ctpC Resolved · high auto-curated
H37Rv Rv3270 · MTBC0 mtbc0_003478 ·
718 aa · 3672669–3674825 (+) ·
RefSeq NP_217787.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | manganese/zinc-exporting P-type ATPase |
|---|---|
| MTBC0 PGAP re-annotation | manganese-exporting P-type ATPase CtpC |
| Revised (this work) | Manganese-exporting P-type ATPase CtpC. 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 |
P9WPT5
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Manganese-exporting P-type ATPase |
| EC (curated) |
EC 7.2.2.22
|
| Curated function | High affinity, slow turnover Mn(2+) transporting ATPase, which is required for virulence. Controls the Mn(2+) cytoplasmic quota and is involved in the uploading of Mn(2+) into secreted metalloproteins. Required for tolerance to Zn(2+) and oxidative stress. Plays a crucial role in the ability to resist zinc poisoning in human macrophages. Shows a preference for Mn(2+), but Zn(2+), Co(2+) and Cu(2+) can act as alternative substrates although at slower turnover rates. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | ctpC |
| eggNOG description | ATPase, P-type (transporting), HAD superfamily, subfamily IC |
| 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 (7) |
GO:0005575, GO:0005576, 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 | 0.281 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 6 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 | 2.9e-23 | 227–315 | P-type ATPase actuator domain |
Hydrolase | PF00702.33 | 4.8e-40 | 402–622 | haloacid dehalogenase-like hydrolase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rmlD (dTDP-4-dehydrorhamnose reductase), medium confidence from genomic context alone (score 494 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3269 hyp |
hypothetical protein | 983 | 981 ctx | neighborhood:870 coexpression:860 |
Rv3267 lcp1 hyp |
hypothetical protein | 716 | 717 ctx | neighborhood:715 |
Rv3268 hyp |
hypothetical protein | 594 | 594 ctx | neighborhood:581 |
Rv0432 sodC |
superoxide dismutase | 554 | 526 | database:462 |
Rv3266c rmlD |
dTDP-4-dehydrorhamnose reductase | 494 | 494 ctx | neighborhood:487 |
Rv2326c |
ABC transporter ATP-binding protein | 419 | 420 ctx | cooccurence:413 |
Rv3265c wbbL1 |
N-acetylglucosaminyl-diphospho-decaprenol L-rhamnosyltransferase | 402 | 402 | |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 401 | 402 | |
Rv0425c ctpH |
metal cation transporting ATPase H | 457 | 326 | |
Rv0107c ctpI |
cation-transporter ATPase I | 472 | 313 | |
Rv2358 smtB |
HTH-type transcriptional regulator SmtB | 406 | 293 | |
Rv3743c ctpJ |
cation transporter ATPase J | 433 | 274 | |
Rv0092 ctpA |
cation transporter ATPase A | 405 | 265 | |
Rv2025c |
cation efflux system protein | 610 | 196 | textmining:536 |
Rv1336 cysM |
O-phosphoserine sulfhydrylase | 478 | 85 | textmining:453 |
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: manganese/zinc-exporting P-type ATPase
- MTBC0 PGAP product: manganese-exporting P-type ATPase CtpC
- Pfam (hmmscan --cut_ga): E1-E2_ATPase PF00122.26 (E=3e-23), Hydrolase PF00702.33 (E=5e-40)
- (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_217787.1)
- 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 P9WPT5 (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 —
17 functional partner(s); context anchor
rmlD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003478|Rv3270|ctpC MTLEVVSDAAGRMRVKVDWVRCDSRRAVAVEEAVAKQNGVRVVHAYPRTGSVVVWYSPRRADRAAVLAAIKGAAHVAAELIPARAPHSAEIRNTDVLRMVIGGVALALLGVRRYVFARPPLLGTTGRTVATGVTIFTGYPFLRGALRSLRSGKAGTDALVSAATVASLILRENVVALTVLWLLNIGEYLQDLTLRRTRRAISELLRGNQDTAWVRLTDPSAGSDAATEIQVPIDTVQIGDEVVVHEHVAIPVDGEVVDGEAIVNQSAITGENLPVSVVVGTRVHAGSVVVRGRVVVRAHAVGNQTTIGRIISRVEEAQLDRAPIQTVGENFSRRFVPTSFIVSAIALLITGDVRRAMTMLLIACPCAVGLSTPTAISAAIGNGARRGILIKGGSHLEQAGRVDAIVFDKTGTLTVGRPVVTNIVAMHKDWEPEQVLAYAASSEIHSRHPLAEAVIRSTEERRISIPPHEECEVLVGLGMRTWADGRTLLLGSPSLLRAEKVRVSKKASEWVDKLRRQAETPLLLAVDGTLVGLISLRDEVRPEAAQVLTKLRANGIRRIVMLTGDHPEIAQVVADELGIDEWRAEVMPEDKLAAVRELQDDGYVVGMVGDGINDAPALAAADIGIAMGLAGTDVAVETADVALANDDLHRLLDVGDLGERAVDVIRQNYGMSIAVNAAGLLIGAGGALSPVLAAILHNASSVAVVANSSRLIRYRLDR