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UniProtKB/Swiss-Prot entry P06134


[Entry info] [Name and origin] [References] [Comments] [Cross-references] [Keywords] [Features] [Sequence] [Tools]

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Entry information
Entry name ADA_ECOLI
Primary accession number P06134
Secondary accession number Q47032
Integrated into Swiss-Prot on January 1, 1988
Sequence was last modified on February 1, 1994 (Sequence version 2)
Annotations were last modified on    November 4, 2008 (Entry version 104)
Name and origin of the protein
Protein name Regulatory protein ada
Synonym Regulatory protein of adaptative response
Contains Methylated-DNA--protein-cysteine methyltransferase
     (EC 2.1.1.63)
     (O-6-methylguanine-DNA alkyltransferase)
Gene name
Name: ada
OrderedLocusNames: b2213, JW2201
From
Escherichia coli (strain K12) [TaxID: 83333] [HAMAP proteome]
Taxonomy Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacteriales; Enterobacteriaceae; Escherichia.
Protein existence 1: Evidence at protein level;
References
[1]
NUCLEOTIDE SEQUENCE [GENOMIC DNA], AND PARTIAL PROTEIN SEQUENCE.
STRAIN=K12;
PubMed=2987251 [NCBI, ExPASy, EBI, Israel, Japan]
Nakabeppu Y., Kondo H., Kawabata S., Iwanaga S., Sekiguchi M.;
"Purification and structure of the intact Ada regulatory protein of Escherichia coli K12, O6-methylguanine-DNA methyltransferase.";
J. Biol. Chem. 260:7281-7288(1985).
[2]
NUCLEOTIDE SEQUENCE [GENOMIC DNA].
STRAIN=B;
PubMed=3887409 [NCBI, ExPASy, EBI, Israel, Japan]
Demple B., Sedgwick B., Robins P., Totty N., Waterfield M.D., Lindahl T.;
"Active site and complete sequence of the suicidal methyltransferase that counters alkylation mutagenesis.";
Proc. Natl. Acad. Sci. U.S.A. 82:2688-2692(1985).
[3]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=K12 / BHB2600;
Richterich P., Lakey N., Gryan G., Jaehn L., Mintz L., Robison K., Church G.M.;
"Automated multiplex sequencing of the E.coli genome.";
Submitted (OCT-1993) to the EMBL/GenBank/DDBJ databases.
[4]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
DOI=10.1093/dnares/3.6.379; PubMed=9097040 [NCBI, ExPASy, EBI, Israel, Japan]
Itoh T., Aiba H., Baba T., Fujita K., 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., Sivasundaram S., Tagami H., Takeda J., Takemoto K., Wada C., Yamamoto Y., Horiuchi T.;
"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(1996).
[5]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=K12 / MG1655 / ATCC 47076;
DOI=10.1126/science.277.5331.1453; PubMed=9278503 [NCBI, ExPASy, EBI, Israel, Japan]
Blattner F.R., Plunkett G. III, 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.;
"The complete genome sequence of Escherichia coli K-12.";
Science 277:1453-1474(1997).
[6]
NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
STRAIN=K12 / W3110 / ATCC 27325 / DSM 5911;
DOI=10.1038/msb4100049; PubMed=16738553 [NCBI, ExPASy, EBI, Israel, Japan]
Hayashi K., Morooka N., Yamamoto Y., Fujita K., Isono K., Choi S., Ohtsubo E., Baba T., Wanner B.L., Mori H., Horiuchi T.;
"Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110.";
Mol. Syst. Biol. 2:E1-E5(2006).
[7]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-49.
STRAIN=K12;
PubMed=2982792 [NCBI, ExPASy, EBI, Israel, Japan]
