Rv1118c Resolved · high
H37Rv Rv1118c · MTBC0 - ·
286 aa · 1241971–1242831 (-) ·
RefSeq NP_215634.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | Circularly permuted NlpC/P60 (YaeF/YiiX-family) cysteine amidase with a structurally competent Cys234-His97 catalytic dyad (Glu115 a candidate third member). RefSeq leaves this locus 'hypothetical protein'; here it is re-annotated by structure-guided active-site mapping. The catalytic histidine partner of the nucleophile Cys234 is His97 (Sgamma-Ndelta1 = 3.6 A on the ESMFold model, 2.9 A on AlphaFold3), invisible to sequence proximity because the fold is circularly permuted - the three sequence-proximal histidines lie 7-23 A away. HHpred matches the permuted Peptidase_C92 / YaeF-YiiX family (>=99.7%) and lipid-acting permuted members (LRAT, H-REV107), and the 86%-hydrophobic pocket points to an N-acyl-amino-acid / lipoprotein amide substrate rather than a peptidoglycan muropeptide. Distinct from the five canonical peptidoglycan-hydrolase NlpC/P60 enzymes of H37Rv (Rv0024, RipA, RipB, RipD, Rv2190c). Catalytic codons essentially invariant across ~250,724 MTBC genomes. A structural prediction, not a biochemical assay. |
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 |
O06570
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)
| Orthologous group | 28P5T |
|---|
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 | 0.518 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 5 missense, 1 nonsense, 1 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 1.05% of strains (1530) · 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 84.6 (confident). 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 |
|---|---|---|---|---|
3kw0-assembly1_B |
1.00 | 0.68 | 4.0e-06 sig | 3kw0-assembly1_B Crystal structure of Cysteine peptidase (NP_982244.1) from BACILLUS CEREUS ATCC 10987 at 2.50 A resolution |
3kw0-assembly1_C |
1.00 | 0.67 | 4.0e-06 sig | 3kw0-assembly1_C Crystal structure of Cysteine peptidase (NP_982244.1) from BACILLUS CEREUS ATCC 10987 at 2.50 A resolution |
3kw0-assembly1_A |
1.00 | 0.67 | 1.9e-05 sig | 3kw0-assembly1_A Crystal structure of Cysteine peptidase (NP_982244.1) from BACILLUS CEREUS ATCC 10987 at 2.50 A resolution |
3kw0-assembly1_D |
1.00 | 0.64 | 2.6e-05 sig | 3kw0-assembly1_D Crystal structure of Cysteine peptidase (NP_982244.1) from BACILLUS CEREUS ATCC 10987 at 2.50 A resolution |
2if6-assembly2_B |
1.00 | 0.58 | 9.4e-05 sig | 2if6-assembly2_B Crystal structure of metalloprotein yiiX from Escherichia coli O157:H7, DUF1105 |
6z1p-assembly1_At |
0.02 | 0.15 | 1.6e+00 | 6z1p-assembly1_At Structure of the mitochondrial ribosome from Tetrahymena thermophila |
5a5k-assembly4_D |
0.01 | 0.23 | 9.0e+00 | 5a5k-assembly4_D AtGSTF2 from Arabidopsis thaliana in complex with camalexin |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: lppW (lipoprotein LppW), medium confidence from genomic context alone (score 521 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) |
|---|---|---|---|---|
Rv1119c hyp |
hypothetical protein | 744 | 744 ctx | neighborhood:710 |
Rv1120c hyp |
hypothetical protein | 743 | 743 ctx | neighborhood:710 |
Rv2905 lppW |
lipoprotein LppW | 520 | 521 ctx | cooccurence:518 |
Rv2027c dosT |
two component sensor histidine kinase DosT | 533 | 485 | |
Rv3132c devS |
two component sensor histidine kinase DevS | 532 | 484 | |
Rv0845 narS |
sensor histidine kinase NarS | 490 | 467 | |
Rv0941c hyp |
hypothetical protein | 460 | 460 ctx | cooccurence:457 |
Rv1121 zwf1 |
glucose-6-phosphate 1-dehydrogenase | 442 | 443 ctx | neighborhood:441 |
Rv1122 gnd2 |
6-phosphogluconate dehydrogenase (decarboxylating) | 411 | 412 ctx | neighborhood:408 |
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
- RefSeq: hypothetical protein
- Active-site mapping: catalytic dyad Cys234-His97 (Sgamma-Ndelta1 3.6 A ESMFold / 2.9 A AlphaFold3); circularly permuted topology
- HHpred: permuted Peptidase_C92 / YaeF-YiiX family >=99.7%; lipid-acting permuted members (LRAT, H-REV107)
- Hydrophobic pocket (86%) -> N-acyl-amino-acid / lipoprotein amide substrate, not peptidoglycan
- Distinct from the 5 canonical peptidoglycan-hydrolase NlpC/P60 enzymes of H37Rv
- Catalytic codons invariant across ~250,724 MTBC genomes (purifying selection)
- Curated against the companion dark-enzymes re-annotation (Guyeux 2026)
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_215634.1)
- 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
28P5T - Curated reference: UniProt O06570 (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 84.6, confident)
- Interaction network: STRING v12.0 (Szklarczyk et al. 2023,
doi:10.1093/nar/gkac1000), taxon 83332, CC-BY 4.0 —
9 functional partner(s); context anchor
lppW - Primary literature: Guyeux C (2026). Structure-guided functional hypotheses for uncharacterised enzymes of Mycobacterium tuberculosis in preparation. doi:10.5281/zenodo.20571950
Ancestral MTBC0 protein sequence
>H37Rv|Rv1118c| MQSGPHLVGRVGTSFPLIARHQGATRDDAGDTGQPDPLPHVAHPDRLYPPMVHGVDPSTLALDRALNETRTGDLWLFRGRSRPDRAIQTLTNAPVNHVGMTVAIDDLPPLIWHAELGDKLLDVWTGTNHRGVQLNDARQVVQQWAGRYRQRCWLRQLTPHANRDQEDKLLRVIARMNGTPFPTTARLTGRWLRGRLPTLNDWLRGIPVLDRKVREQTQRRKQQQRTMGLATAYCAETVAITYEEMGLLVTDKDAHWFDPGKFWSGDSLPLAPGYRLGHEIAVDVGG