ctpV Resolved · high auto-curated
H37Rv Rv0969 · MTBC0 mtbc0_001035 ·
770 aa · 1085958–1088270 (+) ·
RefSeq NP_215484.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | copper-exporting ATPase |
|---|---|
| MTBC0 PGAP re-annotation | copper-translocating P-type ATPase |
| Revised (this work) | Copper-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 |
P9WPS3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable copper-exporting P-type ATPase V |
| EC (curated) |
EC 7.2.2.8
|
| Curated function | Necessary for copper homeostasis and likely functions as a copper exporter. Also required for full virulence. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | copA |
| eggNOG description | possibly catalyzes the transport of undetermined metal cation with hydrolyse of ATP catalytic activity ATP H(2)O undetermined metal cation(in) ADP phosphate undetermined metal cation (out) |
| Orthologous group | COG2217 |
| EC number |
EC 3.6.3.4, EC 3.6.3.54
|
| KEGG orthology |
K01533, K12950, K12951, K12954, K12956, K17686, K21887
|
| KEGG pathways |
map01524, map04016
|
| Gene Ontology (23) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0005887, GO:0008150, GO:0009405, GO:0010035, GO:0010038, GO:0016020, GO:0016021, GO:0030312 +11 more
|
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 | 0.826 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 13 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 |
|---|---|---|---|---|
E1-E2_ATPase | PF00122.26 | 6.4e-31 | 260–359 | P-type ATPase actuator domain |
Hydrolase | PF00702.33 | 2.6e-39 | 454–672 | haloacid dehalogenase-like hydrolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0970 (integral membrane protein), high confidence from genomic context alone (score 811 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0968 hyp |
hypothetical protein | 985 | 929 ctx | neighborhood:631 coexpression:815 textmining:804 |
Rv0970 |
integral membrane protein | 961 | 811 ctx | neighborhood:801 textmining:805 |
Rv0967 csoR |
copper-sensing transcriptional repressor CsoR | 936 | 662 ctx | neighborhood:490 textmining:820 |
Rv0432 sodC |
superoxide dismutase | 649 | 523 | database:462 |
Rv0846c mmcO |
oxidase | 729 | 391 | textmining:574 |
Rv0425c ctpH |
metal cation transporting ATPase H | 457 | 362 | |
Rv0107c ctpI |
cation-transporter ATPase I | 533 | 352 | |
Rv1997 ctpF |
cation transporter ATPase F | 432 | 332 | |
Rv0190 ricR hyp |
hypothetical protein | 656 | 249 | textmining:562 |
Rv0908 ctpE |
metal cation transporter ATPase E | 422 | 243 | |
Rv2963 |
integral membrane protein | 453 | 127 | |
Rv0186A mymT |
metallothionein | 655 | 41 | textmining:655 |
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: copper-exporting ATPase
- MTBC0 PGAP product: copper-translocating P-type ATPase
- Pfam (hmmscan --cut_ga): E1-E2_ATPase PF00122.26 (E=6e-31), Hydrolase PF00702.33 (E=3e-39)
- (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_215484.3)
- 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 P9WPS3 (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 —
12 functional partner(s); context anchor
Rv0970 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001035|Rv0969|ctpV MRVCVTGFNVDAVRAVAIEETVSQVTGVHAVHAYPRTASVVIWYSPELGDTAAVLSAITKAQHVPAELVPARAPHSAGVRGVGVVRKITGGIRRMLSRPPGVDKPLKASRCGGRPRGPVRGSASWPGEQNRRERRTWLPRVWLALPLGLLALGSSMFFGAYPWAGWLAFAATLPVQFVAGWPILRGAVQQARALTSNMDTLIALGTLTAFVYSTYQLFAGGPLFFDTSALIIAFVVLGRHLEARATGKASEAISKLLELGAKEATLLVDGQELLVPVDQVQVGDLVRVRPGEKIPVDGEVTDGRAAVDESMLTGESVPVEKTAGDRVAGATVNLDGLLTVRATAVGADTALAQIVRLVEQAQGDKAPVQRLADRVSAVFVPAVIGVAVATFAGWTLIAANPVAGMTAAVAVLIIACPCALGLATPTAIMVGTGRGAELGILVKGGEVLEASKKIDTVVFDKTGTLTRARMRVTDVIAGQRRQPNQVLRLAAAVESGSEHPIGAAIVAAAHERGLAIPAANAFTAVAGHGVRAQVNGGPVVVGRRKLVDEQHLVLPDHLAAAAVEQEERGRTAVFVGQDGQVVGVLAVADTVKDDAADVVGRLHAMGLQVAMITGDNARTAAAIAKQVGIEKVLAEVLPQDKVAEVRRLQDQGRVVAMVGDGVNDAPALVQADLGIAIGTGTDVAIEASDITLMSGRLDGVVRAIELSRQTLRTIYQNLGWAFGYNTAAIPLAALGALNPVVAGAAMGFSSVSVVTNSLRLRRFGRDGRTA