Rv1869c Resolved · high auto-curated
H37Rv Rv1869c · MTBC0 mtbc0_001982 ·
411 aa · 2137499–2138734 (-) ·
RefSeq NP_216385.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | reductase |
|---|---|
| MTBC0 PGAP re-annotation | FAD-dependent oxidoreductase |
| Revised (this work) | FAD-dependent oxidoreductase. Pfam: Pyr_redox_2 (PF07992.21), Pyr_redox_3 (PF13738.13), Pyr_redox (PF00070.34), Reductase_C (PF14759.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P95146
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | Probable reductase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
S Function unknown
|
|---|---|
| eggNOG description | Reductase C-terminal |
| Orthologous group | COG0446 |
| EC number |
EC 1.18.1.3
|
| KEGG orthology |
K00529
|
| KEGG pathways |
map00071, map00360, map01120, map01220
|
| KEGG modules |
M00545
|
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 | 1.401 · diversifying/relaxed |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 7 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (176) · 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
Pyr_redox_2 | PF07992.21 | 5.0e-71 | 7–304 | Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox_3 | PF13738.13 | 1.5e-07 | 72–279 | Pyridine nucleotide-disulphide oxidoreductase |
Pyr_redox | PF00070.34 | 3.7e-17 | 149–228 | Pyridine nucleotide-disulphide oxidoreductase |
Reductase_C | PF14759.13 | 3.4e-12 | 326–408 | Reductase C-terminal |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: nirD (nitrite reductase small subunit NirD), high confidence from genomic context alone (score 858 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0688 |
ferredoxin reductase | 913 | 914 | database:900 |
Rv0253 nirD |
nitrite reductase small subunit NirD | 865 | 858 ctx | cooccurence:480 coexpression:500 experimental:434 |
Rv1870c hyp |
hypothetical protein | 783 | 783 ctx | neighborhood:773 |
Rv3251c rubA |
rubredoxin RubA | 747 | 732 | coexpression:410 experimental:549 |
Rv3250c rubB |
rubredoxin RubB | 746 | 731 | coexpression:408 experimental:549 |
Rv1871c hyp |
hypothetical protein | 734 | 724 ctx | neighborhood:720 |
Rv2633c hyp |
hypothetical protein | 730 | 714 | coexpression:500 experimental:434 |
Rv3818 hyp |
hypothetical protein | 730 | 713 | coexpression:498 experimental:434 |
Rv3859c gltB |
glutamate synthase large subunit | 709 | 590 ctx | neighborhood:532 |
Rv1161 narG |
nitrate reductase subunit alpha | 520 | 490 | coexpression:475 |
Rv1736c narX |
nitrate reductase-like protein NarX | 517 | 486 | coexpression:471 |
Rv0511 hemD |
uroporphyrin-III C-methyltransferase | 602 | 463 | |
Rv1872c lldD2 |
L-lactate dehydrogenase | 463 | 463 ctx | neighborhood:457 |
Rv3138 pflA |
pyruvate formate lyase activating protein PflA | 461 | 430 | coexpression:417 |
Rv1162 narH |
nitrate reductase subunit beta | 482 | 427 | coexpression: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
- Legacy H37Rv annotation: reductase
- MTBC0 PGAP product: FAD-dependent oxidoreductase
- Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=5e-71), Pyr_redox_3 PF13738.13 (E=1e-07), Pyr_redox PF00070.34 (E=4e-17), Reductase_C PF14759.13 (E=3e-12)
- (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_216385.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21), Pyr_redox_3 (PF13738.13), Pyr_redox (PF00070.34), Reductase_C (PF14759.13)
- 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
COG0446 - Curated reference: UniProt P95146 (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 —
36 functional partner(s); context anchor
nirD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001982|Rv1869c| MASSTTFVIVGGGLAGAKAVEALRRSDFGGRIILFGDEEHLPYDRPPLSKEFLAGKKSLSDFTIQTSDWYRDHDVDVRLGVRVSSLDRSAHTVELPDGAAVRYDKLLLATGSAPRRPPIPGSDAAGVHYLRSYNDAVALNSVLVQGSSLAVVGAGWIGLEVAASARQRGVDVTVVETAIQPLLAALGEAVGKVFADLHRDQGVDLRLQTQLEEITAADGKATGLKMRDGSTVAADAVLVAVGAKPNVELAQQAGLAMGEGGVLVDASLRTSDPDIYAVGDIAAAEHPLLGTRVRTEHWANALKQPAVAAAGMLGRPGEYAELPYLFTDQYDLGMEYVGHAPSCDRVVFRGNVAGREFLSFWLDGDSRVLAGMNVNVWDVVDDVKGLIRSGNPVDVDRLVDPQWPLADLTTN