Rv3618 Resolved · high auto-curated

H37Rv Rv3618 · MTBC0 mtbc0_003835 · 395 aa · 4082402–4083589 (+) · RefSeq NP_218135.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)monooxygenase
MTBC0 PGAP re-annotationLLM class flavin-dependent oxidoreductase
Revised (this work)LLM class flavin-dependent oxidoreductase. Pfam: Bac_luciferase (PF00296.27).

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

Curated reference (UniProt)

UniProt I6X7W8 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible monooxygenase

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namelimB
eggNOG descriptionCOG2141 Coenzyme F420-dependent N5,N10-methylene tetrahydromethanopterin reductase and related flavin-dependent oxidoreductases
Orthologous groupCOG2141
EC number EC 1.14.13.107
KEGG orthology K14733
KEGG pathways map00903

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 0.893 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 8 missense, 0 nonsense, 1 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (175) · 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
Bac_luciferasePF00296.27 2.9e-426–317 Luciferase-like monooxygenase

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

Closest characterised functional partner: ephA (epoxide hydrolase EphA), high confidence from genomic context alone (score 964 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3617 ephA epoxide hydrolase EphA 964 964 ctx neighborhood:789 coexpression:803
Rv2740 ephG epoxide hydrolase 926 901 database:900
Rv0517 acyltransferase 484 485 ctx cooccurence:483
Rv3779 transmembrane protein 476 476 ctx cooccurence:476
Rv3007c oxidoreductase 411 388

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: monooxygenase
  • MTBC0 PGAP product: LLM class flavin-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): Bac_luciferase PF00296.27 (E=3e-42)
  • (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_218135.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Bac_luciferase (PF00296.27)
  • 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 COG2141
  • Curated reference: UniProt I6X7W8 (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 — 5 functional partner(s); context anchor ephA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003835|Rv3618|
MKAPLRFGVFITPFHPTGQSPTVALQYDMERVVALDRLGYDEAWFGEHHSGGYELIACPEVFIAAAAERTTHIRLGTGVVSLPYHHPLMVADRWVLLDHLTRGRVMFGTGPGALPSDAYMMGIDPVEQRRMMQESLEAILALFRAAPDERIDRHSDWFTLREAQLHIRPYTWPYPEIATAAMISPSGPRLAGALGTSLLSLSMSVPGGYAALETAWGVVREQAAKAGRGEPDRADWRVLSIMHLSDSRDQAIDDCTYGLPDFSRYFGAAGFVPLANTVEGTQSSREFVEQYAAKGNCCIGTPDDAIAHIEDLLHRSGGFGTLLLLGHDWAPPPATFHSYELFARAVIPYFKGQLAAPRASHEWARGKRDQLIGRAGEAVVKAITEHVAEQGEAGS