Rv3099c Family assigned · medium auto-curated
H37Rv Rv3099c · MTBC0 mtbc0_003295 ·
283 aa · 3489777–3490628 (-) ·
RefSeq NP_217615.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | maleylpyruvate isomerase family mycothiol-dependent enzyme |
| Revised (this work) | Maleylpyruvate isomerase family mycothiol-dependent enzyme. Pfam: MDMPI_N (PF11716.14), DinB_2 (PF12867.13), MDMPI_C (PF07398.17). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O05777
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 |
S Function unknown
|
|---|---|
| eggNOG description | MDMPI C-terminal domain |
| Orthologous group | 2DMG6 |
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 | 0.532 · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
MDMPI_N | PF11716.14 | 1.7e-27 | 22–160 | Mycothiol maleylpyruvate isomerase N-terminal domain |
DinB_2 | PF12867.13 | 2.3e-08 | 22–155 | DinB superfamily |
MDMPI_C | PF07398.17 | 1.1e-13 | 181–273 | MDMPI C-terminal domain |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ftsX (cell division protein FtsX), high confidence from genomic context alone (score 832 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) |
|---|---|---|---|---|
Rv3101c ftsX |
cell division protein FtsX | 832 | 832 ctx | neighborhood:830 |
Rv3100c smpB |
SsrA-binding protein | 831 | 832 ctx | neighborhood:830 |
Rv3102c ftsE |
cell division ATP-binding protein FtsE | 831 | 831 ctx | neighborhood:830 |
Rv3166c hyp |
hypothetical protein | 745 | 745 ctx | cooccurence:745 |
Rv3163c hyp |
hypothetical protein | 661 | 661 ctx | cooccurence:661 |
Rv1776c |
transcriptional regulator | 657 | 657 ctx | cooccurence:654 |
Rv3435c |
transmembrane protein | 654 | 654 ctx | cooccurence:652 |
Rv3104c |
transmembrane protein | 637 | 637 ctx | neighborhood:635 |
Rv3103c hyp |
hypothetical protein | 633 | 634 ctx | neighborhood:634 |
Rv2423 hyp |
hypothetical protein | 618 | 618 ctx | cooccurence:618 |
Rv3105c prfB |
peptide chain release factor PrfB | 605 | 605 ctx | neighborhood:604 |
Rv3899c hyp |
hypothetical protein | 592 | 592 ctx | cooccurence:592 |
Rv2598 hyp |
hypothetical protein | 584 | 585 ctx | cooccurence:582 |
Rv0048c |
membrane protein | 581 | 581 ctx | cooccurence:581 |
Rv2525c hyp |
hypothetical protein | 538 | 538 ctx | cooccurence:537 |
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
- Legacy H37Rv annotation: hypothetical protein
- MTBC0 PGAP product: maleylpyruvate isomerase family mycothiol-dependent enzyme
- Pfam (hmmscan --cut_ga): MDMPI_N PF11716.14 (E=2e-27), DinB_2 PF12867.13 (E=2e-08), MDMPI_C PF07398.17 (E=1e-13)
- (auto-curated by rules from PGAP + Pfam + Foldseek; not hand-reviewed)
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_217615.1)
- Domains: Pfam-A via hmmscan --cut_ga — MDMPI_N (PF11716.14), DinB_2 (PF12867.13), MDMPI_C (PF07398.17)
- 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
2DMG6 - Curated reference: UniProt O05777 (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 —
30 functional partner(s); context anchor
ftsX - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003295|Rv3099c| MTTPGRPLTTLDKSDVLAGLFAVWHSLDALLDGLLETDWQATSPLPGWDVKAVVSHIIGTESFLLGIAAPEPDTDVSALAHVRNPIGVMNECWVRHLGTESGVGLLERFRAVTSQRRKVLASLSDDEWNAPTTTPSGPDSYGRFMRIRIFDCWMHEQDIRAAVQRPSSDDELGGPASPLVLDEIAATMGFVVGKLAKAPDGSRVLLELTGPLSRSIRVSVDGRARVVDDFGGPAPTATIRLDGLQFTRLAGGRPMSPARSQDVELGGDKELAGHILERLNFVI