Rv3689 Resolved · medium auto-curated

H37Rv Rv3689 · MTBC0 - · 451 aa · 4130357–4131712 (+) · RefSeq NP_218206.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotation
Revised (this work)Transmembrane protein.

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 I6YCR8 TrEMBL · unreviewed · Predicted
UniProt nameProbable conserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category A RNA processing and modification
eggNOG descriptionpathogenesis
Orthologous groupCOG5180

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 1.06 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 8 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
DUF7847PF25231.2 3.3e-08137–410 Domain of unknown function (DUF7847)

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

Closest characterised functional partner: Rv3690 (membrane protein), high confidence from genomic context alone (score 962 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3690 membrane protein 961 962 ctx neighborhood:843 cooccurence:761
Rv3691 hyp hypothetical protein 938 938 ctx neighborhood:737 cooccurence:765
Rv3693 membrane protein 911 911 ctx neighborhood:671 cooccurence:733
Rv3692 moxR2 methanol dehydrogenase transcriptional regulator MoxR 782 783 ctx neighborhood:737
Rv3695 membrane protein 771 772 ctx cooccurence:758
Rv3694c transmembrane protein 752 752 ctx cooccurence:741
Rv3688c hyp hypothetical protein 598 599 ctx neighborhood:596
Rv1616 hyp hypothetical protein 689 561 ctx cooccurence:557
Rv2226 hyp hypothetical protein 502 503 ctx cooccurence:502
Rv2560 hyp hypothetical protein 471 472 ctx cooccurence:464
Rv1006 hyp hypothetical protein 439 439 ctx cooccurence:434
Rv3033 hyp hypothetical protein 420 420 ctx cooccurence:420
Rv1126c hyp hypothetical protein 400 401
Rv1870c hyp hypothetical protein 577 51 textmining:573
Rv2585c lipoprotein 553 51 textmining:549

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): transmembrane protein
  • Pfam (hmmscan --cut_ga): DUF7847 PF25231.2 (E=3e-08)
  • (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_218206.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF7847 (PF25231.2)
  • 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 COG5180
  • Curated reference: UniProt I6YCR8 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 16 functional partner(s); context anchor Rv3690
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3689|
MHKRYAPQRPKPDTETYIEKCTDRRQDGGHDERRQLLRPVSMLPPGYPVEPPPVAPGYAPAGYPPYPATPPGYGPPGYGAPPSYGPPPGYGPPLGYPAAPPGCGPPPGYGPPLGYGPPVAPGAVKPGIIPLRPLTLSDIFNGAVGYIRANPKATLGLTAMVVVTLQIISLVALFGPMTAFGDIVTGEPDELTGAVVGGWSASFGASLLVSWLAGVLLSGMLTVIVGRAVFGSPITVGEAWAKVRGRLLALFGLALLEAAGVVAVLGLAVVILSGVAAAANEAAAALLGFPLLLVVGVSLAYLYVVLLFAPVLIVLERLPIVEAITRSFALVRHGFWRVLGIRLLTVLVVGVVGNAIAAPFMIVGEIVTAVTASDGSVTMRLVGATLSAIGVTIGQIVTAPFSAGVVVLLYTDRRIRAEAFDLVLQTGLEAGPAGGPAPVESTDNLWLTRPF