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 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 Mycobrowser is no longer maintained; its EC numbers predate recent nomenclature revisions, so a class change usually reflects re-numbering, not a conflict.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 Q79FG5 TrEMBL · unreviewed
UniProt nameTVP38/TMEM64 family membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionPFAM SNARE associated Golgi protein
Orthologous groupCOG0398

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 callNE · non-essential
What the call meansnon-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.
CaveatRead 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)

Predictionpredicted membrane protein (3 TM helixes)
DeepTMHMM classTM
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)

Length197 aa
Molecular weight21.2 kDa
Theoretical pI11.81
GRAVY0.083 (hydrophobic)
Aliphatic index81.8
Aromaticity0.081
Instability index86.2 (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)

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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: 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).

PartnerProductScoreNo text-miningChannels (≥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