Rv3468c Resolved · high auto-curated
H37Rv Rv3468c · MTBC0 - ·
364 aa · 3884975–3886069 (-) ·
RefSeq YP_177974.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dTDP-glucose 4,6-dehydratase |
|---|---|
| MTBC0 PGAP re-annotation | — |
| Revised (this work) | DTDP-glucose 4,6-dehydratase. Pfam: RmlD_sub_bind (PF04321.24), Epimerase (PF01370.28), 3Beta_HSD (PF01073.26), GDP_Man_Dehyd (PF16363.12), NAD_binding_10 (PF13460.13), Polysacc_synt_2 (PF02719.22), NAD_binding_4 (PF07993.19). |
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 |
Q6MWX3
TrEMBL · unreviewed
· Predicted
|
|---|---|
| UniProt name | Possible dTDP-glucose 4,6-dehydratase |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| eggNOG description | Polysaccharide biosynthesis protein |
| Orthologous group | COG0451 |
| EC number |
EC 4.2.1.46, EC 5.1.3.2
|
| KEGG orthology |
K01710, K01784
|
| KEGG pathways |
map00052, map00520, map00521, map00523, map00525, map01055, map01100, map01130
|
| KEGG modules |
M00361, M00362, M00632, M00793
|
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 | 0.324 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 10 synonymous, 8 missense, 1 nonsense, 0 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.26% of strains (379) · clonal |
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 | 4.6e-14 | 36–206 | RmlD substrate binding domain |
Epimerase | PF01370.28 | 7.1e-27 | 39–207 | NAD dependent epimerase/dehydratase family |
3Beta_HSD | PF01073.26 | 1.8e-15 | 39–210 | 3-beta hydroxysteroid dehydrogenase/isomerase family |
GDP_Man_Dehyd | PF16363.12 | 1.9e-12 | 39–199 | GDP-mannose 4,6 dehydratase |
NAD_binding_10 | PF13460.13 | 6.6e-09 | 42–152 | NAD(P)H-binding |
Polysacc_synt_2 | PF02719.22 | 1.0e-10 | 72–142 | Polysaccharide biosynthesis protein |
NAD_binding_4 | PF07993.19 | 3.6e-09 | 85–201 | Male sterility protein |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: mhpE (4-hydroxy-2-oxovalerate aldolase MhpE), high confidence from genomic context alone (score 906 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0322 udgA |
UDP-glucose 6-dehydrogenase UdgA | 960 | 958 | coexpression:415 database:900 |
Rv3634c galE1 |
UDP-glucose 4-epimerase | 991 | 935 | database:900 textmining:870 |
Rv3809c glf |
UDP-galactopyranose mutase | 969 | 926 | database:900 textmining:598 |
Rv0501 galE2 |
UDP-glucose 4-epimerase GalE | 916 | 917 | database:900 |
Rv3469c mhpE |
4-hydroxy-2-oxovalerate aldolase MhpE | 906 | 906 ctx | neighborhood:882 |
Rv0993 galU |
UTP--glucose-1-phosphate uridylyltransferase | 909 | 904 | database:900 |
Rv0618 galTa |
Rv0618, (MTCY19H5.03c), len: 231 aa (probable partial CDS). Probable galTa, first part of galactose-1-phosphate uridylyltransferase, highly | 907 | 903 | database:900 |
Rv0705 rpsS |
30S ribosomal protein S19 | 816 | 816 | experimental:463 database:574 |
Rv0682 rpsL |
30S ribosomal protein S12 | 813 | 805 | experimental:463 database:573 |
Rv0710 rpsQ |
30S ribosomal protein S17 | 803 | 797 | experimental:463 database:578 |
Rv0707 rpsC |
30S ribosomal protein S3 | 802 | 795 | experimental:463 database:578 |
Rv0721 rpsE |
30S ribosomal protein S5 | 796 | 789 | experimental:463 database:575 |
Rv0717 rpsN1 |
30S ribosomal protein S14 | 787 | 788 | experimental:436 database:548 |
Rv2056c rpsN2 |
30S ribosomal protein S14 | 787 | 788 | experimental:436 database:548 |
Rv0718 rpsH |
30S ribosomal protein S8 | 793 | 786 | experimental:463 database:578 |
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): dTDP-glucose 4,6-dehydratase
- Pfam (hmmscan --cut_ga): RmlD_sub_bind PF04321.24 (E=5e-14), Epimerase PF01370.28 (E=7e-27), 3Beta_HSD PF01073.26 (E=2e-15), GDP_Man_Dehyd PF16363.12 (E=2e-12), NAD_binding_10 PF13460.13 (E=7e-09), Polysacc_synt_2 PF02719.22 (E=1e-10), NAD_binding_4 PF07993.19 (E=4e-09)
- (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_177974.1)
- Domains: Pfam-A via hmmscan --cut_ga — RmlD_sub_bind (PF04321.24), Epimerase (PF01370.28), 3Beta_HSD (PF01073.26), GDP_Man_Dehyd (PF16363.12), NAD_binding_10 (PF13460.13), Polysacc_synt_2 (PF02719.22), NAD_binding_4 (PF07993.19)
- 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
COG0451 - Curated reference: UniProt Q6MWX3 (TrEMBL, unreviewed; Predicted)
- 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 —
91 functional partner(s); context anchor
mhpE - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3468c| MGTHAATMRVRAGVRSSPLLLHAGTPPTAAAAESGMRTLVTGSSGHLGEALVRTLRARGADIVSLDSRPSRYTNIVGCVSDRALLRDVMAGVEVVFHAAAHHKPQLAFLPRQAFLDTNIIGTQTVLDAAVAANVRAFVMTSSTTVFGDALTPPADQPAAWIDESVTPIPKNIYGVTKASSEDLCQLAHRNDGLACVVLRVARFFVEGDDMPDLYDGRSQDNIKANEYACRRVALEDAVDAHLNAAQRAPQLGFGRYLVSATTPFTRDDLTQLRTDAASVFARRVPLAAAVWTQRGWRFPDRLDRVYVNSRARRDLNWRPRFDLNAVAARLARGQSVHTPLSQLVGSKAYAHSSYHRGVFAPARP