alkA Family assigned · medium auto-curated
H37Rv Rv1317c · MTBC0 mtbc0_001412 ·
496 aa · 1486656–1488146 (-) ·
RefSeq NP_215833.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | bifunctional regulatory protein/DNA repair enzyme AlkA |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional regulatory protein/DNA repair enzyme AlkA |
| Revised (this work) | Bifunctional regulatory protein/DNA repair enzyme AlkA. Pfam: Ada_Zn_binding (PF02805.22), HTH_18 (PF12833.14), AlkA_N (PF06029.18), HhH-GPD (PF00730.32). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WJW3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable bifunctional transcriptional activator/DNA repair enzyme AlkA |
| EC (curated) |
EC 2.1.1.n11, EC 3.2.2.21
|
| Curated function | Is involved in the adaptive response to alkylation damage in DNA caused by alkylating agents. Repairs the Sp diastereomer of DNA methylphosphotriester lesions by a direct and irreversible transfer of the methyl group to one of its own cysteine residues. Also catalyzes the hydrolysis of the deoxyribose N-glycosidic bond to excise 3-methyladenine, 3-methylguanine, 7-methylguanine, O2-methylthymine, and O2-methylcytosine from the damaged DNA polymer formed by alkylation lesions (By similarity)..; FUNCTION: The methylation of Alka by methylphosphotriesters in DNA leads to its activation as a trans. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
K Transcription
|
|---|---|
| Preferred name | alkA |
| eggNOG description | involved in damage reversal and in base excision repair. 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. 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 catalytic activity DNA (containing 6-O- methylguanine) protein -L-cysteine DNA (without 6-O- methylguanine) protein S-methyl-L-cysteine |
| Orthologous group | COG0122 |
| EC number |
EC 3.2.2.21
|
| KEGG orthology |
K13529
|
| KEGG pathways |
map03410
|
| Gene Ontology (60) |
GO:0003674, GO:0003676, GO:0003677, GO:0003684, GO:0003824, GO:0003905, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737 +48 more
|
Orthology-based transfer (eggNOG 5.0.2, diamond). EC/KO/GO/CAZy are computed annotations, not manual curation; cross-check against the primary literature before treating a specific reaction as established.
Conservation & selection (intra-MTBC, 145 209 strains) pseudogene candidate
| pN/pS | 0.369 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 7 synonymous, 6 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 5.26% of strains (7645) · clonal |
pN/pS from segregating SNPs (singletons removed) normalised by possible sites. Low pN/pS = purifying selection (a strong signal that a "hypothetical" is a real, constrained gene). A high pN/pS is ambiguous: relaxed constraint or positive selection (drug resistance, antigenic variation) inflate it; e.g. rpoB/katG/pncA score high here for resistance, not loss of function. A clonal disruption (one allele over a clade) suggests lineage pseudogenisation; a convergent one (many independent alleles) is typical of resistance loss-of-function.
