Rv3222c Still unknown · low auto-curated
H37Rv Rv3222c · MTBC0 mtbc0_002141 ·
59 aa · 2283870–2284049 (-) ·
RefSeq NP_217738.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | hypothetical protein |
| Revised (this work) | Conserved hypothetical protein; no recognised domain. Function unknown. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05844
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Conservation & selection (intra-MTBC, 145 209 strains)
| pN/pS | 0.074 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 1 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: rshA (anti-sigma factor RshA), high confidence from genomic context alone (score 979 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) |
|---|---|---|---|---|
Rv3221A rshA |
anti-sigma factor RshA | 978 | 979 ctx | neighborhood:882 coexpression:826 |
Rv3223c sigH |
ECF RNA polymerase sigma factor SigH | 970 | 967 ctx | neighborhood:882 coexpression:732 |
Rv3221c TB7.3 |
acetyl-CoA carboxylase biotin carboxyl carrier protein subunit | 461 | 462 ctx | neighborhood:435 |
Rv3224 |
iron-regulated short-chain dehydrogenase/reductase | 456 | 456 ctx | neighborhood:448 |
Rv3220c pdtaS |
two component sensor kinase | 425 | 425 ctx | neighborhood:415 |
Rv3224B |
Rv3224B, len: 72 aa. Conserved hypothetical protein (possibly gene fragment), similar to C-terminal part of ML0799|AL583919_131 conserved hy | 418 | 418 ctx | neighborhood:412 |
Rv3224A |
Rv3224A, len: 62 aa. Conserved hypothetical protein (possibly gene fragment), overlaps Rv3224. Similar to N-terminus of ML0799|AL583919_131 | 418 | 418 ctx | neighborhood:412 |
Rv1222 rseA |
anti-sigma E factor RseA | 865 | 69 | textmining:861 |
Rv2788 sirR |
transcriptional repressor SirR | 433 | 47 | textmining:430 |
Rv0093c |
membrane protein | 809 | 46 | textmining:808 |
Rv3413c rsdA |
anti-sigma-D factor RsdA | 870 | 41 | textmining:870 |
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: hypothetical protein
- (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_217738.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- Sequence-level signal: ESM Atlas (EvolutionaryScale × BioHub) — exploratory
- Curated reference: UniProt O05844 (TrEMBL, unreviewed; Predicted)
- Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
- Model confidence: ESMFold per-residue pLDDT (mean 40.6, very low)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
11 functional partner(s); context anchor
rshA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002141|Rv3222c| MGARRRSVLSTVGASGATAGLRRTHRGHHGCRASRAITQRRLGCIGNPSKVTDTRMVHQ