Rv3224A Family assigned · low auto-curated · to review
H37Rv Rv3224A · MTBC0 ·
62 aa ·
3600635–3600823 H37Rv
(+) ·
RefSeq
Genomic neighbourhood (genome browser)
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Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Conserved hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Belongs to the prolyl-tRNA editing family. YbaK EbsC subfamily |
| Functional category (TubercuList) | conserved hypotheticals |
Curation note: Added P16.5d: Mycobrowser-annotated gene absent from RefSeq NC_000962.3 (the atlas' original 3906-CDS reference). Foundation record from the Mycobrowser release + translated H37Rv sequence; heavy enrichment layers (structure, orthology, conservation, interaction) pending.
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).
Legacy record & comparison (Mycobrowser)
| Mycobrowser function | Function unknown |
|---|
The legacy Mycobrowser record is shown for verification. Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.
Curated reference (UniProt)
| UniProt |
Q6MWZ5
TrEMBL · unreviewed
|
|---|---|
| UniProt name | Uncharacterized protein |
UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| Preferred name | ybaK |
| eggNOG description | Belongs to the prolyl-tRNA editing family. YbaK EbsC subfamily |
| Orthologous group | COG2606 |
| KEGG orthology |
ko:K03976
|
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 | 0.386 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 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.
Essentiality (transposon mutagenesis)
| DeJesus 2017 call | NE · non-essential |
|---|---|
| What the call means | non-essential |
| TA sites (Himar1) | 4 in the ORF — 0 in the essential state, 0 growth-defect, 4 non-essential, 0 growth-advantage. Saturation 1.000, mean read count 84.25. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction. |
| Caveat | Statistically thin call: only 4 TA (Himar1) sites in the whole ORF (atlas median 13; genes under 300 nt typically have very few). A DeJesus 2017 call built on so few independent observations is less robust than the same call on a longer gene, in either direction. Cross-check against the CRISPRi vulnerability index (independent of TA-site density) and, if this gene overlaps a neighbour (see Genomic-neighbour overlap section below), verify how many of its TA sites actually fall inside its own ORF. (P20.3) |
Genome-wide Himar1 transposon essentiality in H37Rv (DeJesus 2017). An essential call (ES/ESD/GD) is strong, independent evidence that a "hypothetical" locus encodes a functional, selectively required gene — orthogonal to intra-species conservation.
Proteomics (mass spectrometry) detected
| MS detection | detected in 1 of 16 independent MS datasets |
|---|---|
| Integrated abundance | 16.8 ppm · rank 2434/3519 (30.9th percentile) |
Detection by mass spectrometry is direct, experimental evidence that the protein product exists — orthogonal to sequence conservation and to Tn-seq essentiality, and especially decisive for a "hypothetical" locus. Reproducible detection across several independent datasets (PaxDb) makes the existence claim robust; the integrated abundance places the protein in the proteome's dynamic range.
Physico-chemical properties (computed, ProtParam)
| Length | 62 aa |
|---|---|
| Molecular weight | 6.5 kDa |
| Theoretical pI | 11.31 |
| GRAVY | -0.531 (hydrophilic) |
| Aliphatic index | 72.4 |
| Aromaticity | 0.016 |
| Instability index | 63.8 (unstable) |
Computed from the ancestral MTBC0 sequence with the ExPASy ProtParam method (Biopython). Descriptive biophysical context: a positive GRAVY flags a hydrophobic (often membrane) protein, a high instability index (>40) predicts a short in-vitro half-life, an extreme pI hints at compartment or binding partner.
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)
Explore full network →Node colour = verdict, dashed = hypothetical; edge colour = evidence (green experimental, orange genomic-context, grey co-expression), width ∝ score. Click a partner to open its page; "Explore full network" to walk the graph.
Closest characterised functional partner: Rv3224 (iron-regulated short-chain dehydrogenase/reductase), high confidence from genomic context alone (score 849 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) |
|---|---|---|---|---|
Rv3224 |
iron-regulated short-chain dehydrogenase/reductase | 849 | 849 ctx | neighborhood:781 |
Rv3224B |
Rv3224B, len: 72 aa. Conserved hypothetical protein (possibly gene fragment), similar to C-terminal part of ML0799|AL583919_131 conserved hy | 808 | 808 ctx | neighborhood:781 |
Rv3221A rshA |
anti-sigma factor RshA | 420 | 420 ctx | neighborhood:412 |
Rv3222c hyp |
hypothetical protein | 418 | 418 ctx | neighborhood:412 |
Rv3223c sigH |
ECF RNA polymerase sigma factor SigH | 415 | 415 ctx | neighborhood:412 |
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 exp badge marks an experimentally-supported partner (measured interaction, experimental/database channel ≥400) as opposed to a purely predicted one — but note that the M. tuberculosis experimental interactome is dominated by a noisy bacterial-two-hybrid screen, so a strong measured link that contradicts the operon/localisation context is likely a false positive. 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.
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 )
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG2606 - Curated reference: UniProt Q6MWZ5 (TrEMBL, unreviewed)
- 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 —
5 functional partner(s); context anchor
Rv3224 - Essentiality: genome-wide transposon mutagenesis in H37Rv — DeJesus et al. 2017 (mBio, doi:10.1128/mBio.02133-16, CC BY)
- Proteomics: integrated mass-spectrometry abundance from PaxDb 5.0 (Huang et al. 2023, doi:10.1016/j.mcpro.2023.100640), taxon 83332 — weighted average of 16 datasets, incl. Schubert et al. 2013 (doi:10.1016/j.chom.2013.04.008) and Albrethsen et al. 2013 (doi:10.1074/mcp.M112.018846)
- Functional category: TubercuList scheme (Cole et al. 1998, doi:10.1038/31159), via Mycobrowser (Kapopoulou et al. 2011, doi:10.1016/j.tube.2010.09.006)
- Physico-chemical properties: ExPASy ProtParam method via Biopython (Gasteiger et al. 2005), computed from the MTBC0 sequence
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>|Rv3224A|Rv3224A VRRSASTCGWKTPTRRGTSRPSDSKTLILELPDERAVAIVPVPSKLSLKAAGGPRGAQSGHG
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