cpnT Resolved · high auto-curated
H37Rv Rv3903c · MTBC0 mtbc0_004137 ·
846 aa · 4412144–4414684 (-) ·
RefSeq NP_218420.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | outer membrane channel protein/necrotizing toxin glycohydrolase CpnT |
| Revised (this work) | Outer membrane channel protein/necrotizing toxin glycohydrolase CpnT. Pfam: WXG100_2 (PF25547.2), TNT (PF14021.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05442
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Outer membrane channel protein CpnT |
| EC (curated) |
EC 3.2.2.5
|
| Curated function | Has a dual function in uptake of nutrients and induction of host cell death. The N-terminal domain (NTD) forms an outer membrane channel and is used for uptake of nutrients across the outer membrane. The secreted C-terminal toxic domain (TNT) acts as a glycohydrolase, which hydrolyzes the essential cellular coenzyme NAD(+) in the cytosol of infected macrophages, leading to necrotic host cell death. Both functions are required for survival, replication and cytotoxicity of M.tuberculosis in macrophages. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
P Inorganic ion transport and metabolism
|
|---|---|
| eggNOG description | Belongs to the bacterial solute-binding protein 9 family |
| Orthologous group | COG0803 |
| Gene Ontology (6) |
GO:0005575, 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 | 0.71 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 20 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (662) · 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 |
|---|---|---|---|---|
WXG100_2 | PF25547.2 | 5.9e-07 | 132–230 | WXG100 like domain |
TNT | PF14021.13 | 5.1e-14 | 751–846 | Tuberculosis necrotizing toxin |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: esxE (ESAT-6 like protein EsxE), high confidence from genomic context alone (score 948 excluding text-mining). This association is the citable seed of a function hypothesis for this hypothetical protein.
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3902c ift hyp |
hypothetical protein | 996 | 978 ctx | neighborhood:882 experimental:817 textmining:870 |
Rv3904c esxE |
ESAT-6 like protein EsxE | 985 | 948 ctx | neighborhood:882 coexpression:580 textmining:723 |
Rv3448 eccD4 |
ESX-4 secretion system protein EccD4 | 921 | 920 ctx | cooccurence:595 coexpression:805 |
Rv3905c esxF |
ESAT-6 like protein EsxF | 981 | 900 ctx | neighborhood:880 textmining:825 |
Rv3446c hyp |
hypothetical protein | 867 | 861 | coexpression:770 |
Rv2488c |
LuxR family transcriptional regulator | 820 | 810 | coexpression:804 |
Rv1359 |
transcriptional regulator | 809 | 810 | coexpression:759 |
Rv1917c PPE34 |
PPE family protein PPE34 | 794 | 795 ctx | cooccurence:757 |
Rv0339c iniR |
transcriptional regulator | 799 | 791 ctx | cooccurence:562 coexpression:539 |
Rv3343c PPE54 |
PPE family protein PPE54 | 788 | 788 ctx | cooccurence:760 |
Rv3347c PPE55 |
PPE family protein PPE55 | 787 | 787 ctx | cooccurence:760 |
Rv3350c PPE56 |
PPE family protein PPE56 | 786 | 787 ctx | cooccurence:760 |
Rv0355c PPE8 |
PPE family protein PPE8 | 786 | 787 ctx | cooccurence:759 |
Rv0538 |
membrane protein | 795 | 782 ctx | cooccurence:773 |
Rv0305c PPE6 |
PPE family protein PPE6 | 782 | 782 ctx | cooccurence:755 |
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: hypothetical protein
- MTBC0 PGAP product: outer membrane channel protein/necrotizing toxin glycohydrolase CpnT
- Pfam (hmmscan --cut_ga): WXG100_2 PF25547.2 (E=6e-07), TNT PF14021.13 (E=5e-14)
- (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_218420.1)
- Domains: Pfam-A via hmmscan --cut_ga — WXG100_2 (PF25547.2), TNT (PF14021.13)
- 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
COG0803 - Curated reference: UniProt O05442 (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 —
184 functional partner(s); context anchor
esxE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_004137|Rv3903c|cpnT MAPLAVDPAALDSAGGAVVAAGAGLGAVISSLTAALAGCAGMAGDDPAGAVFGRSYDGSAAALVQAMSVARNGLCNLGDGVRMSAHNYSLAEAMSDVAGRAAPLPAPPPSGCVGVGAPPSAVGGGGGAPKGWGWVAPYIGMIWPNGDSTKLRAAAVAWRSAGTQFALTEIQSTAGPMGVIRAQQLPEAGLIESAFADAYASTTAVVGQCHQLAAQLDAYAARIDAVHAAVLDLLARICDPLTGIKEVWEFLTDQDEDEIQRIAHDIAVVVDQFSGEVDALAAEITAVVSHAEAVITAMADHAGKQWDRFLHSNPVGVVIDGTGQQLKGFGEEAFGMAKDSWDLGPLRASIDPFGWYRSWEEMLTGMAPLAGLGGENAPGVVESWKQFGKSLIHWDEWTTNPNEALGKTVFDAATLALPGGPLSKLGSKGRDILAGVRGLKERLEPTTPHLEPPATPPRPGPQPPRIEPPESGHPAPAPAAKPAPVPANGPLPHSPTESKPPPVDRPAEPVAPSSASAGQPRVSAATTPGTHVPHGLPQPGEHVPAQAPPATTLLGGPPVESAPATAHQPQWATTPAAPAAAPHSTPGGVHSTESGPHGRSLSAHGSEPTHDGASHGSGHGSGSEPPGLHAPHREQQLAMHSNEPAGEGWHRLSDEAVDPQYGEPLSRHWDFTDNPADRSRINPVVAQLMEDPNAPFGRDPQGQPYTQERYQERFNSVGPWGQQYSNFPPNNGAVPGTRIAYTNLEKFLSDYGPQLDRIGGDQGKYLAIMEHGRPASWEQRALHVTSLRDPYHAYTIDWLPEGWFIEVSEVAPGCGQPGGSIQVRIFDHQNEMRKVEELIRRGVLRQ