Rv1954A Still unknown · low auto-curated · to review
H37Rv Rv1954A · MTBC0 ·
100 aa ·
2201277–2201579 H37Rv
(+) ·
RefSeq
Genomic neighbourhood (genome browser)
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Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Functional category (TubercuList) | unknown |
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).
In the literature (TB corpus sweep)
This distinguishes a gene that is dark because nobody has looked from one that is dark despite having been studied. Source: .
Legacy record & comparison (Mycobrowser)
| Mycobrowser 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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.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 |
P0CV86
SwissProt · reviewed
|
|---|---|
| UniProt name | Uncharacterized protein Rv1954A |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2ECQY |
|---|
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 | 0.697 · 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.
Essentiality (transposon mutagenesis)
| DeJesus 2017 call | GA · growth-advantage |
|---|---|
| What the call means | growth-advantage: insertions enriched |
| TA sites (Himar1) | 5 in the ORF — 0 in the essential state, 0 growth-defect, 0 non-essential, 5 growth-advantage. Saturation 1.000, mean read count 302.2. A region of the protein devoid of TA sites is invisible to this assay: nothing can be inferred about it, in either direction. |
| Caveat | Read with some caution: only 5 TA (Himar1) sites in the whole ORF (atlas median 13). The DeJesus 2017 call rests on fewer independent observations than for a longer gene. If this gene overlaps a neighbour (see Genomic-neighbour overlap section below), some of these 5 sites may fall inside the neighbour's ORF rather than its own, leaving even fewer truly informative sites than the raw count suggests. (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 8 of 16 independent MS datasets |
|---|---|
| Integrated abundance | 20.0 ppm · rank 2341/3519 (33.5th 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 | 100 aa |
|---|---|
| Molecular weight | 10.2 kDa |
| Theoretical pI | 10.04 |
| GRAVY | -0.501 (hydrophilic) |
| Aliphatic index | 54.5 |
| Aromaticity | 0.03 |
| Instability index | 47.7 (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: higB (toxin HigB), medium confidence from genomic context alone (score 513 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) |
|---|---|---|---|---|
Rv2450c rpfE exp |
resuscitation-promoting factor RpfE | 881 | 881 | coexpression:490 experimental:769 |
Rv1884c rpfC exp |
resuscitation-promoting factor RpfC | 881 | 881 | coexpression:490 experimental:769 |
Rv2389c rpfD exp |
resuscitation-promoting factor RpfD | 870 | 870 | coexpression:443 experimental:769 |
Rv0867c rpfA exp |
resuscitation-promoting factor RpfA | 870 | 870 | coexpression:443 experimental:769 |
Rv1861 |
transmembrane protein | 543 | 517 | coexpression:508 |
Rv1955 higB |
toxin HigB | 618 | 513 ctx | neighborhood:513 |
Rv3491 hyp |
hypothetical protein | 432 | 432 | coexpression:432 |
Rv3490 otsA |
trehalose-phosphate synthase | 432 | 432 | coexpression:432 |
Rv1957 secBL |
SecB-like chaperone | 661 | 429 ctx | neighborhood:429 textmining:431 |
Rv1956 higA |
antitoxin HigA | 554 | 429 ctx | neighborhood:429 |
Rv2771c hyp |
hypothetical protein | 412 | 413 | coexpression:413 |
Rv0925c hyp |
hypothetical protein | 412 | 413 | coexpression:413 |
Rv3372 otsB2 |
trehalose 6-phosphate phosphatase | 412 | 412 | coexpression:412 |
Rv2006 otsB1 |
trehalose-6-phosphate phosphatase OtsB | 412 | 412 | coexpression:412 |
Rv0887c hyp |
hypothetical protein | 406 | 372 |
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
2ECQY - Curated reference: UniProt P0CV86 (SwissProt, reviewed)
- 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 —
19 functional partner(s); context anchor
higB - 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
>|Rv1954A|Rv1954A MARGRVVCIGDAGCDCTPGVFRATAGGMPVLVVIESGTGGDQMARKATSPGKPAPTSGQYRPVGGGNEVTVPKGHRLPPSPKPGQKWVNVDPTKNKSGRG
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