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Protein

Bifunctional transcriptional activator/DNA repair enzyme Ada

Gene

ada

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: -Experimental evidence at protein leveli

Functioni

Involved in the adaptive response to alkylation damage in DNA caused by alkylating agents. Repairs O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in DNA. Repairs the methylated nucleobase in DNA by stoichiometrically transferring the methyl group to a cysteine residue in the enzyme (Cys-321). Also specifically repairs the Sp diastereomer of DNA methylphosphotriester lesions by the same mechanism, although the methyl transfer occurs onto a different cysteine residue (Cys-38). Cannot demethylate the other diastereomer, Rp-methylphosphotriester. This is a suicide reaction: the enzyme is irreversibly inactivated.1 Publication
The methylation of Ada by methylphosphotriesters in DNA leads to its activation as a transcriptional regulator that activates the transcription of its own gene, ada, and other alkylation resistance genes, alkA, alkB and aidB.1 Publication

Miscellaneous

This enzyme catalyzes only one turnover and therefore is not strictly catalytic. According to one definition, an enzyme is a biocatalyst that acts repeatedly and over many reaction cycles.

Catalytic activityi

DNA (containing Sp-methylphosphotriester) + protein L-cysteine = DNA (without Sp-methylphosphotriester) + protein S-methyl-L-cysteine.1 Publication
DNA (containing 6-O-methylguanine) + protein L-cysteine = DNA (without 6-O-methylguanine) + protein S-methyl-L-cysteine.PROSITE-ProRule annotation1 Publication
DNA (containing 4-O-methylthymine) + protein L-cysteine = DNA (without 4-O-methylthymine) + protein S-methyl-L-cysteine.PROSITE-ProRule annotation1 Publication

Cofactori

Zn2+Note: Binds 1 zinc ion per subunit.

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei34DNA1 Publication1
Active sitei38Nucleophile; methyl group acceptor from methylphosphotriesterPROSITE-ProRule annotation1 Publication1
Metal bindingi38Zinc1
Metal bindingi42Zinc1
Binding sitei43DNA1 Publication1
Binding sitei45DNA1 Publication1
Binding sitei67DNA1 Publication1
Metal bindingi69Zinc1
Metal bindingi72Zinc1
Active sitei321Nucleophile; methyl group acceptor from either O6-methylguanine or O4-methylthyminePROSITE-ProRule annotation1 Publication1

Regions

Feature keyPosition(s)DescriptionActionsGraphical viewLength
DNA bindingi102 – 121H-T-H motifPROSITE-ProRule annotationAdd BLAST20

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionActivator, DNA-binding, Methyltransferase, Multifunctional enzyme, Transferase
Biological processDNA damage, DNA repair, Transcription, Transcription regulation
LigandMetal-binding, Zinc

Enzyme and pathway databases

BioCyciEcoCyc:PD00230
MetaCyc:PD00230

Names & Taxonomyi

Protein namesi
Recommended name:
Bifunctional transcriptional activator/DNA repair enzyme Ada
Alternative name(s):
Regulatory protein of adaptive response
Including the following 2 domains:
Methylphosphotriester-DNA--protein-cysteine S-methyltransferase (EC:2.1.1.n111 Publication)
Alternative name(s):
Methylphosphotriester-DNA methyltransferase
Methylated-DNA--protein-cysteine methyltransferase (EC:2.1.1.631 Publication)
Alternative name(s):
O6-methylguanine-DNA alkyltransferase
Gene namesi
Name:ada
Ordered Locus Names:b2213, JW2201
OrganismiEscherichia coli (strain K12)
Taxonomic identifieri83333 [NCBI]
Taxonomic lineageiBacteriaProteobacteriaGammaproteobacteriaEnterobacteralesEnterobacteriaceaeEscherichia
Proteomesi
  • UP000000318 Componenti: Chromosome
  • UP000000625 Componenti: Chromosome

Organism-specific databases

EcoGeneiEG10029 ada

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000187471 – 354Bifunctional transcriptional activator/DNA repair enzyme AdaAdd BLAST354

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sitei128 – 129Cleavage2
Sitei178 – 179Cleavage2

Proteomic databases

PaxDbiP06134
PRIDEiP06134

Expressioni

Inductioni

Up-regulated by methylated Ada itself in response to the exposure to alkylating agents.

