Rv0307c Family assigned · low

H37Rv Rv0307c · MTBC0 mtbc0_000327 · 160 aa · 379896–380378 (-) · RefSeq NP_214821.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)PH/GRAM-superfamily fold (pleckstrin-homology-like beta-sandwich, typically lipid/membrane-binding); specific function undetermined RefSeq leaves this locus uncharacterised.

Curated reference (UniProt)

UniProt O07234 TrEMBL · unreviewed · Evidence at protein level
UniProt nameUncharacterized protein

UniProt still lists this protein as Uncharacterized protein; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group29ZRI

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 0.182 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 1 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.

Domains (Pfam, hmmscan --cut_ga)

No Pfam-A domain above the gathering threshold (or not yet scanned).

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 89.4 (confident). A confident model makes the fold comparison meaningful.

Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.

TargetProbTME-valueDescription
8ujw-assembly1_A 0.33 0.33 6.3e-02 8ujw-assembly1_A Crystal structure of the KETc7 antigen from Taenia solium
2dtc-assembly1_B 0.30 0.30 7.0e-02 2dtc-assembly1_B Crystal structure of MS0666
2lfu-assembly1_A 0.13 0.30 1.8e-01 2lfu-assembly1_A The structure of a N. meningitides protein targeted for vaccine development
1r0u-assembly1_A 0.10 0.33 1.2e+00 1r0u-assembly1_A Crystal structure of ywiB protein from Bacillus subtilis
7cso-assembly2_B 0.07 0.29 1.0e+00 7cso-assembly2_B Structure of Ephexin4 DH-PH-SH3
3o12-assembly1_A 0.04 0.21 5.3e-01 3o12-assembly1_A The crystal structure of a functionally unknown protein from Saccharomyces cerevisiae.
2vdu-assembly2_B 0.04 0.34 3.0e+00 2vdu-assembly2_B Structure of trm8-trm82, THE YEAST TRNA m7G methylation complex
8j07-assembly1_3G 0.04 0.27 1.9e+00 8j07-assembly1_3G 96nm repeat of human respiratory doublet microtubule and associated axonemal complexes

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: Rv0308 (integral membrane protein), high confidence from genomic context alone (score 789 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0308 integral membrane protein 788 789 ctx neighborhood:787
Rv0309 hyp hypothetical protein 685 685 ctx neighborhood:684
Rv0306 bluB oxidoreductase 554 554 ctx neighborhood:544
Rv0296c sulfatase 546 547 ctx neighborhood:544

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 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.

Evidence

  • HHpred (Neff 5.76): convergent PH-superfamily hits - GRAM domain 93% (E1), methylosome pICln PH-domain 87%, Vps36 GLUE/PH-domain (ESCRT-II lipid-binding) 78%; fold-level assignment
  • HHpred web (MPI Bioinformatics Toolkit, profile-profile remote homology), interpreted in project 'Still unknown gene function', 2026-06-10. A fold/family-level assignment, not a demonstrated 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 NP_214821.1)
  • 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 29ZRI
  • Curated reference: UniProt O07234 (TrEMBL, unreviewed; Evidence at protein level)
  • Intra-MTBC selection: pN/pS and disruption from SPDI variants of 145 209 MTBC strains (this work, local collection vs H37Rv NC_000962.3)
  • Model confidence: ESMFold per-residue pLDDT (mean 89.4, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 4 functional partner(s); context anchor Rv0308
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000327|Rv0307c|
MAVIVRKWFGLGRLPADLRCQVEAEGLIYLAEYVAVTRRFTGVIPGLRASHSIASYVGALAFTEQRVLGTLSMVPKLAGRVVDARWDGPQAGAATAEISPTGLQLDLDVADVDPKFSGQLALHFKATIGEDVLSRLPRRSLAFDVPAEYVNLAVGVTYSP