Transcription Factor

						

			
Accessions: ECK120004502 (RegulonDB 7.5)

			
Names: Ada, Ada DNA-binding transcriptional dual regulator
Organisms: ECK12
Libraries: RegulonDB 7.5 1
1 Salgado H, Peralta-Gil M, Gama-Castro S, Santos-Zavaleta A, Muniz-Rascado L, Garcia-Sotelo JS, Weiss V, Solano-Lira H, Martinez-Flores I, Medina-Rivera A, Salgado-Osorio G, Alquicira-Hernandez S, Alquicira-Hernandez K, Lopez-Fuentes A, Porron-Sotelo L, Huerta AM, Bonavides-Martinez C, Balderas-Martinez YI, Pannier L, Olvera M, Labastida A, Jimenez-Jacinto V, Vega-Alvarado L, Del Moral-Chavez V, Hernandez-Alvarez A, Morett E, Collado-Vides J. RegulonDB v8.0: omics data sets, evolutionary conservation, regulatory phrases, cross-validated gold standards and more. Nucleic Acids Res. 2013 Jan 1;41(D1):D203-D213. [Pubmed]
Notes: The transcription factor Ada, for Adaptive response to alkylation damage, is positively autoregulated Saget BM,1994; Nakamura T,1988and controls the transcription of the genes involved in the process of reparation of alkylated DNA Saget BM,1994; Landini P,1995; Volkert MR,1994; Nakabeppu Y,1986; Landini P,1999; Saget BM,1994 also called the adaptive response Takahashi K,1988; Nieminuszczy J,2007; Landini P,2000 O6-methylguanine and O4-methylthymine are the major mutagenic lesions resulting from exposure of DNA to simple alkylating agents such as N-methyl-N'-nitro-N-nitrosoguanidine (MNNG), N-methyl-N-nitrosourea (MNU) and, to a lesser degree, methane methanesulfonate (MMS) Takahashi K,1988; Saget BM,1994; Nieminuszczy J,2007 The O6-methylguanine and O4-methylthymine alkylation products constitute potentially mutagenic lesions due to their tendency to mispair with thymine and with guanine, respectively, forming transition mutations; In Escherichia coli there are two separate direct repair mechanisms 
for the reversal of these types of alkylating lesions through the involvement of two methyltransferases, Ada and Ogt Nieminuszczy J,2007This regulator contains two functional domains: an N-terminal domain, which contains a motif for DNA binding, and the C-terminal domain, which is involved in the interaction with the RNA polymerase Landini P,2000; Demple B,1985; Teo I,1984; Shevell DE,1991; Shevell DE,1988; Sakumi K,1993; Landini P,1998 This regulator removes methyl groups (as well as larger groups) from the guanine and thymine substrates and transfers them to its own cysteine residue (Cys-321) in the C-terminal domain; The Ada protein also transfers methyl groups to a second cysteine residue (Cys-69) in the N-terminal domain, from alkylphosphotriesters in DNA Lindahl T,1982; Landini P,2000; Sakashita H,1995; Yoshikai T,1988; Takano K,1988 This reaction converts the Ada protein into a strong transcriptional activator of several genes; This regulator acts as an activator by binding to cis-acting elements that 
overlap the upstream elements (UP) of the promoters regulated Landini P,1995; Sakumi K,1989A model of the mechanism of action of Ada has been proposed Landini P,2000; Landini P,1998The solution structure of the methylated N-terminal domain of Ada has been determined by NMR and mass spectrometry Takinowaki H,2006We have modified the reported length of the binding site of this protein to 13 bp, according to the proposal by Teo et al Teo I,1986; Other authors have proposed different lengths and consensus sequences for Ada Sakumi K,1989; Landini P,1995, but Nakamura et al showed that deletions in this consensus sequence (AAANNAAAGCGCA) decrease the activity of β-galactosidase Nakamura T,1988.; DNA repair; methylated-DNA—[protein]-cysteine S-methyltransferase; operon; activator; Transcription related; cytoplasm; methylation; metabolic process; sequence-specific DNA binding; transferase activity; zinc ion binding; methyltransferase activity; response to DNA damage stimulus; regulation of 
transcription, DNA-dependent; intracellular; catalytic activity; sequence-specific DNA binding transcription factor activity; DNA binding; methylated-DNA-[protein]-cysteine S-methyltransferase activity; transcription, DNA-dependent; transcription activator activity; transcription repressor activity; repressor
Length: 355
Pfam Domains:     10-75 Metal binding domain of Ada
   98-133 Bacterial regulatory helix-turn-helix proteins, AraC family
  105-182 Helix-turn-helix domain
  140-182 Bacterial regulatory helix-turn-helix proteins, AraC family
  189-266 6-O-methylguanine DNA methyltransferase, ribonuclease-like domain
  269-349 6-O-methylguanine DNA methyltransferase, DNA binding domain
Sequence: 
(in bold interface residues)		   1 MKKATCLTDDQRWQSVLARDPNADGEFVFAVRTTGIFCRPSCRARHALRENVSFYANASE   60
  61 ALAAGFRPCKRCQPEKANAQQHRLDKITHACRLLEQETPVTLEALADQVAMSPFHLHRLF  120
 121 KATTGMTPKAWQQAWRARRLRESLAKGESVTTSILNAGFPDSSSYYRKADETLGMTAKQF  180
 181 RHGGENLAVRYALADCELGRCLVAESERGICAILLGDDDATLISELQQMFPAADNAPADL  240
 241 MFQQHVREVIASLNQRDTPLTLPLDIRGTAFQQQVWQALRTIPCGETVSYQQLANAIGKP  300
 301 KAVRAVASACAANKLAIIIPCHRVVRGDGTLSGYRWGVSRKAQLLRREAENEER*
Interface Residues: 34, 44, 45, 71, 112, 114, 115, 117, 118, 121, 129, 163, 167, 171, 304, 305, 308
3D-footprint Homologues: 1zgw_A, 7vwz_G, 1xs9_A, 3gx4_X, 4wx9_A, 1yfh_A
Binding Motifs: Ada AMkbWWWdmSCAR
Binding Sites: ECK120012597
ECK120012905
ECK120012982
ECK125110266
			
