ribF Resolved · high auto-curated

H37Rv Rv2786c · MTBC0 - · 331 aa · 3093905–3094900 (-) · RefSeq NP_217302.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)bifunctional riboflavin kinase /FMN adenylyltransferase
MTBC0 PGAP re-annotation
Revised (this work)Bifunctional riboflavin kinase /FMN adenylyltransferase. Pfam: FAD_syn (PF06574.19), CTP_transf_like (PF01467.33), Flavokinase (PF01687.24).

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

Annotated on the H37Rv protein: this gene has no 1:1 ancestral MTBC0 anchor (PE/PPE, paralogue, IS element, or otherwise unanchored CDS).

Curated reference (UniProt)

UniProt I6X5C9 TrEMBL · unreviewed · Evidence at protein level
UniProt nameRiboflavin biosynthesis protein [Includes: Riboflavin kinase
EC (curated) EC 2.7.1.26, EC 2.7.7.2
Curated functionCatalyzes the phosphorylation of riboflavin to FMN followed by the adenylation of FMN to FAD.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred nameribF
eggNOG descriptionBelongs to the ribF family
Orthologous groupCOG0196
EC number EC 2.7.1.26, EC 2.7.7.2
KEGG orthology K11753
KEGG pathways map00740, map01100, map01110
KEGG modules M00125
Gene Ontology (95) GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005739, GO:0005740, GO:0005743, GO:0006139, GO:0006725 +83 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 0.232 · purifying
Polymorphic sites (≥ 0.1% of strains) 6 synonymous, 4 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
FAD_synPF06574.19 8.2e-5219–167 FAD synthetase
CTP_transf_likePF01467.33 3.9e-0426–180 Cytidylyltransferase-like
FlavokinasePF01687.24 4.8e-39195–328 Riboflavin kinase

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

Closest characterised functional partner: truB (tRNA pseudouridine synthase B), high confidence from genomic context alone (score 810 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1412 ribC riboflavin synthase 933 913 database:900
Rv1416 ribH 6,7-dimethyl-8-ribityllumazine synthase 974 883 coexpression:762 database:500 textmining:787
Rv2793c truB tRNA pseudouridine synthase B 944 810 ctx fusion:614 coexpression:412 textmining:720
Rv2785c rpsO 30S ribosomal protein S15 935 759 ctx neighborhood:749 textmining:745
Rv2784c lppU lipoprotein LppU 744 745 ctx neighborhood:745
Rv1712 cmk cytidylate kinase 741 725 ctx fusion:545
Rv2788 sirR transcriptional repressor SirR 699 699 ctx neighborhood:696
Rv2783c gpsI bifunctional guanosine pentaphosphate synthetase/polyribonucleotide nucleotidyltransferase 654 653 ctx neighborhood:651
Rv2782c pepR zinc protease 652 652 ctx neighborhood:651
Rv2965c kdtB phosphopantetheine adenylyltransferase 840 611 ctx cooccurence:594 textmining:608
Rv1409 ribG bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas 930 555 coexpression:412 textmining:851
Rv2787 hyp hypothetical protein 488 488 ctx neighborhood:488
Rv2883c pyrH uridylate kinase 459 459 ctx cooccurence:411
Rv1710 scpB segregation and condensation protein ScpB 459 459 coexpression:442
Rv1631 coaE dephospho-CoA kinase CoaE 769 440 textmining:606

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

  • Annotation from H37Rv (no MTBC0 1:1 anchor; H37Rv protein used): bifunctional riboflavin kinase /FMN adenylyltransferase
  • Pfam (hmmscan --cut_ga): FAD_syn PF06574.19 (E=8e-52), CTP_transf_like PF01467.33 (E=4e-04), Flavokinase PF01687.24 (E=5e-39)
  • (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_217302.1)
  • Domains: Pfam-A via hmmscan --cut_ga — FAD_syn (PF06574.19), CTP_transf_like (PF01467.33), Flavokinase (PF01687.24)
  • 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 COG0196
  • Curated reference: UniProt I6X5C9 (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 — 51 functional partner(s); context anchor truB
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv2786c|ribF
MRRRLAIVQRWRGQDEIPTDWGRCVLTIGVFDGVHRGHAELIAHAVKAGRARGVPAVLMTFDPHPMEVVYPGSHPAQLTTLTRRAELVQDLGIEVFLVMPFTTDFMKLTPDRFIHELLVEHLHVVEVVVGENFTFGKKAAGNVDTLRRAGERFGFAVESMSLVSEHHSNETVTFSSTYIRSCVDAGDMVAAMEALGRPHRVEGVVVRGEGRGAELGFPTANVAPPMYSAIPADGVYAAWFTVLGHGPVTGTVVPGERYQAAVSVGTNPTFSGRTRTVEAFVLDTTADLYGQHVALDFVGRIRGQKKFESVRQLVAAMGADTERARDLLSTG