Rv3346c Still unknown · low auto-curated

H37Rv Rv3346c · MTBC0 mtbc0_003558 · 85 aa · 3769952–3770209 (-) · RefSeq NP_217863.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationDUF3017 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF3017. 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 O50377 TrEMBL · unreviewed · Predicted
UniProt nameConserved transmembrane protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionProtein of unknown function (DUF3017)
Orthologous group2DRQP

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, 1 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
DUF3017PF11222.14 2.5e-1818–77 Protein of unknown function (DUF3017)

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

Closest characterised functional partner: aftC (alpha-(1->3)-arabinofuranosyltransferase), high confidence from genomic context alone (score 757 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2673 aftC alpha-(1->3)-arabinofuranosyltransferase 756 757 ctx cooccurence:755
Rv1476 membrane protein 756 756 ctx cooccurence:755
Rv3035 hyp hypothetical protein 755 755 ctx cooccurence:754
Rv3802c membrane protein 748 749 ctx cooccurence:748
Rv3805c aftB terminal beta-(1->2)-arabinofuranosyltransferase 743 744 ctx cooccurence:742
Rv1275 lprC lipoprotein LprC 734 734 ctx cooccurence:732
Rv1274 lprB lipoprotein LprB 732 733 ctx cooccurence:729
Rv0531 membrane protein 732 733 ctx cooccurence:732
Rv3668c protease 723 724 ctx cooccurence:722
Rv0466 hyp hypothetical protein 716 716 ctx cooccurence:715
Rv3635 transmembrane protein 704 705 ctx cooccurence:703
Rv0226c transmembrane protein 695 696 ctx cooccurence:694
Rv3244c lpqB lipoprotein LpqB 687 688 ctx cooccurence:686
Rv1100 hyp hypothetical protein 687 688 ctx cooccurence:687
Rv2001 hyp hypothetical protein 669 669 ctx cooccurence:667

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: transmembrane protein
  • MTBC0 PGAP product: DUF3017 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF3017 PF11222.14 (E=3e-18)
  • (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_217863.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF3017 (PF11222.14)
  • 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 2DRQP
  • Curated reference: UniProt O50377 (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 — 83 functional partner(s); context anchor aftC
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003558|Rv3346c|
MTVRAVLRRTVGAQWPILAGVNFWRRGALLIGIGVGVAAVLRLVLSEERAGLLVVRSKGIDFVTTVTVAAAMVYIASTIDPLGTG