Interactioni

Binary interactionsi

WithEntry#Exp.IntActNotes
hdaP699313EBI-1119501,EBI-545453

Protein-protein interaction databases

BioGridi4261923, 99 interactors
DIPiDIP-9055N
IntActiP06134, 13 interactors
STRINGi316385.ECDH10B_2370

Structurei

Secondary structure

1354
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details

3D structure databases

ProteinModelPortaliP06134
SMRiP06134
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP06134

Family & Domainsi

Domains and Repeats

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Domaini85 – 183HTH araC/xylS-typePROSITE-ProRule annotationAdd BLAST99

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 171Methylphosphotriester-DNA--protein-cysteine methyltransferaseAdd BLAST171
Regioni181 – 354Methylated-DNA--protein-cysteine methyltransferaseAdd BLAST174

Domaini

Consists of two domains. The 20 kDa N-terminal domain repairs the Sp diastereomer of methylphosphotriesters and, in its methylated form, binds DNA in a sequence-specific manner. The 19 kDa C-terminal domain repairs the mutagenic lesions O6-methylguanine. Each domain retains its activity when separated form the other.1 Publication

Sequence similaritiesi

In the C-terminal section; belongs to the MGMT family.Curated

Phylogenomic databases

eggNOGiENOG4105K85 Bacteria
COG0350 LUCA
COG2169 LUCA
HOGENOMiHOG000244139
InParanoidiP06134
KOiK10778
OMAiKTTGVYC
PhylomeDBiP06134

Family and domain databases

CDDicd06445 ATase, 1 hit
Gene3Di1.10.10.10, 1 hit
3.40.10.10, 1 hit
InterProiView protein in InterPro
IPR035451 Ada-like_dom_sf
IPR004026 Ada_DNA_repair_Zn-bd
IPR016221 Bifunct_regulatory_prot_Ada
IPR009057 Homeobox-like_sf
IPR018060 HTH_AraC
IPR018062 HTH_AraC-typ_CS
IPR001497 MethylDNA_cys_MeTrfase_AS
IPR014048 MethylDNA_cys_MeTrfase_DNA-bd
IPR036217 MethylDNA_cys_MeTrfase_DNAb
IPR008332 MethylG_MeTrfase_N
IPR036631 MGMT_N_sf
IPR036388 WH-like_DNA-bd_sf
PfamiView protein in Pfam
PF02805 Ada_Zn_binding, 1 hit
PF01035 DNA_binding_1, 1 hit
PF12833 HTH_18, 1 hit
PF02870 Methyltransf_1N, 1 hit
PIRSFiPIRSF000409 Ada, 1 hit
SMARTiView protein in SMART
SM00342 HTH_ARAC, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
SSF46767 SSF46767, 1 hit
SSF53155 SSF53155, 1 hit
SSF57884 SSF57884, 1 hit
TIGRFAMsiTIGR00589 ogt, 1 hit
PROSITEiView protein in PROSITE
PS00041 HTH_ARAC_FAMILY_1, 2 hits
PS01124 HTH_ARAC_FAMILY_2, 1 hit
PS00374 MGMT, 1 hit

Sequencei

Sequence statusi: Complete.

P06134-1 [UniParc]FASTAAdd to basket
« Hide
        10         20         30         40         50
MKKATCLTDD QRWQSVLARD PNADGEFVFA VRTTGIFCRP SCRARHALRE
60 70 80 90 100
NVSFYANASE ALAAGFRPCK RCQPEKANAQ QHRLDKITHA CRLLEQETPV
110 120 130 140 150
TLEALADQVA MSPFHLHRLF KATTGMTPKA WQQAWRARRL RESLAKGESV
160 170 180 190 200
TTSILNAGFP DSSSYYRKAD ETLGMTAKQF RHGGENLAVR YALADCELGR
210 220 230 240 250
CLVAESERGI CAILLGDDDA TLISELQQMF PAADNAPADL MFQQHVREVI
260 270 280 290 300
ASLNQRDTPL TLPLDIRGTA FQQQVWQALR TIPCGETVSY QQLANAIGKP
310 320 330 340 350
KAVRAVASAC AANKLAIIIP CHRVVRGDGT LSGYRWGVSR KAQLLRREAE

NEER
Length:354
Mass (Da):39,324
Last modified:February 1, 1994 - v2
Checksum:i4163E585C768C2F4
GO

Experimental Info

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Sequence conflicti134A → R in AAA23412 (PubMed:2987251).Curated1

Natural variant

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Natural varianti75E → D in strain: B. 1
Natural varianti79 – 80AQ → PR in strain: B. 2
Natural varianti318I → V in strain: B. 1
Natural varianti330T → S in strain: B. 1

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M10211 Genomic DNA Translation: AAA23412.1
M10315 Genomic DNA Translation: AAA23413.1
U00008 Genomic DNA Translation: AAA16408.1
U00096 Genomic DNA Translation: AAC75273.1
AP009048 Genomic DNA Translation: BAA15996.1
J02607 Genomic DNA Translation: AAA23415.1
M13155 Genomic DNA Translation: AAA23418.1
M13828 Genomic DNA Translation: AAA23417.1
PIRiC64991 XYECO2
RefSeqiNP_416717.1, NC_000913.3
WP_000710375.1, NZ_LN832404.1

