ADA_SALTY
ID ADA_SALTY Reviewed; 353 AA.
AC P26189;
DT 01-MAY-1992, integrated into UniProtKB/Swiss-Prot.
DT 23-JAN-2002, sequence version 2.
DT 03-AUG-2022, entry version 156.
DE RecName: Full=Regulatory protein ada;
DE AltName: Full=Regulatory protein of adaptive response;
DE Contains:
DE RecName: Full=Methylated-DNA--protein-cysteine methyltransferase;
DE EC=2.1.1.63 {ECO:0000250|UniProtKB:P06134};
DE AltName: Full=O-6-methylguanine-DNA alkyltransferase;
GN Name=ada; OrderedLocusNames=STM2265;
OS Salmonella typhimurium (strain LT2 / SGSC1412 / ATCC 700720).
OC Bacteria; Proteobacteria; Gammaproteobacteria; Enterobacterales;
OC Enterobacteriaceae; Salmonella.
OX NCBI_TaxID=99287;
RN [1]
RP NUCLEOTIDE SEQUENCE [GENOMIC DNA].
RX PubMed=1904855; DOI=10.1128/jb.173.12.3663-3672.1991;
RA Hakura A., Morimoto K., Sofuni T., Nohmi T.;
RT "Cloning and characterization of the Salmonella typhimurium ada gene, which
RT encodes O6-methylguanine-DNA methyltransferase.";
RL J. Bacteriol. 173:3663-3672(1991).
RN [2]
RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
RC STRAIN=LT2 / SGSC1412 / ATCC 700720;
RX PubMed=11677609; DOI=10.1038/35101614;
RA McClelland M., Sanderson K.E., Spieth J., Clifton S.W., Latreille P.,
RA Courtney L., Porwollik S., Ali J., Dante M., Du F., Hou S., Layman D.,
RA Leonard S., Nguyen C., Scott K., Holmes A., Grewal N., Mulvaney E.,
RA Ryan E., Sun H., Florea L., Miller W., Stoneking T., Nhan M., Waterston R.,
RA Wilson R.K.;
RT "Complete genome sequence of Salmonella enterica serovar Typhimurium LT2.";
RL Nature 413:852-856(2001).
CC -!- FUNCTION: Involved in the cellular defense against the biological
CC effects of O6-methylguanine (O6-MeG) and O4-methylthymine (O4-MeT) in
CC DNA. Repairs the methylated nucleobase in DNA by stoichiometrically
CC transferring the methyl group to a cysteine residue in the enzyme. This
CC is a suicide reaction: the enzyme is irreversibly inactivated.
CC -!- FUNCTION: The methylated ADA protein acts as a positive regulator of
CC its own synthesis, as well as that of other proteins. The
CC transcription-activating function of the ADA protein resides in its N-
CC terminus. It activates the transcription of alkA, alkB and aidB.
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 6-O-methyl-2'-deoxyguanosine in DNA + L-cysteinyl-[protein]
CC = a 2'-deoxyguanosine in DNA + S-methyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:24000, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132,
CC Rhea:RHEA-COMP:11367, Rhea:RHEA-COMP:11368, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:82612, ChEBI:CHEBI:85445, ChEBI:CHEBI:85448; EC=2.1.1.63;
CC Evidence={ECO:0000250|UniProtKB:P06134, ECO:0000255|PROSITE-
CC ProRule:PRU10017};
CC -!- CATALYTIC ACTIVITY:
CC Reaction=a 4-O-methyl-thymidine in DNA + L-cysteinyl-[protein] = a
CC thymidine in DNA + S-methyl-L-cysteinyl-[protein];
CC Xref=Rhea:RHEA:53428, Rhea:RHEA-COMP:10131, Rhea:RHEA-COMP:10132,
CC Rhea:RHEA-COMP:13555, Rhea:RHEA-COMP:13556, ChEBI:CHEBI:29950,
CC ChEBI:CHEBI:82612, ChEBI:CHEBI:137386, ChEBI:CHEBI:137387;
CC EC=2.1.1.63; Evidence={ECO:0000250|UniProtKB:P06134,
CC ECO:0000255|PROSITE-ProRule:PRU10017};
CC -!- COFACTOR:
CC Name=Zn(2+); Xref=ChEBI:CHEBI:29105; Evidence={ECO:0000250};
CC Note=Binds 1 zinc ion per subunit. {ECO:0000250};
CC -!- MISCELLANEOUS: This enzyme catalyzes only one turnover and therefore is
CC not strictly catalytic. According to one definition, an enzyme is a
CC biocatalyst that acts repeatedly and over many reaction cycles.
CC -!- SIMILARITY: In the C-terminal section; belongs to the MGMT family.
CC {ECO:0000305}.
CC -!- SEQUENCE CAUTION:
CC Sequence=BAA14252.1; Type=Erroneous initiation; Evidence={ECO:0000305};
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DR EMBL; D90221; BAA14252.1; ALT_INIT; Genomic_DNA.
DR EMBL; AE006468; AAL21167.1; -; Genomic_DNA.
DR PIR; A39433; XYEBOT.
DR RefSeq; NP_461208.1; NC_003197.2.
DR RefSeq; WP_000975956.1; NC_003197.2.
DR AlphaFoldDB; P26189; -.
DR SMR; P26189; -.
DR STRING; 99287.STM2265; -.
DR PaxDb; P26189; -.
DR EnsemblBacteria; AAL21167; AAL21167; STM2265.
DR GeneID; 1253787; -.
