ribA1 Resolved · high auto-curated

H37Rv Rv1940 · MTBC0 - · 353 aa · 2192606–2193667 (+) · RefSeq YP_177851.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)riboflavin biosynthesis protein RibA
MTBC0 PGAP re-annotation
Revised (this work)Riboflavin biosynthesis protein RibA. Pfam: DHBP_synthase (PF00926.25), GTP_cyclohydro2 (PF00925.26).

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 L7N669 TrEMBL · unreviewed · Inferred from homology
UniProt name3,4-dihydroxy-2-butanone-4-phosphate synthase
EC (curated) EC 4.1.99.12
Curated functionCatalyzes the conversion of D-ribulose 5-phosphate to formate and 3,4-dihydroxy-2-butanone 4-phosphate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred nameribA1
eggNOG descriptionbelongs to the DHBP synthase family
Orthologous groupCOG0108
EC number EC 3.5.4.25, EC 4.1.99.12
KEGG orthology K14652
KEGG pathways map00740, map00790, map01100, map01110
KEGG modules M00125, M00840

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 1.505 · diversifying/relaxed
Polymorphic sites (≥ 0.1% of strains) 1 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
DHBP_synthasePF00926.25 5.3e-5710–194 3,4-dihydroxy-2-butanone 4-phosphate synthase
GTP_cyclohydro2PF00925.26 1.4e-20207–289 GTP cyclohydrolase II

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

Closest characterised functional partner: ribG (bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas), high confidence from genomic context alone (score 1000 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1409 ribG bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas 999 1000 ctx neighborhood:544 cooccurence:772 coexpression:980 experimental:759 database:900 textmining:805
Rv1416 ribH 6,7-dimethyl-8-ribityllumazine synthase 999 1000 ctx cooccurence:774 coexpression:985 database:900 textmining:418
Rv1412 ribC riboflavin synthase 999 998 ctx fusion:436 cooccurence:774 coexpression:985 textmining:418
Rv1937 oxygenase 983 981 ctx neighborhood:882 coexpression:845
Rv1939 oxidoreductase 971 970 ctx neighborhood:807 coexpression:852
Rv1938 ephB epoxide hydrolase EphB 967 966 ctx neighborhood:787 coexpression:846
Rv1415 ribA2 bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase 943 921 database:900
Rv3609c folE GTP cyclohydrolase I 972 908 database:900 textmining:715
Rv3109 moaA1 cyclic pyranopterin monophosphate synthase 909 906 database:900
Rv0869c moaA2 molybdenum cofactor biosynthesis protein MoaA 906 903 database:900
Rv2445c ndkA nucleoside diphosphate kinase 903 898 database:800
Rv1941 short-chain type dehydrogenase/reductase 887 882 ctx neighborhood:881
Rv1936 monooxygenase 854 849 ctx neighborhood:760
Rv2583c relA bifunctional (p)ppGpp synthase/hydrolase RelA 840 834 database:800
Rv3645 transmembrane protein 812 812 database:800

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): riboflavin biosynthesis protein RibA
  • Pfam (hmmscan --cut_ga): DHBP_synthase PF00926.25 (E=5e-57), GTP_cyclohydro2 PF00925.26 (E=1e-20)
  • (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 YP_177851.1)
  • Domains: Pfam-A via hmmscan --cut_ga — DHBP_synthase (PF00926.25), GTP_cyclohydro2 (PF00925.26)
  • 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 COG0108
  • Curated reference: UniProt L7N669 (TrEMBL, unreviewed; Inferred from homology)
  • 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 — 134 functional partner(s); context anchor ribG
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv1940|ribA1
MKTTDVRVRRAITAMAGGHAVVLTGDPNGDGYLVFAAQAATPRLVAFAVRHTSGYLRVALPGAECERLHLPPMCDRDTTHCVSVDVRGTGTGISASDRAWTIAALASATSVAADFQRPGHVVPVQAQADGVLGRRGPAEAAVDLARLAERRPAAALCEIVSPDNPVQMAHHAESVEFAVEHGLAMVSIGELVAYRRRIEPQVVRFTAATLPTWAGASRVIGFRDVYDLGEHLAVIVGAVGAGVPVPLHVHIECLTGDVFGSTACRCGEELNGALARMSAQGSGVVLYLRPPGPAQACGLFARGDAATDVMPETVTWILRDLGVYAIRLSDDVPGFGLVMFGAIREASTLAAAG