Lemotte P.K., Walker G.C.;
"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(1985).
[8]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 287-354.
PubMed=3536913 [NCBI, ExPASy, EBI, Israel, Japan]
Kondo H., Nakabeppu Y., Kataoka H., Kuhara S., Kawabata S., Sekiguchi M.;
"Structure and expression of the alkB gene of Escherichia coli related to the repair of alkylated DNA.";
J. Biol. Chem. 261:15772-15777(1986).
[9]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-29.
DOI=10.1016/0092-8674(86)90396-X; PubMed=3009022 [NCBI, ExPASy, EBI, Israel, Japan]
Teo I., Sedgwick B., Kilpatrick M.W., McCarthy T.V., Lindahl T.;
"The intracellular signal for induction of resistance to alkylating agents in E. coli.";
Cell 45:315-324(1986).
[10]
NUCLEOTIDE SEQUENCE [GENOMIC DNA] OF 1-27.
PubMed=3529081 [NCBI, ExPASy, EBI, Israel, Japan]
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. 83:6297-6301(1986).
[11]
ZINC-BINDING.
DOI=10.1021/bi00134a002; PubMed=1581309 [NCBI, ExPASy, EBI, Israel, Japan]
Myers L.C., Terranova M.P., Nash H.M., Markus M.A., Verdine G.L.;
"Zinc binding by the methylation signaling domain of the Escherichia coli Ada protein.";
Biochemistry 31:4541-4547(1992).
[12]
CHARACTERIZATION.
DOI=10.1093/nar/22.9.1613; PubMed=8202360 [NCBI, ExPASy, EBI, Israel, Japan]
Liem L.-K., Lim A., Li B.F.L.;
"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(1994).
[13]
STRUCTURE BY NMR OF 1-129.
DOI=10.1016/0014-5793(93)81351-Y; PubMed=8500619 [NCBI, ExPASy, EBI, Israel, Japan]
Sakashita H., Sakuma T., Ohkubo T., Kainosho M., Sakumi K., Sekiguchi M., Morikawa K.;
"Folding topology and DNA binding of the N-terminal fragment of Ada protein.";
FEBS Lett. 323:252-256(1993).
[14]
STRUCTURE BY NMR OF 1-92 IN COMPLEX WITH ZINC IONS.
PubMed=8395079 [NCBI, ExPASy, EBI, Israel, Japan]
Myers L.C., Terranova M.P., Ferentz A.E., Wagner G., Verdine G.L.;
"Repair of DNA methylphosphotriesters through a metalloactivated cysteine nucleophile.";
Science 261:1164-1167(1993).
[15]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 175-354.
STRAIN=B;
PubMed=8156986 [NCBI, ExPASy, EBI, Israel, Japan]
Moore M.H., Gulbis J.M., Dodson E.J., Demple B., Moody P.C.E.;
"Crystal structure of a suicidal DNA repair protein: the Ada O6-methylguanine-DNA methyltransferase from E. coli.";
EMBO J. 13:1495-1501(1994).
[16]
STRUCTURE BY NMR OF 1-92 IN COMPLEX WITH ZINC IONS, AND INTERACTION WITH DNA.
DOI=10.1021/bi002109p; PubMed=11284682 [NCBI, ExPASy, EBI, Israel, Japan]
Lin Y., Doetsch V., Wintner T., Peariso K., Myers L.C., Penner-Hahn J.E., Verdine G.L., Wagner G.;
"Structural basis for the functional switch of the E. coli Ada protein.";
Biochemistry 40:4261-4271(2001).
[17]
X-RAY CRYSTALLOGRAPHY (2.1 ANGSTROMS) OF 9-139 IN COMPLEX WITH DNA AND ZINC IONS, STRUCTURE BY NMR OF 9-139, MASS SPECTROMETRY, AND ACTIVE SITE.
DOI=10.1016/j.molcel.2005.08.013; PubMed=16209950 [NCBI, ExPASy, EBI, Israel, Japan]
He C., Hus J.-C., Sun L.J., Zhou P., Norman D.P.G., Doetsch V., Wei H., Gross J.D., Lane W.S., Wagner G., Verdine G.L.;
"A methylation-dependent electrostatic switch controls DNA repair and transcriptional activation by E. coli ada.";
Mol. Cell 20:117-129(2005).
[18]