DR KEGG; stm:STM2265; -.
DR PATRIC; fig|99287.12.peg.2399; -.
DR HOGENOM; CLU_000445_52_0_6; -.
DR OMA; RFAIGQC; -.
DR PhylomeDB; P26189; -.
DR BioCyc; SENT99287:STM2265-MON; -.
DR Proteomes; UP000001014; Chromosome.
DR GO; GO:0003700; F:DNA-binding transcription factor activity; IEA:InterPro.
DR GO; GO:0003908; F:methylated-DNA-[protein]-cysteine S-methyltransferase activity; IEA:UniProtKB-EC.
DR GO; GO:0043565; F:sequence-specific DNA binding; IEA:InterPro.
DR GO; GO:0008270; F:zinc ion binding; IEA:InterPro.
DR GO; GO:0006304; P:DNA modification; IEA:UniProt.
DR GO; GO:0006281; P:DNA repair; IEA:UniProtKB-KW.
DR GO; GO:0032259; P:methylation; IEA:UniProtKB-KW.
DR CDD; cd06445; ATase; 1.
DR Gene3D; 1.10.10.10; -; 1.
DR Gene3D; 3.40.10.10; -; 1.
DR InterPro; IPR035451; Ada-like_dom_sf.
DR InterPro; IPR004026; Ada_DNA_repair_Zn-bd.
DR InterPro; IPR016221; Bifunct_regulatory_prot_Ada.
DR InterPro; IPR009057; Homeobox-like_sf.
DR InterPro; IPR018060; HTH_AraC.
DR InterPro; IPR018062; HTH_AraC-typ_CS.
DR InterPro; IPR001497; MethylDNA_cys_MeTrfase_AS.
DR InterPro; IPR014048; MethylDNA_cys_MeTrfase_DNA-bd.
DR InterPro; IPR036217; MethylDNA_cys_MeTrfase_DNAb.
DR InterPro; IPR008332; MethylG_MeTrfase_N.
DR InterPro; IPR036631; MGMT_N_sf.
DR InterPro; IPR036388; WH-like_DNA-bd_sf.
DR Pfam; PF02805; Ada_Zn_binding; 1.
DR Pfam; PF01035; DNA_binding_1; 1.
DR Pfam; PF12833; HTH_18; 1.
DR Pfam; PF02870; Methyltransf_1N; 1.
DR PIRSF; PIRSF000409; Ada; 1.
DR SMART; SM00342; HTH_ARAC; 1.
DR SUPFAM; SSF46689; SSF46689; 1.
DR SUPFAM; SSF46767; SSF46767; 1.
DR SUPFAM; SSF53155; SSF53155; 1.
DR SUPFAM; SSF57884; SSF57884; 1.
DR TIGRFAMs; TIGR00589; ogt; 1.
DR PROSITE; PS00041; HTH_ARAC_FAMILY_1; 2.
DR PROSITE; PS01124; HTH_ARAC_FAMILY_2; 1.
DR PROSITE; PS00374; MGMT; 1.
PE 3: Inferred from homology;
KW Activator; DNA damage; DNA repair; DNA-binding; Metal-binding;
KW Methyltransferase; Reference proteome; Transcription;
KW Transcription regulation; Transferase; Zinc.
FT CHAIN 1..353
FT /note="Regulatory protein ada"
FT /id="PRO_0000018749"
FT CHAIN 179..353
FT /note="Methylated-DNA--protein-cysteine methyltransferase"
FT /id="PRO_0000018750"
FT DOMAIN 94..183
FT /note="HTH araC/xylS-type"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00593"
FT DNA_BIND 103..124
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00593"
FT DNA_BIND 150..173
FT /note="H-T-H motif"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU00593"
FT ACT_SITE 38
FT /note="Nucleophile; methyl group acceptor from
FT phosphotriester"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10017"
FT ACT_SITE 321
FT /note="Nucleophile; methyl group acceptor"
FT /evidence="ECO:0000255|PROSITE-ProRule:PRU10017"
FT BINDING 34
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 38
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 42
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 43
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 67
FT /ligand="DNA"
FT /ligand_id="ChEBI:CHEBI:16991"
FT /evidence="ECO:0000250"
FT BINDING 69
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT BINDING 72
FT /ligand="Zn(2+)"
FT /ligand_id="ChEBI:CHEBI:29105"
FT /evidence="ECO:0000250"
FT SITE 128..129
FT /note="Cleavage"
FT /evidence="ECO:0000250"
FT SITE 178..179
FT /note="Cleavage"
FT /evidence="ECO:0000250"
SQ SEQUENCE 353 AA; 39348 MW; ACE9E13C7EF6C114 CRC64;
MMKKALLIDD ECWLRVQARD ASADGRFVFA VRTTGVFCRP SCRSKRALRK NVRFFANAQQ
ALDAGFRPCK RCQPDNARAQ QRRLDKIACA CRLLEQETPV TLAFLAQAVA MSPFHLHRLF
KASTGMTPKG WQQAWRARRL REALAKGEPI TAAIYRAGFP DSSSYYRHAD QTLGMTAKQF
RKGGDNVSVR YALTDWVYGR CLVAESERGI CAILPGDSDD ALLAELHTLF PSARHEPADA
LFQQRVRQVV AAINTRDVLL SLPLDIQGTA FQQQVWQALC AIPCGETVSY QQLAATIGKP
TAVRAVASAC GANKLAMVIP CHRVVRRDGA LSGYRWGVRR KAQLLKREAQ KEE
