gmdA Resolved · high auto-curated
H37Rv Rv1511 · MTBC0 mtbc0_001614 ·
40 aa · 1709768–1709887 (+) ·
RefSeq NP_216027.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | GDP-D-mannose dehydratase GmdA |
|---|---|
| MTBC0 PGAP re-annotation | GDP-mannose 4%2C6-dehydratase |
| Revised (this work) | GDP-mannose 4%2C6-dehydratase. Pfam: Epimerase (PF01370.28), GDP_Man_Dehyd (PF16363.12). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P71790
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | GDP-mannose 4,6-dehydratase |
| EC (curated) |
EC 4.2.1.47
|
| Curated function | Catalyzes the conversion of GDP-D-mannose to GDP-4-dehydro-6-deoxy-D-mannose. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
M Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | gmd |
| eggNOG description | GDP-mannose 4,6-dehydratase activity |
| Orthologous group | COG1089 |
| EC number |
EC 4.2.1.47
|
| KEGG orthology |
K01711
|
| KEGG pathways |
map00051, map00520, map01100
|
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 | 0.439 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 3 synonymous, 4 missense, 0 nonsense, 1 frameshift |
| Disruption | 1 distinct premature-stop/frameshift site(s); most common in 0.12% of strains (180) · 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 |
|---|---|---|---|---|
Epimerase | PF01370.28 | 1.7e-70 | 4–247 | NAD dependent epimerase/dehydratase family |
GDP_Man_Dehyd | PF16363.12 | 1.2e-135 | 5–315 | GDP-mannose 4,6 dehydratase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: epiA (nucleotide-sugar epimerase EpiA), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1512 epiA |
nucleotide-sugar epimerase EpiA | 999 | 999 ctx | neighborhood:882 fusion:723 cooccurence:772 database:900 textmining:812 |
Rv0112 gca |
GDP-mannose 4,6-dehydratase | 956 | 955 | database:900 |
Rv3264c manB |
D-alpha-D-mannose-1-phosphate guanylyltransferase ManB | 914 | 906 | database:900 |
Rv1513 hyp |
hypothetical protein | 932 | 803 ctx | neighborhood:801 textmining:668 |
Rv0702 rplD |
50S ribosomal protein L4 | 677 | 677 ctx | fusion:674 |
Rv1514c |
glycosyltransferase | 682 | 671 ctx | cooccurence:622 |
Rv3725 |
oxidoreductase | 448 | 422 | |
Rv0139 |
oxidoreductase | 446 | 419 | |
Rv1106c |
3 beta-hydroxysteroid dehydrogenase/delta 5-->4-isomerase | 444 | 418 | |
Rv0501 galE2 |
UDP-glucose 4-epimerase GalE | 444 | 418 | |
Rv3468c |
dTDP-glucose 4,6-dehydratase | 444 | 418 | |
Rv1868 hyp |
hypothetical protein | 444 | 418 | |
Rv3634c galE1 |
UDP-glucose 4-epimerase | 444 | 418 | |
Rv2047c hyp |
hypothetical protein | 444 | 418 | |
Rv0536 galE3 |
UDP-glucose 4-epimerase GalE | 442 | 416 |
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: GDP-D-mannose dehydratase GmdA
- MTBC0 PGAP product: GDP-mannose 4%2C6-dehydratase
- Pfam (hmmscan --cut_ga): Epimerase PF01370.28 (E=2e-70), GDP_Man_Dehyd PF16363.12 (E=1e-135)
- (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_216027.1)
- Domains: Pfam-A via hmmscan --cut_ga — Epimerase (PF01370.28), GDP_Man_Dehyd (PF16363.12)
- 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
COG1089 - Curated reference: UniProt P71790 (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 —
35 functional partner(s); context anchor
epiA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001614|Rv1511|gmdA MEVYFCWATRNYRELYGLLAVNSIWFNHESPRHGETFMTR