ribC Resolved · high auto-curated

H37Rv Rv1412 · MTBC0 mtbc0_001513 · 201 aa · 1597911–1598516 (+) · RefSeq NP_215928.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)riboflavin synthase
MTBC0 PGAP re-annotationriboflavin synthase
Revised (this work)Riboflavin synthase. Pfam: Lum_binding (PF00677.24).

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

Curated reference (UniProt)

UniProt P9WK35 SwissProt · reviewed · Evidence at protein level
UniProt nameRiboflavin synthase
EC (curated) EC 2.5.1.9
Curated functionCatalyzes the dismutation of two molecules of 6,7-dimethyl-8-ribityllumazine, resulting in the formation of riboflavin and 5-amino-6-(D-ribitylamino)uracil.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred nameribE
eggNOG descriptionriboflavin synthase alpha
Orthologous groupCOG0307
EC number EC 2.5.1.9
KEGG orthology K00793
KEGG pathways map00740, map01100, map01110
KEGG modules M00125
Gene Ontology (41) GO:0003674, GO:0003824, GO:0004746, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006766, GO:0006767, GO:0006771, GO:0006807 +29 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 0.742 · relaxed/neutral
Polymorphic sites (≥ 0.1% of strains) 1 synonymous, 2 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
Lum_bindingPF00677.24 3.1e-26100–187 Lumazine binding domain

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

Closest characterised functional partner: ribA2 (bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1415 ribA2 bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase 999 1000 ctx neighborhood:505 fusion:896 cooccurence:774 coexpression:985 textmining:418
Rv1416 ribH 6,7-dimethyl-8-ribityllumazine synthase 999 999 ctx neighborhood:675 cooccurence:774 coexpression:853 database:900 textmining:638
Rv1409 ribG bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas 999 999 ctx fusion:662 cooccurence:772 coexpression:987 textmining:627
Rv1940 ribA1 riboflavin biosynthesis protein RibA 999 998 ctx fusion:436 cooccurence:774 coexpression:985 textmining:418
Rv2786c ribF bifunctional riboflavin kinase /FMN adenylyltransferase 933 913 database:900
Rv1410c aminoglycosides/tetracycline-transport integral membrane protein 893 805 ctx neighborhood:783 textmining:474
Rv1411c lprG lipoprotein LprG 786 786 ctx neighborhood:783
Rv2671 ribD bifunctional diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino)uracil reductase 839 755 coexpression:703
Rv1298 rpmE 50S ribosomal protein L31 685 686 coexpression:686
Rv0331 dehydrogenase/reductase 684 684 coexpression:684
Rv1417 membrane protein 678 677 ctx neighborhood:675
Rv2122c hisE phosphoribosyl-ATP pyrophosphatase 495 496 coexpression:411
Rv1392 metK S-adenosylmethionine synthetase 504 473
Rv1414 hyp hypothetical protein 471 471 ctx neighborhood:468
Rv1413 hyp hypothetical protein 469 470 ctx neighborhood:468

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: riboflavin synthase
  • MTBC0 PGAP product: riboflavin synthase
  • Pfam (hmmscan --cut_ga): Lum_binding PF00677.24 (E=3e-26)
  • (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_215928.1)
  • Domains: Pfam-A via hmmscan --cut_ga — Lum_binding (PF00677.24)
  • 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 COG0307
  • Curated reference: UniProt P9WK35 (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 — 30 functional partner(s); context anchor ribA2
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001513|Rv1412|ribC
MFTGIVEERGEVTGREALVDAARLTIRGPMVTADAGHGDSIAVNGVCLTVVDVLPDGQFTADVMAETLNRSNLGELRPGSRVNLERAAALGSRLGGHIVQGHVDATGEIVARCPSEHWEVVRIEMPASVARYVVEKGSITVDGISLTVSGLGAEQRDWFEVSLIPTTRELTTLGSAAVGTRVNLEVDVVAKYVERLMRSAG