Genome annotation databases

EnsemblBacteriaiAAC75273; AAC75273; b2213
BAA15996; BAA15996; BAA15996
GeneIDi946710
KEGGiecj:JW2201
eco:b2213
PATRICifig|1411691.4.peg.22

Similar proteinsi

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
M10211 Genomic DNA Translation: AAA23412.1
M10315 Genomic DNA Translation: AAA23413.1
U00008 Genomic DNA Translation: AAA16408.1
U00096 Genomic DNA Translation: AAC75273.1
AP009048 Genomic DNA Translation: BAA15996.1
J02607 Genomic DNA Translation: AAA23415.1
M13155 Genomic DNA Translation: AAA23418.1
M13828 Genomic DNA Translation: AAA23417.1
PIRiC64991 XYECO2
RefSeqiNP_416717.1, NC_000913.3
WP_000710375.1, NZ_LN832404.1

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB entryMethodResolution (Å)ChainPositionsPDBsum
1ADNNMR-A1-92[»]
1EYFNMR-A1-92[»]
1SFEX-ray2.10A175-354[»]
1U8BX-ray2.10A9-139[»]
1WPKNMR-A1-146[»]
1ZGWNMR-A1-139[»]
ProteinModelPortaliP06134
SMRiP06134
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi4261923, 99 interactors
DIPiDIP-9055N
IntActiP06134, 13 interactors
STRINGi316385.ECDH10B_2370

Proteomic databases

PaxDbiP06134
PRIDEiP06134

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsemblBacteriaiAAC75273; AAC75273; b2213
BAA15996; BAA15996; BAA15996
GeneIDi946710
KEGGiecj:JW2201
eco:b2213
PATRICifig|1411691.4.peg.22

Organism-specific databases

EchoBASEiEB0028
EcoGeneiEG10029 ada

Phylogenomic databases

eggNOGiENOG4105K85 Bacteria
COG0350 LUCA
COG2169 LUCA
HOGENOMiHOG000244139
InParanoidiP06134
KOiK10778
OMAiKTTGVYC
PhylomeDBiP06134

Enzyme and pathway databases

BioCyciEcoCyc:PD00230
MetaCyc:PD00230

Miscellaneous databases

EvolutionaryTraceiP06134
PROiPR:P06134

Family and domain databases

CDDicd06445 ATase, 1 hit
Gene3Di1.10.10.10, 1 hit
3.40.10.10, 1 hit
InterProiView protein in InterPro
IPR035451 Ada-like_dom_sf
IPR004026 Ada_DNA_repair_Zn-bd
IPR016221 Bifunct_regulatory_prot_Ada
IPR009057 Homeobox-like_sf
IPR018060 HTH_AraC
IPR018062 HTH_AraC-typ_CS
IPR001497 MethylDNA_cys_MeTrfase_AS
IPR014048 MethylDNA_cys_MeTrfase_DNA-bd
IPR036217 MethylDNA_cys_MeTrfase_DNAb
IPR008332 MethylG_MeTrfase_N
IPR036631 MGMT_N_sf
IPR036388 WH-like_DNA-bd_sf
PfamiView protein in Pfam
PF02805 Ada_Zn_binding, 1 hit
PF01035 DNA_binding_1, 1 hit
PF12833 HTH_18, 1 hit
PF02870 Methyltransf_1N, 1 hit
PIRSFiPIRSF000409 Ada, 1 hit
SMARTiView protein in SMART
SM00342 HTH_ARAC, 1 hit
SUPFAMiSSF46689 SSF46689, 1 hit
SSF46767 SSF46767, 1 hit
SSF53155 SSF53155, 1 hit
SSF57884 SSF57884, 1 hit
TIGRFAMsiTIGR00589 ogt, 1 hit
PROSITEiView protein in PROSITE
PS00041 HTH_ARAC_FAMILY_1, 2 hits
PS01124 HTH_ARAC_FAMILY_2, 1 hit
PS00374 MGMT, 1 hit
ProtoNetiSearch...

Entry informationi

Entry nameiADA_ECOLI
AccessioniPrimary (citable) accession number: P06134
Secondary accession number(s): Q47032
Entry historyiIntegrated into UniProtKB/Swiss-Prot: January 1, 1988
Last sequence update: February 1, 1994
Last modified: March 28, 2018
This is version 187 of the entry and version 2 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programProkaryotic Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

3D-structure, Complete proteome, Direct protein sequencing, Reference proteome

Documents

  1. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  2. SIMILARITY comments
    Index of protein domains and families
  3. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
UniProt is an ELIXIR core data resource
Main funding by: National Institutes of Health

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