fbiB Resolved · high auto-curated

H37Rv Rv3262 · MTBC0 mtbc0_003470 · 448 aa · 3663678–3665024 (+) · RefSeq NP_217779.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)coenzyme F420:L-glutamate ligase
MTBC0 PGAP re-annotationcoenzyme F420-0:L-glutamate ligase
Revised (this work)Coenzyme F420-0:L-glutamate ligase. Pfam: F420_ligase (PF01996.22), Nitroreductase (PF00881.30).

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

Curated reference (UniProt)

UniProt P9WP79 SwissProt · reviewed · Evidence at protein level
UniProt nameBifunctional F420 biosynthesis protein FbiB [Includes: Coenzyme F420:L-glutamate ligase
EC (curated) EC 1.3.8.17, EC 6.3.2.31, EC 6.3.2.34
Curated functionBifunctional enzyme that catalyzes the GTP-dependent successive addition of multiple gamma-linked L-glutamates to the L-lactyl phosphodiester of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (F420-0) to form polyglutamated F420 derivatives, and the FMNH2-dependent reduction of dehydro-F420-0 to form F420-0.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namefbiB
eggNOG descriptionCatalyzes the GTP-dependent successive addition of multiple gamma-linked L-glutamates to the L-lactyl phosphodiester of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (F420-0) to form polyglutamated F420 derivatives
Orthologous groupCOG0778
EC number EC 6.3.2.31, EC 6.3.2.34
KEGG orthology K12234
KEGG pathways map00680, map01120
KEGG modules M00378
Gene Ontology (16) GO:0005575, GO:0005623, GO:0005886, GO:0006732, GO:0008150, GO:0008152, GO:0009058, GO:0009108, GO:0009987, GO:0016020, GO:0044237, GO:0044249 +4 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 0.748 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 6 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
F420_ligasePF01996.22 1.9e-5019–219 F420-0:Gamma-glutamyl ligase
NitroreductasePF00881.30 7.5e-30260–428 Nitroreductase family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: fbiA (2-phospho-L-lactate transferase), high confidence from genomic context alone (score 999 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3261 fbiA 2-phospho-L-lactate transferase 999 999 ctx neighborhood:882 cooccurence:773 coexpression:797 database:900 textmining:908
Rv2983 cofC 2-phospho-L-lactate guanylyltransferase 992 784 ctx cooccurence:742 textmining:965
Rv3520c coenzyme F420-dependent oxidoreductase 786 773 ctx cooccurence:742
Rv3093c oxidoreductase 781 767 ctx cooccurence:737
Rv3300c hyp hypothetical protein 767 765 coexpression:757
Rv3547 ddn deazaflavin-dependent nitroreductase 974 745 ctx cooccurence:737 textmining:903
Rv2951c phthiodiolone/phenolphthiodiolone dimycocerosates ketoreductase 765 740 ctx cooccurence:706
Rv0132c fgd2 F420-dependent glucose-6-phosphate dehydrogenase 888 735 ctx cooccurence:701 textmining:596
Rv1261c hyp hypothetical protein 824 732 ctx cooccurence:729
Rv3263 DNA methylase 726 726 ctx neighborhood:718
Rv2893 oxidoreductase 787 718 ctx cooccurence:683
Rv0044c oxidoreductase 734 718 ctx cooccurence:680
Rv3178 nitroreductase 836 717 ctx cooccurence:707 textmining:446
Rv1558 hyp hypothetical protein 812 717 ctx cooccurence:707
Rv2161c hyp hypothetical protein 727 710 ctx cooccurence:669

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: coenzyme F420:L-glutamate ligase
  • MTBC0 PGAP product: coenzyme F420-0:L-glutamate ligase
  • Pfam (hmmscan --cut_ga): F420_ligase PF01996.22 (E=2e-50), Nitroreductase PF00881.30 (E=8e-30)
  • (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_217779.1)
  • Domains: Pfam-A via hmmscan --cut_ga — F420_ligase (PF01996.22), Nitroreductase (PF00881.30)
  • 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 COG0778
  • Curated reference: UniProt P9WP79 (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 — 58 functional partner(s); context anchor fbiA
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003470|Rv3262|fbiB
MTGPEHGSASTIEILPVIGLPEFRPGDDLSAAVAAAAPWLRDGDVVVVTSKVVSKCEGRLVPAPEDPEQRDRLRRKLIEDEAVRVLARKDRTLITENRLGLVQAAAGVDGSNVGRSELALLPVDPDASAATLRAGLRERLGVTVAVVITDTMGRAWRNGQTDAAVGAAGLAVLRNYAGVRDPYGNELVVTEVAVADEIAAAADLVKGKLTATPVAVVRGFGVSDDGSTARQLLRPGANDLFWLGTAEALELGRQQAQLLRRSVRRFSTDPVPGDLVEAAVAEALTAPAPHHTRPTRFVWLQTPAIRARLLDRMKDKWRSDLTSDGLPADAIERRVARGQILYDAPEVVIPMLVPDGAHSYPDAARTDAEHTMFTVAVGAAVQALLVALAVRGLGSCWIGSTIFAADLVRDELDLPVDWEPLGAIAIGYADEPSGLRDPVPAADLLILK