fprA Resolved · high auto-curated
H37Rv Rv3106 · MTBC0 mtbc0_003302 ·
456 aa · 3495372–3496742 (+) ·
RefSeq NP_217622.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | NADPH-ferredoxin reductase FprA |
|---|---|
| MTBC0 PGAP re-annotation | ferredoxin--NADP(+) reductase FprA |
| Revised (this work) | Ferredoxin--NADP(+) reductase FprA. Pfam: Pyr_redox_2 (PF07992.21). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WIQ3
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | NADPH-ferredoxin reductase FprA |
| EC (curated) |
EC 1.18.1.2
|
| Curated function | Transports electrons between ferredoxin and NADPH. May supply electrons to P450 systems. The enzyme can use both NADPH and NADH as a reductant, but the catalytic efficiency is two orders of magnitude higher with NADPH. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
E Amino acid transport and metabolism
|
|---|---|
| Preferred name | fprA |
| eggNOG description | oxidoreductase |
| Orthologous group | COG0493 |
| EC number |
EC 1.18.1.2, EC 1.19.1.1
|
| KEGG orthology |
K00528
|
| Gene Ontology (32) |
GO:0000166, GO:0003674, GO:0003824, GO:0004324, GO:0005488, GO:0005575, GO:0005618, GO:0005622, GO:0005623, GO:0005737, GO:0008150, GO:0008152 +20 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 | 0.469 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 7 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 |
|---|---|---|---|---|
Pyr_redox_2 | PF07992.21 | 6.5e-09 | 6–166 | Pyridine nucleotide-disulphide oxidoreductase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gltB (glutamate synthase large subunit), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3859c gltB |
glutamate synthase large subunit | 999 | 1000 ctx | neighborhood:455 coexpression:999 experimental:999 textmining:519 |
Rv1937 |
oxygenase | 992 | 989 | experimental:973 database:568 |
Rv0886 fprB |
ferredoxin/ferredoxin--NADP reductase | 945 | 943 | database:900 |
Rv2391 sirA |
sulfite reductase | 839 | 815 | coexpression:770 |
Rv2392 cysH |
phosphoadenosine phosphosulfate reductase | 836 | 812 | coexpression:766 |
Rv3340 metC |
O-acetylhomoserine sulfhydrylase | 798 | 789 | coexpression:787 |
Rv3105c prfB |
peptide chain release factor PrfB | 781 | 781 ctx | neighborhood:780 |
Rv3104c |
transmembrane protein | 780 | 780 ctx | neighborhood:780 |
Rv3554 fdxB |
electron transfer protein FdxB | 821 | 753 | experimental:430 database:568 |
Rv3571 kshB |
3-ketosteroid-9-alpha-hydroxylase reductase subunit | 778 | 752 | experimental:430 database:568 |
Rv2776c |
oxidoreductase | 778 | 752 | experimental:430 database:568 |
Rv3230c |
stearoyl-CoA 9-desaturase electron transfer protein | 777 | 751 | experimental:430 database:568 |
Rv3103c hyp |
hypothetical protein | 717 | 718 ctx | neighborhood:718 |
Rv3059 cyp136 |
cytochrome P450 Cyp136 | 589 | 565 | database:485 |
Rv0764c cyp51 |
lanosterol 14-alpha demethylase | 682 | 559 | database:485 |
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: NADPH-ferredoxin reductase FprA
- MTBC0 PGAP product: ferredoxin--NADP(+) reductase FprA
- Pfam (hmmscan --cut_ga): Pyr_redox_2 PF07992.21 (E=7e-09)
- (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_217622.1)
- Domains: Pfam-A via hmmscan --cut_ga — Pyr_redox_2 (PF07992.21)
- 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
COG0493 - Curated reference: UniProt P9WIQ3 (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 —
61 functional partner(s); context anchor
gltB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003302|Rv3106|fprA MRPYYIAIVGSGPSAFFAAASLLKAADTTEDLDMAVDMLEMLPTPWGLVRSGVAPDHPKIKSISKQFEKTAEDPRFRFFGNVVVGEHVQPGELSERYDAVIYAVGAQSDRMLNIPGEDLPGSIAAVDFVGWYNAHPHFEQVSPDLSGARAVVIGNGNVALDVARILLTDPDVLARTDIADHALESLRPRGIQEVVIVGRRGPLQAAFTTLELRELADLDGVDVVIDPAELDGITDEDAAAVGKVCKQNIKVLRGYADREPRPGHRRMVFRFLTSPIEIKGKRKVERIVLGRNELVSDGSGRVAAKDTGEREELPAQLVVRSVGYRGVPTPGLPFDDQSGTIPNVGGRINGSPNEYVVGWIKRGPTGVIGTNKKDAQDTVDTLIKDLGNAKEGAECKSFPEDHADQVADWLAARQPKLVTSAHWQVIDAFERAAGEPHGRPRVKLASLAELLRIGLG