Rv2998A Family assigned · low auto-curated · to review
H37Rv Rv2998A · MTBC0 ·
67 aa ·
3357225–3357428 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 | — |
| 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).
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 | 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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.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 |
Q6MX20
TrEMBL · unreviewed
|
|---|---|
| UniProt name | histidine kinase |
| EC (curated) |
EC 2.7.13.3
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
T Signal transduction mechanisms
|
|---|---|
| eggNOG description | HAMP (Histidine kinases, Adenylyl cyclases, Methyl binding proteins, Phosphatases) domain |
| Orthologous group | COG0642 |
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 | 0.0 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 0 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.11% of strains (161) · clonal |
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 | Uncertain · uncertain |
|---|---|
| What the call means | uncertain (short or TA-poor ORF): no call possible |
| TA sites (Himar1) | 2 in the ORF — 0 in the essential state, 0 growth-defect, 2 non-essential, 0 growth-advantage. Saturation 0.500, mean read count 5. 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 2 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) not detected
Not detected in the mass-spectrometry datasets integrated by PaxDb. This is not evidence of absence: low-abundance, condition-specific, or MS-refractory proteins (e.g. small, highly hydrophobic, or repetitive PE/PPE families with few tryptic peptides) are systematically under-sampled.
Physico-chemical properties (computed, ProtParam)
| Length | 67 aa |
|---|---|
| Molecular weight | 7.6 kDa |
| Theoretical pI | 6.92 |
| GRAVY | -0.488 (hydrophilic) |
| Aliphatic index | 96.3 |
| Aromaticity | 0.045 |
| Instability index | 32.8 (stable) |
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: tcrA (two component DNA binding transcriptional regulator TcrA), high confidence from genomic context alone (score 751 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) |
|---|---|---|---|---|
Rv0602c tcrA |
two component DNA binding transcriptional regulator TcrA | 759 | 751 ctx | cooccurence:408 |
Rv1248c kgd exp |
multifunctional 2-oxoglutarate dehydrogenase E1 component /2-oxoglutarate dehydrogenase dihydrolipoyllysine-residue succinyltransferase | 757 | 728 | experimental:422 database:538 |
Rv2496c bkdB exp |
3-methyl-2-oxobutanoate dehydrogenase subunit beta | 742 | 728 | database:590 |
Rv1734c hyp exp |
hypothetical protein | 726 | 715 | experimental:401 database:538 |
Rv2215 dlaT exp |
pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase | 725 | 715 | experimental:401 database:538 |
Rv2495c bkdC exp |
branched-chain keto acid dehydrogenase E2 component | 724 | 713 | experimental:401 database:538 |
Rv1017c prsA exp |
ribose-phosphate pyrophosphokinase | 712 | 696 | database:586 |
Rv0981 mprA |
two-component response regulator MrpA | 666 | 654 | |
Rv1033c trcR |
two component transcriptional regulator TrcR | 652 | 640 | |
Rv0757 phoP |
two component system response transcriptional positive regulator PhoP | 649 | 636 | |
Rv3765c tcrX |
two component transcriptional regulator TcrX | 644 | 631 | |
Rv2299c htpG exp |
chaperone protein HtpG | 627 | 604 | database:537 |
Rv0794c exp |
oxidoreductase | 610 | 594 | database:527 |
Rv2713 sthA exp |
pyridine nucleotide transhydrogenase | 607 | 591 | database:527 |
Rv3303c lpdA exp |
NAD(P)H quinone reductase LpdA | 606 | 589 | database:527 |
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
COG0642 - Curated reference: UniProt Q6MX20 (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)
- Genome-wide structure: AlphaFold DB model (Jumper et al. 2021, doi:10.1038/s41586-021-03819-2; Varadi et al. 2024, doi:10.1093/nar/gkad1011) searched vs PDB with Foldseek (mean pLDDT 91.1)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
52 functional partner(s); context anchor
tcrA - Essentiality: genome-wide transposon mutagenesis in H37Rv — DeJesus et al. 2017 (mBio, doi:10.1128/mBio.02133-16, CC BY)
- 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
>|Rv2998A|Rv2998A VERMRIRAAGISATDPHARLPLPLARDEIRYLGTTFNDLLQRLQDALERERQFVSDAGHELRTPLAS
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