Rv3415c Family assigned · low auto-curated · to review

H37Rv Rv3415c · MTBC0 mtbc0_003629 · 275 aa · 3859133–3859960 (-) · RefSeq NP_217932.1

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 8rsv-assembly1_A Rap from bacteriophage Phi3T in presence of pheromone RRGHTAS (prob 1.00, TM 0.65). 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 I6YG27 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 group2F0NR

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 2.676 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 6 missense, 1 nonsense, 1 frameshift
Disruption 2 distinct premature-stop/frameshift site(s); most common in 0.55% of strains (801) · clonal

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 96.8 (very high). 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
8rsv-assembly1_A 1.00 0.65 6.2e-04 sig 8rsv-assembly1_A Rap from bacteriophage Phi3T in presence of pheromone RRGHTAS
8rte-assembly1_B 1.00 0.63 5.7e-04 sig 8rte-assembly1_B Rap from bacteriophage Phi105 with peptide ERPVGT
8rsv-assembly2_B 1.00 0.61 1.3e-03 sig 8rsv-assembly2_B Rap from bacteriophage Phi3T in presence of pheromone RRGHTAS
7t7t-assembly2_B 1.00 0.71 4.0e-03 sig 7t7t-assembly2_B Structure of TSK/BRU1 bound to histone H3.1
8jau-assembly1_A 1.00 0.68 3.8e-03 sig 8jau-assembly1_A Structure of CRL2APPBP2 bound with the C-degron of MRPL28 (dimer)
1hz4-assembly1_A 1.00 0.53 6.8e-04 sig 1hz4-assembly1_A CRYSTAL STRUCTURE OF TRANSCRIPTION FACTOR MALT DOMAIN III
8rsu-assembly1_A 1.00 0.61 2.3e-03 sig 8rsu-assembly1_A Rap from bacteriophage Phi3T in presence of pheromone RRGHTA
5a7d-assembly4_D 1.00 0.55 3.2e-03 sig 5a7d-assembly4_D Tetrameric assembly of LGN with Inscuteable

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

Closest characterised functional partner: rsdA (anti-sigma-D factor RsdA), high confidence from genomic context alone (score 869 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3413c rsdA anti-sigma-D factor RsdA 868 869 ctx neighborhood:767 cooccurence:459
Rv3414c sigD ECF RNA polymerase sigma factor SigD 783 784 ctx neighborhood:783
Rv2695 hyp hypothetical protein 771 771 ctx cooccurence:768
Rv2418c octT hyp hypothetical protein 771 771 ctx cooccurence:770
Rv2186c hyp hypothetical protein 763 763 ctx cooccurence:762
Rv0383c ttfA hyp hypothetical protein 758 758 ctx cooccurence:758
Rv1111c hyp hypothetical protein 743 743 ctx cooccurence:743
Rv2091c membrane protein 741 741 ctx cooccurence:741
Rv1109c hyp hypothetical protein 736 736 ctx cooccurence:736
Rv2743c hyp hypothetical protein 732 732 ctx cooccurence:731
Rv0250c hyp hypothetical protein 731 731 ctx cooccurence:730
Rv3212 hyp hypothetical protein 731 731 ctx cooccurence:730
Rv0556 transmembrane protein 721 721 ctx cooccurence:721
Rv0481c hyp hypothetical protein 718 719 ctx cooccurence:717
Rv0996 transmembrane protein 717 717 ctx cooccurence:717

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: 8rsv-assembly1_A Rap from bacteriophage Phi3T in presence of pheromone RRGHTAS (prob 1.00, E=6e-04, TM=0.65)
  • (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_217932.1)
  • 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 2F0NR
  • Curated reference: UniProt I6YG27 (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 96.8, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 121 functional partner(s); context anchor rsdA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003629|Rv3415c|
MNETPHAPVVEQVLVAAAFGNQPGSWPLPTAITPHHLWLRAVAAGGQGRYAHAYGDLSVLRRLVPAGPLASLAHSTQGSLLRQLGWHTLARGWDGRALALAGADREAGADALIGLAADALGVGRFAAAGALLDRADPLVVSPLVADRLAVRRRWVAAELAMATGDGATAVRHAEEAVELTQAMAVASARHRVKSDVVLAAALCSAGAVARARAVGEEALDATARFGLLPLRWALACLLIDIGTVTFSAQQLRELTKIRNICAGQVRRAGGCWRTA