Rv1356c Resolved · high
H37Rv Rv1356c · MTBC0 - ·
263 aa · 1524029–1524820 (-) ·
RefSeq NP_215872.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | TrzA: N-acyl amino acid transferase. N-acylates L-tryptophan (highest specificity for C5:0-CoA) in the trzAS cluster for N-acylated tryptazolone biosynthesis. RefSeq still annotates it hypothetical. |
Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).
Curated reference (UniProt)
| UniProt |
P9WM09
SwissProt · reviewed
· Predicted
|
|---|---|
| UniProt name | Uncharacterized protein Rv1356c |
UniProt still lists this protein as Uncharacterized protein Rv1356c; the revised annotation above is ahead of the current UniProt record.
Functional vocabulary (eggNOG-mapper, orthology transfer)
| Orthologous group | 2C4J7 |
|---|
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 | 0.082 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 0 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (169) · 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 91.1 (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 |
|---|---|---|---|---|
2g0b-assembly1_A |
1.00 | 0.74 | 1.6e-05 sig | 2g0b-assembly1_A The structure of FeeM, an N-acyl amino acid synthase from uncultured soil microbes |
2g0b-assembly11_D |
1.00 | 0.69 | 5.4e-06 sig | 2g0b-assembly11_D The structure of FeeM, an N-acyl amino acid synthase from uncultured soil microbes |
2g0b-assembly7_G |
1.00 | 0.73 | 2.7e-05 sig | 2g0b-assembly7_G The structure of FeeM, an N-acyl amino acid synthase from uncultured soil microbes |
5w8a-assembly1_A |
1.00 | 0.60 | 3.3e-06 sig | 5w8a-assembly1_A The structure of a COA-dependent acyl-homoserine lactone synthase, BjaI, with SAM and isopentyl-CoA |
6wns-assembly1_A |
1.00 | 0.62 | 4.5e-06 sig | 6wns-assembly1_A The structure of a CoA-dependent acyl-homoserine lactone synthase, MesI |
2g0b-assembly8_H |
1.00 | 0.70 | 3.6e-05 sig | 2g0b-assembly8_H The structure of FeeM, an N-acyl amino acid synthase from uncultured soil microbes |
2g0b-assembly10_B |
1.00 | 0.66 | 2.0e-05 sig | 2g0b-assembly10_B The structure of FeeM, an N-acyl amino acid synthase from uncultured soil microbes |
1vhs-assembly2_B |
1.00 | 0.65 | 1.5e-05 sig | 1vhs-assembly2_B Crystal structure of a putative phosphinothricin N-acetyltransferase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: moeY (molybdopterin biosynthesis protein MoeY), high confidence from genomic context alone (score 967 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) |
|---|---|---|---|---|
Rv1354c hyp |
hypothetical protein | 991 | 968 ctx | neighborhood:811 coexpression:839 textmining:742 |
Rv1355c moeY |
molybdopterin biosynthesis protein MoeY | 994 | 967 ctx | neighborhood:773 coexpression:860 textmining:837 |
Rv1353c |
HTH-type transcriptional regulator | 972 | 929 ctx | neighborhood:732 coexpression:746 textmining:628 |
Rv1357c hyp |
hypothetical protein | 864 | 864 | coexpression:860 |
Rv1358 |
transcriptional regulator | 846 | 846 | coexpression:846 |
Rv0895 |
diacyglycerol O-acyltransferase | 744 | 744 | coexpression:744 |
Rv3114 hyp |
hypothetical protein | 422 | 423 | coexpression:423 |
Rv1638 uvrA |
excinuclease ABC subunit UvrA | 455 | 55 | textmining:447 |
Rv1633 uvrB |
excinuclease ABC subunit UvrB | 550 | 47 | textmining:548 |
Rv1625c cya |
adenylate cyclase | 439 | 47 | textmining:436 |
Rv1420 uvrC |
excinuclease ABC subunit UvrC | 551 | 45 | textmining:550 |
Rv3764c tcrY |
two component sensor kinase TcrY | 513 | 45 | textmining:511 |
Rv1163 narJ |
nitrate reductase subunit delta | 510 | 41 | textmining:510 |
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
- Foldseek: 2g0b-assembly1_A The structure of FeeM, an N-acyl amino acid synthase (E=2e-05, TM=0.74)
- Experimentally characterised as TrzA by Kleetz et al. 2025
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_215872.1)
- 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
2C4J7 - Curated reference: UniProt P9WM09 (SwissProt, reviewed; Predicted)
- 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 91.1, very high)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
13 functional partner(s); context anchor
moeY - Primary literature: Kleetz J, et al. (2025). Characterization of TrzA, an N-acyl amino acid transferase from Mycobacterium tuberculosis Journal of Biological Chemistry. doi:10.1016/j.jbc.2025.111079
Ancestral MTBC0 protein sequence
>H37Rv|Rv1356c| MLIAGYLTDWRIMTTAQLRPIAPQKLHFSENLSVWVSDAQCRLVVSQPALDPTLWNTYLQGALRAYSKHGVECTLDLDAISDGSDTQLFFAAIDIGGDVVGGARVIGPLRSADDSHAVVEWAGNPGLSAVRKMINDRAPFGVVEVKSGWVNSDAQRSDAIAAALARALPLSMSLLGVQFVMGTAAAHALDRWRSSGGVIAARIPAAAYPDERYRTKMIWWDRRTLANHAEPKQLSRMLVESRKLLRDVEALSATTAATAGAEQ