RegulonDB

RegulonDB RegulonDB 10.10: Operon Form

alkA operon and associated TUs in Escherichia coli K-12 genome

Operon
Name:	alkA
This page displays every known transcription unit of this operon and their known regulation.

Transcription unit

Name:	alkA
Synonym(s):	OP00002
Gene(s):	alkA Genome Browser M3D Gene expression COLOMBOS
Note(s):	Both the unmethylated and methylated forms of the Ada protein can activate alkA transcription in vivo and in vitro Landini P,1999
Evidence:	[AISGDTU] Automated inference that a single-gene directon is a transcription unit
Reference(s):	[1] Nakabeppu Y., et al., 1984 [2] Volkert MR. 1988
Promoter
Name:	alkAp2
+1:	2147559
Sigma Factor:	Sigma38 Sigmulon
Distance from start of the gene:	19
Sequence:	tcgcgacaaccggaatatgaaagcaaagcgcagcgtctgaataacgtttatgctgaaagcGgatgaataaggagatgcgat -35 -10 +1
Note(s):	σ⁷⁰ is the sigma factor principally responsible for the alkA transcription. However alkA is highly dependent on alternative factor σ³⁸ (RpoS) during the stationary phase. In contrast, the transcription factor Ada in its methylated state negatively regulates σ³⁸-dependent transcription Landini P,1999. Eσ^S is more efficient than Eσ⁷⁰ in carrying out transcription from the alkA promoter in the absence of Ada (Ada is a repressor for Eσ^S) Landini P,1999
Evidence:	[CV(RPF/RS-EPT-CBR)] [ICWHO] [IDA] [IEP] [RPF] [RS-EPT-CBR]
Reference(s):	[3] Huerta AM., et al., 2003 [4] Lai CF., et al., 1999 [5] Landini P., et al., 1999 [6] Landini P., et al., 1999 [7] Salgado H, et al., 2012

TF binding sites (TFBSs)

[Ada,+] Phrase

Type	Transcription factor	Function	Promoter	Binding Sites				Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
Type	Transcription factor	Function	Promoter	LeftPos	RightPos	Central Rel-Pos	Sequence	Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
proximal	Ada	activator	alkAp2	2147589	2147613	-41.5	gccgtcgcgaCAACCGGAATATGAAAGCAAAGCGCagcgtctgaa	nd	[GEA], [APIORCISFBSCS], [BPP], [SM]	[5], [6], [8], [9], [10], [11], [12], [13]

Transcription factor	Function	Promoter	Binding Sites	Evidence (Confirmed, Strong, Weak)	Reference(s)
Ada	activator	alkAp2	2147589	2147613	-41.5	gccgtcgcgaCAACCGGAATATGAAAGCAAAGCGCagcgtctgaa	[GEA]	[5], [6], [8], [9], [10], [11], [12], [13]

Transcription unit

Name:	alkA
Synonym(s):	OP00002
Gene(s):	alkA Genome Browser M3D Gene expression COLOMBOS
Note(s):	Both the unmethylated and methylated forms of the Ada protein can activate alkA transcription in vivo and in vitro Landini P,1999
Evidence:	[AISGDTU] Automated inference that a single-gene directon is a transcription unit
Reference(s):	[1] Nakabeppu Y., et al., 1984 [2] Volkert MR. 1988
Promoter
Name:	alkAp
+1:	2147559
Sigma Factor:	Sigma70 Sigmulon
Distance from start of the gene:	19
Sequence:	tcgcgacaaccggaatatgaaagcaaagcgcagcgtctgaataacgtttatgctgaaagcGgatgaataaggagatgcgat -35 -10 +1
Note(s):	σ⁷⁰ is the sigma factor principally responsible for the alkA transcription. However alkA is highly dependent on alternative factor σ³⁸ (RpoS) during the stationary phase. In contrast, the transcription factor Ada in its methylated state negatively regulates σ³⁸-dependent transcription Landini P,1999. Eσ^S is more efficient than Eσ⁷⁰ in carrying out transcription from the alkA promoter in the absence of Ada (Ada is a repressor for Eσ^S) Landini P,1999
Evidence:	[CV(RPF/RS-EPT-CBR)] [ICWHO] [IDA] [IEP] [RPF] [RS-EPT-CBR]
Reference(s):	[3] Huerta AM., et al., 2003 [4] Lai CF., et al., 1999 [5] Landini P., et al., 1999 [6] Landini P., et al., 1999 [7] Salgado H, et al., 2012

TF binding sites (TFBSs)

[Ada,+] Phrase

Type	Transcription factor	Function	Promoter	Binding Sites				Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
Type	Transcription factor	Function	Promoter	LeftPos	RightPos	Central Rel-Pos	Sequence	Growth Conditions	Evidence (Confirmed, Strong, Weak)	Reference(s)
proximal	Ada	activator	alkAp	2147589	2147613	-41.5	gccgtcgcgaCAACCGGAATATGAAAGCAAAGCGCagcgtctgaa	nd	[GEA], [APIORCISFBSCS], [BPP], [SM]	[5], [6], [8], [9], [10], [11], [12], [13]

