ctpA Resolved · high auto-curated
H37Rv Rv0092 · MTBC0 mtbc0_000102 ·
761 aa · 100746–103031 (+) ·
RefSeq NP_214606.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cation transporter ATPase A |
|---|---|
| MTBC0 PGAP re-annotation | heavy metal translocating P-type ATPase |
| Revised (this work) | Heavy metal translocating P-type ATPase. Pfam: HMA (PF00403.33), 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 |
P9WPU1
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Copper-exporting P-type ATPase |
| EC (curated) |
EC 7.2.2.8
|
| Curated function | Involved in copper export. Could be involved in the copper detoxification of mycobacterial cells. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | ctpA |
| eggNOG description | ATPase, P-type (transporting), HAD superfamily, subfamily IC |
| Orthologous group | COG2217 |
| EC number |
EC 3.6.3.54
|
| KEGG orthology |
K12949, K17686
|
| KEGG pathways |
map01524, map04016
|
| Gene Ontology (7) |
GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0030312, GO:0044464, GO:0071944
|
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 | 0.517 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 14 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
HMA | PF00403.33 | 1.1e-11 | 18–75 | Heavy-metal-associated domain |
E1-E2_ATPase | PF00122.26 | 1.1e-20 | 242–342 | P-type ATPase actuator domain |
Hydrolase | PF00702.33 | 6.4e-36 | 437–649 | haloacid dehalogenase-like hydrolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mtn (5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase), medium confidence from genomic context alone (score 541 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0103c ctpB |
cation-transporter P-type ATPase B | 904 | 903 | database:900 |
Rv0091 mtn |
5'-methylthioadenosine/S-adenosylhomocysteine nucleosidase | 559 | 541 ctx | neighborhood:525 |
Rv0432 sodC |
superoxide dismutase | 585 | 525 | database:462 |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 402 | 402 | |
Rv1674c |
transcriptional regulator | 402 | 372 | |
Rv0324 |
transcriptional regulator | 400 | 369 | |
Rv0846c mmcO |
oxidase | 503 | 360 | |
Rv0425c ctpH |
metal cation transporting ATPase H | 437 | 358 | |
Rv0107c ctpI |
cation-transporter ATPase I | 429 | 327 | |
Rv0967 csoR |
copper-sensing transcriptional repressor CsoR | 492 | 317 | |
Rv1994c cmtR |
HTH-type transcriptional regulator CmtR | 412 | 278 | |
Rv1992c ctpG |
cation transporter ATPase G | 456 | 271 | |
Rv3270 ctpC |
manganese/zinc-exporting P-type ATPase | 405 | 265 | |
Rv0970 |
integral membrane protein | 451 | 70 | textmining:434 |
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 A
- MTBC0 PGAP product: heavy metal translocating P-type ATPase
- Pfam (hmmscan --cut_ga): HMA PF00403.33 (E=1e-11), E1-E2_ATPase PF00122.26 (E=1e-20), Hydrolase PF00702.33 (E=6e-36)
- (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_214606.1)
- Domains: Pfam-A via hmmscan --cut_ga — HMA (PF00403.33), 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 P9WPU1 (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 —
14 functional partner(s); context anchor
mtn - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000102|Rv0092|ctpA MTTAVTGEHHASVQRIQLRISGMSCSACAHRVESTLNKLPGVRAAVNFGTRVATIDTSEAVDAAALCQAVRRAGYQADLCTDDGRSASDPDADHARQLLIRLAIAAVLFVPVADLSVMFGVVPATRFTGWQWVLSALALPVVTWAAWPFHRVAMRNARHHAASMETLISVGITAATIWSLYTVFGNHSPIERSGIWQALLGSDAIYFEVAAGVTVFVLVGRYFEARAKSQAGSALRALAALSAKEVAVLLPDGSEMVIPADELKEQQRFVVRPGQIVAADGLAVDGSAAVDMSAMTGEAKPTRVRPGGQVIGGTTVLDGRLIVEAAAVGADTQFAGMVRLVEQAQAQKADAQRLADRISSVFVPAVLVIAALTAAGWLIAGGQPDRAVSAALAVLVIACPCALGLATPTAMMVASGRGAQLGIFLKGYKSLEATRAVDTVVFDKTGTLTTGRLQVSAVTAAPGWEADQVLALAATVEAASEHSVALAIAAATTRRDAVTDFRAIPGRGVSGTVSGRAVRVGKPSWIGSSSCHPNMRAARRHAESLGETAVFVEVDGEPCGVIAVADAVKDSARDAVAALADRGLRTMLLTGDNPESAAAVATRVGIDEVIADILPEGKVDVIEQLRDRGHVVAMVGDGINDGPALARADLGMAIGRGTDVAIGAADIILVRDHLDVVPLALDLARATMRTVKLNMVWAFGYNIAAIPVAAAGLLNPLVAGAAMAFSSFFVVSNSLRLRKFGRYPLGCGTVGGPQMTAPSSA