STRUCTURE BY NMR OF 1-146 IN COMPLEX WITH ZINC IONS, MASS SPECTROMETRY, AND ACTIVE SITE.
DOI=10.1110/ps.051786306; PubMed=16452614 [NCBI, ExPASy, EBI, Israel, Japan]
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. 15:487-497(2006).
Comments
  • FUNCTION: Repair of alkylated guanine in DNA by stoichiometrically transferring the alkyl group at the O-6 position to a cysteine residue in the enzyme. This is a suicide reaction: the enzyme is irreversibly inactivated. Can also repair O-4-methylthymine.
  • 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.
  • CATALYTIC ACTIVITY: DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine.
  • COFACTOR: Binds 1 zinc ion per subunit.
  • SIMILARITY: In the C-terminal section; belongs to the MGMT family.
  • SIMILARITY: Contains 1 HTH araC/xylS-type DNA-binding domain.
Copyright
Copyrighted by the UniProt Consortium, see http://www.uniprot.org/terms. Distributed under the Creative Commons Attribution-NoDerivs License.
Cross-references
Sequence databases
EMBL
M10211; AAA23412.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M10315; AAA23413.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U00008; AAA16408.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
U00096; AAC75273.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
AP009048; BAA15996.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
J02607; AAA23415.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M13155; AAA23418.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
M13828; AAA23417.1; -; Genomic_DNA.[EMBL / GenBank / DDBJ] [CoDingSequence]
PIR C64991; XYECO2.
RefSeq AP_002809.1; -.
NP_416717.1; -.
3D structure databases
PDB
1ADN; NMR; -; A=1-92.[ExPASy / RCSB / EBI]
1EYF; NMR; -; A=1-92.[ExPASy / RCSB / EBI]
1SFE; X-ray; 2.10 A; A=175-354.[ExPASy / RCSB / EBI]
1U8B; X-ray; 2.10 A; A=9-139.[ExPASy / RCSB / EBI]
1WPK; NMR; -; A=1-146.[ExPASy / RCSB / EBI]
1ZGW; NMR; -; A=1-139.[ExPASy / RCSB / EBI]
Detailed list of linked structures.
PDBsum 1ADN; -.
1EYF; -.
1SFE; -.
1U8B; -.
1WPK; -.
1ZGW; -.
ModBase P06134.
Protein-protein interaction databases
DIP DIP:9055N; -.
Protein family/group databases
AraC-XylS P06134.
Enzyme and pathway databases
BioCyc EcoCyc:PD00230; -.
2D gel databases
ECO2DBASE I039.5; 6TH EDITION.
Organism-specific databases
EchoBASE EB0028; -.
EcoGene EG10029; ada.
Family and domain databases
InterPro IPR004026; Ada_DNA_repair_Zn-bd.
IPR016221; Bifunct_regulatory_prot_Ada.
IPR000005; HTHAraC.
IPR001497; MethylDNA_cys_MeTrfase_AS.
IPR014048; MethylDNA_cys_MeTrfase_DNA_bd.
IPR008332; MethylG_MeTrfase.
IPR011991; Wing_hlx_DNA_bd.
Graphical view of domain structure.
Gene3D G3DSA:3.40.10.10; Ada_DNA_repair_Zn-bd; 1.
G3DSA:1.10.10.10; Wing_hlx_DNA_bd; 1.
PANTHER PTHR10815; MethylDNA_cys_mtrans_DNA_bd; 1.
Pfam PF02805; Ada_Zn_binding; 1.
PF01035; DNA_binding_1; 1.
PF00165; HTH_AraC; 2.
PF02870; Methyltransf_1N; 1.
Pfam graphical view of domain structure.
PIRSF PIRSF000409; Ada; 1.
PRINTS PR00032; HTHARAC.
SMART SM00342; HTH_ARAC; 1.
SMART graphical view of domain structure.
TIGRFAMs TIGR00589; ogt; 1.
PROSITE PS00041; HTH_ARAC_FAMILY_1; 2.
PS01124; HTH_ARAC_FAMILY_2; 1.
PS00374; MGMT; 1.
PROSITE graphical view of domain structure (profiles).
BLOCKS P06134.
ProtoNet P06134.
Other