Publications: Landini P., Busby SJ. 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 (1999). [Pubmed]


Landini P., Volkert MR. RNA polymerase alpha subunit binding site in positively controlled promoters: a new model for RNA polymerase-promoter interaction and transcriptional activation in the Escherichia coli ada and aidB genes. EMBO J. 14(17):4329-35 (1995). [Pubmed]


Nakabeppu Y., Sekiguchi M. Regulatory mechanisms for induction of synthesis of repair enzymes in response to alkylating agents: ada protein acts as a transcriptional regulator. Proc Natl Acad Sci U S A. 83(17):6297-301 (1986). [Pubmed]


Volkert MR., Hajec LI., Matijasevic Z., Fang FC., Prince R. Induction of the Escherichia coli aidB gene under oxygen-limiting conditions requires a functional rpoS (katF) gene. J Bacteriol. 176(24):7638-45 (1994). [Pubmed]


Landini P., Volkert MR. Transcriptional activation of the Escherichia coli adaptive response gene aidB is mediated by binding of methylated Ada protein. Evidence for a new consensus sequence for Ada-binding sites. J Biol Chem. 270(14):8285-9 (1995). [Pubmed]


Nakamura T., Tokumoto Y., Sakumi K., Koike G., Nakabeppu Y., Sekiguchi M. Expression of the ada gene of Escherichia coli in response to alkylating agents. Identification of transcriptional regulatory elements. J Mol Biol. 202(3):483-94 (1988). [Pubmed]


Saget BM., Walker GC. 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 (1994). [Pubmed]


Takahashi K., Kawazoe Y., Sakumi K., Nakabeppu Y., Sekiguchi M. Activation of Ada protein as a transcriptional regulator by direct alkylation with methylating agents. J Biol Chem. 263(27):13490-2 (1988). [Pubmed]


