rmlC Resolved · high auto-curated
H37Rv Rv3465 · MTBC0 mtbc0_003683 ·
202 aa · 3908774–3909382 (+) ·
RefSeq NP_217982.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | dTDP-4-dehydrorhamnose 3,5-epimerase |
|---|---|
| MTBC0 PGAP re-annotation | dTDP-4-dehydrorhamnose 3%2C5-epimerase |
| Revised (this work) | DTDP-4-dehydrorhamnose 3%2C5-epimerase. Pfam: dTDP_sugar_isom (PF00908.24). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WH11
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | dTDP-4-dehydrorhamnose 3,5-epimerase |
| EC (curated) |
EC 5.1.3.13
|
| Curated function | Catalyzes the epimerization of the C3' and C5'positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4-hexulose. 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 | rmlC |
| eggNOG description | Catalyzes the epimerization of the C3' and C5'positions of dTDP-6-deoxy-D-xylo-4-hexulose, forming dTDP-6-deoxy-L-lyxo-4- hexulose |
| Orthologous group | COG1898 |
| EC number |
EC 5.1.3.13
|
| KEGG orthology |
K01790
|
| 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:0008830, 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 | 0.272 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 6 synonymous, 5 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 |
|---|---|---|---|---|
dTDP_sugar_isom | PF00908.24 | 1.0e-60 | 6–179 | dTDP-4-dehydrorhamnose 3,5-epimerase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: rmlD (dTDP-4-dehydrorhamnose reductase), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv3266c rmlD |
dTDP-4-dehydrorhamnose reductase | 999 | 999 ctx | fusion:837 cooccurence:773 coexpression:857 database:900 textmining:949 |
Rv3464 rmlB |
dTDP-glucose 4,6-dehydratase | 999 | 999 ctx | neighborhood:882 fusion:460 cooccurence:663 coexpression:742 database:900 textmining:965 |
Rv0334 rmlA |
glucose-1-phosphate thymidylyltransferase | 999 | 992 ctx | fusion:715 cooccurence:763 coexpression:858 textmining:963 |
Rv3784 |
dTDP-glucose 4,6-dehydratase | 987 | 980 | coexpression:731 database:900 |
Rv0536 galE3 |
UDP-glucose 4-epimerase GalE | 887 | 881 | coexpression:409 database:800 |
Rv1510 hyp |
hypothetical protein | 901 | 873 | coexpression:856 |
Rv0322 udgA |
UDP-glucose 6-dehydrogenase UdgA | 899 | 868 | coexpression:857 |
Rv3809c glf |
UDP-galactopyranose mutase | 911 | 864 | coexpression:853 |
Rv3265c wbbL1 |
N-acetylglucosaminyl-diphospho-decaprenol L-rhamnosyltransferase | 930 | 806 ctx | cooccurence:712 textmining:659 |
Rv3264c manB |
D-alpha-D-mannose-1-phosphate guanylyltransferase ManB | 846 | 800 | coexpression:783 |
Rv3463 hyp |
hypothetical protein | 791 | 791 ctx | neighborhood:790 |
Rv3630 |
integral membrane protein | 774 | 744 | coexpression:729 |
Rv3468c |
dTDP-glucose 4,6-dehydratase | 781 | 703 | coexpression:411 database:500 |
Rv3462c infA |
translation initiation factor IF-1 | 687 | 688 ctx | neighborhood:680 |
Rv0115 hddA |
D-alpha-D-heptose-7-phosphate kinase HddA | 596 | 581 | coexpression:546 |
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 3,5-epimerase
- MTBC0 PGAP product: dTDP-4-dehydrorhamnose 3%2C5-epimerase
- Pfam (hmmscan --cut_ga): dTDP_sugar_isom PF00908.24 (E=1e-60)
- (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_217982.1)
- Domains: Pfam-A via hmmscan --cut_ga — dTDP_sugar_isom (PF00908.24)
- 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
COG1898 - Curated reference: UniProt P9WH11 (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 —
59 functional partner(s); context anchor
rmlD - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003683|Rv3465|rmlC MKARELDVPGAWEITPTIHVDSRGLFFEWLTDHGFRAFAGHSLDVRQVNCSVSSAGVLRGLHFAQLPPSQAKYVTCVSGSVFDVVVDIREGSPTFGRWDSVLLDDQDRRTIYVSEGLAHGFLALQDNSTVMYLCSAEYNPQREHTICATDPTLAVDWPLVDGAAPSLSDRDAAAPSFEDVRASGLLPRWEQTQRFIGEMRGT