SWISS-3DIMAGE P06134.
Genome annotation databases
GeneID 946710; -.
GenomeReviews U00096_GR; b2213.
AP009048_GR; JW2201.
KEGG ecj:JW2201; -.
eco:b2213; -.
Phylogenomic databases
HOGENOM P06134; -.
Other
LinkHub P06134; -.
Genome annotation databases
CMR P06134; b2213.
Other
UniRef View cluster of proteins with at least 50% / 90% / 100% identity.
Keywords
3D-structure; Activator; Complete proteome; Direct protein sequencing; DNA damage; DNA repair; DNA-binding; Metal-binding; Methyltransferase; Transcription; Transcription regulation; Transferase; Zinc.
Features
SEVIEWER logo Feature table viewer FT aligner logo Feature aligner
KeyFrom   To Length Description FTId
CHAIN   1   354  354     Regulatory protein ada. PRO_0000018747
CHAIN   179   354  176     Methylated-DNA--protein-cysteine methyltransferase. PRO_0000018748
DNA_BIND   102   121  20     H-T-H motif. 
ACT_SITE   38    38        Nucleophile; methyl group acceptor from phosphotriester. 
ACT_SITE   321   321        Nucleophile; methyl group acceptor. 
METAL   38    38        Zinc. 
METAL   42    42        Zinc. 
METAL   69    69        Zinc. 
METAL   72    72        Zinc. 
BINDING   34    34        DNA. 
BINDING   43    43        DNA. 
BINDING   45    45        DNA. 
BINDING   67    67        DNA. 
SITE   128   129  2     Cleavage. 
SITE   178   179  2     Cleavage. 
VARIANT   75    75  1     E -> D (in strain: B). 
VARIANT   79    80  2     AQ -> PR (in strain: B). 
VARIANT   318   318  1     I -> V (in strain: B). 
VARIANT   330   330  1     T -> S (in strain: B). 
CONFLICT   134   134        A -> R (in Ref. 1; AAA23412). 
HELIX   9    17  9      
TURN   24    26  3      
STRAND   28    31  4      
TURN   32    34  3      
STRAND   36    38  3      
HELIX   49    51  3      
STRAND   52    57  6      
HELIX   58    63  6      
TURN   70    72  3      
STRAND   79    81  3      
STRAND   190   196  7      
STRAND   199   205  7      
STRAND   207   217  11      
HELIX   219   229  11      
HELIX   240   254  15      
STRAND   255   257  3      
HELIX   270   279  10      
HELIX   290   296  7      
HELIX   303   311  9      
HELIX   321   323  3      
HELIX   338   348  11      
Sequence information
Length: 354 AA [This is the length of the unprocessed precursor] Molecular weight: 39324 Da [This is the MW of the unprocessed precursor] CRC64: 4163E585C768C2F4 [This is a checksum on the sequence]
        10         20         30         40         50         60 
MKKATCLTDD QRWQSVLARD PNADGEFVFA VRTTGIFCRP SCRARHALRE NVSFYANASE 

        70         80         90        100        110        120 
ALAAGFRPCK RCQPEKANAQ QHRLDKITHA CRLLEQETPV TLEALADQVA MSPFHLHRLF 

       130        140        150        160        170        180 
KATTGMTPKA WQQAWRARRL RESLAKGESV TTSILNAGFP DSSSYYRKAD ETLGMTAKQF 

       190        200        210        220        230        240 
RHGGENLAVR YALADCELGR CLVAESERGI CAILLGDDDA TLISELQQMF PAADNAPADL 

       250        260        270        280        290        300 
MFQQHVREVI ASLNQRDTPL TLPLDIRGTA FQQQVWQALR TIPCGETVSY QQLANAIGKP 

       310        320        330        340        350 
KAVRAVASAC AANKLAIIIP CHRVVRGDGT LSGYRWGVSR KAQLLRREAE NEER 

P06134 in FASTA format

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