Rv2991 Resolved · high auto-curated
H37Rv Rv2991 · MTBC0 mtbc0_003176 ·
163 aa · 3369291–3369782 (+) ·
RefSeq NP_217507.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | hypothetical protein |
|---|---|
| MTBC0 PGAP re-annotation | PPOX class F420-dependent oxidoreductase |
| Revised (this work) | PPOX class F420-dependent oxidoreductase. Pfam: PNPOx_N (PF01243.28), Pyridox_ox_2 (PF12900.14). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
O53240
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 |
P Inorganic ion transport and metabolism
|
|---|---|
| eggNOG description | Pyridoxamine 5'-phosphate oxidase |
| Orthologous group | COG0748 |
| KEGG orthology |
K07005
|
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 | 1.276 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 4 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 |
|---|---|---|---|---|
PNPOx_N | PF01243.28 | 2.7e-25 | 13–145 | Pyridoxamine 5'-phosphate oxidase |
Pyridox_ox_2 | PF12900.14 | 2.9e-10 | 13–138 | Pyridoxamine 5'-phosphate oxidase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv0910 (toxin), medium confidence from genomic context alone (score 544 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) |
|---|---|---|---|---|
Rv0910 |
toxin | 543 | 544 ctx | cooccurence:541 |
Rv2216 |
epimerase family protein | 511 | 511 | coexpression:507 |
Rv2990c hyp |
hypothetical protein | 476 | 476 ctx | neighborhood:472 |
Rv1125 hyp |
hypothetical protein | 450 | 450 ctx | cooccurence:450 |
Rv1001 arcA |
arginine deiminase | 441 | 442 | coexpression:442 |
Rv3391 acrA1 |
acyl-CoA-reductase AcrA | 427 | 427 | |
Rv2323c hyp |
hypothetical protein | 422 | 422 | coexpression:420 |
Rv2876 |
transmembrane protein | 413 | 413 ctx | cooccurence:413 |
Rv1015c rplY |
50S ribosomal protein L25/general stress protein Ctc | 406 | 406 | coexpression:406 |
Rv2250c |
HTH-type transcriptional regulator | 405 | 405 | |
Rv2043c pncA |
pyrazinamidase/nicotinamidase PncA | 401 | 402 | coexpression:402 |
Rv1155 |
pyridoxine/pyridoxamine 5'-phosphate oxidase | 895 | 228 | textmining:870 |
Rv1261c hyp |
hypothetical protein | 408 | 202 | |
Rv3178 |
nitroreductase | 778 | 179 | textmining:741 |
Rv3369 hyp |
hypothetical protein | 829 | 170 | textmining:803 |
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: PPOX class F420-dependent oxidoreductase
- Pfam (hmmscan --cut_ga): PNPOx_N PF01243.28 (E=3e-25), Pyridox_ox_2 PF12900.14 (E=3e-10)
- (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_217507.1)
- Domains: Pfam-A via hmmscan --cut_ga — PNPOx_N (PF01243.28), Pyridox_ox_2 (PF12900.14)
- 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
COG0748 - Curated reference: UniProt O53240 (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 —
25 functional partner(s); context anchor
Rv0910 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003176|Rv2991| MGTKQRADIVMSEAEIADFVNSSRTGTLATIGPDGQPHLTAMWYAVIDGEIWLETKAKSQKAVNLRRDPRVSFLLEDGDTYDTLRGVSFEGVAEIVEEPEALHRVGVSVWERYTGPYTDECKPMVDQMMNKRVGVRIVARRTRSWDHRKLGLPHMSVGGSTAP