P06134 · ADA_ECOLI
- ProteinBifunctional transcriptional activator/DNA repair enzyme Ada
- Geneada
- StatusUniProtKB reviewed (Swiss-Prot)
- Organism
- Amino acids354 (go to sequence)
- Protein existenceEvidence at protein level
- Annotation score5/5
Function
function
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.
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.
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 activity
- (2'-deoxyribonucleoside 5'-methylphosphotriester)-DNA + L-cysteinyl-[protein] = 2'-deoxyribonucleotide-DNA + H+ + S-methyl-L-cysteinyl-[protein]
Cofactor
Note: Binds 1 zinc ion per subunit.
Features
Showing features for binding site, active site, dna binding, site.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Binding site | 34 | DNA (UniProtKB | ChEBI) | ||||
Sequence: T | ||||||
Active site | 38 | Nucleophile; methyl group acceptor from methylphosphotriester | ||||
Sequence: C | ||||||
Binding site | 38 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 42 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 43 | DNA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 45 | DNA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 67 | DNA (UniProtKB | ChEBI) | ||||
Sequence: R | ||||||
Binding site | 69 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
Binding site | 72 | Zn2+ (UniProtKB | ChEBI) | ||||
Sequence: C | ||||||
DNA binding | 102-121 | H-T-H motif | ||||
Sequence: LEALADQVAMSPFHLHRLFK | ||||||
Site | 128-129 | Cleavage | ||||
Sequence: PK | ||||||
Site | 178-179 | Cleavage | ||||
Sequence: KQ | ||||||
Active site | 321 | Nucleophile; methyl group acceptor from either O6-methylguanine or O4-methylthymine | ||||
Sequence: C |
GO annotations
Aspect | Term | |
---|---|---|
Molecular Function | DNA-binding transcription factor activity | |
Molecular Function | methylated-DNA-[protein]-cysteine S-methyltransferase activity | |
Molecular Function | sequence-specific DNA binding | |
Molecular Function | zinc ion binding | |
Biological Process | DNA alkylation repair | |
Biological Process | DNA damage response | |
Biological Process | methylation | |
Biological Process | negative regulation of DNA-templated transcription | |
Biological Process | positive regulation of DNA-templated transcription |
Keywords
- Molecular function
- Biological process
- Ligand
Enzyme and pathway databases
Names & Taxonomy
Protein names
- Recommended nameBifunctional transcriptional activator/DNA repair enzyme Ada
- Alternative names
Including 2 domains:
- Recommended nameMethylphosphotriester-DNA--protein-cysteine S-methyltransferase
- EC number
- Alternative names
- Recommended nameMethylated-DNA--protein-cysteine methyltransferase
- EC number
- Alternative names
Gene names
Organism names
- Organism
- Strains
- Taxonomic lineageBacteria > Pseudomonadota > Gammaproteobacteria > Enterobacterales > Enterobacteriaceae > Escherichia
Accessions
- Primary accessionP06134
- Secondary accessions
Proteomes
Phenotypes & Variants
Features
Showing features for natural variant.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Natural variant | 75 | in strain: B | ||||
Sequence: E → D | ||||||
Natural variant | 79-80 | in strain: B | ||||
Sequence: AQ → PR | ||||||
Natural variant | 318 | in strain: B | ||||
Sequence: I → V | ||||||
Natural variant | 330 | in strain: B | ||||
Sequence: T → S |
Variants
We now provide the "Disease & Variants" viewer in its own tab.
The viewer provides 4 variants from UniProt as well as other sources including ClinVar and dbSNP.
PTM/Processing
Features
Showing features for chain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Chain | PRO_0000018747 | 1-354 | Bifunctional transcriptional activator/DNA repair enzyme Ada | |||
Sequence: MKKATCLTDDQRWQSVLARDPNADGEFVFAVRTTGIFCRPSCRARHALRENVSFYANASEALAAGFRPCKRCQPEKANAQQHRLDKITHACRLLEQETPVTLEALADQVAMSPFHLHRLFKATTGMTPKAWQQAWRARRLRESLAKGESVTTSILNAGFPDSSSYYRKADETLGMTAKQFRHGGENLAVRYALADCELGRCLVAESERGICAILLGDDDATLISELQQMFPAADNAPADLMFQQHVREVIASLNQRDTPLTLPLDIRGTAFQQQVWQALRTIPCGETVSYQQLANAIGKPKAVRAVASACAANKLAIIIPCHRVVRGDGTLSGYRWGVSRKAQLLRREAENEER |
Proteomic databases
Expression
Induction
Up-regulated by methylated Ada itself in response to the exposure to alkylating agents.
Interaction
Binary interactions
Type | Entry 1 | Entry 2 | Number of experiments | Intact | |
---|---|---|---|---|---|
BINARY | P06134 | hda P69931 | 3 | EBI-1119501, EBI-545453 |
Protein-protein interaction databases
Structure
Family & Domains
Features
Showing features for region, domain.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Region | 1-171 | Methylphosphotriester-DNA--protein-cysteine methyltransferase | ||||
Sequence: MKKATCLTDDQRWQSVLARDPNADGEFVFAVRTTGIFCRPSCRARHALRENVSFYANASEALAAGFRPCKRCQPEKANAQQHRLDKITHACRLLEQETPVTLEALADQVAMSPFHLHRLFKATTGMTPKAWQQAWRARRLRESLAKGESVTTSILNAGFPDSSSYYRKADE | ||||||
Domain | 85-183 | HTH araC/xylS-type | ||||
Sequence: DKITHACRLLEQETPVTLEALADQVAMSPFHLHRLFKATTGMTPKAWQQAWRARRLRESLAKGESVTTSILNAGFPDSSSYYRKADETLGMTAKQFRHG | ||||||
Region | 181-354 | Methylated-DNA--protein-cysteine methyltransferase | ||||
Sequence: RHGGENLAVRYALADCELGRCLVAESERGICAILLGDDDATLISELQQMFPAADNAPADLMFQQHVREVIASLNQRDTPLTLPLDIRGTAFQQQVWQALRTIPCGETVSYQQLANAIGKPKAVRAVASACAANKLAIIIPCHRVVRGDGTLSGYRWGVSRKAQLLRREAENEER |
Domain
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.
Sequence similarities
In the C-terminal section; belongs to the MGMT family.
Phylogenomic databases
Family and domain databases
Sequence
- Sequence statusComplete
- Length354
- Mass (Da)39,324
- Last updated1994-02-01 v2
- Checksum4163E585C768C2F4
Features
Showing features for sequence conflict.
Type | ID | Position(s) | Description | |||
---|---|---|---|---|---|---|
Sequence conflict | 134 | in Ref. 1; AAA23412 | ||||
Sequence: A → R |
Keywords
- Technical term
Sequence databases
Nucleotide Sequence | Protein Sequence | Molecule Type | Status | |
---|---|---|---|---|
M10211 EMBL· GenBank· DDBJ | AAA23412.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M10315 EMBL· GenBank· DDBJ | AAA23413.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U00008 EMBL· GenBank· DDBJ | AAA16408.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
U00096 EMBL· GenBank· DDBJ | AAC75273.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
AP009048 EMBL· GenBank· DDBJ | BAA15996.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
J02607 EMBL· GenBank· DDBJ | AAA23415.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M13155 EMBL· GenBank· DDBJ | AAA23418.1 EMBL· GenBank· DDBJ | Genomic DNA | ||
M13828 EMBL· GenBank· DDBJ | AAA23417.1 EMBL· GenBank· DDBJ | Genomic DNA |