Rv0499 Family assigned · medium auto-curated
H37Rv Rv0499 · MTBC0 mtbc0_000525 ·
291 aa · 592524–593399 (+) ·
RefSeq NP_215013.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | thioesterase family protein |
| Revised (this work) | Thioesterase family protein. Pfam: 4HBT_3 (PF13622.13), 4HBT_3C (PF20789.4). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WKT9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Uncharacterized protein Rv0499 |
UniProt still lists this protein as Uncharacterized protein Rv0499; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | Thioesterase-like superfamily |
| Orthologous group | COG2050 |
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) pseudogene candidate
| pN/pS | 0.733 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 1.86% of strains (2701) · 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 |
|---|---|---|---|---|
4HBT_3 | PF13622.13 | 3.7e-19 | 32–119 | Acyl-CoA thioesterase N-terminal domain |
4HBT_3C | PF20789.4 | 1.1e-22 | 171–288 | Acyl-CoA thioesterase C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0497 (transmembrane protein), high confidence from genomic context alone (score 907 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) |
|---|---|---|---|---|
Rv0498 hyp |
hypothetical protein | 964 | 965 ctx | neighborhood:863 coexpression:754 |
Rv0497 |
transmembrane protein | 906 | 907 ctx | neighborhood:846 cooccurence:403 |
Rv0500 proC |
pyrroline-5-carboxylate reductase | 847 | 848 ctx | neighborhood:846 |
Rv0496 ppx1 hyp |
hypothetical protein | 847 | 847 ctx | neighborhood:846 |
Rv0495c hyp |
hypothetical protein | 745 | 746 ctx | neighborhood:744 |
Rv2360c hyp |
hypothetical protein | 681 | 681 ctx | cooccurence:679 |
Rv2418c octT hyp |
hypothetical protein | 658 | 637 ctx | cooccurence:619 |
Rv1836c hyp |
hypothetical protein | 614 | 614 ctx | cooccurence:605 |
Rv0383c ttfA hyp |
hypothetical protein | 611 | 611 ctx | cooccurence:611 |
Rv2138 lppL |
lipoprotein LppL | 604 | 604 ctx | cooccurence:602 |
Rv1109c hyp |
hypothetical protein | 603 | 603 ctx | cooccurence:603 |
Rv0472c |
HTH-type transcriptional regulator | 578 | 579 ctx | cooccurence:576 |
Rv3415c hyp |
hypothetical protein | 578 | 578 ctx | cooccurence:574 |
Rv2609c |
membrane protein | 592 | 577 | |
Rv0475 hbhA |
heparin binding hemagglutinin HbhA | 574 | 575 ctx | cooccurence:572 |
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: thioesterase family protein
- Pfam (hmmscan --cut_ga): 4HBT_3 PF13622.13 (E=4e-19), 4HBT_3C PF20789.4 (E=1e-22)
- (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_215013.1)
- Domains: Pfam-A via hmmscan --cut_ga — 4HBT_3 (PF13622.13), 4HBT_3C (PF20789.4)
- 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
COG2050 - Curated reference: UniProt P9WKT9 (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 —
90 functional partner(s); context anchor
Rv0497 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000525|Rv0499| MNALFTTAMALRPLDSDPGNPACRVFEGELNEHWTIGPKVHGGAMVALCANAARTAYGAAGQQPMRQPVAVSASFLWAPDPGTMRLVTSIRKRGRRISVADVELTQGGRTAVHAVVTLGEPEHFLPGVDGSGGASGTAPLLSANPVVELMAPEPPEGVVPIGPGHQLAGLVHLGEGCDVRPVLSTLRSATDGRPPVIQLWARPRGVAPDALFALLCGDLSAPVTFAVDRTGWAPTVALTAYLRALPADGWLRVLCTCVEIGQDWFDEDHIVVDRLGRIVVQTRQLAMVPAQ