Teo I., Sedgwick B., Kilpatrick MW., McCarthy TV., Lindahl T. The intracellular signal for induction of resistance to alkylating agents in E. coli. Cell. 45(2):315-24 (1986). [Pubmed]


Takinowaki H., Matsuda Y., Yoshida T., Kobayashi Y., Ohkubo T. The solution structure of the methylated form of the N-terminal 16-kDa domain of Escherichia coli Ada protein. Protein Sci. 15(3):487-97 (2006). [Pubmed]


Sakumi K., Sekiguchi M. 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 (1989). [Pubmed]


Takano K., Nakabeppu Y., Sekiguchi M. Functional sites of the Ada regulatory protein of Escherichia coli. Analysis by amino acid substitutions. J Mol Biol. 201(2):261-71 (1988). [Pubmed]


Yoshikai T., Nakabeppu Y., Sekiguchi M. Proteolytic cleavage of Ada protein that carries methyltransferase and transcriptional regulator activities. J Biol Chem. 263(35):19174-80 (1988). [Pubmed]


Nieminuszczy J., Grzesiuk E. Bacterial DNA repair genes and their eukaryotic homologues: 3. AlkB dioxygenase and Ada methyltransferase in the direct repair of alkylated DNA. Acta Biochim Pol. 54(3):459-68 (2007). [Pubmed]


Landini P., Volkert MR. Regulatory responses of the adaptive response to alkylation damage: a simple regulon with complex regulatory features. J Bacteriol. 182(23):6543-9 (2000). [Pubmed]


Demple B., Sedgwick B., Robins P., Totty N., Waterfield MD., Lindahl T. Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis. Proc Natl Acad Sci U S A. 82(9):2688-92 (1985). [Pubmed]


Teo I., Sedgwick B., Demple B., Li B., Lindahl T. Induction of resistance to alkylating agents in E. coli: the ada+ gene product serves both as a regulatory protein and as an enzyme for repair of mutagenic damage. EMBO J. 3(9):2151-7 (1984). [Pubmed]


Shevell DE., Walker GC. A region of the Ada DNA-repair protein required for the activation of ada transcription is not necessary for activation of alkA. Proc Natl Acad Sci U S A. 88(20):9001-5 (1991). [Pubmed]


Shevell DE., LeMotte PK., Walker GC. Alteration of the carboxyl-terminal domain of Ada protein influences its inducibility, specificity, and strength as a transcriptional activator. J Bacteriol. 170(11):5263-71 (1988). [Pubmed]


Sakumi K., Igarashi K., Sekiguchi M., Ishihama A. The Ada protein is a class I transcription factor of Escherichia coli. J Bacteriol. 175(8):2455-7 (1993). [Pubmed]


Landini P., Bown JA., Volkert MR., Busby SJ. Ada protein-RNA polymerase sigma subunit interaction and alpha subunit-promoter DNA interaction are necessary at different steps in transcription initiation at the Escherichia coli Ada and aidB promoters. J Biol Chem. 273(21):13307-12 (1998). [Pubmed]


Lindahl T., Demple B., Robins P. Suicide inactivation of the E. coli O6-methylguanine-DNA methyltransferase. EMBO J. 1(11):1359-63 (1982). [Pubmed]


Sakashita H., Sakuma T., Akitomo Y., Ohkubo T., Kainosho M., Sekiguchi M., Morikawa K. Sequence-specific DNA recognition of the Escherichia coli Ada protein associated with the methylation-dependent functional switch for transcriptional regulation. J Biochem. 118(6):1184-91 (1995). [Pubmed]
Related annotations: PaperBLAST

	
			


			

				

				
				
				
				

			

			

		

	
Disclaimer and license


These data are available AS IS and at your own risk. The EEAD/CSIC do not give any representation or warranty nor assume any liability or responsibility for the data nor the results posted (whether as to their accuracy, completeness, quality or otherwise). Access to these data is available free of charge for ordinary use in the course of research. Downloaded data have CC-BY-NC-SA license. FootprintDB is also available at RSAT::Plants, part of the INB/ELIXIR-ES resources portfolio.