Rv2306A Family assigned · low auto-curated · to review
H37Rv Rv2306A · MTBC0 ·
197 aa ·
2577108–2577701 H37Rv
(+) ·
RefSeq
Genomic neighbourhood (genome browser)
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Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | Possible conserved membrane protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Possible conserved membrane protein |
| Functional category (TubercuList) | cell wall and cell processes |
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 | 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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.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 |
Q79FG5
TrEMBL · unreviewed
|
|---|---|
| UniProt name | TVP38/TMEM64 family membrane protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | PFAM SNARE associated Golgi protein |
| Orthologous group | COG0398 |
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 | 1.17 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 3 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) | 8 in the ORF — 0 in the essential state, 0 growth-defect, 8 non-essential, 0 growth-advantage. Saturation 0.875, mean read count 143.428571429. 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 8 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 8 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) 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.
Predicted localisation (DeepTMHMM + lipobox)
| Prediction | predicted membrane protein (3 TM helixes) |
|---|---|
| DeepTMHMM class | TM |
| TM helices (DeepTMHMM) | 3 |
Transmembrane topology and signal peptide from DeepTMHMM (deep-learning reference predictor); lipoproteins from a (myco)bacterial lipobox motif. A sequence-based prediction of subcellular context.
Physico-chemical properties (computed, ProtParam)
| Length | 197 aa |
|---|---|
| Molecular weight | 21.2 kDa |
| Theoretical pI | 11.81 |
| GRAVY | 0.083 (hydrophobic) |
| Aliphatic index | 81.8 |
| Aromaticity | 0.081 |
| Instability index | 86.2 (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).
Transcriptional regulation (signed TRN: ChIP-seq + TFOE)
| Regulated by (1 TF) |
Rv1990c (represses)
|
|---|
Regulatory edges from the ISB signed transcriptional regulatory network (TF ChIP-seq binding, Minch 2015 + TF-overexpression response, Rustad 2014). An edge is regulatory evidence (binding and/or expression change), not necessarily direct. For a "hypothetical", membership in a known regulon (e.g. DosR dormancy, PhoP virulence) is a strong physiological-context lead.
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: Rv2306B (Rv2306B, len: 144 aa. Possible conserved membrane protein, similar to C-terminal part of several hypothetical membrane proteins from Mycobac), high confidence from genomic context alone (score 797 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2306B |
Rv2306B, len: 144 aa. Possible conserved membrane protein, similar to C-terminal part of several hypothetical membrane proteins from Mycobac | 797 | 797 ctx | neighborhood:773 |
Rv2305 hyp |
hypothetical protein | 774 | 774 ctx | neighborhood:770 |
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
COG0398 - Curated reference: UniProt Q79FG5 (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 —
2 functional partner(s); context anchor
Rv2306B - 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)
- Transcriptional regulation: ISB signed TRN — TF ChIP-seq (Minch et al. 2015, doi:10.1038/ncomms6829) + TF overexpression (Rustad et al. 2014, doi:10.1186/gb-2014-15-11-502)
- Physico-chemical properties: ExPASy ProtParam method via Biopython (Gasteiger et al. 2005), computed from the MTBC0 sequence
- Predicted localisation: DeepTMHMM (Hallgren et al. 2022, doi:10.1101/2022.04.08.487609) for transmembrane topology and signal peptide
- Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>|Rv2306A|Rv2306A MTDNECPADSRRRHVLRLALFAGILLGLFYLVAVARVIHVDGVRSAIVVATGPIAPLAYVVVSAALGALFVPGPILAAGSGVLFGPLLDTFVTLPAFSAGAQAGMTPRRCWVSIAPIASMHRSNGADCGRWSVSASSPASRMRWPRTPSGRSEFRCGRWSLGRSSGRRHGCSSTPRWARRSPTCRRRWFTRRSRCGA
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