ribH Resolved · high auto-curated
H37Rv Rv1416 · MTBC0 mtbc0_001516 ·
160 aa · 1601015–1601497 (+) ·
RefSeq NP_215932.2
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 6,7-dimethyl-8-ribityllumazine synthase |
|---|---|
| MTBC0 PGAP re-annotation | 6%2C7-dimethyl-8-ribityllumazine synthase |
| Revised (this work) | 6%2C7-dimethyl-8-ribityllumazine synthase. Pfam: DMRL_synthase (PF00885.25). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WHE9
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | 6,7-dimethyl-8-ribityllumazine synthase |
| EC (curated) |
EC 2.5.1.78
|
| Curated function | Catalyzes the formation of 6,7-dimethyl-8-ribityllumazine by condensation of 5-amino-6-(D-ribitylamino)uracil with 3,4-dihydroxy-2-butanone 4-phosphate. This is the penultimate step in the biosynthesis of riboflavin. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
H Coenzyme transport and metabolism
|
|---|---|
| Preferred name | ribH |
| eggNOG description | Catalyzes the formation of 6,7-dimethyl-8- ribityllumazine by condensation of 5-amino-6-(D- ribitylamino)uracil with 3,4-dihydroxy-2-butanone 4-phosphate. This is the penultimate step in the biosynthesis of riboflavin |
| Orthologous group | COG0054 |
| EC number |
EC 2.5.1.78
|
| KEGG orthology |
K00794
|
| KEGG pathways |
map00740, map01100, map01110
|
| KEGG modules |
M00125
|
| Gene Ontology (42) |
GO:0000906, GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0006766, GO:0006767, GO:0006771, GO:0006807 +30 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 | 0.385 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 1 synonymous, 1 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 |
|---|---|---|---|---|
DMRL_synthase | PF00885.25 | 9.1e-49 | 18–152 | 6,7-dimethyl-8-ribityllumazine synthase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: ribA1 (riboflavin biosynthesis protein RibA), high confidence from genomic context alone (score 1000 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1940 ribA1 |
riboflavin biosynthesis protein RibA | 999 | 1000 ctx | cooccurence:774 coexpression:985 database:900 textmining:418 |
Rv1415 ribA2 |
bifunctional riboflavin biosynthesis GTP cyclohydrolase II/3,4-dihydroxy-2-butanone 4-phosphate synthase | 999 | 1000 ctx | neighborhood:881 cooccurence:774 coexpression:986 database:900 textmining:885 |
Rv1412 ribC |
riboflavin synthase | 999 | 999 ctx | neighborhood:675 cooccurence:774 coexpression:853 database:900 textmining:638 |
Rv1392 metK |
S-adenosylmethionine synthetase | 991 | 991 | coexpression:987 |
Rv0985c mscL |
large-conductance ion mechanosensitive channel | 988 | 987 | coexpression:987 |
Rv1409 ribG |
bifunctional riboflavin biosynthesis diaminohydroxyphosphoribosylaminopyrimidine deaminase/5-amino-6-(5-phosphoribosylamino) uracil reductas | 995 | 978 ctx | cooccurence:772 coexpression:824 textmining:796 |
Rv1380 pyrB |
aspartate carbamoyltransferase | 948 | 948 | coexpression:945 |
Rv1417 |
membrane protein | 976 | 885 ctx | neighborhood:881 textmining:803 |
Rv2786c ribF |
bifunctional riboflavin kinase /FMN adenylyltransferase | 974 | 883 | coexpression:762 database:500 textmining:787 |
Rv1418 lprH |
lipoprotein LprH | 850 | 851 ctx | neighborhood:846 |
Rv1407 fmu |
16S rRNA m5C967 methyltransferase | 815 | 741 | coexpression:660 |
Rv2442c rplU |
50S ribosomal protein L21 | 733 | 733 | coexpression:733 |
Rv3443c rplM |
50S ribosomal protein L13 | 699 | 700 | coexpression:698 |
Rv1422 cuvA hyp |
hypothetical protein | 691 | 692 ctx | neighborhood:682 |
Rv1421 rapZ hyp |
hypothetical protein | 689 | 689 ctx | neighborhood:682 |
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: 6,7-dimethyl-8-ribityllumazine synthase
- MTBC0 PGAP product: 6%2C7-dimethyl-8-ribityllumazine synthase
- Pfam (hmmscan --cut_ga): DMRL_synthase PF00885.25 (E=9e-49)
- (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_215932.2)
- Domains: Pfam-A via hmmscan --cut_ga — DMRL_synthase (PF00885.25)
- 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
COG0054 - Curated reference: UniProt P9WHE9 (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 —
92 functional partner(s); context anchor
ribA1 - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001516|Rv1416|ribH MKGGAGVPDLPSLDASGVRLAIVASSWHGKICDALLDGARKVAAGCGLDDPTVVRVLGAIEIPVVAQELARNHDAVVALGVVIRGQTPHFDYVCDAVTQGLTRVSLDSSTPIANGVLTTNTEEQALDRAGLPTSAEDKGAQATVAALATALTLRELRAHS