Rv2994 Resolved · high auto-curated

H37Rv Rv2994 · MTBC0 - · 445 aa · 3351269–3352606 (+) · RefSeq NP_217510.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)MFS-type transporter
MTBC0 PGAP re-annotation
Revised (this work)MFS-type transporter. Pfam: MFS_1 (PF07690.22).

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 P9WJW7 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized MFS-type transporter Rv2994

UniProt still lists this protein as Uncharacterized MFS-type transporter Rv2994; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
eggNOG descriptionMajor facilitator superfamily
Orthologous groupCOG2271
KEGG orthology K02445
Gene Ontology (2) GO:0005575, GO:0005576

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 0.528 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 6 missense, 1 nonsense, 3 frameshift
Disruption 4 distinct premature-stop/frameshift site(s); most common in 17.35% of strains (25190) · convergent

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
MFS_1PF07690.22 5.7e-4921–356 Major Facilitator Superfamily

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

Closest characterised functional partner: Rv2993c (2-hydroxyhepta-2,4-diene-1,7-dioate isomerase), high confidence from genomic context alone (score 763 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2993c 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase 763 763 ctx neighborhood:728
Rv2992c gltS glutamate--tRNA ligase 741 731 ctx neighborhood:728
Rv1773c transcriptional regulator 403 372
Rv0220 lipC esterase LipC 811 81 textmining:803
Rv0230c php phosphotriesterase 635 55 textmining:630
Rv2957 PGL/p-HBAD biosynthesis glycosyltransferase 806 49 textmining:805
Rv3347c PPE55 PPE family protein PPE55 657 47 textmining:655
Rv2958c PGL/p-HBAD biosynthesis glycosyltransferase 803 44 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): MFS-type transporter
  • Pfam (hmmscan --cut_ga): MFS_1 PF07690.22 (E=6e-49)
  • (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_217510.1)
  • Domains: Pfam-A via hmmscan --cut_ga — MFS_1 (PF07690.22)
  • 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 COG2271
  • Curated reference: UniProt P9WJW7 (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)
  • Interaction network: STRING v12.0 (Szklarczyk et al. 2023, doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 — 8 functional partner(s); context anchor Rv2993c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2994|
MSRDPTGVGARWAIMIVSLGVTASSFLFINGVAFLIPRLENARGTPLSHAGLLASMPSWGLVVTMFAWGYLLDHVGERMVMAVGSALTAAAAYAAASVHSLLWIGVFLFLGGMAAGGCNSAGGRLVSGWFPPQQRGLAMGIRQTAQPLGIASGALVIPELAERGVHAGLMFPAVVCTLAAVASVLGIVDPPRKSRTKASEQELASPYRGSSILWRIHAASALLMMPQTVTVTFMLVWLINHHGWSVAQAGVLVTISQLLGALGRVAVGRWSDHVGSRMRPVRLIAAAAAATLFLLAAVDNEGSRYDVLLMIAISVIAVLDNGLEATAITEYAGPYWSGRALGIQNTTQRLMAAAGPPLFGSLITTAAYPTAWALCGVFPLAAVPLVPVRLLPPGLETRARRQSVRRHRWWQAVRCHAWPNGPRRPGPPGQPRRVRQGGTAITPPT