Rv2074 Resolved · high auto-curated
H37Rv Rv2074 · MTBC0 mtbc0_002208 ·
137 aa · 2359606–2360019 (+) ·
RefSeq NP_216590.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | pyridoxamine 5'-phosphate oxidase |
|---|---|
| MTBC0 PGAP re-annotation | F420-dependent biliverdin reductase |
| Revised (this work) | F420-dependent biliverdin reductase. Pfam: PNPOx_N (PF01243.28). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WLL7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | F420H(2)-dependent biliverdin reductase |
| EC (curated) |
EC 1.3.98.-
|
| Curated function | Catalyzes the F420H(2)-dependent reduction of biliverdin-IXalpha at C10 position, leading to bilirubin-IXalpha, a potent antioxidant. As biliverdin-IXalpha is produced in high amounts in macrophages infected with M.tuberculosis, its reduction by Rv2074 may play a role in protecting mycobacteria against oxidative stress, aiding the persistence of M.tuberculosis infection. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | PFAM pyridoxamine 5'-phosphate |
| Orthologous group | COG3871 |
| Gene Ontology (30) |
GO:0003674, GO:0003824, GO:0005488, GO:0005515, GO:0005575, GO:0005576, GO:0005618, GO:0005623, GO:0008150, GO:0008152, GO:0016491, GO:0016627 +18 more
|
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 | 0.365 · 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 |
|---|---|---|---|---|
PNPOx_N | PF01243.28 | 6.0e-15 | 12–128 | Pyridoxamine 5'-phosphate oxidase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: Rv2073c (oxidoreductase), high confidence from genomic context alone (score 804 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv2073c |
oxidoreductase | 803 | 804 ctx | neighborhood:790 |
Rv2070c cobK |
precorrin-6A reductase | 764 | 764 ctx | neighborhood:731 |
Rv2071c cobM |
precorrin-4 C(11)-methyltransferase | 732 | 732 ctx | neighborhood:731 |
Rv2072c cobL |
precorrin-6Y C(5,15)-methyltransferase | 731 | 731 ctx | neighborhood:731 |
Rv2216 |
epimerase family protein | 515 | 516 | coexpression:512 |
Rv1156 hyp |
hypothetical protein | 506 | 506 ctx | cooccurence:500 |
Rv1558 hyp |
hypothetical protein | 487 | 466 ctx | cooccurence:464 |
Rv1001 arcA |
arginine deiminase | 443 | 443 | coexpression:443 |
Rv2323c hyp |
hypothetical protein | 416 | 416 | coexpression:414 |
Rv0052 hyp |
hypothetical protein | 406 | 407 | |
Rv1015c rplY |
50S ribosomal protein L25/general stress protein Ctc | 406 | 406 | coexpression:406 |
Rv2043c pncA |
pyrazinamidase/nicotinamidase PncA | 403 | 403 | coexpression:403 |
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: pyridoxamine 5'-phosphate oxidase
- MTBC0 PGAP product: F420-dependent biliverdin reductase
- Pfam (hmmscan --cut_ga): PNPOx_N PF01243.28 (E=6e-15)
- (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_216590.1)
- Domains: Pfam-A via hmmscan --cut_ga — PNPOx_N (PF01243.28)
- 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
COG3871 - Curated reference: UniProt P9WLL7 (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 —
12 functional partner(s); context anchor
Rv2073c - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_002208|Rv2074| MAMVNTTTRLSDDALAFLSERHLAMLTTLRADNSPHVVAVGFTFDPKTHIARVITTGGSQKAVNADRSGLAVLSQVDGARWLSLEGRAAVNSDIDAVRDAELRYAQRYRTPRPNPRRVVIEVQIERVLGSADLLDRA