Rv3784 Resolved · high auto-curated
H37Rv Rv3784 · MTBC0 - ·
326 aa · 4230256–4231236 (+) ·
RefSeq YP_178015.1
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), Polysacc_synt_2 (PF02719.22), GDP_Man_Dehyd (PF16363.12), 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.
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 |
P72050
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| 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 4.1.1.35, EC 4.2.1.46
|
| KEGG orthology |
K01710, K08678, K21211
|
| KEGG pathways |
map00520, map00521, map00523, map00525, map01055, map01059, map01100, map01130
|
| KEGG modules |
M00361, 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) pseudogene candidate
| pN/pS | 0.739 · relaxed/neutral |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 7 missense, 0 nonsense, 2 frameshift |
| Disruption | 2 distinct premature-stop/frameshift site(s); most common in 2.24% of strains (3253) · 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 | 2.4e-16 | 1–181 | RmlD substrate binding domain |
Epimerase | PF01370.28 | 7.3e-60 | 3–235 | NAD dependent epimerase/dehydratase family |
Polysacc_synt_2 | PF02719.22 | 5.5e-11 | 3–119 | Polysaccharide biosynthesis protein |
GDP_Man_Dehyd | PF16363.12 | 6.9e-58 | 4–300 | GDP-mannose 4,6 dehydratase |
3Beta_HSD | PF01073.26 | 2.2e-24 | 4–229 | 3-beta hydroxysteroid dehydrogenase/isomerase family |
NAD_binding_4 | PF07993.19 | 1.2e-16 | 5–185 | Male sterility protein |
NAD_binding_10 | PF13460.13 | 2.9e-12 | 7–175 | NAD(P)H-binding |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rmlA (glucose-1-phosphate thymidylyltransferase), high confidence from genomic context alone (score 985 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0334 rmlA |
glucose-1-phosphate thymidylyltransferase | 991 | 985 ctx | cooccurence:435 coexpression:733 database:900 textmining:415 |
Rv3465 rmlC |
dTDP-4-dehydrorhamnose 3,5-epimerase | 987 | 980 | coexpression:731 database:900 |
Rv3266c rmlD |
dTDP-4-dehydrorhamnose reductase | 975 | 966 | coexpression:714 database:800 |
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 934 | 922 | database:900 |
Rv0536 galE3 |
UDP-glucose 4-epimerase GalE | 858 | 852 | database:800 |
Rv0322 udgA |
UDP-glucose 6-dehydrogenase UdgA | 838 | 788 | coexpression:704 |
Rv1510 hyp |
hypothetical protein | 789 | 760 | coexpression:731 |
Rv3809c glf |
UDP-galactopyranose mutase | 740 | 707 | coexpression:690 |
Rv3630 |
integral membrane protein | 707 | 680 | coexpression:669 |
Rv1752 hyp |
hypothetical protein | 686 | 664 | coexpression:645 |
Rv1503c |
Rv1503c, (MTCY277.25c), len: 182 aa. Conserved hypothetical protein, similar to C-terminal region of P27833|RFFA_ECOLI lipopolysaccharide bi | 651 | 629 | coexpression:616 |
Rv1504c |
Rv1504c, (MTCY277.26c), len: 199 aa. Conserved hypothetical protein, similar to N-terminal region of P27833|RFFA_ECOLI lipopolysaccharide bi | 626 | 603 | coexpression:529 |
Rv3264c manB |
D-alpha-D-mannose-1-phosphate guanylyltransferase ManB | 640 | 594 | coexpression:469 |
Rv3402c hyp |
hypothetical protein | 605 | 581 | coexpression:478 |
Rv3785 hyp |
hypothetical protein | 942 | 575 ctx | neighborhood:548 textmining:870 |
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=2e-16), Epimerase PF01370.28 (E=7e-60), Polysacc_synt_2 PF02719.22 (E=5e-11), GDP_Man_Dehyd PF16363.12 (E=7e-58), 3Beta_HSD PF01073.26 (E=2e-24), NAD_binding_4 PF07993.19 (E=1e-16), NAD_binding_10 PF13460.13 (E=3e-12)
- (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_178015.1)
- Domains: Pfam-A via hmmscan --cut_ga — RmlD_sub_bind (PF04321.24), Epimerase (PF01370.28), Polysacc_synt_2 (PF02719.22), GDP_Man_Dehyd (PF16363.12), 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
COG0451 - Curated reference: UniProt P72050 (TrEMBL, unreviewed; 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 —
51 functional partner(s); context anchor
rmlA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>H37Rv|Rv3784| MEILVTGGAGFQGSHLTESLLANGHWVTVLDKSSRNAVRNMQGFRSHDRAAFISGSVTDGQTIDRAVRDHHVVFHLAAHVNVDQSLGDPESFLETNVMGTYRVLEAVRRYRNRLIYVSTCEVYGDGHNLKEGERLDEHAELKPNSPYGASKAAADRLCYSYFRSYGLDVTIVRPFNIFGVRQKAGRFGALIPRLVRQGINGEGLTIFGAGSATRDYLYVSDIVGAYNLVLRTPTLRGQAINFASGKDTRVRDIVEYVADKFGARIEHRDARPGEVQRFPADISLAKSIGFQPQVEIWDGIDRYINWAKDQPQYPYEQDGFSGSSVL