Rv0272c Family assigned · medium
H37Rv Rv0272c · MTBC0 mtbc0_000289 ·
377 aa · 328957–330090 (-) ·
RefSeq NP_214786.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | alpha/beta hydrolase |
| Revised (this work) | Alpha/beta-hydrolase-fold enzyme (PGAP; Foldseek significant match to a cold-adapted esterase fold, E=7e-6, TM=0.65). Putative esterase/hydrolase; specific substrate not established. |
Curated reference (UniProt)
| UniProt |
P95229
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Alpha/beta hydrolase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | alpha beta |
| Orthologous group | COG1073 |
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 | 0.222 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 2 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 1.59% of strains (2315) · 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)
No Pfam-A domain above the gathering threshold (or not yet scanned).
Structural neighbours (Foldseek on the ESMFold model, exploratory)
ESMFold model confidence: mean pLDDT 95.6 (very high). A confident model makes the fold comparison meaningful.
Best matches against the PDB, ranked by Foldseek homology probability. A high probability / TM-score suggests a shared fold; unless flagged sig (E < 0.01) these are fold hypotheses, not assignments.
| Target | Prob | TM | E-value | Description |
|---|---|---|---|---|
4ao8-assembly1_A-2 |
1.00 | 0.65 | 7.1e-06 sig | 4ao8-assembly1_A-2 PEG-bound complex of a novel cold-adapted esterase from an Arctic intertidal metagenomic library |
8qzu-assembly1_A |
1.00 | 0.55 | 3.1e-07 sig | 8qzu-assembly1_A XhpG hydrolase mutant S98A of Xenorhabdus hominickii |
4ao7-assembly1_A-2 |
1.00 | 0.65 | 1.6e-05 sig | 4ao7-assembly1_A-2 Zinc bound structure of a novel cold-adapted esterase from an Arctic intertidal metagenomic library |
4ao6-assembly1_A-2 |
1.00 | 0.65 | 4.3e-05 sig | 4ao6-assembly1_A-2 Native structure of a novel cold-adapted esterase from an Arctic intertidal metagenomic library |
6y9f-assembly1_A |
1.00 | 0.54 | 3.4e-06 sig | 6y9f-assembly1_A Crystal structure of putative ancestral haloalkane dehalogenase AncHLD3 (node 3) |
2vax-assembly1_A |
1.00 | 0.43 | 4.4e-07 sig | 2vax-assembly1_A Crystal structure of deacetylcephalosporin C acetyltransferase (Cephalosporin C-soak) |
2vav-assembly2_B |
1.00 | 0.41 | 8.5e-07 sig | 2vav-assembly2_B Crystal structure of deacetylcephalosporin C acetyltransferase (DAC-Soak) |
2vav-assembly1_A |
1.00 | 0.41 | 1.2e-06 sig | 2vav-assembly1_A Crystal structure of deacetylcephalosporin C acetyltransferase (DAC-Soak) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0273c (transcriptional regulator), high confidence from genomic context alone (score 970 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) |
|---|---|---|---|---|
Rv0273c |
transcriptional regulator | 969 | 970 ctx | neighborhood:881 cooccurence:751 |
Rv0274 hyp |
hypothetical protein | 898 | 898 ctx | neighborhood:598 cooccurence:753 |
Rv0271c fadE6 |
acyl-CoA dehydrogenase FadE6 | 802 | 802 ctx | neighborhood:757 |
Rv0311 hyp |
hypothetical protein | 724 | 725 ctx | cooccurence:723 |
Rv0138 hyp |
hypothetical protein | 701 | 701 ctx | cooccurence:701 |
Rv0767c |
HTH-type transcriptional regulator | 694 | 694 ctx | cooccurence:689 |
Rv3169 hyp |
hypothetical protein | 643 | 644 ctx | cooccurence:639 |
Rv0774c hyp |
hypothetical protein | 646 | 625 ctx | cooccurence:625 |
Rv0519c |
membrane protein | 615 | 615 ctx | cooccurence:615 |
Rv3810 pirG |
cell surface protein | 576 | 576 ctx | cooccurence:567 |
Rv1874 hyp |
hypothetical protein | 555 | 555 ctx | cooccurence:550 |
Rv0518 hyp |
hypothetical protein | 542 | 541 ctx | cooccurence:541 |
Rv0762c hyp |
hypothetical protein | 525 | 526 ctx | cooccurence:523 |
Rv1867 hyp |
hypothetical protein | 506 | 507 ctx | cooccurence:494 |
Rv3707c hyp |
hypothetical protein | 484 | 485 ctx | cooccurence:482 |
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: 'alpha/beta hydrolase'
- Pfam: none above threshold
- Foldseek on the ESMFold model: significant match to an alpha/beta-hydrolase esterase fold (E=7e-6, TM=0.65)
ESM Atlas signal (exploratory)
Ancestral protein hash 4d0ce477e917476314fb73a828536186 ·
10 ESM-space neighbours (max similarity 0.926).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 11080 |
1.15 | AB hydrolase charge-relay motif |
| 2 | 13086 |
1.13 | ABH cap/lid activation hotspots |
| 3 | 10282 |
1.09 | AB-hydrolase cap/lid segments |
| 4 | 11204 |
1.06 | AB-hydrolase N-terminal cap |
| 5 | 5107 |
1.00 | Serine-hydrolase nucleophile elbow |
| 6 | 3636 |
0.99 | AB-hydrolase catalytic His segment |
| 7 | 13198 |
0.97 | ABH lipase-box catalytic motif |
| 8 | 13972 |
0.93 | Alpha/beta hydrolase nucleophile/oxyanion 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_214786.1)
- Domains: Pfam-A via hmmscan --cut_ga — none above threshold
- 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
COG1073 - Curated reference: UniProt P95229 (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)
- Model confidence: ESMFold per-residue pLDDT (mean 95.6, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
38 functional partner(s); context anchor
Rv0273c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000289|Rv0272c| MTGRAATPGVIREFVGLPSRTAGRAAAGGHPCQGLYHHSVGRKPKVALIAAHYQIDFSEHYLAEYMAIRGIGFLGWNTRFRGFESSFLLDHALVDIGVGVRWLREVQGVETVVLLGNSGGGSLMAAYQSQAVDPNVTPLDGMRPAAGVTELPAADAYVAAAAHPGRPDVLTAWMDAAVIDENDPVATDPELDLFDERNGPPYSPEFISRYRSAQVKRNHTITDWAESELKRVRAAGFSDRPFSVMRTWADPRMVDPSIEPTKRRPNQCYAGTPVKANRSAHGIAAACTLRGWLGMWSLRVAQTRAAPHLARITCPALVLNAEADTGIFPSDAQQIYDGLASSDKTQVSIDTDHYFTTPGARSEQADTIAKWIAKRWR