Rv3122 Still unknown · low auto-curated

H37Rv Rv3122 · MTBC0 - · 156 aa · 3488089–3488559 (+) · RefSeq NP_217638.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF6788. Function unknown. Foldseek best (non-significant) hit: 2w9j-assembly1_A The crystal structure of SRP14 from the Schizosacchar (prob 0.41, TM 0.31).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

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 O07033 TrEMBL · unreviewed · Predicted
UniProt nameDUF6788 domain-containing protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

Orthologous group2C62F

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 n/a
Polymorphic sites (≥ 0.1% of strains) 0 synonymous, 4 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.20% of strains (291) · 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)

PfamAccessioni-EvalueResiduesDescription
DUF6788PF20586.4 1.3e-1621–98 Domain of unknown function (DUF6788)

Structural neighbours (Foldseek on the ESMFold model, exploratory)

ESMFold model confidence: mean pLDDT 90.6 (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
2w9j-assembly1_A 0.41 0.31 9.7e-02 2w9j-assembly1_A The crystal structure of SRP14 from the Schizosaccharomyces pombe signal recognition particle
3v47-assembly1_C 0.14 0.42 1.6e+00 3v47-assembly1_C Crystal structure of the N-terminal fragment of zebrafish TLR5 in complex with Salmonella flagellin
5m3k-assembly1_E 0.11 0.40 3.4e+00 5m3k-assembly1_E A multi-component acyltransferase PhlABC from Pseudomonas protegens
7qcd-assembly1_A 0.11 0.43 2.5e+00 7qcd-assembly1_A CryoEM structure of the Smc5/6-holocomplex (composite structure)
6vy1-assembly1_G 0.09 0.33 2.1e+00 6vy1-assembly1_G Cryo-EM structure of filamentous PFD from Methanocaldococcus jannaschii
4rbr-assembly1_B 0.07 0.40 5.0e+00 4rbr-assembly1_B Crystal structure of Repressor of Toxin (Rot), a central regulator of Staphylococcus aureus virulence
4r79-assembly1_B 0.05 0.18 9.8e-01 4r79-assembly1_B Mos1 transposase paired-end complex with left transposon end
2pmz-assembly2_V 0.04 0.23 3.2e+00 2pmz-assembly2_V Archaeal RNA polymerase from Sulfolobus solfataricus

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

PartnerProductScoreNo text-miningChannels (≥400)
Rv3123 hyp hypothetical protein 773 773 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 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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
  • Pfam (hmmscan --cut_ga): DUF6788 PF20586.4 (E=1e-16)
  • Foldseek best: 2w9j-assembly1_A The crystal structure of SRP14 from the Schizosaccharomyces pom (prob 0.41, E=1e-01, TM=0.31)
  • (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_217638.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF6788 (PF20586.4)
  • 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 2C62F
  • Curated reference: UniProt O07033 (TrEMBL, unreviewed; Predicted)
  • 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 90.6, very high)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 1 functional partner(s)
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3122|
MYSGCWINNQNGETRVGEDSLEDLEQRRARLYDQLAATGDFRRGSISENYRRCGKPNCVCAQEGHPGHGPRYLWTRTVAGRGTKGRQLSVEEVDKVRAELANYHRFAQVSEQIVAVNEAICEARPPNPAATAPPAGTTGHKKGGSATRSRRSSPPR