Rv3236c Resolved · high auto-curated

H37Rv Rv3236c · MTBC0 - · 385 aa · 3611959–3613116 (-) · RefSeq YP_177949.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)integral membrane transport protein
MTBC0 PGAP re-annotation
Revised (this work)Integral membrane transport protein. Pfam: Na_H_Exchanger (PF00999.27).

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 L7N665 TrEMBL · unreviewed · Inferred from homology
UniProt nameProbable conserved integral membrane transport protein

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
eggNOG descriptionProbably involved in transport of undeterminated substrate (possibly cations Na H) across the membrane. thought to be responsible for the translocation of the substrate across the membrane
Orthologous groupCOG0475
KEGG orthology K03455

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 0.354 · purifying
Polymorphic sites (≥ 0.1% of strains) 8 synonymous, 7 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
Na_H_ExchangerPF00999.27 2.0e-4015–369 Sodium/hydrogen exchanger, transmembrane

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

Closest characterised functional partner: mddA (integral membrane protein), high confidence from genomic context alone (score 718 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3237c hyp hypothetical protein 985 984 ctx neighborhood:881 cooccurence:774 coexpression:439
Rv3238c mddA integral membrane protein 718 718 ctx neighborhood:706
Rv3240c secA1 protein translocase subunit SecA 694 694 ctx neighborhood:694
Rv3241c raiA hyp hypothetical protein 687 687 ctx neighborhood:659
Rv3239c transmembrane transport protein 596 501 ctx neighborhood:485
Rv0425c ctpH metal cation transporting ATPase H 448 412
Rv0107c ctpI cation-transporter ATPase I 538 388
Rv0908 ctpE metal cation transporter ATPase E 457 302
Rv3242c hyp hypothetical protein 539 299
Rv2287 yjcE Na(+)/H(+) transporter 407 226
Rv0994 moeA1 molybdopterin molybdenumtransferase 1 415 208
Rv3659c conjugal transfer protein 806 50 textmining:805
Rv3654c hyp hypothetical protein 513 41 textmining:513

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): integral membrane transport protein
  • Pfam (hmmscan --cut_ga): Na_H_Exchanger PF00999.27 (E=2e-40)
  • (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 YP_177949.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Na_H_Exchanger (PF00999.27)
  • 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 COG0475
  • Curated reference: UniProt L7N665 (TrEMBL, unreviewed; Inferred from homology)
  • 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 — 13 functional partner(s); context anchor mddA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv3236c|
MEVSRALLFELGVLLAVLAVLGAVARRFALSPIPVYLLAGLSLGNGGILGVAAAGEFIATGAPIGVVLLLLALGLEFSATEFASSLRHHLPSAGVDIVLNATPGAVAGWLLGLDGVAILGLAGVTYISSSGVIARLLEDLRRLGNRETPAVLSVLVLEDFAMAAYLPLFAVLATDGSWLEAVVGMTVAIAALLGAFAASYRWGHHVGRLVTHPDSEQLLLRVLGITLIVAAVAESLHASAAVGAFLVGLTLTGETADRARMVLTPLRDLFATIFFLGIGLSVDPGKLVSMLPVALALAAVTAATKVATGMFAARREGVARRGQLRAGTALVARGEFSLIIIGLAGASIPGVAALATAYVFVMAIVGPILARYTGGGLPAAAVASN