Rv0074 Family assigned · medium
H37Rv Rv0074 · MTBC0 mtbc0_000082 ·
411 aa · 82911–84146 (+) ·
RefSeq NP_214588.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | amidohydrolase family protein |
| Revised (this work) | Amidohydrolase-superfamily metalloenzyme (Pfam Amidohydro_1 PF01979 + Amidohydro_3). A TIM-barrel metal-dependent hydrolase; the specific substrate in M. tuberculosis is not established. |
Curated reference (UniProt)
| UniProt |
O53619
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 |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| eggNOG description | amidohydrolase |
| Orthologous group | COG1228 |
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 | 0.311 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 8 synonymous, 7 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 17.64% of strains (25616) · 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 |
|---|---|---|---|---|
Amidohydro_1 | PF01979.27 | 1.1e-57 | 65–396 | Amidohydrolase family |
Amidohydro_3 | PF07969.18 | 1.7e-16 | 99–398 | Amidohydrolase family |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0075 (aminotransferase), high confidence from genomic context alone (score 934 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) |
|---|---|---|---|---|
Rv0075 |
aminotransferase | 934 | 934 ctx | neighborhood:777 coexpression:716 |
Rv0073 |
glutamine ABC transporter ATP-binding protein | 676 | 664 ctx | neighborhood:605 |
Rv0072 |
glutamine ABC transporter permease | 627 | 627 ctx | neighborhood:605 |
Rv0552 hyp |
hypothetical protein | 572 | 572 ctx | cooccurence:570 |
Rv2052c hyp |
hypothetical protein | 511 | 511 ctx | cooccurence:503 |
Rv1922 |
lipoprotein | 450 | 451 ctx | cooccurence:450 |
Rv2216 |
epimerase family protein | 437 | 437 | coexpression:405 |
Rv3306c amiB1 |
amidase AmiB | 438 | 416 | |
Rv2947c pks15 |
polyketide synthase | 489 | 67 | textmining:475 |
Rv0071 |
maturase | 870 | 47 | textmining:870 |
Rv2352c PPE38 |
PPE family protein PPE38 | 551 | 46 | textmining:549 |
Rv3346c |
transmembrane protein | 805 | 45 | textmining:805 |
Rv2628 hyp |
hypothetical protein | 653 | 44 | textmining:652 |
Rv2623 TB31.7 |
universal stress protein | 428 | 44 | textmining:427 |
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: 'amidohydrolase family protein'
- Pfam: Amidohydro_1 PF01979 (E=1.1e-57), Amidohydro_3 PF07969 (E=1.7e-16)
ESM Atlas signal (exploratory)
Ancestral protein hash 611e052a07eda841fe07d051ebf1c198 ·
10 ESM-space neighbours (max similarity 0.863).
SAE features are orienting indices, not validated domains.
| # | Index | Activation | Interpretation |
|---|---|---|---|
| 1 | 10492 |
1.39 | Metalloenzyme active-site helix |
| 2 | 7206 |
1.17 | Metal-proximal gating segment |
| 3 | 12199 |
1.14 | Metal-dependent hydrolase metallocenter |
| 4 | 5844 |
1.14 | Generalized metal-binding motif |
| 5 | 11701 |
1.13 | N-terminal metal-binding scaffold |
| 6 | 8911 |
1.11 | C-terminal active-site flanks |
| 7 | 3152 |
1.10 | Metallo-amidohydrolase C-terminal cap |
| 8 | 4689 |
1.07 | Amido/urease acidic Gly-rich cap 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_214588.1)
- Domains: Pfam-A via hmmscan --cut_ga — Amidohydro_1 (PF01979.27), Amidohydro_3 (PF07969.18)
- 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
COG1228 - Curated reference: UniProt O53619 (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 —
14 functional partner(s); context anchor
Rv0075 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_000082|Rv0074| MGDLSISQVSARPGRIGIRARQMFDGYRFQRGPVLVVVEDGRISAVDFAGSACPDMNLVDLGESTLLPGLVDAHAHLCWDPDGRPEDLAGDPHAVLVGRARRHAAAALRSGITTIRDLGDRDYAALALREEYRQKTTVGPELVVSGPPLTRSGGHCWFLGGVADSVEELVDAVQERAARGADWIKVMATGGFVTTASDPWQPQYGSGQLAAVVAAAEQVGLPVTAHAHATAGIAAAVAAGVDGIEHCTFLSEGSAAASPDVVEAIVAQGVWCGMTIPRVYPEMPENLVAVVQDGWRNIRRLIDAGARVALSTDAGVAPGRRHDVLPDDLVYLSRHGFTSTEVLTGATAAAAASCGLGHRKGRIAPGYDADLLAVAAGVDHDPAGLCDVKAVWRSGTQVPLQASAVGYNTPS