Rv2025c Family assigned · medium auto-curated

H37Rv Rv2025c · MTBC0 mtbc0_002158 · 332 aa · 2299363–2300361 (-) · RefSeq NP_216541.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)cation efflux system protein
MTBC0 PGAP re-annotationcation diffusion facilitator family transporter
Revised (this work)Cation diffusion facilitator family transporter. Pfam: Cation_efflux (PF01545.27), ZT_dimer (PF16916.12).

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

Curated reference (UniProt)

UniProt P9WGF5 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable cation efflux system protein Rv2025c

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
eggNOG descriptionBelongs to the cation diffusion facilitator (CDF) transporter (TC 2.A.4) family
Orthologous groupCOG0053

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 1.619 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 2 synonymous, 9 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
Cation_effluxPF01545.27 2.2e-4644–237 Cation efflux transmembrane domain
ZT_dimerPF16916.12 1.5e-13242–315 Cation efflux protein, cytoplasmic domain

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

Closest characterised functional partner: Rv2026c (universal stress protein), medium confidence from genomic context alone (score 523 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1240 mdh malate dehydrogenase 679 679 coexpression:668
Rv0827c kmtR HTH-type transcriptional regulator KmtR 912 539 textmining:817
Rv2026c universal stress protein 523 523 ctx neighborhood:517
Rv2027c dosT two component sensor histidine kinase DosT 494 489 ctx neighborhood:467
Rv2226 hyp hypothetical protein 483 484 ctx cooccurence:479
Rv2028c universal stress protein 477 478
Rv1712 cmk cytidylate kinase 420 420 coexpression:401
Rv0648 alpha-mannosidase 417 418 coexpression:418
Rv0846c mmcO oxidase 417 380
Rv1674c transcriptional regulator 482 304
Rv2856 nicT nickel-transport integral membrane protein NicT 409 241
Rv3270 ctpC manganese/zinc-exporting P-type ATPase 610 196 textmining:536
Rv3743c ctpJ cation transporter ATPase J 616 195 textmining:544
Rv1469 ctpD cobalt/nickel-exporting P-type ATPase 637 188 textmining:572
Rv0052 hyp hypothetical protein 447 155

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: cation efflux system protein
  • MTBC0 PGAP product: cation diffusion facilitator family transporter
  • Pfam (hmmscan --cut_ga): Cation_efflux PF01545.27 (E=2e-46), ZT_dimer PF16916.12 (E=1e-13)
  • (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_216541.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Cation_efflux (PF01545.27), ZT_dimer (PF16916.12)
  • 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 COG0053
  • Curated reference: UniProt P9WGF5 (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 — 22 functional partner(s); context anchor Rv2026c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002158|Rv2025c|
MTHDHAHSRGVPAMIKEIFAPHSHDAADSVDDTLESTAAGIRTVKISLLVLGLTALIQIVIVVMSGSVALAADTIHNFADALTAVPLWIAFALGAKPATRRYTYGFGRVEDLAGSFVVAMITMSAIIAGYEAIARLIHPQQIEHVGWVALAGLVGFIGNEWVALYRIRVGHRIGSAALIADGLHARTDGFTSLAVLCSAGGVALGFPLADPIVGLLITAAILAVLRTAARDVFRRLLDGVDPAMVDAAEQALAARPGVQAVRSVRMRWIGHRLHADAELDVDPALDLAQAHRIAHDAEHELTHTVPKLTTALIHAYPAEHGSSIPDRGRTVE