ahpD Resolved · high auto-curated

H37Rv Rv2429 · MTBC0 mtbc0_002587 · 177 aa · 2751054–2751587 (+) · RefSeq NP_216945.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)alkyl hydroperoxide reductase AphD
MTBC0 PGAP re-annotationalkyl hydroperoxide reductase
Revised (this work)Alkyl hydroperoxide reductase. Pfam: CMD (PF02627.26).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WQB5 SwissProt · reviewed · Evidence at protein level
UniProt nameAlkyl hydroperoxide reductase AhpD
EC (curated) EC 1.11.1.28
Curated functionAntioxidant protein with alkyl hydroperoxidase activity. Required for the reduction of the AhpC active site cysteine residues and for the regeneration of the AhpC enzyme activity.; FUNCTION: Together with AhpC, DlaT and Lpd, constitutes an NADH-dependent peroxidase active against hydrogen and alkyl peroxides as well as serving as a peroxynitrite reductase, thus protecting the bacterium against reactive nitrogen intermediates and oxidative stress generated by the host immune system.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category O Post-translational modification, protein turnover, chaperones
Preferred nameahpD
eggNOG descriptionAntioxidant protein with alkyl hydroperoxidase activity. Required for the reduction of the AhpC active site cysteine residues and for the regeneration of the AhpC enzyme activity
Orthologous groupCOG0599
KEGG orthology K04756
Gene Ontology (29) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005886, GO:0008150, GO:0008152, GO:0009987, GO:0015036 +17 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)

pN/pS 0.337 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 1 missense, 0 nonsense, 0 frameshift

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)

PfamAccessioni-EvalueResiduesDescription
CMDPF02627.26 1.3e-14101–174 Carboxymuconolactone decarboxylase family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: ahpC (alkyl hydroperoxide reductase subunit AhpC), high confidence from genomic context alone (score 994 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2428 ahpC alkyl hydroperoxide reductase subunit AhpC 999 994 ctx neighborhood:844 cooccurence:766 coexpression:837 textmining:902
Rv2427A oxyR Rv2427A, Pseudogene oxyR', inactivated by multiple mutations; identical to sequence in u16243 (see Deretic et al., 1995). 578 489 ctx neighborhood:489
Rv1286 cysC adenylyl-sulfate kinase 525 482 coexpression:482
Rv1874 hyp hypothetical protein 480 481 ctx neighborhood:401
Rv0477 hyp hypothetical protein 471 471 ctx cooccurence:471
Rv2399c cysT sulfate ABC transporter permease CysT 406 407 coexpression:407
Rv0433 carboxylate-amine ligase 403 404 coexpression:404
Rv2391 sirA sulfite reductase 451 310
Rv3846 sodA superoxide dismutase 731 71 textmining:723
Rv2238c ahpE peroxiredoxin 665 54 textmining:661
Rv1649 pheS phenylalanine--tRNA ligase subunit alpha 412 52 textmining:406
Rv0432 sodC superoxide dismutase 639 50 textmining:636
Rv3600c coaX type III pantothenate kinase 460 50 textmining:456
Rv2215 dlaT pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase 880 47 textmining:880
Rv2037c transmembrane protein 451 47 textmining:448

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: alkyl hydroperoxide reductase AphD
  • MTBC0 PGAP product: alkyl hydroperoxide reductase
  • Pfam (hmmscan --cut_ga): CMD PF02627.26 (E=1e-14)
  • (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_216945.1)
  • Domains: Pfam-A via hmmscan --cut_ga — CMD (PF02627.26)
  • 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 COG0599
  • Curated reference: UniProt P9WQB5 (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 — 17 functional partner(s); context anchor ahpC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002587|Rv2429|ahpD
MSIEKLKAALPEYAKDIKLNLSSITRSSVLDQEQLWGTLLASAAATRNPQVLADIGAEATDHLSAAARHAALGAAAIMGMNNVFYRGRGFLEGRYDDLRPGLRMNIIANPGIPKANFELWSFAVSAINGCSHCLVAHEHTLRTVGVDREAIFEALKAAAIVSGVAQALATIEALSPS