Rv2161c Family assigned · medium auto-curated

H37Rv Rv2161c · MTBC0 mtbc0_002297 · 288 aa · 2449654–2450520 (-) · RefSeq NP_216677.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationTIGR03619 family F420-dependent LLM class oxidoreductase
Revised (this work)TIGR03619 family F420-dependent LLM class 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 O06216 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
eggNOG descriptionCOG2141 Coenzyme F420-dependent N5,N10-methylene tetrahydromethanopterin reductase and related flavin-dependent oxidoreductases
Orthologous groupCOG2141

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 3.987 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 11 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
Bac_luciferasePF00296.27 2.9e-3820–232 Luciferase-like monooxygenase

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

Closest characterised functional partner: Rv2160c (Rv2160c, (MTCY270.08), len: 113 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator, similar to C-terminal ), high confidence from genomic context alone (score 859 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2160A Rv2160A, len: 211 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator,similar to N-terminal half of AL51266 876 876 coexpression:860
Rv2160c Rv2160c, (MTCY270.08), len: 113 aa. Conserved hypothetical protein, possibly a TetR-family transcriptional regulator, similar to C-terminal 980 859 ctx neighborhood:484 coexpression:738 textmining:870
Rv2159c hyp hypothetical protein 978 842 coexpression:819 textmining:870
Rv3093c oxidoreductase 730 730 ctx cooccurence:730
Rv3520c coenzyme F420-dependent oxidoreductase 719 720 ctx cooccurence:709
Rv2951c phthiodiolone/phenolphthiodiolone dimycocerosates ketoreductase 718 718 ctx cooccurence:717
Rv3262 fbiB coenzyme F420:L-glutamate ligase 727 710 ctx cooccurence:669
Rv1936 monooxygenase 676 677 ctx cooccurence:673
Rv0044c oxidoreductase 658 658 ctx cooccurence:655
Rv3178 nitroreductase 676 656 ctx cooccurence:653
Rv3261 fbiA 2-phospho-L-lactate transferase 675 655 ctx cooccurence:637
Rv0407 fgd1 F420-dependent glucose-6-phosphate dehydrogenase 645 645 ctx cooccurence:641
Rv3547 ddn deazaflavin-dependent nitroreductase 628 605 ctx cooccurence:605
Rv1261c hyp hypothetical protein 597 598 ctx cooccurence:595
Rv2162c PE_PGRS38 PE-PGRS family protein PE_PGRS38 905 540 ctx neighborhood:540 textmining:803

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: TIGR03619 family F420-dependent LLM class oxidoreductase
  • Pfam (hmmscan --cut_ga): Bac_luciferase PF00296.27 (E=3e-38)
  • (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_216677.1)
  • 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 O06216 (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 — 23 functional partner(s); context anchor Rv2160c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002297|Rv2161c|
MLVSLMQFVTDLTPPPQLVAVWAEERGFAGLYVPEKTHVPISRSTPWPGGELPDWYRRCYDPVVALAAAAAVTTRLRVGTGACLVAVHDPILLAKQIASLCAMSGERFVLGVGFGWNVEELADHGVPFADRIAVTVDKLAAMRALWAAEPVHYEGTHASVPPSWAWPKPAVAPPVLFGCRPSARAFEVIARHGDGWQPIEGYGELLGALPMLHAAFERAGRDPATAQVCVYSSAGDPATLHEYRRAGVAEVALALPSAGRDQVLAALDRSAPLVDAFAGDDREVKSHA