ctpD Resolved · high auto-curated
H37Rv Rv1469 · MTBC0 mtbc0_001571 ·
657 aa · 1666768–1668741 (+) ·
RefSeq NP_215985.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | cobalt/nickel-exporting P-type ATPase |
|---|---|
| MTBC0 PGAP re-annotation | cobalt-translocating P-type ATPase CtpD |
| Revised (this work) | Cobalt-translocating P-type ATPase CtpD. 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 |
P9WPT3
SwissProt · reviewed
· Inferred from homology
|
|---|---|
| UniProt name | Probable cobalt/nickel-exporting P-type ATPase |
| EC (curated) |
EC 7.2.2.-
|
| Curated function | Involved in heavy metal homeostasis. Probably exports nickel and cobalt ions out of the cell (By similarity). |
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
|
| Gene Ontology (6) |
GO:0005575, GO:0005623, GO:0005886, GO:0016020, 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 | 1.805 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 13 missense, 1 nonsense, 2 frameshift |
| Disruption | 3 distinct premature-stop/frameshift site(s); most common in 0.47% of strains (681) · 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 | 4.9e-30 | 145–245 | P-type ATPase actuator domain |
Hydrolase | PF00702.33 | 6.5e-27 | 343–554 | haloacid dehalogenase-like hydrolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: trxA (thioredoxin TrxA), medium confidence from genomic context alone (score 690 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0312 hyp |
hypothetical protein | 816 | 808 | coexpression:785 |
Rv0888 spmT hyp |
hypothetical protein | 799 | 800 | coexpression:799 |
Rv1470 trxA |
thioredoxin TrxA | 848 | 690 ctx | neighborhood:677 textmining:530 |
Rv1471 trxB1 |
thioredoxin | 754 | 657 ctx | neighborhood:648 |
Rv1472 echA12 |
enoyl-CoA hydratase EchA12 | 847 | 574 ctx | neighborhood:570 textmining:656 |
Rv0432 sodC |
superoxide dismutase | 552 | 525 | database:462 |
Rv1468c PE_PGRS29 |
PE-PGRS family protein PE_PGRS29 | 759 | 490 ctx | neighborhood:490 textmining:548 |
Rv1473 |
macrolide ABC transporter ATP-binding protein | 489 | 489 ctx | neighborhood:489 |
Rv3744 nmtR |
HTH-type transcriptional regulator NmtR | 662 | 467 | |
Rv3313c add |
adenosine deaminase | 463 | 463 | coexpression:462 |
Rv1690 lprJ |
lipoprotein LprJ | 457 | 458 | coexpression:458 |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 400 | 400 | |
Rv0846c mmcO |
oxidase | 427 | 390 | |
Rv0827c kmtR |
HTH-type transcriptional regulator KmtR | 562 | 357 | |
Rv0425c ctpH |
metal cation transporting ATPase H | 432 | 292 |
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: cobalt/nickel-exporting P-type ATPase
- MTBC0 PGAP product: cobalt-translocating P-type ATPase CtpD
- Pfam (hmmscan --cut_ga): E1-E2_ATPase PF00122.26 (E=5e-30), Hydrolase PF00702.33 (E=7e-27)
- (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_215985.1)
- 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 P9WPT3 (SwissProt, reviewed; 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 —
31 functional partner(s); context anchor
trxA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001571|Rv1469|ctpD MTLTACEVTAAEAPFDRVSKTIPHPLSWGAALWSVVSVRWATVALLLFLAGLVAQLNGAPEAMWWTLYLACYLAGGWGSAWAGAQALRNKALDVDLLMIAAAVGAVAIGQIFDGALLIVIFATSGALDDIATRHTAESVKGLLDLAPDQAVVVQGDGSERVVAASELVVGDRVVVRPGDRIPADGAVLSGASDVDQRSITGESMPVAKARGDEVFAGTVNGSGVLHLVVTRDPSQTVVARIVELVADASATKAKTQLFIEKIEQRYSLGMVAATLALIVIPLMFGADLRPVLLRAMTFMIVASPCAVVLATMPPLLSAIANAGRHGVLVKSAVVVERLADTSIVALDKTGTLTRGIPRLASVAPLDPNVVDARRLLQLAAAAEQSSEHPLGRAIVAEARRRGIAIPPAKDFRAVPGCGVHALVGNDFVEIASPQSYRGAPLAELAPLLSAGATAAIVLLDGVAIGVLGLTDQLRPDAVESVAAMAALTAAPPVLLTGDNGRAAWRVARNAGITDVRAALLPEQKVEVVRNLQAGGHQVLLVGDGVNDAPAMAAARAAVAMGAGADLTLQTADGVTIRDELHTIPTIIGLARQARRVVTVNLAIAATFIAVLVLWDLFGQLPLPLGVVGHEGSTVLVALNGMRLLTNRSWRAAASAAR