fbiC Resolved · high auto-curated
H37Rv Rv1173 · MTBC0 mtbc0_001262 ·
856 aa · 1311372–1313942 (+) ·
RefSeq NP_215689.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | FO synthase |
|---|---|
| MTBC0 PGAP re-annotation | bifunctional FO biosynthesis protein CofGH |
| Revised (this work) | Bifunctional FO biosynthesis protein CofGH. Pfam: Radical_SAM (PF04055.28), CofH_C (PF19288.5). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WP77
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | FO synthase [Includes: 7,8-didemethyl-8-hydroxy-5-deazariboflavin synthase |
| EC (curated) |
EC 2.5.1.147, EC 4.3.1.32
|
| Curated function | Catalyzes the radical-mediated synthesis of 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) from 5-amino-6-(D-ribitylamino)uracil and L-tyrosine. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | fbiC |
| eggNOG description | catalyzes radical-mediated transfer of hydroxybenzyl group from 4-hydroxyphenylpyruvate (HPP) to 5-amino-6-ribitylamino-2,4(1H,3H)-pyrimidinedione to form 7,8-didemethyl-8-hydroxy-5-deazariboflavin (FO) |
| Orthologous group | COG1060 |
| EC number |
EC 2.5.1.77
|
| KEGG orthology |
K11779
|
| KEGG pathways |
map00680, map01120
|
| KEGG modules |
M00378
|
| Gene Ontology (24) |
GO:0003674, GO:0003824, GO:0005575, GO:0005623, GO:0005886, GO:0006732, GO:0006950, GO:0008150, GO:0008152, GO:0009058, GO:0009108, GO:0009987 +12 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 | 0.882 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 2 synonymous, 5 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 |
|---|---|---|---|---|
Radical_SAM | PF04055.28 | 8.8e-17 | 552–724 | Radical SAM superfamily |
CofH_C | PF19288.5 | 5.4e-12 | 735–832 | CofH/MqnC C-terminal region |
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 975 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1364c |
sigma factor regulatory protein | 999 | 999 | coexpression:999 |
Rv3261 fbiA |
2-phospho-L-lactate transferase | 997 | 975 ctx | cooccurence:727 database:900 textmining:893 |
Rv0417 thiG |
thiazole synthase | 915 | 889 | coexpression:804 experimental:413 |
Rv0423c thiC |
phosphomethylpyrimidine synthase | 859 | 817 | coexpression:802 |
Rv0414c thiE |
thiamine-phosphate synthase | 850 | 804 | coexpression:788 |
Rv3287c rsbW |
anti-sigma factor RsbW | 780 | 780 | coexpression:732 |
Rv0416 thiS |
sulfur carrier protein ThiS | 771 | 761 | coexpression:741 |
Rv1354c hyp |
hypothetical protein | 789 | 758 | coexpression:726 |
Rv1172c PE12 |
PE family protein PE12 | 740 | 740 ctx | neighborhood:740 |
Rv3262 fbiB |
coenzyme F420:L-glutamate ligase | 973 | 684 ctx | cooccurence:636 textmining:920 |
Rv3687c rsfB |
anti-anti-sigma factor RsfB | 659 | 660 | coexpression:649 |
Rv1904 hyp |
hypothetical protein | 658 | 659 | coexpression:648 |
Rv1365c rsfA |
anti-sigma-F factor antagonist RsfA | 658 | 659 | coexpression:648 |
Rv2638 hyp |
hypothetical protein | 658 | 659 | coexpression:648 |
Rv0516c oprA |
anti-anti-sigma factor | 658 | 658 | coexpression:647 |
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: FO synthase
- MTBC0 PGAP product: bifunctional FO biosynthesis protein CofGH
- Pfam (hmmscan --cut_ga): Radical_SAM PF04055.28 (E=9e-17), CofH_C PF19288.5 (E=5e-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_215689.1)
- Domains: Pfam-A via hmmscan --cut_ga — Radical_SAM (PF04055.28), CofH_C (PF19288.5)
- 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
COG1060 - Curated reference: UniProt P9WP77 (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 —
65 functional partner(s); context anchor
fbiA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001262|Rv1173|fbiC MPQPVGRKSTALPSPVVPPQANASALRRVLRRARDGVTLNVDEAAIAMTARGDELADLCASAARVRDAGLVSAGRHGPSGRLAISYSRKVFIPVTRLCRDNCHYCTFVTVPGKLRAQGSSTYMEPDEILDVARRGAEFGCKEALFTLGDRPEARWRQAREWLGERGYDSTLSYVRAMAIRVLEQTGLLPHLNPGVMSWSEMSRLKPVAPSMGMMLETTSRRLFETKGLAHYGSPDKDPAVRLRVLTDAGRLSIPFTTGLLVGIGETLSERADTLHAIRKSHKEFGHIQEVIVQNFRAKEHTAMAAFPDAGIEDYLATVAVARLVLGPGMRIQAPPNLVSGDECRALVGAGVDDWGGVSPLTPDHVNPERPWPALDELAAVTAEAGYDMVQRLTAQPKYVQAGAAWIDPRVRGHVVALADPATGLARDVNPVGMPWQEPDDVASWGRVDLGAAIDTQGRNTAVRSDLASAFGDWESIREQVHELAVRAPERIDTDVLAALRSAERAPAGCTDGEYLALATADGPALEAVAALADSLRRDVVGDEVTFVVNRNINFTNICYTGCRFCAFAQRKGDADAYSLSVGEVADRAWEAHVAGATEVCMQGGIDPELPVTGYADLVRAVKARVPSMHVHAFSPMEIANGVTKSGLSIREWLIGLREAGLDTIPGTAAEILDDEVRWVLTKGKLPTSLWIEIVTTAHEVGLRSSSTMMYGHVDSPRHWVAHLNVLRDIQDRTGGFTEFVPLPFVHQNSPLYLAGAARPGPSHRDNRAVHALARIMLHGRISHIQTSWVKLGVRRTQVMLEGGANDLGGTLMEETISRMAGSEHGSAKTVAELVAIAEGIGRPARQRTTTYALLAA