Rv3161c Family assigned · medium auto-curated

H37Rv Rv3161c · MTBC0 mtbc0_003360 · 382 aa · 3554838–3555986 (-) · RefSeq NP_217677.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)dioxygenase
MTBC0 PGAP re-annotationaromatic ring-hydroxylating dioxygenase subunit alpha
Revised (this work)Aromatic ring-hydroxylating dioxygenase subunit alpha. Pfam: Rieske (PF00355.33), Ring_hydroxyl_A (PF00848.26).

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

Curated reference (UniProt)

UniProt O53311 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible dioxygenase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
eggNOG descriptionRieske 2Fe-2S
Orthologous groupCOG4638
KEGG orthology K00479

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 0.517 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 8 missense, 0 nonsense, 2 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (664) · 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)

PfamAccessioni-EvalueResiduesDescription
RieskePF00355.33 1.2e-1952–136 Rieske [2Fe-2S] domain
Ring_hydroxyl_APF00848.26 1.5e-18188–372 Ring hydroxylating alpha subunit (catalytic domain)

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

Closest characterised functional partner: Rv3160c (TetR family transcriptional regulator), high confidence from genomic context alone (score 797 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3160c TetR family transcriptional regulator 923 797 ctx neighborhood:797 textmining:637
Rv2776c oxidoreductase 732 650 ctx cooccurence:519
Rv3163c hyp hypothetical protein 580 580 ctx neighborhood:580
Rv3162c integral membrane protein 580 580 ctx neighborhood:580
Rv3166c hyp hypothetical protein 513 513 ctx neighborhood:513
Rv3165c hyp hypothetical protein 513 513 ctx neighborhood:513
Rv3164c moxR3 methanol dehydrogenase transcriptional regulator MoxR 513 513 ctx neighborhood:513
Rv1937 oxygenase 686 484 coexpression:404 textmining:417
Rv3159c PPE53 PPE family protein PPE53 672 475 ctx neighborhood:475 textmining:401
Rv1215c hyp hypothetical protein 421 421 ctx cooccurence:415
Rv0316 muconolactone isomerase 463 409
Rv3554 fdxB electron transfer protein FdxB 541 400
Rv2964 purU formyltetrahydrofolate deformylase 427 400
Rv3377c type B diterpene cyclase 402 391
Rv3230c stearoyl-CoA 9-desaturase electron transfer protein 471 307

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: dioxygenase
  • MTBC0 PGAP product: aromatic ring-hydroxylating dioxygenase subunit alpha
  • Pfam (hmmscan --cut_ga): Rieske PF00355.33 (E=1e-19), Ring_hydroxyl_A PF00848.26 (E=1e-18)
  • (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_217677.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Rieske (PF00355.33), Ring_hydroxyl_A (PF00848.26)
  • 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 COG4638
  • Curated reference: UniProt O53311 (TrEMBL, unreviewed; 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 — 32 functional partner(s); context anchor Rv3160c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003360|Rv3161c|
MLSTDNRAELGDILTDIGDYLDDNPPALSLPPAAYTSSELWQLERERIFNRSWMLVAHVDQLAKTGDYVTVSVAGEPVMVVRDVDGQLHALSPICRHRLMLMVEPGAGRIDTLTCQYHLWRYGLDGRLRGAPHMAANLDFNRRECRLPQFAVATWNGLVWINLDADAEPIAAHLDLTDDEFAGYRLGEMVQVESWSHEWRANWKVAAENGHENYHVLGLHRQTLEPFVPGGGDLDVRQYSRWALRLRVPFTVPVEAKSLQLNEVQKSNLVVLWTFPNSALAIAGERVVWFGFIPQSIDRVQVLGGVLTTPELAADAAATAQTSQFVMAMINDEDRLGLEAVQVGAGSRFAERGHLSSKEWPGMLAFYRNLAMALVGDHPGAS