Rv0464c Family assigned · medium auto-curated
H37Rv Rv0464c · MTBC0 mtbc0_000488 ·
190 aa · 557678–558250 (-) ·
RefSeq NP_214978.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | carboxymuconolactone decarboxylase family protein |
| Revised (this work) | Carboxymuconolactone decarboxylase family protein. Pfam: CMD (PF02627.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53749
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Conserved protein |
UniProt still lists this protein as Conserved protein; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Carboxymuconolactone decarboxylase |
| Orthologous group | COG2128 |
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 | 0.175 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 1 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 |
|---|---|---|---|---|
CMD | PF02627.26 | 1.7e-11 | 52–122 | Carboxymuconolactone decarboxylase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ramB (HTH-type transcriptional regulator), high confidence from genomic context alone (score 883 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) |
|---|---|---|---|---|
Rv0465c ramB |
HTH-type transcriptional regulator | 883 | 883 ctx | neighborhood:882 |
Rv1683 |
bifunctional long-chain acyl-CoA synthase/lipase | 696 | 671 ctx | cooccurence:662 |
Rv0466 hyp |
hypothetical protein | 667 | 667 ctx | neighborhood:538 |
Rv3249c |
TetR family transcriptional regulator | 660 | 661 ctx | cooccurence:653 |
Rv0885 hyp |
hypothetical protein | 657 | 657 ctx | cooccurence:656 |
Rv3346c |
transmembrane protein | 642 | 642 ctx | cooccurence:641 |
Rv0226c |
transmembrane protein | 538 | 539 ctx | cooccurence:537 |
Rv1476 |
membrane protein | 515 | 515 ctx | cooccurence:509 |
Rv2673 aftC |
alpha-(1->3)-arabinofuranosyltransferase | 504 | 505 ctx | cooccurence:498 |
Rv1590 hyp |
hypothetical protein | 481 | 482 ctx | cooccurence:477 |
Rv2001 hyp |
hypothetical protein | 478 | 478 ctx | cooccurence:455 |
Rv1286 cysC |
adenylyl-sulfate kinase | 476 | 477 | coexpression:477 |
Rv3802c |
membrane protein | 423 | 423 ctx | cooccurence:419 |
Rv0433 |
carboxylate-amine ligase | 410 | 411 | coexpression:411 |
Rv1319c |
adenylate cyclase | 410 | 410 ctx | cooccurence:410 |
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: carboxymuconolactone decarboxylase family protein
- Pfam (hmmscan --cut_ga): CMD PF02627.26 (E=2e-11)
- (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_214978.1)
- Domains: Pfam-A via hmmscan --cut_ga — CMD (PF02627.26)
- 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
COG2128 - Curated reference: UniProt O53749 (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 —
18 functional partner(s); context anchor
ramB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000488|Rv0464c| MTGQNGQVARISPGKFRQLGPVNWLVAKLAARAVGAPQMHLFTTLGYRQYLFWTFAIYTGRLLHGRLPGVDTELVILRVAHLRSCEYELQHHRRMARRRGLDANTQATIFAWPDVPDGDGPRKVLSARQQALLQATDELIKDRTITAGTWERLATHLDPRLLIEFCLLATQYDAIAATITALAIPPDNPQ