Rv2993c Resolved · high auto-curated
H37Rv Rv2993c · MTBC0 - ·
239 aa · 3350274–3350993 (-) ·
RefSeq NP_217509.3
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase. Pfam: Rv2993c-like_N (PF10370.15), FAA_hydrolase (PF01557.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
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 |
I6Y276
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Protein Rv2993c |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
Q Secondary metabolites biosynthesis, transport and catabolism
|
|---|---|
| Preferred name | odx |
| eggNOG description | 2-keto-4-pentenoate hydratase 2-oxohepta-3-ene-1,7-dioic acid hydratase |
| Orthologous group | COG0179 |
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 | 0.342 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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 |
|---|---|---|---|---|
Rv2993c-like_N | PF10370.15 | 1.2e-09 | 2–31 | Rv2993c-like, N-terminal |
FAA_hydrolase | PF01557.24 | 2.7e-73 | 36–234 | Fumarylacetoacetate (FAA) hydrolase C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gltS (glutamate--tRNA ligase), high confidence from genomic context alone (score 925 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2992c gltS |
glutamate--tRNA ligase | 927 | 925 ctx | neighborhood:881 |
Rv2994 |
MFS-type transporter | 763 | 763 ctx | neighborhood:728 |
Rv2858c aldC |
aldehyde dehydrogenase AldC | 547 | 525 | coexpression:445 |
Rv1187 rocA |
pyrroline-5-carboxylate dehydrogenase RocA | 518 | 494 | |
Rv3293 pcd |
piperideine-6-carboxylic acid dehydrogenase | 459 | 432 | |
Rv0768 aldA |
aldehyde dehydrogenase AldA | 459 | 432 | |
Rv1731 gabD2 |
succinate-semialdehyde dehydrogenase | 458 | 431 | |
Rv0147 |
aldehyde dehydrogenase | 457 | 430 | |
Rv0223c |
aldehyde dehydrogenase | 457 | 430 | |
Rv0234c gabD1 |
succinate-semialdehyde dehydrogenase | 457 | 430 | |
Rv0753c mmsA |
methylmalonate-semialdehyde dehydrogenase | 456 | 429 | |
Rv0458 |
aldehyde dehydrogenase | 455 | 428 | |
Rv0896 gltA2 |
citrate synthase 1 | 419 | 418 | coexpression:416 |
Rv1017c prsA |
ribose-phosphate pyrophosphokinase | 430 | 411 | |
Rv0889c citA |
citrate synthase 2 | 413 | 411 | coexpression:409 |
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
- Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): 2-hydroxyhepta-2,4-diene-1,7-dioate isomerase
- Pfam (hmmscan --cut_ga): Rv2993c-like_N PF10370.15 (E=1e-09), FAA_hydrolase PF01557.24 (E=3e-73)
- (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_217509.3)
- Domains: Pfam-A via hmmscan --cut_ga — Rv2993c-like_N (PF10370.15), FAA_hydrolase (PF01557.24)
- 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
COG0179 - Curated reference: UniProt I6Y276 (SwissProt, reviewed; 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 —
21 functional partner(s); context anchor
gltS - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv2993c| MTAREIAEHPFGTPTFTGRSWPLADVRLLAPILASKVVCVGKNYADHIAEMGGRPPADPVIFLKPNTAIIGPNTPIRLPANASPVHFEGELAIVIGRACKDVPAAQAVDNILGYTIGNDVSARDQQQSDGQWTRAKGHDTFCPVGPWIVTDLAPFDPADLELRTVVNGDVKQHARTSLMIHDIGAIVEWISAIMTLLPGDLILTGTPAGVGPIEDGDTVSITIEGIGTLTNPVVRKGKP