chaA Resolved · high auto-curated

H37Rv Rv1607 · MTBC0 mtbc0_001713 · 360 aa · 1818145–1819227 (+) · RefSeq NP_216123.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ionic transporter integral membrane protein ChaA
MTBC0 PGAP re-annotationcalcium:proton antiporter
Revised (this work)Calcium:proton antiporter. Pfam: Na_Ca_ex (PF01699.30).

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

Curated reference (UniProt)

UniProt O53910 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable ionic transporter integral membrane protein ChaA

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category P Inorganic ion transport and metabolism
Preferred namechaA
eggNOG descriptionSodium/calcium exchanger protein
Orthologous groupCOG0387
KEGG orthology K07300

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 0.958 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 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_Ca_exPF01699.30 1.3e-15216–358 Sodium/calcium exchanger protein

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

Closest characterised functional partner: vapC21 (ribonuclease VapC21), medium confidence from genomic context alone (score 502 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2757c vapC21 ribonuclease VapC21 502 502 ctx cooccurence:499
Rv1605 hisF imidazole glycerol phosphate synthase subunit HisF 489 490 ctx neighborhood:482
Rv1604 impA inositol-monophosphatase ImpA 485 486 ctx neighborhood:473
Rv1606 hisI phosphoribosyl-AMP cyclohydrolase 484 485 ctx neighborhood:474
Rv1603 hisA 1-(5-phosphoribosyl)-5-((5-phosphoribosylamino)methylideneamino)imidazole-4-carboxamide isomerase 505 480 ctx neighborhood:472
Rv1602 hisH imidazole glycerol phosphate synthase subunit HisH 474 475 ctx neighborhood:467
Rv1599 hisD histidinol dehydrogenase 474 474 ctx neighborhood:466
Rv0529 ccsA cytochrome C-type biogenesis protein CcsA 474 474 coexpression:474
Rv1601 hisB imidazole glycerol-phosphate dehydratase 471 471 ctx neighborhood:467
Rv1600 hisC1 histidinol-phosphate aminotransferase 457 457 ctx neighborhood:452
Rv3335c yhjD integral membrane protein 446 447 coexpression:429
Rv2707 hyp hypothetical protein 440 441 coexpression:423
Rv0229c vapC51 hyp hypothetical protein 440 440 ctx cooccurence:439
Rv2323c hyp hypothetical protein 427 427 coexpression:424
Rv3846 sodA superoxide dismutase 422 423 coexpression:423

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: ionic transporter integral membrane protein ChaA
  • MTBC0 PGAP product: calcium:proton antiporter
  • Pfam (hmmscan --cut_ga): Na_Ca_ex PF01699.30 (E=1e-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_216123.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Na_Ca_ex (PF01699.30)
  • 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 COG0387
  • Curated reference: UniProt O53910 (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 — 22 functional partner(s); context anchor vapC21
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001713|Rv1607|chaA
MLKRVPWTVVLPSLAFVALVLTWGKQIGPVVGLLAAVLLAGAVLAAVNHAEVVAARVGEPFGSLVLAVAVTTIEVALIVALMVSGGDDAATLARDTVFAAVMITTNGIAGLSLLLGSLRYGVTLFNPHGSGAALATVTTLATLSLVLPTFTTSQSGPELSPGQLIFAGAASLGLYVLFLFTQTVRHRDFFLPVAQKGAVEDDSHADPPSTRAALLSLGLLLVALVAVVGLAKVESPVIEEVVSAAGFPQSFVGVVIATLVLLPETLAAARAARQGRLQTSLNLAYGSAMASIGLTIPTIALASLWLSGPLQLGLGAIQLVLLVLTVVVSVLTVVPGRATRLQGEVHLVLLAAYLFLAVVP