Rv2269c Family assigned · low
H37Rv Rv2269c · MTBC0 mtbc0_002411 ·
110 aa · 2570394–2570726 (-) ·
RefSeq NP_216785.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Gene of the sulfomenaquinone (SMK) biosynthetic operon. RefSeq leaves it of unknown function. Rv2269c is part of the operon (with the sulfotransferase stf3 and the cytochrome P450 cyp128) producing SMK, an MTBC-specific virulence-modulating menaquinone derivative; rv2269c shows promoter activity, while cyp128 and stf3 are sufficient for SMK biosynthesis (Sogi 2016). Specific role unfixed. |
Curated reference (UniProt)
| UniProt |
P9WLF9
SwissProt · reviewed
· Evidence at transcript level
|
|---|---|
| UniProt name | Uncharacterized protein Rv2269c |
| Curated function | May play a regulatory role in sulfomenaquinone (SMK) biosynthesis. Not essential for SMK biosynthesis. |
UniProt still lists this protein as Uncharacterized protein Rv2269c; the revised annotation above is ahead of the current UniProt record.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.752 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: cyp128 (cytochrome P450 Cyp128), high confidence from genomic context alone (score 767 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2268c cyp128 |
cytochrome P450 Cyp128 | 968 | 767 ctx | neighborhood:765 textmining:870 |
Rv2267c stf3 hyp |
hypothetical protein | 968 | 766 ctx | neighborhood:765 textmining:870 |
Rv2270 lppN |
lipoprotein LppN | 573 | 573 ctx | neighborhood:561 |
Rv2266 cyp124 |
cytochrome P450 Cyp124 | 546 | 50 | textmining:542 |
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
- Member of the SMK (sulfomenaquinone) biosynthetic operon with stf3/cyp128; promoter activity (Sogi 2016, PMID 27933784)
- Curated from the literature crible (project 'Still unknown gene function', 2026-06-09)
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_216785.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Curated reference: UniProt P9WLF9 (SwissProt, reviewed; Evidence at transcript 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 —
4 functional partner(s); context anchor
cyp128 - Primary literature: Sogi KM, Holsclaw CM, Fragiadakis GK, Nomura DK, Leary JA, Bertozzi CR (2016). Biosynthesis and Regulation of Sulfomenaquinone, a Metabolite Associated with Virulence in Mycobacterium tuberculosis ACS Infect Dis 2(11):800-806. doi:10.1021/acsinfecdis.6b00106 PMID:27933784
Ancestral MTBC0 protein sequence
>mtbc0_002411|Rv2269c| MANDARPLARLANCRVGDQSSATHAYTVGPVLGVPPTGGVDLRYGGRAGIGRSETVTDHGAVGRRYHQPCAGQIRLSELRVTILLRCETLCETAQLLRCPPLPCDCSTPL