rmlD Resolved · high auto-curated
H37Rv Rv3266c · MTBC0 mtbc0_003474 ·
304 aa · 3669038–3669952 (-) ·
RefSeq NP_217783.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dTDP-4-dehydrorhamnose reductase |
|---|---|
| MTBC0 PGAP re-annotation | dTDP-4-dehydrorhamnose reductase |
| Revised (this work) | DTDP-4-dehydrorhamnose reductase. Pfam: RmlD_sub_bind (PF04321.24), Epimerase (PF01370.28), GDP_Man_Dehyd (PF16363.12), 3Beta_HSD (PF01073.26), 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.
Curated reference (UniProt)
| UniProt |
P9WH09
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | dTDP-4-dehydrorhamnose reductase |
| EC (curated) |
EC 1.1.1.133
|
| Curated function | 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. Catalyzes the reduction of dTDP-6-deoxy-L-lyxo-4-hexulose to yield dTDP-L-rhamnose (By similarity). |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | rmlD |
| eggNOG description | Catalyzes the reduction of dTDP-6-deoxy-L-lyxo-4- hexulose to yield dTDP-L-rhamnose |
| Orthologous group | COG1091 |
| EC number |
EC 1.1.1.133
|
| KEGG orthology |
K00067
|
| KEGG pathways |
map00521, map00523, map01130
|
| KEGG modules |
M00793
|
| Gene Ontology (49) |
GO:0000271, GO:0003674, GO:0003824, GO:0005975, GO:0005976, GO:0006139, GO:0006725, GO:0006807, GO:0008150, GO:0008152, GO:0008831, GO:0009058 +37 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 | 0.368 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 3 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 | 1.0e-107 | 7–287 | RmlD substrate binding domain |
Epimerase | PF01370.28 | 6.4e-26 | 9–212 | NAD dependent epimerase/dehydratase family |
GDP_Man_Dehyd | PF16363.12 | 3.5e-09 | 38–144 | GDP-mannose 4,6 dehydratase |
3Beta_HSD | PF01073.26 | 3.6e-11 | 38–201 | 3-beta hydroxysteroid dehydrogenase/isomerase family |
Polysacc_synt_2 | PF02719.22 | 6.5e-05 | 41–105 | Polysaccharide biosynthesis protein |
NAD_binding_4 | PF07993.19 | 2.0e-09 | 45–158 | Male sterility protein |
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 | fusion:837 cooccurence:773 coexpression:857 database:900 textmining:949 |
Rv3265c wbbL1 |
N-acetylglucosaminyl-diphospho-decaprenol L-rhamnosyltransferase | 996 | 984 ctx | neighborhood:880 cooccurence:715 database:500 textmining:775 |
Rv0334 rmlA |
glucose-1-phosphate thymidylyltransferase | 998 | 969 ctx | cooccurence:763 coexpression:853 textmining:963 |
Rv3784 |
dTDP-glucose 4,6-dehydratase | 975 | 966 | coexpression:714 database:800 |
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 989 | 962 | coexpression:715 database:800 textmining:745 |
Rv0536 galE3 |
UDP-glucose 4-epimerase GalE | 944 | 941 | database:900 |
Rv3264c manB |
D-alpha-D-mannose-1-phosphate guanylyltransferase ManB | 958 | 935 ctx | neighborhood:879 coexpression:481 |
Rv3267 lcp1 hyp |
hypothetical protein | 931 | 787 ctx | neighborhood:784 textmining:693 |
Rv0524 hemL |
glutamate-1-semialdehyde 2,1-aminomutase | 745 | 746 | coexpression:733 |
Rv0321 dcd |
deoxycytidine triphosphate deaminase | 645 | 645 | coexpression:645 |
Rv0501 galE2 |
UDP-glucose 4-epimerase GalE | 658 | 639 | |
Rv3268 hyp |
hypothetical protein | 578 | 578 ctx | neighborhood:565 |
Rv0112 gca |
GDP-mannose 4,6-dehydratase | 558 | 533 | |
Rv0139 |
oxidoreductase | 551 | 526 | |
Rv3634c galE1 |
UDP-glucose 4-epimerase | 531 | 505 |
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-4-dehydrorhamnose reductase
- MTBC0 PGAP product: dTDP-4-dehydrorhamnose reductase
- Pfam (hmmscan --cut_ga): RmlD_sub_bind PF04321.24 (E=1e-107), Epimerase PF01370.28 (E=6e-26), GDP_Man_Dehyd PF16363.12 (E=3e-09), 3Beta_HSD PF01073.26 (E=4e-11), Polysacc_synt_2 PF02719.22 (E=6e-05), NAD_binding_4 PF07993.19 (E=2e-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 NP_217783.1)
- Domains: Pfam-A via hmmscan --cut_ga — RmlD_sub_bind (PF04321.24), Epimerase (PF01370.28), GDP_Man_Dehyd (PF16363.12), 3Beta_HSD (PF01073.26), 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
COG1091 - Curated reference: UniProt P9WH09 (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 —
40 functional partner(s); context anchor
rmlC - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003474|Rv3266c|rmlD MAGRSERLVITGAGGQLGSHLTAQAAREGRDMLALTSSQWDITDPAAAERIIRHGDVVINCAAYTDVDGAESNEAVAYAVNATGPQHLARACARVGARLIHVSTDYVFDGDFGGAEPRPYEPTDETAPQGVYARSKLAGEQAVLAAFPEAAVVRTAWVYTGGTGKDFVAVMRRLAAGHGRVDVVDDQTGSPTYVADLAEALLALADAGVRGRVLHAANEGVVSRFGQARAVFEECGADPQRVRPVSSAQFPRPAPRPSYSALSSRQWALAGLTPLRHWRSALATALAAPANSTSIDRRLPSTRD