Domains (Pfam, hmmscan --cut_ga)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Ada_Zn_binding | PF02805.22 | 3.9e-28 | 8–71 | Metal binding domain of Ada |
HTH_18 | PF12833.14 | 3.8e-15 | 106–185 | Helix-turn-helix domain |
AlkA_N | PF06029.18 | 1.6e-35 | 202–316 | AlkA N-terminal domain |
HhH-GPD | PF00730.32 | 7.0e-06 | 322–470 | HhH-GPD superfamily base excision DNA repair protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ogt (methylated-DNA--protein-cysteine methyltransferase), high confidence from genomic context alone (score 954 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1316c ogt |
methylated-DNA--protein-cysteine methyltransferase | 987 | 954 ctx | neighborhood:881 coexpression:567 textmining:742 |
Rv1318c |
adenylate cyclase | 785 | 786 ctx | neighborhood:786 |
Rv0427c xthA |
exodeoxyribonuclease III protein XthA | 894 | 759 | database:651 textmining:579 |
Rv1321 nucS |
endonuclease NucS | 715 | 682 ctx | neighborhood:678 |
Rv1322 hyp |
hypothetical protein | 648 | 649 ctx | neighborhood:588 |
Rv3394c hyp |
hypothetical protein | 664 | 549 | |
Rv1631 coaE |
dephospho-CoA kinase CoaE | 546 | 547 ctx | neighborhood:544 |
Rv1998c hyp |
hypothetical protein | 546 | 546 ctx | cooccurence:404 |
Rv1307 atpH |
ATP synthase subunit b/delta | 544 | 544 ctx | neighborhood:544 |
Rv1319c |
adenylate cyclase | 488 | 488 ctx | neighborhood:488 |
Rv2737c recA |
recombinase A | 860 | 473 | textmining:746 |
Rv1537 dinX |
DNA polymerase IV | 917 | 440 | textmining:859 |
Rv1650 pheT |
phenylalanine--tRNA ligase subunit beta | 438 | 439 ctx | neighborhood:425 |
Rv3056 dinP |
DNA polymerase IV 2 | 810 | 438 | textmining:677 |
Rv1320c |
adenylate cyclase | 429 | 429 ctx | neighborhood:429 |
STRING combines evidence channels (neighborhood, fusion, cooccurrence, coexpression, experimental, database, text-mining) into a 0–1000 score. The ctx badge marks edges carried by the genomic-context channels (conserved neighborhood, fusion, phylogenetic co-occurrence), which are independent of orthology and structure and the strongest signal for an unknown gene. The no text-mining column recomputes the score from data alone, so a link that does not depend on the literature is visible. Association is a function hypothesis, not proof: corroborate with the operon context and the primary literature before assigning a function.
Evidence
- Legacy H37Rv annotation: bifunctional regulatory protein/DNA repair enzyme AlkA
- MTBC0 PGAP product: bifunctional regulatory protein/DNA repair enzyme AlkA
- Pfam (hmmscan --cut_ga): Ada_Zn_binding PF02805.22 (E=4e-28), HTH_18 PF12833.14 (E=4e-15), AlkA_N PF06029.18 (E=2e-35), HhH-GPD PF00730.32 (E=7e-06)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
Sources
- Ancestral sequence & coordinates: Harrison LB et al. (2024), An imputed ancestral reference genome for the MTBC, doi:10.1101/2023.09.07.556366
- Product annotation: NCBI PGAP on MTBC0; legacy from H37Rv NC_000962.3 (RefSeq NP_215833.1)
- Domains: Pfam-A via hmmscan --cut_ga — Ada_Zn_binding (PF02805.22), HTH_18 (PF12833.14), AlkA_N (PF06029.18), HhH-GPD (PF00730.32)
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Controlled vocabulary: eggNOG-mapper 2.1.12 (Cantalapiedra et al. 2021,
doi:10.1093/molbev/msab293), eggNOG 5.0 DB
(Huerta-Cepas et al. 2019) — OG
COG0122 - Curated reference: UniProt P9WJW3 (SwissProt, reviewed; Evidence at protein level)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
54 functional partner(s); context anchor
ogt - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001412|Rv1317c|alkA MHDDFERCYRAVQSKDARFDGWFVVAVLTTGVYCRPSCPVRPPFARNVRFLPTAAAAQGEGFRACKRCRPDASPGSPEWNVRSDVVARAMRLIADGTVDRDGVSGLAAQLGYTIRQLERLLQAVVGAGPLALARAQRMQTARVLIETTNLPFGDVAFAAGFSSIRQFNDTVRLACDGTPTALRARAAARFESATASAGTVSLRLPVRAPFAFEGVFGHLAATAVPGCEEVRDGAYRRTLRLPWGNGIVSLTPAPDHVRCLLVLDDFRDLMTATARCRRLLDLDADPEAIVEALGADPDLRAVVGKAPGQRIPRTVDEAEFAVRAVLAQQVSTKAASTHAGRLVAAYGRPVHDRHGALTHTFPSIEQLAEIDPGHLAVPKARQRTINALVASLADKSLVLDAGCDWQRARGQLLALPGVGPWTAEVIAMRGLGDPDAFPASDLGLRLAAKKLGLPAQRRALTVHSARWRPWRSYATQHLWTTLEHPVNQWPPQEKIA