Rv3054c Resolved · high auto-curated

H37Rv Rv3054c · MTBC0 mtbc0_003246 · 184 aa · 3436731–3437285 (-) · RefSeq NP_217570.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationNADPH-dependent FMN reductase
Revised (this work)NADPH-dependent FMN reductase. Pfam: FMN_red (PF03358.21), Flavodoxin_2 (PF02525.23).

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

Curated reference (UniProt)

UniProt P95105 TrEMBL · unreviewed · Evidence at protein level
UniProt nameNADPH-dependent FMN reductase-like domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionFMN reductase
Orthologous groupCOG0431

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 0.681 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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
FMN_redPF03358.21 1.9e-388–155 NADPH-dependent FMN reductase
Flavodoxin_2PF02525.23 1.9e-069–118 Flavodoxin-like fold

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

Closest characterised functional partner: Rv3055 (TetR family transcriptional regulator), high confidence from genomic context alone (score 824 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3055 TetR family transcriptional regulator 828 824 ctx neighborhood:736
Rv3056 dinP DNA polymerase IV 2 778 778 ctx neighborhood:778
Rv2466c hyp hypothetical protein 745 745 coexpression:729
Rv3463 hyp hypothetical protein 960 696 coexpression:639 textmining:875
Rv1251c hyp hypothetical protein 422 423 coexpression:403
Rv2400c subI sulfate ABC transporter substrate-binding lipoprotein SubI 403 350
Rv2643 arsC arsenic-transport integral membrane protein ArsC 644 319 textmining:500
Rv1286 cysC adenylyl-sulfate kinase 443 179
Rv3223c sigH ECF RNA polymerase sigma factor SigH 657 115 textmining:629
Rv3913 trxB2 thioredoxin reductase 509 103 textmining:475
Rv3914 trxC thioredoxin TrxC 489 78 textmining:469
Rv0331 dehydrogenase/reductase 881 73 textmining:878
Rv2050 rbpA RNA polymerase-binding protein RbpA 657 55 textmining:652
Rv0352 dnaJ1 chaperone protein DnaJ 441 51 textmining:436

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: hypothetical protein
  • MTBC0 PGAP product: NADPH-dependent FMN reductase
  • Pfam (hmmscan --cut_ga): FMN_red PF03358.21 (E=2e-38), Flavodoxin_2 PF02525.23 (E=2e-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_217570.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FMN_red (PF03358.21), Flavodoxin_2 (PF02525.23)
  • 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 COG0431
  • Curated reference: UniProt P95105 (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 — 14 functional partner(s); context anchor Rv3055
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003246|Rv3054c|
MSDTKSDIKILALVGSLRAASFNRQIAELAAKVAPDGVTVTMFEGLGDLPFYNEDIDTATEVPAPVSALREAASDAHAALVVTPEYNGSIPAVIKNAIDWLSRPFGDGALKDKPLAVIGGSMGRYGGVWAHDETRKSFSIAGTRVVDAIKLSVPFQTLGKSVADDAGLAANVRDAVGNLAAEVG