Rv2668 Family assigned · low auto-curated · to review

H37Rv Rv2668 · MTBC0 mtbc0_002842 · 173 aa · 3006936–3007457 (+) · RefSeq NP_217184.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationhypothetical protein
Revised (this work)No Pfam domain above threshold; Foldseek indicates a fold similar to 3cfu-assembly1_A Crystal structure of the yjhA protein from Bacillus subtilis. N (prob 1.00, TM 0.61). Structure-based, putative.

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed (flagged for human review).

Curated reference (UniProt)

UniProt P71965 TrEMBL · unreviewed · Evidence at protein level
UniProt namePossible exported alanine and valine rich protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2ARUH

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 0.875 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 5 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 84.5 (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
3cfu-assembly1_A 1.00 0.61 2.7e-04 sig 3cfu-assembly1_A Crystal structure of the yjhA protein from Bacillus subtilis. Northeast Structural Genomics Consortium target SR562
3cfu-assembly2_B 1.00 0.66 8.0e-04 sig 3cfu-assembly2_B Crystal structure of the yjhA protein from Bacillus subtilis. Northeast Structural Genomics Consortium target SR562
5bxg-assembly1_A 1.00 0.52 8.9e-04 sig 5bxg-assembly1_A Crystal structure of an uncharacterized beta-sandwich protein (CD630_09570) from Clostridium difficile 630 at 1.90 A resolution
4les-assembly1_A 0.99 0.49 1.4e-02 4les-assembly1_A 2.2 Angstrom Crystal Structure of Conserved Hypothetical Protein from Bacillus anthracis.
3nrf-assembly1_B 0.98 0.48 1.2e-02 3nrf-assembly1_B Crystal structure of an apag protein (PA1934) from pseudomonas aeruginosa pao1 at 1.50 A resolution
4eae-assembly1_B 0.96 0.43 9.9e-03 sig 4eae-assembly1_B The crystal structure of a functionally unknown protein from Listeria monocytogenes EGD-e
4eae-assembly1_A 0.95 0.41 8.9e-03 sig 4eae-assembly1_A The crystal structure of a functionally unknown protein from Listeria monocytogenes EGD-e
1tza-assembly1_B 0.72 0.36 2.1e-02 1tza-assembly1_B X-ray structure of Northeast Structural Genomics Consortium target SoR45

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

Closest characterised functional partner: Rv2669 (GCN5-like N-acetyltransferase), high confidence from genomic context alone (score 841 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv2669 GCN5-like N-acetyltransferase 841 841 ctx neighborhood:839
Rv2667 clpC2 ATP-dependent protease ATP-binding subunit ClpC 787 787 ctx neighborhood:786
Rv2666 Probable transposase for insertion sequence element IS1081 (fragment); Required for the transposition of the insertion element. 518 518 ctx neighborhood:518

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

  • Legacy H37Rv annotation: hypothetical protein
  • MTBC0 PGAP product: hypothetical protein
  • Foldseek best: 3cfu-assembly1_A Crystal structure of the yjhA protein from Bacillus subtilis. N (prob 1.00, E=3e-04, TM=0.61)
  • (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)

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_217184.1)
  • 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 2ARUH
  • Curated reference: UniProt P71965 (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 84.5, confident)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 3 functional partner(s); context anchor Rv2669
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002842|Rv2668|
MRRWLIVLATLLVAAAGVAAANDVPRAWAGDAPIGHIGDTLRVDTGTYVADVTVSSVVPVDPPPGFGYTRSGVPVKSFPDSSVTRADVTVRAVRVPNSFILATNFSFTGVTPFADAYKPRPCDASDWLDAALGNAPQGSIVRGGVYWDAYRDPVSVVVLLDKKTGQHLAQWNL