Rv3690 Still unknown · low auto-curated

H37Rv Rv3690 · MTBC0 mtbc0_003911 · 217 aa · 4155687–4156340 (+) · RefSeq NP_218207.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)membrane protein
MTBC0 PGAP re-annotationDUF4129 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF4129. Function unknown.

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

Curated reference (UniProt)

UniProt O69658 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable conserved membrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF4129)
Orthologous group2CT9V

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 0.0 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 0 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
DUF4129PF13559.12 5.8e-11122–188 Domain of unknown function (DUF4129)

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

Closest characterised functional partner: Rv3689 (transmembrane protein), high confidence from genomic context alone (score 962 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3691 hyp hypothetical protein 986 986 ctx neighborhood:760 cooccurence:774 coexpression:767
Rv3689 transmembrane protein 961 962 ctx neighborhood:843 cooccurence:761
Rv3693 membrane protein 949 947 ctx neighborhood:684 cooccurence:772
Rv3692 moxR2 methanol dehydrogenase transcriptional regulator MoxR 803 804 ctx neighborhood:760
Rv3694c transmembrane protein 789 790 ctx cooccurence:773
Rv3695 membrane protein 785 785 ctx cooccurence:773
Rv3688c hyp hypothetical protein 770 769 ctx neighborhood:766
Rv2226 hyp hypothetical protein 462 441 ctx cooccurence:412
Rv0518 hyp hypothetical protein 432 433 ctx cooccurence:426
Rv2332 mez malate oxidoreductase 428 428 coexpression:418
Rv2531c amino acid decarboxylase 436 412 experimental:405

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: membrane protein
  • MTBC0 PGAP product: DUF4129 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF4129 PF13559.12 (E=6e-11)
  • (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_218207.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF4129 (PF13559.12)
  • 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 2CT9V
  • Curated reference: UniProt O69658 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 11 functional partner(s); context anchor Rv3689
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003911|Rv3690|
MPSIDIDREAAHQAAQRELDKPIYPKDSLTKELTDWIDEQLYRILEKGSSIPGGWFTITVLLILLMIAVTAAVQIARRTMRTNRGGDYQLFDAGQLTAAQHRSTAESYAAEGNWAAAIRHRLQAVARELEETGMLNPAAGRTANELASDAGEVLPHLAGELTQAATAFNDVTYGERPGTQGAYQMIADLDDHLRSRSPAVVSAVQHPAVFDSWAQVR