Rv2219 Still unknown · low auto-curated

H37Rv Rv2219 · MTBC0 mtbc0_002355 · 250 aa · 2512392–2513144 (+) · RefSeq NP_216735.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)transmembrane protein
MTBC0 PGAP re-annotationDUF4191 domain-containing protein
Revised (this work)Conserved hypothetical protein; DUF domain(s) DUF4191. 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 P9WLI1 SwissProt · reviewed · Evidence at protein level
UniProt nameUncharacterized protein Rv2219

UniProt still lists this protein as Uncharacterized protein Rv2219; the revised annotation above is ahead of the current UniProt record.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category S Function unknown
eggNOG descriptionDomain of unknown function (DUF4191)
Orthologous group2AUFS
Gene Ontology (14) GO:0005575, GO:0005623, GO:0005886, GO:0005887, GO:0008150, GO:0016020, GO:0016021, GO:0031224, GO:0031226, GO:0040007, GO:0044425, GO:0044459 +2 more

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 0.372 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 4 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
DUF4191PF13829.12 1.4e-8623–242 Domain of unknown function (DUF4191)

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

Closest characterised functional partner: lipB (octanoyltransferase), high confidence from genomic context alone (score 847 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2217 lipB octanoyltransferase 846 847 ctx neighborhood:843
Rv2218 lipA lipoyl synthase 846 847 ctx neighborhood:843
Rv2216 epimerase family protein 786 787 ctx neighborhood:780
Rv2215 dlaT pyruvate dehydrogenase E2 component dihydrolipoamide acyltransferase 782 783 ctx neighborhood:780
Rv2708c hyp hypothetical protein 755 755 ctx cooccurence:753
Rv1830 HTH-type transcriptional regulator 750 751 ctx cooccurence:747
Rv2050 rbpA RNA polymerase-binding protein RbpA 736 737 ctx cooccurence:733
Rv2413c hyp hypothetical protein 725 726 ctx cooccurence:725
Rv2680 hyp hypothetical protein 711 712 ctx cooccurence:710
Rv3195 hyp hypothetical protein 709 709 ctx cooccurence:709
Rv1002c pmt dolichyl-phosphate-mannose--protein mannosyltransferase 698 699 ctx cooccurence:696
Rv2699c hyp hypothetical protein 696 696 ctx cooccurence:693
Rv2731 hyp hypothetical protein 693 694 ctx cooccurence:692
Rv1440 secG protein-export membrane protein SecG 693 694 ctx cooccurence:686
Rv3753c hyp hypothetical protein 691 692 ctx cooccurence:690

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: DUF4191 domain-containing protein
  • Pfam (hmmscan --cut_ga): DUF4191 PF13829.12 (E=1e-86)
  • (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_216735.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DUF4191 (PF13829.12)
  • 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 2AUFS
  • Curated reference: UniProt P9WLI1 (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 — 67 functional partner(s); context anchor lipB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002355|Rv2219|
MAKPRNAAESKAAKAQANAARKAAARQRRAQLWQAFTLQRKEDKRLLPYMIGAFLLIVGASVGVGVWAGGFTMFTMIPLGVLLGALVAFVIFGRRAQRTVYRKAEGQTGAAAWALDNLRGKWRVTPGVAATGNLDAVHRVIGRPGVIFVGEGSAARVKPLLAQEKKRTARLVGDVPIYDIIVGNGDGEVPLAKLERHLTRLPANITVKQMDTVESRLAALGSRAGAGVMPKGPLPTTAKMRSVQRTVRRK