Rv3067 Still unknown · low auto-curated

H37Rv Rv3067 · MTBC0 - · 136 aa · 3431428–3431838 (+) · RefSeq NP_217583.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotation
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF732. Function unknown. Foldseek best (non-significant) hit: 3j9x-assembly1_A A Virus that Infects a Hyperthermophile Encapsidates (prob 0.16, TM 0.56).

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 I6YB21 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv3067

UniProt still lists this protein as Uncharacterized protein Rv3067; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF732)
Orthologous group2AY8K

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 1.096 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 6 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)

PfamAccessioni-EvalueResiduesDescription
DUF732PF05305.20 1.1e-1558–126 Protein of unknown function (DUF732)

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
3j9x-assembly1_A 0.16 0.56 5.1e+00 3j9x-assembly1_A A Virus that Infects a Hyperthermophile Encapsidates A-Form DNA
8pv8-assembly1_CS 0.04 0.24 5.1e+00 8pv8-assembly1_CS Chaetomium thermophilum pre-60S State 4 - post-5S rotation with Rix1 complex without Foot - composite structure

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

Closest characterised functional partner: Rv3066 (DeoR family transcriptional regulator), medium confidence from genomic context alone (score 558 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3066 DeoR family transcriptional regulator 559 558 ctx neighborhood:556
Rv3091 hyp hypothetical protein 544 544 ctx neighborhood:544
Rv3065 mmr multidrug resistance protein Mmr 534 534 ctx neighborhood:527
Rv0711 atsA arylsulfatase AtsA 803 45 textmining:803
Rv3537 kstD 3-oxosteroid 1-dehydrogenase 438 44 textmining:437
Rv0145 S-adenosylmethionine-dependent methyltransferase 759 42 textmining:759
Rv2466c hyp hypothetical protein 654 42 textmining:654
Rv3001c ilvC ketol-acid reductoisomerase 652 42 textmining:652
Rv0140 hyp hypothetical protein 803 41 textmining:803

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): DUF732 PF05305.20 (E=1e-15)
  • Foldseek best: 3j9x-assembly1_A A Virus that Infects a Hyperthermophile Encapsidates A-Form DNA (prob 0.16, E=5e+00, TM=0.56)
  • (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_217583.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF732 (PF05305.20)
  • 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 2AY8K
  • Curated reference: UniProt I6YB21 (SwissProt, reviewed; 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 — 9 functional partner(s); context anchor Rv3066
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3067|
MLTVGVGIGAAILLGWFTLAHRHPDQPGAAATPPPAGLTTRSAPTAAPPSTLQSPDLDSVFLGNLHDRGISFTNPDAAVYNGKMVCTNLGGGMTVQQVVEALQSSSPALGDRTTAYVAVSIRTYCPKYDAVLPPGS