fprB Resolved · high auto-curated

H37Rv Rv0886 · MTBC0 mtbc0_000941 · 575 aa · 987017–988744 (+) · RefSeq NP_215401.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)ferredoxin/ferredoxin--NADP reductase
MTBC0 PGAP re-annotationFAD-dependent oxidoreductase
Revised (this work)FAD-dependent oxidoreductase. Pfam: Fer4 (PF00037.33), Pyr_redox_2 (PF07992.21), NAD_binding_8 (PF13450.13).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WJI1 SwissProt · reviewed · Evidence at protein level
UniProt nameProbable ferredoxin/ferredoxin--NADP reductase
EC (curated) EC 1.18.1.2

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category C Energy production and conversion
Preferred namefprB
eggNOG descriptionferredoxin
Orthologous groupCOG0493
EC number EC 1.18.1.2, EC 1.19.1.1
KEGG orthology K00528
Gene Ontology (15) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005886, GO:0008150, GO:0008152, GO:0016020, GO:0016491, GO:0044424 +3 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 0.277 · purifying
Polymorphic sites (≥ 0.1% of strains) 4 synonymous, 3 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)

PfamAccessioni-EvalueResiduesDescription
Fer4PF00037.33 6.4e-0640–61 4Fe-4S binding domain
Pyr_redox_2PF07992.21 6.2e-08114–272 Pyridine nucleotide-disulphide oxidoreductase
NAD_binding_8PF13450.13 5.9e-05117–161 NAD(P)-binding Rossmann-like domain

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).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3859c gltB glutamate synthase large subunit 999 1000 ctx neighborhood:544 coexpression:999 experimental:999 textmining:621
Rv1937 oxygenase 995 990 experimental:973 database:568 textmining:519
Rv0885 hyp hypothetical protein 983 978 ctx neighborhood:857 coexpression:798
Rv3106 fprA NADPH-ferredoxin reductase FprA 945 943 database:900
Rv2455c korA 2-oxoglutarate oxidoreductase subunit KorA 941 856 ctx neighborhood:544 coexpression:698 textmining:611
Rv3554 fdxB electron transfer protein FdxB 918 776 experimental:430 database:568 textmining:651
Rv3230c stearoyl-CoA 9-desaturase electron transfer protein 867 775 experimental:430 database:568 textmining:436
Rv3571 kshB 3-ketosteroid-9-alpha-hydroxylase reductase subunit 866 773 experimental:430 database:568 textmining:436
Rv2776c oxidoreductase 866 773 experimental:430 database:568 textmining:436
Rv1240 mdh malate dehydrogenase 787 748 coexpression:699
Rv0884c serC phosphoserine aminotransferase 749 748 ctx neighborhood:742
Rv0066c icd2 isocitrate dehydrogenase 746 709 coexpression:698
Rv0883c sepH hyp hypothetical protein 669 670 ctx neighborhood:670
Rv3338 Rv3338, (MTV016.38), len: 214 aa. Hypothetical protein, equivalent to C-termini of Q49926|ML0685 TPEA (putative hydrolase) from Mycobacteriu 609 609 coexpression:553
Rv1286 cysC adenylyl-sulfate kinase 743 579 ctx neighborhood:509 textmining:417

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: ferredoxin/ferredoxin--NADP reductase
  • MTBC0 PGAP product: FAD-dependent oxidoreductase
  • Pfam (hmmscan --cut_ga): Fer4 PF00037.33 (E=6e-06), Pyr_redox_2 PF07992.21 (E=6e-08), NAD_binding_8 PF13450.13 (E=6e-05)
  • (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_215401.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Fer4 (PF00037.33), Pyr_redox_2 (PF07992.21), NAD_binding_8 (PF13450.13)
  • 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 COG0493
  • Curated reference: UniProt P9WJI1 (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 — 86 functional partner(s); context anchor gltB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_000941|Rv0886|fprB
MPHVITQSCCNDASCVFACPVNCIHPTPDEPGFATSEMLYIDPVACVDCGACVTACPVSAIAPNTRLDFEQLPFVEINASYYPKRPAGVKLAPTSKLAPVTPAAEVRVRRQPLTVAVVGSGPAAMYAADELLVQQGVQVNVFEKLPTPYGLVRSGVAPDHQNTKRVTRLFDRIAGHRRFRFYLNVEIGKHLGHAELLAHHHAVLYAVGAPDDRRLTIDGMGLPGTGTATELVAWLNGHPDFNDLPVDLSHERVVIIGNGNVALDVARVLAADPHELAATDIADHALSALRNSAVREVVVAARRGPAHSAFTLPELIGLTAGADVVLDPGDHQRVLDDLAIVADPLTRNKLEILSTLGDGSAPARRVGRPRIRLAYRLTPRRVLGQRRAGGVQFSVTGTDELRQLDAGLVLTSIGYRGKPIPDLPFDEQAALVPNDGGRVIDPGTGEPVPGAYVAGWIKRGPTGFIGTNKSCSMQTVQALVADFNDGRLTDPVATPTALDQLVQARQPQAIGCAGWRAIDAAEIARGSADGRVRNKFTDVAEMLAAATSAPKEPLRRRVLARLRDLGQPIVLTVPL