Rv0108c Family assigned · low

H37Rv Rv0108c · MTBC0 - · 69 aa · 130895–131104 (-) · RefSeq NP_214622.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Small OB-fold / twisted beta-sandwich protein; ambiguous fold-level match (phage head-to-tail joining gpFII-like and/or EF-P/eIF5A OB-fold); function undetermined RefSeq leaves this locus uncharacterised.

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt O53630 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 group2AYND

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 0.318 · purifying
Polymorphic sites (≥ 0.1% of strains) 1 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 81.2 (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
1yby-assembly1_A 1.00 0.71 1.6e-02 1yby-assembly1_A Conserved hypothetical protein Cth-95 from Clostridium thermocellum
1yby-assembly1_B 1.00 0.69 4.4e-02 1yby-assembly1_B Conserved hypothetical protein Cth-95 from Clostridium thermocellum
1ueb-assembly1_A 1.00 0.63 1.5e-02 1ueb-assembly1_A Crystal structure of translation elongation factor P from Thermus thermophilus HB8
4v6a-assembly2_CV 1.00 0.70 5.4e-02 4v6a-assembly2_CV Structure of EF-P bound to the 70S ribosome.
5wxk-assembly1_B 1.00 0.66 4.9e-02 5wxk-assembly1_B EarP bound with domain I of EF-P
3a5z-assembly1_B 1.00 0.70 8.0e-02 3a5z-assembly1_B Crystal structure of Escherichia coli GenX in complex with elongation factor P
8qzv-assembly1_A 1.00 0.71 1.3e-01 8qzv-assembly1_A Crystal structure of translation factor eIF5A from Trichomonas vaginalis
1ueb-assembly2_B 1.00 0.60 2.5e-02 1ueb-assembly2_B Crystal structure of translation elongation factor P from Thermus thermophilus HB8

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

Closest characterised functional partner: Rv0110 (integral membrane protein), medium confidence from genomic context alone (score 620 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv0110 integral membrane protein 619 620 ctx neighborhood:618
Rv0109 PE_PGRS1 PE-PGRS family protein PE_PGRS1 445 446 ctx neighborhood:446
Rv0107c ctpI cation-transporter ATPase I 417 418 ctx neighborhood:412
Rv0863 hyp hypothetical protein 871 50 textmining:870
Rv0546c hyp hypothetical protein 497 47 textmining:494
Rv3279c birA bifunctional biotin operon repressor/biotin--[acetyl-CoA-carboxylase 653 46 textmining:652
Rv2814c Probable transposase; Rv2814c, (MTCY16B7.29), len: 328 aa. Probable transposase subunit for IS6110. Identical to many other M. tuberculosis 511 44 textmining:510
Rv0180c transmembrane protein 806 41 textmining:806
Rv1779c integral membrane protein 446 41 textmining:446
Rv2961 transposase 430 41 textmining:430

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 1.85 low, no significant E): phage head-tail joining 92% E0.65 + EF-P/eIF5A 84-68%; fold-level only, weak profile
  • 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_214622.1)
  • 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 2AYND
  • Curated reference: UniProt O53630 (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 81.2, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 10 functional partner(s); context anchor Rv0110
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0108c|
MVPVETLHSGDPITDVNGGGQRYIVLESKTVGDSCVVLELESRVNHQLQVIEKSFPAGYHVGRAHHRIL