Transcription factor	Function	Promoter	Binding Sites	Evidence (Confirmed, Strong, Weak)	Reference(s)
Ada	activator	alkAp	2147589	2147613	-41.5	gccgtcgcgaCAACCGGAATATGAAAGCAAAGCGCagcgtctgaa	[GEA]	[5], [6], [8], [9], [10], [11], [12], [13]

RNA cis-regulatory element

Regulation, transcriptional elongation
Attenuator type:	Transcriptional
Strand:	reverse
Evidence:	[ICA] Inferred by computational analysis
Reference(s):	[14] Merino E, et al., 2005

Structure type	Energy	LeftPos	RightPos	Sequence (RNA-strand)
terminator	-9.3	2147747	2147780	gcaaagcattGAAGGCAGCAGCGTGCTGTCGTTTTCCATTTTTagcaaatgcg
anti-terminator	-12.9	2147768	2147815	tacagccattCGCTTACCGCTTCACGCGTTGGCGCGCAAAGCATTGAAGGCAGCAGCgtgctgtcgt
anti-anti-terminator	-8.0	2147813	2147841	cgtctgccggAACATCATGATGGCGGTACAGCCATTCGcttaccgctt

Notes: "The provided "Sequence" is that of the RNA strand, i.e. U's are shown instead of T's and regulators on the reverse strand will appear as the reverse complement of the sequence delimited by LeftPos-RigtPos"

Evidence
[CV(RPF/RS-EPT-CBR)] cross validation(RPF/RS-EPT-CBR)
[ICWHO] Inferred computationally without human oversight
[IDA] Inferred from direct assay
[IEP] Inferred from expression pattern
[RPF] RNA polymerase footprinting
[RS-EPT-CBR] RNA-seq using two enrichment strategies for primary transcripts and consistent biological replicates
[GEA] Gene expression analysis
[APIORCISFBSCS] A person inferred or reviewed a computer inference of sequence function based on similarity to a consensus sequence.
[BPP] Binding of purified proteins
[SM] Site mutation

Reference(s)
[1] Nakabeppu Y., Miyata T., Kondo H., Iwanaga S., Sekiguchi M., 1984, Structure and expression of the alkA gene of Escherichia coli involved in adaptive response to alkylating agents., J Biol Chem 259(22):13730-6
[2] Volkert MR., 1988, Adaptive response of Escherichia coli to alkylation damage., Environ Mol Mutagen 11(2):241-55
[3] Huerta AM., Collado-Vides J., 2003, Sigma70 promoters in Escherichia coli: specific transcription in dense regions of overlapping promoter-like signals., J Mol Biol 333(2):261-78
[4] Lai CF., Ripperger J., Wang Y., Kim H., Hawley RB., Baumann H., 1999, The STAT3-independent signaling pathway by glycoprotein 130 in hepatic cells., J Biol Chem 274(12):7793-802
[5] Landini P., Busby SJ., 1999, The Escherichia coli Ada protein can interact with two distinct determinants in the sigma70 subunit of RNA polymerase according to promoter architecture: identification of the target of Ada activation at the alkA promoter., J Bacteriol 181(5):1524-9
[6] Landini P., Busby SJ., 1999, Expression of the Escherichia coli ada regulon in stationary phase: evidence for rpoS-dependent negative regulation of alkA transcription., J Bacteriol 181(21):6836-9
[7] Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muñiz-Rascado L, García-Sotelo JS, Weiss V, Solano-Lira H, Martínez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernández S, Alquicira-Hernández K, López-Fuentes A, Porrón-Sotelo L, Huerta AM, Bonavides-Martínez C, Balderas-Martínez YI, Pannier L, Olvera M, Labastida A, Jiménez-Jacinto V, Vega-Alvarado L, Del Moral-Chávez V, Hernández-Alvarez A, Morett E, Collado-Vides J., 2012, RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more., Nucleic Acids Res.
[8] Furuichi M., Yu CG., Anai M., Sakumi K., Sekiguchi M., 1992, Regulatory elements for expression of the alkA gene in response to alkylating agents., Mol Gen Genet 236(1):25-32
[9] Landini P., Gaal T., Ross W., Volkert MR., 1997, The RNA polymerase alpha subunit carboxyl-terminal domain is required for both basal and activated transcription from the alkA promoter., J Biol Chem 272(25):15914-9
[10] Saget BM., Shevell DE., Walker GC., 1995, Alteration of lysine 178 in the hinge region of the Escherichia coli ada protein interferes with activation of ada, but not alkA, transcription., J Bacteriol 177(5):1268-74
[11] Saget BM., Walker GC., 1994, The Ada protein acts as both a positive and a negative modulator of Escherichia coli's response to methylating agents., Proc Natl Acad Sci U S A 91(21):9730-4
[12] Sakumi K., Sekiguchi M., 1989, Regulation of expression of the ada gene controlling the adaptive response. Interactions with the ada promoter of the Ada protein and RNA polymerase., J Mol Biol 205(2):373-85
[13] Teo I., Sedgwick B., Kilpatrick MW., McCarthy TV., Lindahl T., 1986, The intracellular signal for induction of resistance to alkylating agents in E. coli., Cell 45(2):315-24
[14] Merino E, Yanofsky C., 2005, Transcription attenuation: a highly conserved regulatory strategy used by bacteria., Trends Genet. 2005 May;21(5):260-4.

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