Rv0163 Family assigned · medium
H37Rv Rv0163 · MTBC0 mtbc0_000176 ·
151 aa · 193463–193918 (+) ·
RefSeq NP_214677.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | thioesterase family protein |
| Revised (this work) | Thioesterase of the hotdog-fold superfamily (Pfam 4HBT_2 PF13279 + 4HBT PF03061). Putative acyl-CoA / acyl-ACP thioesterase; the specific substrate is not established. |
Curated reference (UniProt)
| UniProt |
O07408
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 | thioesterase |
| Orthologous group | COG0824 |
| KEGG orthology |
K07107
|
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 | 0.453 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 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 |
|---|---|---|---|---|
4HBT_2 | PF13279.13 | 9.1e-15 | 24–142 | Thioesterase-like superfamily |
4HBT | PF03061.29 | 5.6e-14 | 31–111 | Thioesterase superfamily |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: adhE1 (zinc-type alcohol dehydrogenase subunit E), medium confidence from genomic context alone (score 631 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) |
|---|---|---|---|---|
Rv1527c pks5 |
polyketide synthase | 931 | 911 | coexpression:470 experimental:816 |
Rv2048c pks12 |
polyketide synthase | 931 | 911 | coexpression:470 experimental:816 |
Rv2933 ppsC |
phthiocerol synthesis polyketide synthase type I PpsC | 930 | 911 | coexpression:469 experimental:816 |
Rv3825c pks2 |
phthioceranic/hydroxyphthioceranic acid synthase | 930 | 910 | coexpression:467 experimental:816 |
Rv2940c mas |
multifunctional mycocerosic acid synthase | 930 | 910 | coexpression:467 experimental:816 |
Rv2946c pks1 |
polyketide synthase | 844 | 826 | coexpression:651 experimental:454 |
Rv2932 ppsB |
phthiocerol synthesis polyketide synthase type I PpsB | 833 | 818 | coexpression:648 experimental:454 |
Rv0164 TB18.5 hyp |
hypothetical protein | 809 | 809 ctx | neighborhood:807 |
Rv1661 pks7 |
polyketide synthase | 746 | 719 | coexpression:463 experimental:454 |
Rv1181 pks4 |
polyketide beta-ketoacyl synthase | 745 | 718 | coexpression:460 experimental:454 |
Rv0405 pks6 |
membrane bound polyketide synthase | 721 | 702 | coexpression:458 experimental:454 |
Rv3800c pks13 |
polyketide synthase | 737 | 700 | coexpression:455 experimental:454 |
Rv2931 ppsA |
phthiocerol synthesis polyketide synthase type I PpsA | 720 | 700 | coexpression:455 experimental:454 |
Rv2524c fas |
fatty acid synthase | 789 | 655 | coexpression:404 textmining:415 |
Rv0162c adhE1 |
zinc-type alcohol dehydrogenase subunit E | 652 | 631 ctx | neighborhood:622 |
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
- MTBC0 PGAP product: 'thioesterase family protein'
- Pfam: 4HBT_2 PF13279 (E=9.1e-15), 4HBT PF03061 (E=5.6e-14) -- hotdog-fold thioesterase
ESM Atlas signal (exploratory)
Ancestral protein hash 631994740a367df20c5f08e7b057b58b ·
10 ESM-space neighbours (max similarity 0.930).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 12865 |
1.00 | HotDog/MaoC domain scaffold |
| 2 | 3698 |
0.94 | Hot-dog fold dehydratase/thioesterase |
| 3 | 1045 |
0.90 | Acyl-chain pocket beta-strand |
| 4 | 2298 |
0.89 | Transit peptides and PTS1 |
| 5 | 9112 |
0.82 | Acyl-binding groove beta-strands |
| 6 | 1188 |
0.76 | Acyl-thioester catalytic loop |
| 7 | 3306 |
0.71 | Core beta-hairpin motifs |
| 8 | 1621 |
0.65 | Acyl-thioester active-site loop |
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_214677.1)
- Domains: Pfam-A via hmmscan --cut_ga — 4HBT_2 (PF13279.13), 4HBT (PF03061.29)
- 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
COG0824 - Curated reference: UniProt O07408 (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 —
34 functional partner(s); context anchor
adhE1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000176|Rv0163| MAALPAPEKLLRSDFPVLWPVGTRWADNDMFGHLNNAVYYQLFDTAINAWINTSTGVDPLAMPVLGIVAESGCRYFSELRFPESLMVGLAVTRLGRSSVTYRLGVFKEPDDAGVITALGHWVHVYVDRTSRRPVPIPEAIRSLLSTACVSG