Rv0375c Family assigned · medium auto-curated
H37Rv Rv0375c · MTBC0 - ·
286 aa · 452294–453154 (-) ·
RefSeq NP_214889.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | carbon monoxyde dehydrogenase medium subunit |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Carbon monoxyde dehydrogenase medium subunit. Pfam: FAD_binding_5 (PF00941.28), CO_deh_flav_C (PF03450.23). |
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 |
I6Y7N2
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable carbon monoxyde dehydrogenase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
C Energy production and conversion
|
|---|---|
| eggNOG description | Dehydrogenase |
| Orthologous group | COG1319 |
| EC number |
EC 1.2.5.3
|
| KEGG orthology |
K03519
|
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 | 0.382 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.46% of strains (661) · 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 |
|---|---|---|---|---|
FAD_binding_5 | PF00941.28 | 7.5e-37 | 2–166 | FAD binding domain in molybdopterin dehydrogenase |
CO_deh_flav_C | PF03450.23 | 1.9e-25 | 173–272 | CO dehydrogenase flavoprotein C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0373c (carbon monoxyde dehydrogenase large subunit), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0373c |
carbon monoxyde dehydrogenase large subunit | 999 | 999 ctx | neighborhood:860 cooccurence:774 coexpression:436 experimental:928 textmining:934 |
Rv0374c |
carbon monoxyde dehydrogenase small subunit | 999 | 999 ctx | neighborhood:869 cooccurence:773 coexpression:440 experimental:928 textmining:895 |
Rv0372c hyp |
hypothetical protein | 993 | 992 ctx | neighborhood:811 cooccurence:772 coexpression:835 |
Rv0376c hyp |
hypothetical protein | 974 | 971 ctx | neighborhood:790 cooccurence:744 coexpression:505 |
Rv0371c hyp |
hypothetical protein | 956 | 951 ctx | neighborhood:775 cooccurence:700 |
Rv0368c hyp |
hypothetical protein | 939 | 940 ctx | neighborhood:754 cooccurence:758 |
Rv0370c |
oxidoreductase | 939 | 937 ctx | neighborhood:850 cooccurence:588 |
Rv0369c |
membrane oxidoreductase | 938 | 935 ctx | neighborhood:754 cooccurence:730 |
Rv0377 |
HTH-type transcriptional regulator | 853 | 854 ctx | neighborhood:725 cooccurence:483 |
Rv2426c hyp |
hypothetical protein | 492 | 469 ctx | cooccurence:403 |
Rv0345 hyp |
hypothetical protein | 517 | 461 | |
Rv0365c hyp |
hypothetical protein | 441 | 440 ctx | neighborhood:440 |
Rv0367c hyp |
hypothetical protein | 403 | 403 | |
Rv1847 |
esterase | 428 | 49 | textmining:424 |
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): carbon monoxyde dehydrogenase medium subunit
- Pfam (hmmscan --cut_ga): FAD_binding_5 PF00941.28 (E=8e-37), CO_deh_flav_C PF03450.23 (E=2e-25)
- (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_214889.1)
- Domains: Pfam-A via hmmscan --cut_ga — FAD_binding_5 (PF00941.28), CO_deh_flav_C (PF03450.23)
- 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
COG1319 - Curated reference: UniProt I6Y7N2 (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 —
14 functional partner(s); context anchor
Rv0373c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv0375c| MDHAIGLLDRLGEGARVVAGGHSLLPMMKLRIANPEYLVDINDLAPELGYVVVGGINNPNLVRLGAMTRHREILDSDALAAVCPIFRDAERVIADPVVRNRGTLGGSLCQADPAEDLSTVCTVLDAVCLAKGPSGEREIAIDDFLVGPYETALAHNEVLIEVRIPLRHNTSSAYAKVERRVGDWAITAAGAAVTLDGQTILAARVGLTAVNPDPVALAELSAGLVGQPATEEVFAEAGRRAAQACTPVTDVRGTAEYKRHLAGELTVRTLRTAAGRVLGAPAAPEA