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 functionUnknown

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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.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 nameUncharacterized protein Rv1954A

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2ECQY

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 callGA · growth-advantage
What the call meansgrowth-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.
CaveatRead 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 detectiondetected in 8 of 16 independent MS datasets
Integrated abundance20.0 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)

Length100 aa
Molecular weight10.2 kDa
Theoretical pI10.04
GRAVY-0.501 (hydrophilic)
Aliphatic index54.5
Aromaticity0.03
Instability index47.7 (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)

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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.

PartnerProductScoreNo text-miningChannels (≥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