Rv3237c Family assigned · medium auto-curated

H37Rv Rv3237c · MTBC0 mtbc0_003445 · 160 aa · 3635264–3635746 (-) · RefSeq NP_217754.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)hypothetical protein
MTBC0 PGAP re-annotationcation:proton antiporter regulatory subunit
Revised (this work)Cation:proton antiporter regulatory subunit. Pfam: KhtT_N (PF25991.1), TrkA_C (PF02080.27).

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

Curated reference (UniProt)

UniProt O05882 TrEMBL · unreviewed · Evidence at protein level
UniProt nameConserved protein

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

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
eggNOG descriptionregulatory, ligand-binding protein related to C-terminal domains of K channels
Orthologous groupCOG0490
KEGG orthology K07228

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, 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
KhtT_NPF25991.1 1.4e-251–70 K(+)/H(+) antiporter subunit KhtT, N-terminal domain
TrkA_CPF02080.27 5.9e-1592–155 TrkA-C domain

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

Closest characterised functional partner: Rv3236c (integral membrane transport protein), high confidence from genomic context alone (score 984 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.

PartnerProductScoreNo text-miningChannels (≥400)
Rv3236c integral membrane transport protein 985 984 ctx neighborhood:881 cooccurence:774 coexpression:439
Rv3238c mddA integral membrane protein 760 761 ctx neighborhood:759
Rv3240c secA1 protein translocase subunit SecA 696 696 ctx neighborhood:694
Rv3241c raiA hyp hypothetical protein 668 669 ctx neighborhood:659
Rv3239c transmembrane transport protein 483 474 ctx neighborhood:471
Rv0806c cpsY exopolysaccharide phosphotransferase CpsY 426 426 ctx cooccurence:421
Rv2692 ceoC TRK system potassium uptake protein CeoC 508 91 textmining:481
Rv3200c transmembrane cation transporter 515 90 textmining:489
Rv2691 ceoB TRK system potassium uptake protein CeoB 510 89 textmining:485

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: hypothetical protein
  • MTBC0 PGAP product: cation:proton antiporter regulatory subunit
  • Pfam (hmmscan --cut_ga): KhtT_N PF25991.1 (E=1e-25), TrkA_C PF02080.27 (E=6e-15)
  • (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_217754.1)
  • Domains: Pfam-A via hmmscan --cut_ga — KhtT_N (PF25991.1), TrkA_C (PF02080.27)
  • 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 COG0490
  • Curated reference: UniProt O05882 (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 — 9 functional partner(s); context anchor Rv3236c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003445|Rv3237c|
MDVKEVLLPGVGLRYEFTSYRGDRIGIVARRSGGFDVVLYGRDDPDEARPVLRLTDEEAEAVAQILGAPRIAERFTELTREVPGLKAGQIHIRAGSLFVDRPLGDTRARTRTGASIVAIVRDEDVLASPGPTDVLRAGDVLIVIGTEDGIAGVEQIVEKG