ctpH Resolved · high auto-curated
H37Rv Rv0425c · MTBC0 mtbc0_000447 ·
1539 aa · 514067–518686 (-) ·
RefSeq NP_214939.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | metal cation transporting ATPase H |
|---|---|
| MTBC0 PGAP re-annotation | cation-translocating P-type ATPase |
| Revised (this work) | Cation-translocating P-type ATPase. Pfam: E1-E2_ATPase (PF00122.26), Hydrolase (PF00702.33), Cation_ATPase (PF13246.13), Cation_ATPase_C (PF00689.27). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P96271
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable cation-transporting ATPase I |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| Preferred name | ctpH |
| eggNOG description | ATPase, P-type (transporting), HAD superfamily, subfamily IC |
| Orthologous group | COG0474 |
| KEGG orthology |
K12955
|
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 | 0.448 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 12 synonymous, 14 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.15% of strains (219) · 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 | 2.1e-25 | 765–864 | P-type ATPase actuator domain |
Hydrolase | PF00702.33 | 8.7e-15 | 960–1241 | haloacid dehalogenase-like hydrolase |
Cation_ATPase | PF13246.13 | 6.6e-09 | 1009–1136 | P-type ATPase, cytoplasmic domain N |
Cation_ATPase_C | PF00689.27 | 7.7e-16 | 1313–1463 | Cation transporting ATPase, C-terminus |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0426c (transmembrane protein), medium confidence from genomic context alone (score 665 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2851c |
GCN5-like N-acetyltransferase | 756 | 756 | coexpression:756 |
Rv0426c |
transmembrane protein | 666 | 665 ctx | neighborhood:662 |
Rv0424c hyp |
hypothetical protein | 652 | 652 ctx | neighborhood:647 |
Rv1305 atpE |
ATP synthase subunit C | 655 | 607 | database:551 |
Rv1747 |
ABC transporter ATP-binding protein/permease | 620 | 595 | coexpression:437 |
Rv3008 hyp |
hypothetical protein | 554 | 527 | coexpression:421 |
Rv1811 mgtC |
Mg2+ transport P-type ATPase MgtC | 548 | 520 | coexpression:413 |
Rv3005c hyp |
hypothetical protein | 495 | 495 | |
Rv1796 mycP5 |
membrane-anchored mycosin MycP | 515 | 494 | |
Rv0291 mycP3 |
membrane-anchored mycosin MycP | 512 | 491 | |
Rv2483c plsC |
bifunctional L-3-phosphoserine phosphatase/1-acyl-sn-glycerol-3-phosphate acyltransferase | 510 | 488 | database:451 |
Rv1488 hyp |
hypothetical protein | 509 | 481 | |
Rv3064c |
integral membrane protein | 481 | 481 | |
Rv3486 hyp |
hypothetical protein | 479 | 480 | |
Rv2182c |
1-acylglycerol-3-phosphate O-acyltransferase | 479 | 478 | database:451 |
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: metal cation transporting ATPase H
- MTBC0 PGAP product: cation-translocating P-type ATPase
- Pfam (hmmscan --cut_ga): E1-E2_ATPase PF00122.26 (E=2e-25), Hydrolase PF00702.33 (E=9e-15), Cation_ATPase PF13246.13 (E=7e-09), Cation_ATPase_C PF00689.27 (E=8e-16)
- (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_214939.1)
- Domains: Pfam-A via hmmscan --cut_ga — E1-E2_ATPase (PF00122.26), Hydrolase (PF00702.33), Cation_ATPase (PF13246.13), Cation_ATPase_C (PF00689.27)
- 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
COG0474 - Curated reference: UniProt P96271 (TrEMBL, unreviewed; 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 —
60 functional partner(s); context anchor
Rv0426c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000447|Rv0425c|ctpH MPVRAVATGFRATATLTGASITAATAVSATLAKTGVGTGMKVAIIPLRAGAKALSGELSRETLGRNCWRGERRAWIEVRGLRSGGDDELGRVVLNAIQAHPGVGSASLNYPLSRVVVAIDDPDTSLRELCRIVDDAEKAERHRHPDQAADQLAQSPGSLPGDGVLLAVRAVTVAATAAGLGLALGGRALRWPRFPLVIEAAVAAVDHQPLLRRLLEDRIGTAATATVLELAMAAAHTVTLSPAALSVDLTIQALKAAECRAGARAWRRHEPQLALHADEPADQPQSLWPRPARSTQPVQRSVARFALIQALSAVLVGAGTRDADMAATATLVATPKASRTTPEAFAAALGQGLADQHAVLPLRPESLRRLDRVDAIVIDPRVLCTDDLRVARIRGCGADELSTAWNRAQLVLTESGLRPGWHRVPGVSASGSDSAVEALFRPMHDRLASAVVAEAHRTGADLVSVDVDALGELRPVFDDIRPLDDGASGSLDEALARAVAELRQAGRTVAVLSSVGKQALSAADVALGVLPPPGAGAPPWYADVLLPDLGAAWRVLHAIPAARAARQRGNEISGGASALGALLMLPGVRGLGPGPVTTGAAAGLLSGYLLARKVVDAQAPRPAPAHEWHAMSVEQVRKALPSPDEQAPAKAPPSPYPARALAGGLHTAKRGAQITQAPLNALWQLTKAVRAELSDPLTPMLALGAMASAVLGSPVDAVMVGSVLTGNSILAASQRLRAESRLNRLLAQQIPPARKVLAGADDQPRYIEVRAEELRPGDIIEVRTHEVVPADARVIEEVDVEVDESALTGESLSVTKQVEPTPGVDLIERRCMLYAGTTVVSGTAVAVVTAVGPDTQERRAAELVSGDLSSVGLQHQLSRLTNQAWPVSMTGGALVTGLGLLRRRGLRQAVASGIAVTVAAVPEGMPLVATLAQQASARRLSHFGALVRIPRSVEALGRVDMVCFDKTGTLSENRLRVAQVRPVAGHSREEVLRCAAHAAPASNGPQVHATDVAIVQAAAAAAASGTDGAEPGAAEPAAHLPFRSGRSFSASVSGTELTVKGAPEVVLAACEGIGSSMDDAVAELAANGLRVIAVAHRQLTAQQAQSVVDDPDEIARLCRDELSLVGFLGLSDTPRAQAAALLADLHEHDLDIRLITGDHPITAAAIAEELGMQVSPEQVISGAEWDALSRKDQERAVAERVIFARMTPENKVQIVQTLEHSGRVCAMVGDGSNDAAAIRAATVGIGVVAHGSDPARVAADLVLVDGRIESLLPAILEGRQLWQRVQAAVSVLLGGNAGEVAFAIIGSAITGTSPLNTRQLLLVNMLTDALPAAALAVSKPSDPVTPATRGPDQRELWRAVGIRGATTAAAATVAWVMAGFTGLPRRASTVALVALVAAQLGQTLVDSHAWLVVLTALGSLAALATLISIPVVSQLLGCTPLDPLGWAQATAAATAATVAVAVLNRVLTGRDKSGQPNPQPPETDALSRDASPGAPPGPRRRRRATARRKAPVKAPSATRQTTKPKGPPAHRSSSTYPRR