Identification
Name:Regulatory protein ada
Synonyms:
  • Regulatory protein of adaptative response
  • Methylated-DNA--protein-cysteine methyltransferase
  • O-6-methylguanine-DNA alkyltransferase
Gene Name:ada
Enzyme Class:
Biological Properties
General Function:Nucleotide transport and metabolism
Specific Function:The methylated ADA protein acts as a positive regulator of its own synthesis, as well as that of other proteins. The transcription-activating function of the ADA protein resides in its N-terminus. It activates the transcription of alkA, alkB and aidB
Cellular Location:Cytoplasmic
SMPDB Pathways:Not Available
KEGG Pathways:Not Available
KEGG Reactions:
1.0DNA containing 6-O-methylguanine+1.0Protein L-cysteine1.0DNA+1.0Protein S-methyl-L-cysteine
1.0DNA containing 6-O-methylguanine + 1.0Protein L-cysteine ↔ 1.0DNA + 1.0Protein S-methyl-L-cysteine
ReactionCard
Complex Reactions:
1.0DNA (containing Sp-methylphosphotriester)+1.0protein L-cysteine1.0DNA (without Sp-methylphosphotriester)+1.0protein S-methyl-L-cysteine
1.0DNA (containing Sp-methylphosphotriester) + 1.0protein L-cysteine → 1.0DNA (without Sp-methylphosphotriester) + 1.0protein S-methyl-L-cysteine
ReactionCard
Metabolites:
ECMDB IDNameView
GO Classification:
Component
cell part
intracellular
Function
binding
catalytic activity
cation binding
DNA binding
ion binding
metal ion binding
methylated-DNA-[protein]-cysteine S-methyltransferase activity
methyltransferase activity
nucleic acid binding
S-methyltransferase activity
sequence-specific DNA binding
sequence-specific DNA binding transcription factor activity
transferase activity
transferase activity, transferring one-carbon groups
transition metal ion binding
zinc ion binding
Process
biological regulation
cellular macromolecule metabolic process
DNA metabolic process
DNA repair
macromolecule metabolic process
metabolic process
regulation of biological process
regulation of gene expression
regulation of macromolecule metabolic process
regulation of metabolic process
regulation of transcription
regulation of transcription, DNA-dependent
Gene Properties
Blattner:Not Available
Gene OrientationNot Available
Centisome Percentage:Not Available
Left Sequence EndNot Available
Right Sequence EndNot Available
Gene Sequence:
>1065 bp
ATGAAAAAAGCCACATGCTTAACTGACGATCAACGCTGGCAATCTGTCTTAGCCCGCGAC
CCGAATGCCGACGGCGAATTCGTTTTCGCCGTGCGTACCACAGGCATCTTTTGCCGTCCG
TCTTGCCGCGCCAGACATGCTTTGCGGGAAAACGTCTCCTTCTACGCAAATGCCAGCGAG
GCACTCGCCGCTGGCTTTCGCCCCTGCAAACGTTGTCAGCCAGAAAAAGCCAATGCCCAG
CAACATCGGTTGGATAAAATCACCCACGCGTGTCGACTGCTGGAACAGGAAACGCCTGTA
ACGCTGGAAGCCTTAGCCGACCAGGTGGCGATGAGTCCATTTCATCTACATCGGTTGTTT
AAAGCGACTACCGGAATGACGCCTAAAGCCTGGCAACAGCGCTGGCGCGCTCGCCGTTTG
CGCGAATCGCTGGCGAAAGGGGAGAGCGTGACGACGTCTATTCTTAACGCCGGATTCCCC
GACAGCAGCAGTTACTATCGCAAAGCTGACGAAACGCTGGGCATGACGGCTAAACAATTC
CGTCACGGTGGCGAAAATCTGGCGGTGCGTTACGCGCTGGCTGATTGTGAGCTGGGTCGT
TGCCTGGTGGCAGAAAGCGAGCGGGGGATTTGCGCGATATTGCTGGGCGATGATGACGCG
ACACTAATCAGCGAGTTGCAGCAGATGTTTCCCGCTGCCGACAACGCGCCTGCCGATCTG
ATGTTTCAGCAACATGTGCGTGAAGTGATCGCCAGCCTCAATCAACGCGATACGCCGCTG
ACGTTACCGCTGGACATTCGCGGCACTGCTTTTCAGCAACAAGTCTGGCAGGCACTGCGC
ACGATACCTTGCGGTGAAACCGTCAGTTATCAGCAACTGGCTAACGCCATCGGCAAACCG
AAAGCGGTACGGGCCGTTGCCAGCGCCTGTGCCGCCAACAAGCTGGCTATCATAATACCC
TGTCATCGGGTGGTCCGTGGTGATGGCACACTTTCCGGTTACCGCTGGGGCGTGTCGCGT
AAAGCGCAACTGCTGCGCCGCGAAGCTGAAAATGAGGAGAGGTAA
Protein Properties
Pfam Domain Function:
Protein Residues:354
Protein Molecular Weight:39323
Protein Theoretical pI:9
PDB File:1SFE
Signaling Regions:
  • None
Transmembrane Regions:
  • None
Protein Sequence:
>Regulatory protein ada
MKKATCLTDDQRWQSVLARDPNADGEFVFAVRTTGIFCRPSCRARHALRENVSFYANASE
ALAAGFRPCKRCQPEKANAQQHRLDKITHACRLLEQETPVTLEALADQVAMSPFHLHRLF
KATTGMTPKAWQQAWRARRLRESLAKGESVTTSILNAGFPDSSSYYRKADETLGMTAKQF
RHGGENLAVRYALADCELGRCLVAESERGICAILLGDDDATLISELQQMFPAADNAPADL
MFQQHVREVIASLNQRDTPLTLPLDIRGTAFQQQVWQALRTIPCGETVSYQQLANAIGKP
KAVRAVASACAANKLAIIIPCHRVVRGDGTLSGYRWGVSRKAQLLRREAENEER
References
External Links:
ResourceLink
Uniprot ID:P06134
Uniprot Name:ADA_ECOLI
GenBank Gene ID:M10211
Genebank Protein ID:145189
PDB ID:1SFE
CCDB:ADA_ECOLI
General Reference:
  • Blattner, F. R., Plunkett, G. 3rd, Bloch, C. A., Perna, N. T., Burland, V., Riley, M., Collado-Vides, J., Glasner, J. D., Rode, C. K., Mayhew, G. F., Gregor, J., Davis, N. W., Kirkpatrick, H. A., Goeden, M. A., Rose, D. J., Mau, B., Shao, Y. (1997). "The complete genome sequence of Escherichia coli K-12." Science 277:1453-1462. Pubmed: 9278503
  • Demple, B., Sedgwick, B., Robins, P., Totty, N., Waterfield, M. D., Lindahl, T. (1985). "Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis." Proc Natl Acad Sci U S A 82:2688-2692. Pubmed: 3887409
  • Hayashi, K., Morooka, N., Yamamoto, Y., Fujita, K., Isono, K., Choi, S., Ohtsubo, E., Baba, T., Wanner, B. L., Mori, H., Horiuchi, T. (2006). "Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110." Mol Syst Biol 2:2006.0007. Pubmed: 16738553
  • He, C., Hus, J. C., Sun, L. J., Zhou, P., Norman, D. P., Dotsch, V., Wei, H., Gross, J. D., Lane, W. S., Wagner, G., Verdine, G. L. (2005). "A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada." Mol Cell 20:117-129. Pubmed: 16209950
  • Itoh, T., Aiba, H., Baba, T., Hayashi, K., Inada, T., Isono, K., Kasai, H., Kimura, S., Kitakawa, M., Kitagawa, M., Makino, K., Miki, T., Mizobuchi, K., Mori, H., Mori, T., Motomura, K., Nakade, S., Nakamura, Y., Nashimoto, H., Nishio, Y., Oshima, T., Saito, N., Sampei, G., Seki, Y., Horiuchi, T., et, a. l. .. (1996). "A 460-kb DNA sequence of the Escherichia coli K-12 genome corresponding to the 40.1-50.0 min region on the linkage map." DNA Res 3:379-392. Pubmed: 9097040
  • Kondo, H., Nakabeppu, Y., Kataoka, H., Kuhara, S., Kawabata, S., Sekiguchi, M. (1986). "Structure and expression of the alkB gene of Escherichia coli related to the repair of alkylated DNA." J Biol Chem 261:15772-15777. Pubmed: 3536913
  • Lemotte, P. K., Walker, G. C. (1985). "Induction and autoregulation of ada, a positively acting element regulating the response of Escherichia coli K-12 to methylating agents." J Bacteriol 161:888-895. Pubmed: 2982792
  • Liem, L. K., Lim, A., Li, B. F. (1994). "Specificities of human, rat and E. coli O6-methylguanine-DNA methyltransferases towards the repair of O6-methyl and O6-ethylguanine in DNA." Nucleic Acids Res 22:1613-1619. Pubmed: 8202360
  • Lin, Y., Dotsch, V., Wintner, T., Peariso, K., Myers, L. C., Penner-Hahn, J. E., Verdine, G. L., Wagner, G. (2001). "Structural basis for the functional switch of the E. coli Ada protein." Biochemistry 40:4261-4271. Pubmed: 11284682
  • Moore, M. H., Gulbis, J. M., Dodson, E. J., Demple, B., Moody, P. C. (1994). "Crystal structure of a suicidal DNA repair protein: the Ada O6-methylguanine-DNA methyltransferase from E. coli." EMBO J 13:1495-1501. Pubmed: 8156986
  • Myers, L. C., Terranova, M. P., Ferentz, A. E., Wagner, G., Verdine, G. L. (1993). "Repair of DNA methylphosphotriesters through a metalloactivated cysteine nucleophile." Science 261:1164-1167. Pubmed: 8395079
  • Myers, L. C., Terranova, M. P., Nash, H. M., Markus, M. A., Verdine, G. L. (1992). "Zinc binding by the methylation signaling domain of the Escherichia coli Ada protein." Biochemistry 31:4541-4547. Pubmed: 1581309
  • Nakabeppu, Y., Kondo, H., Kawabata, S., Iwanaga, S., Sekiguchi, M. (1985). "Purification and structure of the intact Ada regulatory protein of Escherichia coli K12, O6-methylguanine-DNA methyltransferase." J Biol Chem 260:7281-7288. Pubmed: 2987251
  • Nakabeppu, Y., Sekiguchi, M. (1986). "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 83:6297-6301. Pubmed: 3529081
  • Sakashita, H., Sakuma, T., Ohkubo, T., Kainosho, M., Sakumi, K., Sekiguchi, M., Morikawa, K. (1993). "Folding topology and DNA binding of the N-terminal fragment of Ada protein." FEBS Lett 323:252-256. Pubmed: 8500619
  • Takinowaki, H., Matsuda, Y., Yoshida, T., Kobayashi, Y., Ohkubo, T. (2006). "The solution structure of the methylated form of the N-terminal 16-kDa domain of Escherichia coli Ada protein." Protein Sci 15:487-497. Pubmed: 16452614
  • Teo, I., Sedgwick, B., Kilpatrick, M. W., McCarthy, T. V., Lindahl, T. (1986). "The intracellular signal for induction of resistance to alkylating agents in E. coli." Cell 45:315-324. Pubmed: 3009022