Rv0185 Family assigned · low
H37Rv Rv0185 · MTBC0 mtbc0_000198 ·
169 aa · 216063–216572 (+) ·
RefSeq NP_214699.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | TIGR04338 family metallohydrolase |
| Revised (this work) | Putative metallohydrolase (PGAP TIGR04338 family). No Pfam domain above threshold, but Foldseek weakly matches an M61-type aminopeptidase fold: a possible metal-dependent hydrolase/peptidase, not firmly assigned. |
Curated reference (UniProt)
| UniProt |
O07429
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | TIGR04338 family metallohydrolase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2DPFG |
|---|
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 | 0.545 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 3 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)
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 |
|---|---|---|---|---|
7xyo-assembly1_A |
0.28 | 0.37 | 3.7e-01 | 7xyo-assembly1_A Crystal Structure of a M61 aminopeptidase family member from Myxococcus fulvus |
3hq2-assembly1_B |
0.20 | 0.34 | 4.7e-01 | 3hq2-assembly1_B BsuCP Crystal Structure |
7xyo-assembly1_B |
0.18 | 0.30 | 2.4e-01 | 7xyo-assembly1_B Crystal Structure of a M61 aminopeptidase family member from Myxococcus fulvus |
5k78-assembly3_C |
0.12 | 0.53 | 2.5e+00 | 5k78-assembly3_C Dbr1 in complex with 16-mer branched RNA |
2hy1-assembly1_A-2 |
0.10 | 0.53 | 3.3e+00 | 2hy1-assembly1_A-2 Crystal structure of Rv0805 |
1bqb-assembly1_A |
0.10 | 0.39 | 2.2e+00 | 1bqb-assembly1_A AUREOLYSIN, STAPHYLOCOCCUS AUREUS METALLOPROTEINASE |
8g7m-assembly1_G |
0.07 | 0.17 | 2.2e-01 | 8g7m-assembly1_G ATP-bound mtHsp60 V72I focus |
6knc-assembly1_A |
0.07 | 0.46 | 4.1e+00 | 6knc-assembly1_A PolD-PCNA-DNA (form B) |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: bglS (beta-glucosidase BglS), high confidence from genomic context alone (score 917 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) |
|---|---|---|---|---|
Rv0184 hyp |
hypothetical protein | 995 | 996 ctx | neighborhood:882 cooccurence:774 coexpression:850 |
Rv0186 bglS |
beta-glucosidase BglS | 916 | 917 ctx | neighborhood:652 coexpression:770 |
Rv0183 |
lysophospholipase | 822 | 822 ctx | neighborhood:821 |
Rv2792c |
resolvase | 797 | 797 | coexpression:797 |
Rv0606 |
Possible transposase (fragment); Rv0606, (MTCY19H5.16c), len: 247 aa. Possible truncated transposase for IS_1536 element, highly similar to | 797 | 797 | coexpression:797 |
Rv2791c tnpB |
transposase | 791 | 791 | coexpression:791 |
Rv2978c tnpB |
transposase | 778 | 778 | coexpression:778 |
Rv3585 radA |
DNA repair protein RadA | 761 | 761 | coexpression:761 |
Rv3035 hyp |
hypothetical protein | 751 | 751 ctx | cooccurence:749 |
Rv0605 |
IS1536 family serine type transposase | 734 | 734 | coexpression:734 |
Rv2979c |
resolvase | 734 | 734 | coexpression:734 |
Rv2977c thiL |
thiamine-monophosphate kinase | 732 | 732 | coexpression:732 |
Rv1125 hyp |
hypothetical protein | 730 | 731 ctx | cooccurence:730 |
Rv1274 lprB |
lipoprotein LprB | 717 | 718 ctx | cooccurence:716 |
Rv1303 hyp |
hypothetical protein | 700 | 700 ctx | cooccurence:700 |
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: 'TIGR04338 family metallohydrolase'
- Pfam: none above threshold
- Foldseek on the ESMFold model: weak similarity to an M61 aminopeptidase (suggestive)
ESM Atlas signal (exploratory)
Ancestral protein hash cb2ac15fb8eaf37482d33c46df8308fc ·
9 ESM-space neighbours (max similarity 0.871).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 9223 |
1.13 | Active-site-adjacent scaffold patches |
| 2 | 15945 |
1.05 | Zn metalloprotease accessory regions |
| 3 | 2253 |
1.02 | Metalloprotease pre-active-site scaffold |
| 4 | 14536 |
1.00 | Metalloenzyme active site scaffold |
| 5 | 7592 |
1.00 | Post-HExxH zinc-binding segment |
| 6 | 9122 |
0.97 | Zinc metallohydrolase flanking segments |
| 7 | 10697 |
0.90 | HExxH metalloprotease active site |
| 8 | 1025 |
0.90 | Metallohydrolase N-terminal scaffold |
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_214699.1)
- 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
2DPFG - Curated reference: UniProt O07429 (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 —
67 functional partner(s); context anchor
bglS - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000198|Rv0185| MIGADVPRDSQRARVYAAEAFVRTLFDRVTAHGSPTVEFFGTQLTLPPEGRFGSVASVQRYVDDVLALPAVGQNWPTVSPVRVRARRAATAAHYENHGGTGTIAVPDRHTAGWAMRELVVLHEVAHHLCQVPPPHGPEFVATVCTLTELVMGPEVGHVFRVVYAQEGVR