ctpJ Resolved · high auto-curated
H37Rv Rv3743c · MTBC0 mtbc0_003966 ·
660 aa · 4217512–4219494 (-) ·
RefSeq NP_218260.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cation transporter ATPase J |
|---|---|
| MTBC0 PGAP re-annotation | heavy metal translocating P-type ATPase |
| Revised (this work) | Heavy metal translocating P-type ATPase. Pfam: E1-E2_ATPase (PF00122.26), Hydrolase (PF00702.33). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WPT7
SwissProt · reviewed
· Evidence at transcript level
|
|---|---|
| UniProt name | Probable cation-transporting P-type ATPase J |
| EC (curated) |
EC 7.2.2.-
|
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | cadA |
| eggNOG description | ATPase, P-type (transporting), HAD superfamily, subfamily IC |
| Orthologous group | COG2217 |
| EC number |
EC 3.6.3.3, EC 3.6.3.4, EC 3.6.3.5, EC 3.6.3.54
|
| KEGG orthology |
K01533, K01534, K12950, K12951, K12954, K12956, K17686, K21887
|
| KEGG pathways |
map01524, map04016
|
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 | 0.593 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 12 missense, 0 nonsense, 3 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.48% of strains (696) · clonal |
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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
E1-E2_ATPase | PF00122.26 | 5.2e-29 | 138–239 | P-type ATPase actuator domain |
Hydrolase | PF00702.33 | 1.4e-32 | 337–556 | haloacid dehalogenase-like hydrolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nmtR (HTH-type transcriptional regulator NmtR), high confidence from genomic context alone (score 774 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3744 nmtR |
HTH-type transcriptional regulator NmtR | 889 | 774 ctx | neighborhood:580 textmining:532 |
Rv3742c |
oxidoreductase | 673 | 532 ctx | neighborhood:497 |
Rv3741c |
oxidoreductase | 535 | 531 ctx | neighborhood:497 |
Rv0432 sodC |
superoxide dismutase | 551 | 523 | database:462 |
Rv3740c |
diacyglycerol O-acyltransferase | 500 | 500 ctx | neighborhood:497 |
Rv0846c mmcO |
oxidase | 426 | 390 | |
Rv1674c |
transcriptional regulator | 415 | 373 | |
Rv0827c kmtR |
HTH-type transcriptional regulator KmtR | 653 | 370 | textmining:473 |
Rv0425c ctpH |
metal cation transporting ATPase H | 435 | 298 | |
Rv3270 ctpC |
manganese/zinc-exporting P-type ATPase | 433 | 274 | |
Rv2025c |
cation efflux system protein | 616 | 195 | textmining:544 |
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 transporter ATPase J
- MTBC0 PGAP product: heavy metal translocating P-type ATPase
- Pfam (hmmscan --cut_ga): E1-E2_ATPase PF00122.26 (E=5e-29), Hydrolase PF00702.33 (E=1e-32)
- (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_218260.1)
- Domains: Pfam-A via hmmscan --cut_ga — E1-E2_ATPase (PF00122.26), Hydrolase (PF00702.33)
- 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
COG2217 - Curated reference: UniProt P9WPT7 (SwissProt, reviewed; Evidence at transcript 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 —
11 functional partner(s); context anchor
nmtR - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003966|Rv3743c|ctpJ MAVRELSPARCTSASPLVLARRTKLFALSEMRWAALALGLFSAGLLTQLCGAPQWVRWALFLACYATGGWEPGLAGLQALQRRTLDVDLLMVVAAIGAAAIGQIAEGALLIVIFATSGALEALVTARTADSVRGLMGLAPGTATRVGAGGGEETVNAADLRIGDIVLVRPGERISADATVLAGGSEVDQATVTGEPLPVDKSIGDQVFAGTVNGTGALRIRVDRLARDSVVARIATLVEQASQTKARTQLFIEKVEQRYSIGMVAVTLAVFAVPPLWGETLQRALLRAMTFMIVASPCAVVLATMPPLLAAIANAGRHGVLAKSAIVMEQLGTTTRIAFDKTGTLTRGTPELAGIWVYERRFTDDELLRLAAAAEYPSEHPLGAAIVKAAQSRRIRLPTVGEFTAHPGCRVTARVDGHVIAVGSATALLGTAGAAALEASMITAVDFLQGEGYTVVVVVCDSHPVGLLAITDQLRPEAAAAISAATKLTGAKPVLLTGDNRATADRLGVQVGIDDVRAGLLPDDKVAAVRQLQAGGARLTVVGDGINDAPALAAAHVGIAMGSARSELTLQTADAVVVRDDLTTIPTVIAMSRRARRIVVANLIVAVTFIAGLVVWDLAFTLPLPLGVARHEGSTIIVGLNGLRLLRHTAWRRAAGTAHR