 2984209 nd , , [10]
  Nac repressor nd nd nd 3897635 3897652 nd , , [10]
  Nac repressor nd nd nd 1053207 1053224 nd , , [10]
  Nac repressor yjeH nd nd 4370473 4370490 nd , , [10]
  Nac repressor nd nd nd 2971243 2971260 nd , , [10]
  Nac repressor nd nd nd 2489116 2489133 nd , , [10]
  Nac repressor kdgR nd nd 1910262 1910279 nd , , [10]
  Nac repressor nd nd nd 2089156 2089173 nd , , [10]
  Nac repressor nd nd nd 2413286 2413303 nd , , [10]
  Nac repressor nd nd nd 4148594 4148611 nd , , [10]
  Nac repressor nd nd nd 3536753 3536770 nd , , [10]
  Nac repressor nd nd nd 800726 800743 nd , , [10]


Alignment and PSSM for Nac TFBSs    

Aligned TFBS of Nac   
  Sequence
  GGATTTTCTTATGCGGA
  AAATTTTCTCAGGGGCG
  GGAATTGCTGATGTCGC
  TTATTTTTTGATATGTT
  ATAATCTCTTATTTGAC
  TATATTTTTTATATGAA
  TGATTATTGCATGTGTG
  AGCTTCGTTTATTGCAA
  GAGTAATCTCATAACCA
  TCATTCTATTTTAGCCT
  GATTGTGCTTATGTTGT
  AAATAATATTGCGGCAA
  GTATTAATATATAAGGG
  TCACATTCTTGATGGTA

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

Consensus   
;	consensus.strict             	ggattttcTtatgggga
;	consensus.strict.rc          	TCCCCATAAGAAAATCC
;	consensus.IUPAC              	krattykyTyatrkssr
;	consensus.IUPAC.rc           	YSSMYATRARMRAATYM
;	consensus.regexp             	[gt][ag]att[ct][gt][ct]T[ct]at[ag][gt][cg][cg][ag]
;	consensus.regexp.rc          	[CT][CG][CG][AC][CT]AT[AG]A[AG][AC][AG]AAT[CT][AC]

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

 [AIBSPD] Automated inference based on sequence pattern discovery

 [CE] ChIP-seq evidence

 [RE] RNA-seq evidence

 [MCIBSPD] Manually curated inference based on sequence pattern discovery



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] Aquino P., Honda B., Jaini S., Lyubetskaya A., Hosur K., Chiu JG., Ekladious I., Hu D., Jin L., Sayeg MK., Stettner AI., Wang J., Wong BG., Wong WS., Alexander SL., Ba C., Bensussen SI., Bernstein DB., Braff D., Cha S., Cheng DI., Cho JH., Chou K., Chuang J., Gastler DE., Grasso DJ., Greifenberger JS., Guo C., Hawes AK., Israni DV., Jain SR., Kim J., Lei J., Li H., Li D., Li Q., Mancuso CP., Mao N., Masud SF., Meisel CL., Mi J., Nykyforchyn CS., Park M., Peterson HM., Ramirez AK., Reynolds DS., Rim NG., Saffie JC., Su H., Su WR., Su Y., Sun M., Thommes MM., Tu T., Varongchayakul N., Wagner TE., Weinberg BH., Yang R., Yaroslavsky A., Yoon C., Zhao Y., Zollinger AJ., Stringer AM., Foster JW., Wade J., Raman S., Broude N., Wong WW., Galagan JE., 2017, Coordinated regulation of acid resistance in Escherichia coli., BMC Syst Biol 11(1):1

 [11] Muse WB, Bender RA, 1999, The amino-terminal 100 residues of the nitrogen assimilation control protein (NAC) encode all known properties of NAC from Klebsiella aerogenes and Escherichia coli., J Bacteriol, 1999 Feb

 [12] Rosario CJ, Frisch RL, Bender RA, 2010, The LysR-type nitrogen assimilation control protein forms complexes with both long and short DNA binding sites in the absence of coeffectors., J Bacteriol, 2010 Oct

 [13] Switzer A, Brown DR, Wigneshweraraj S, 2018, New insights into the adaptive transcriptional response to nitrogen starvation in Escherichia coli., Biochem Soc Trans, 2018 Dec 17



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