rmlB Resolved · high auto-curated
H37Rv Rv3464 · MTBC0 mtbc0_003682 ·
331 aa · 3907777–3908772 (+) ·
RefSeq NP_217981.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dTDP-glucose 4,6-dehydratase |
|---|---|
| MTBC0 PGAP re-annotation | dTDP-glucose 4%2C6-dehydratase |
| Revised (this work) | DTDP-glucose 4%2C6-dehydratase. Pfam: RmlD_sub_bind (PF04321.24), Polysacc_synt_2 (PF02719.22), GDP_Man_Dehyd (PF16363.12), Epimerase (PF01370.28), 3Beta_HSD (PF01073.26), NAD_binding_4 (PF07993.19), NAD_binding_10 (PF13460.13). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WN65
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | dTDP-glucose 4,6-dehydratase |
| EC (curated) |
EC 4.2.1.46
|
| Curated function | Catalyzes the dehydration of dTDP-D-glucose to form dTDP-6-deoxy-D-xylo-4-hexulose via a three-step process involving oxidation, dehydration and reduction (By similarity). Involved in the biosynthesis of the dTDP-L-rhamnose which is a component of the critical linker, D-N-acetylglucosamine-L-rhamnose disaccharide, which connects the galactan region of arabinogalactan to peptidoglycan via a phosphodiester linkage. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | rmlB |
| eggNOG description | Belongs to the NAD(P)-dependent epimerase dehydratase family. dTDP-glucose dehydratase subfamily |
| Orthologous group | COG1088 |
| EC number |
EC 4.2.1.46
|
| KEGG orthology |
K01710
|
| KEGG pathways |
map00521, map00523, map00525, map01055, map01130
|
| KEGG modules |
M00793
|
| Gene Ontology (67) |
GO:0000166, GO:0000271, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005618, GO:0005623, GO:0005975, GO:0005976, GO:0006139, GO:0006725 +55 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 | 0.147 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 9 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)
| Pfam | Accession | i-Evalue | Residues | Description |
|---|---|---|---|---|
RmlD_sub_bind | PF04321.24 | 6.7e-18 | 1–164 | RmlD substrate binding domain |
Polysacc_synt_2 | PF02719.22 | 6.6e-12 | 3–122 | Polysaccharide biosynthesis protein |
GDP_Man_Dehyd | PF16363.12 | 3.6e-71 | 4–303 | GDP-mannose 4,6 dehydratase |
Epimerase | PF01370.28 | 2.1e-63 | 4–238 | NAD dependent epimerase/dehydratase family |
3Beta_HSD | PF01073.26 | 1.4e-18 | 4–160 | 3-beta hydroxysteroid dehydrogenase/isomerase family |
NAD_binding_4 | PF07993.19 | 5.1e-12 | 5–176 | Male sterility protein |
NAD_binding_10 | PF13460.13 | 1.2e-07 | 7–159 | NAD(P)H-binding |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rmlC (dTDP-4-dehydrorhamnose 3,5-epimerase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3465 rmlC |
dTDP-4-dehydrorhamnose 3,5-epimerase | 999 | 999 ctx | neighborhood:882 fusion:460 cooccurence:663 coexpression:742 database:900 textmining:965 |
Rv0334 rmlA |
glucose-1-phosphate thymidylyltransferase | 999 | 995 ctx | cooccurence:772 coexpression:734 database:900 textmining:965 |
Rv3266c rmlD |
dTDP-4-dehydrorhamnose reductase | 989 | 962 | coexpression:715 database:800 textmining:745 |
Rv3784 |
dTDP-glucose 4,6-dehydratase | 934 | 922 | database:900 |
Rv0536 galE3 |
UDP-glucose 4-epimerase GalE | 829 | 822 | database:800 |
Rv0338c |
iron-sulfur-binding reductase | 811 | 812 | coexpression:812 |
Rv3463 hyp |
hypothetical protein | 792 | 792 ctx | neighborhood:790 |
Rv1510 hyp |
hypothetical protein | 809 | 784 | coexpression:731 |
Rv0322 udgA |
UDP-glucose 6-dehydrogenase UdgA | 822 | 735 | coexpression:704 |
Rv3809c glf |
UDP-galactopyranose mutase | 867 | 708 | coexpression:691 textmining:566 |
Rv3462c infA |
translation initiation factor IF-1 | 681 | 682 ctx | neighborhood:680 |
Rv3630 |
integral membrane protein | 707 | 680 | coexpression:669 |
Rv1752 hyp |
hypothetical protein | 685 | 663 | coexpression:644 |
Rv0501 galE2 |
UDP-glucose 4-epimerase GalE | 640 | 623 ctx | cooccurence:576 |
Rv3466 hyp |
hypothetical protein | 573 | 573 ctx | neighborhood:571 |
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: dTDP-glucose 4,6-dehydratase
- MTBC0 PGAP product: dTDP-glucose 4%2C6-dehydratase
- Pfam (hmmscan --cut_ga): RmlD_sub_bind PF04321.24 (E=7e-18), Polysacc_synt_2 PF02719.22 (E=7e-12), GDP_Man_Dehyd PF16363.12 (E=4e-71), Epimerase PF01370.28 (E=2e-63), 3Beta_HSD PF01073.26 (E=1e-18), NAD_binding_4 PF07993.19 (E=5e-12), NAD_binding_10 PF13460.13 (E=1e-07)
- (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_217981.1)
- Domains: Pfam-A via hmmscan --cut_ga — RmlD_sub_bind (PF04321.24), Polysacc_synt_2 (PF02719.22), GDP_Man_Dehyd (PF16363.12), Epimerase (PF01370.28), 3Beta_HSD (PF01073.26), NAD_binding_4 (PF07993.19), NAD_binding_10 (PF13460.13)
- 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
COG1088 - Curated reference: UniProt P9WN65 (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 —
57 functional partner(s); context anchor
rmlC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003682|Rv3464|rmlB MRLLVTGGAGFIGTNFVHSAVREHPDDAVTVLDALTYAGRRESLADVEDAIRLVQGDITDAELVSQLVAESDAVVHFAAESHVDNALDNPEPFLHTNVIGTFTILEAVRRHGVRLHHISTDEVYGDLELDDRARFTESTPYNPSSPYSATKAGADMLVRAWVRSYGVRATISNCSNNYGPYQHVEKFIPRQITNVLTGRRPKLYGAGANVRDWIHVDDHNSAVRRILDRGRIGRTYLISSEGERDNLTVLRTLLRLMDRDPDDFDHVTDRVGHDLRYAIDPSTLYDELCWAPKHTDFEEGLRTTIDWYRDNESWWRPLKDATEARYQERGQ