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Protein

Bifunctional transcriptional activator/DNA repair enzyme Ada

Gene

ada

Organism
Escherichia coli (strain K12)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-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

  • bacterial-type RNA polymerase transcription factor activity, sequence-specific DNA binding Source: EcoCyc
  • methylated-DNA-[protein]-cysteine S-methyltransferase activity Source: EcoCyc
  • sequence-specific DNA binding Source: InterPro
  • zinc ion binding Source: EcoliWiki

GO - Biological processi

  • cellular response to DNA damage stimulus Source: EcoCyc
  • DNA dealkylation involved in DNA repair Source: EcoliWiki
  • DNA demethylation Source: EcoCyc
  • negative regulation of transcription, DNA-templated Source: EcoCyc
  • peptidyl-cysteine methylation Source: EcoCyc
  • positive regulation of transcription, DNA-templated Source: EcoCyc
  • transcription, DNA-templated Source: UniProtKB-KW

Keywordsi

Molecular functionActivator, DNA-binding, Methyltransferase, 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.
MINTiMINT-1310041.
STRINGi316385.ECDH10B_2370.

Structurei

Secondary structure

1354
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi4 – 6Combined sources3
Helixi9 – 17Combined sources9
Helixi21 – 23Combined sources3
Turni24 – 26Combined sources3
Beta strandi27 – 31Combined sources5
Turni32 – 34Combined sources3
Beta strandi36 – 38Combined sources3
Helixi49 – 51Combined sources3
Beta strandi52 – 57Combined sources6
Helixi58 – 63Combined sources6
Beta strandi67 – 69Combined sources3
Turni70 – 72Combined sources3
Beta strandi76 – 78Combined sources3
Helixi79 – 93Combined sources15
Beta strandi96 – 98Combined sources3
Helixi102 – 109Combined sources8
Helixi113 – 123Combined sources11
Helixi128 – 137Combined sources10
Turni142 – 144Combined sources3
Beta strandi190 – 196Combined sources7
Beta strandi199 – 205Combined sources7
Beta strandi207 – 217Combined sources11
Helixi219 – 229Combined sources11
Helixi240 – 254Combined sources15
Beta strandi255 – 257Combined sources3
Helixi270 – 279Combined sources10
Helixi290 – 296Combined sources7
Helixi303 – 311Combined sources9
Helixi321 – 323Combined sources3
Helixi338 – 348Combined sources11

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...

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.
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_domain.
IPR004026. Ada_DNA_repair_Zn-bd.
IPR016221. Bifunct_regulatory_prot_Ada.
IPR009057. Homeobox-like.
IPR018060. HTH_AraC.
IPR018062. HTH_AraC-typ_CS.
IPR001497. MethylDNA_cys_MeTrfase_AS.
IPR014048. MethylDNA_cys_MeTrfase_DNA-bd.
IPR008332. MethylG_MeTrfase_N.
IPR011991. WHTH_DNA-bd_dom.
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

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: August 30, 2017
This is version 183 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, Multifunctional enzyme, Reference proteome

Documents

  1. Escherichia coli
    Escherichia coli (strain K12): entries and cross-references to EcoGene
  2. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  3. SIMILARITY comments
    Index of protein domains and families