Rv0376c Family assigned · medium auto-curated
H37Rv Rv0376c · MTBC0 - ·
380 aa · 453230–454372 (-) ·
RefSeq NP_214890.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Contains XdhC_CoxI (PF02625.22), XdhC_C (PF13478.13) domain(s); putative function inferred from the domain architecture. |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
O53711
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | XshC-Cox1 family protein |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
O Post-translational modification, protein turnover, chaperones
|
|---|---|
| Preferred name | xdhC |
| eggNOG description | Xanthine and CO dehydrogenases maturation factor, XdhC CoxF family |
| Orthologous group | COG1975 |
| KEGG orthology |
K07402
|
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 | 0.679 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 9 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.67% of strains (977) · 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 |
|---|---|---|---|---|
XdhC_CoxI | PF02625.22 | 3.6e-24 | 4–70 | XdhC and CoxI family |
XdhC_C | PF13478.13 | 6.7e-42 | 198–344 | XdhC Rossmann domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0375c (carbon monoxyde dehydrogenase medium subunit), high confidence from genomic context alone (score 971 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) |
|---|---|---|---|---|
Rv0375c |
carbon monoxyde dehydrogenase medium subunit | 974 | 971 ctx | neighborhood:790 cooccurence:744 coexpression:505 |
Rv0374c |
carbon monoxyde dehydrogenase small subunit | 961 | 958 ctx | neighborhood:782 cooccurence:767 |
Rv0371c hyp |
hypothetical protein | 947 | 944 ctx | neighborhood:719 cooccurence:686 coexpression:419 |
Rv0373c |
carbon monoxyde dehydrogenase large subunit | 929 | 922 ctx | neighborhood:619 cooccurence:752 |
Rv0369c |
membrane oxidoreductase | 898 | 898 ctx | neighborhood:700 cooccurence:672 |
Rv0345 hyp |
hypothetical protein | 870 | 862 ctx | cooccurence:691 coexpression:409 |
Rv0368c hyp |
hypothetical protein | 848 | 848 ctx | neighborhood:700 cooccurence:508 |
Rv0377 |
HTH-type transcriptional regulator | 824 | 824 ctx | neighborhood:788 |
Rv0370c |
oxidoreductase | 820 | 820 ctx | neighborhood:768 |
Rv0372c hyp |
hypothetical protein | 799 | 800 ctx | neighborhood:719 |
Rv0365c hyp |
hypothetical protein | 539 | 539 ctx | neighborhood:537 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): hypothetical protein
- Pfam (hmmscan --cut_ga): XdhC_CoxI PF02625.22 (E=4e-24), XdhC_C PF13478.13 (E=7e-42)
- (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_214890.1)
- Domains: Pfam-A via hmmscan --cut_ga — XdhC_CoxI (PF02625.22), XdhC_C (PF13478.13)
- 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
COG1975 - Curated reference: UniProt O53711 (TrEMBL, unreviewed; Predicted)
- 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 —
11 functional partner(s); context anchor
Rv0375c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0376c| MAIWAAGDTAGVATVVRTLRSAPRPPGAAMVVAPDGSVSGSVSGGCVEGAVYELAAEVAQTGIPRLEHYGVSDDTAFAVGLTCGGIIDVFVEPVSRATFPELGELADDIGAQRPVAIATVIAHPDERRVGRRLVIRPDTKSPVTGSLGSARADAAVIDDARGLLAVGRSEILEYGPDGQRRGEGMEVFVSSHAPRPRMLVFGAIDFAAALARQGSFLGYRVTVCDARAVFATPARFPTADDVVVAWPHRYLAAQAEAGGIDERTVICVLTHDPKFDVPVLEVALRLGVGYVGAMGSRKTHDDRMDRLRAAGLTDAELSRLSSPIGLDLGARTPEETAVSIAADIIARRWGGGGRPLADIAGRIHHDAQVAGEFKDYLTRH