Rv2061c Resolved · high auto-curated

H37Rv Rv2061c · MTBC0 mtbc0_002194 · 134 aa · 2345294–2345698 (-) · RefSeq NP_216577.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationPPOX class F420-dependent oxidoreductase
Revised (this work)PPOX class F420-dependent oxidoreductase. Pfam: PNPOx_N (PF01243.28).

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

Curated reference (UniProt)

UniProt O86340 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 S Function unknown
eggNOG descriptionPyridoxamine 5-phosphate
Orthologous groupCOG3871
KEGG orthology K07006

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 0.703 · 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
PNPOx_NPF01243.28 7.0e-108–104 Pyridoxamine 5'-phosphate oxidase

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

Closest characterised functional partner: cobN (cobalamin biosynthesis protein CobN), medium confidence from genomic context alone (score 612 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2062c cobN cobalamin biosynthesis protein CobN 612 612 ctx neighborhood:607
Rv1558 hyp hypothetical protein 475 475 ctx cooccurence:468
Rv0044c oxidoreductase 474 474 ctx cooccurence:471
Rv2066 cobIJ bifunctional S-adenosyl-L-methionine-precorrin-2 methyl transferase/precorrin-3 methylase 451 451 ctx neighborhood:446
Rv2064 cobG precorrin-3B synthase 448 448 ctx neighborhood:443
Rv2065 cobH precorrin-8X methylmutase 463 441 ctx neighborhood:438
Rv0407 fgd1 F420-dependent glucose-6-phosphate dehydrogenase 438 438 ctx cooccurence:422
Rv0868c moaD2 cyclic pyranopterin monophosphate synthase 425 425 ctx cooccurence:404
Rv2063 mazE7 antitoxin MazE7 409 409 ctx neighborhood:407
Rv2063A mazF7 mRNA interferase MazF7 407 407 ctx neighborhood:407
Rv3196 hyp hypothetical protein 405 405
Rv2609c membrane protein 402 403

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: PPOX class F420-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): PNPOx_N PF01243.28 (E=7e-10)
  • (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_216577.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PNPOx_N (PF01243.28)
  • 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 COG3871
  • Curated reference: UniProt O86340 (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 — 12 functional partner(s); context anchor cobN
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002194|Rv2061c|
MTPTFSDLAEAQYLLLTTFTKDGRPKPVPIWAALDTDRGDRLLVITEKKSWKVKRIRNTPRVTLATCTLRGRPTSEAVEATAAILDESQTGAVYDAIVKRYGIQGKLFTFVSKLRGGMRNNIGLELKVAESETG