epiA Resolved · high auto-curated
H37Rv Rv1512 · MTBC0 mtbc0_001619 ·
322 aa · 1713902–1714870 (+) ·
RefSeq NP_216028.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | nucleotide-sugar epimerase EpiA |
|---|---|
| MTBC0 PGAP re-annotation | GDP-L-fucose synthase |
| Revised (this work) | GDP-L-fucose synthase. Pfam: RmlD_sub_bind (PF04321.24), 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 |
P71791
TrEMBL · unreviewed
· Evidence at protein level
|
|---|---|
| UniProt name | GDP-L-fucose synthase |
| EC (curated) |
EC 1.1.1.271
|
| Curated function | Catalyzes the two-step NADP-dependent conversion of GDP-4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
G Carbohydrate transport and metabolismM Cell wall / membrane / envelope biogenesis
|
|---|---|
| Preferred name | fcl |
| eggNOG description | Catalyzes the two-step NADP-dependent conversion of GDP- 4-dehydro-6-deoxy-D-mannose to GDP-fucose, involving an epimerase and a reductase reaction |
| Orthologous group | COG0451 |
| EC number |
EC 1.1.1.271
|
| KEGG orthology |
K02377
|
| 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 | 0.185 · strong purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 4 synonymous, 2 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 | 3.5e-07 | 15–75 | RmlD substrate binding domain |
Epimerase | PF01370.28 | 1.0e-60 | 16–247 | NAD dependent epimerase/dehydratase family |
GDP_Man_Dehyd | PF16363.12 | 1.2e-15 | 48–271 | GDP-mannose 4,6 dehydratase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gmdA (GDP-D-mannose dehydratase GmdA), high confidence from genomic context alone (score 999 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv1511 gmdA |
GDP-D-mannose dehydratase GmdA | 999 | 999 ctx | neighborhood:882 fusion:723 cooccurence:772 database:900 textmining:812 |
Rv0112 gca |
GDP-mannose 4,6-dehydratase | 911 | 912 | database:900 |
Rv1508A hyp |
hypothetical protein | 880 | 875 ctx | cooccurence:774 |
Rv1513 hyp |
hypothetical protein | 978 | 839 ctx | neighborhood:801 textmining:870 |
Rv0705 rpsS |
30S ribosomal protein S19 | 817 | 817 | experimental:463 database:574 |
Rv0682 rpsL |
30S ribosomal protein S12 | 814 | 806 | experimental:463 database:573 |
Rv0710 rpsQ |
30S ribosomal protein S17 | 804 | 798 | experimental:463 database:578 |
Rv0707 rpsC |
30S ribosomal protein S3 | 803 | 796 | experimental:463 database:578 |
Rv0721 rpsE |
30S ribosomal protein S5 | 797 | 790 | experimental:463 database:575 |
Rv0717 rpsN1 |
30S ribosomal protein S14 | 788 | 789 | 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 |
Rv0700 rpsJ |
30S ribosomal protein S10 | 790 | 786 | experimental:463 database:557 |
Rv0702 rplD |
50S ribosomal protein L4 | 787 | 781 | experimental:463 database:575 |
Rv2785c rpsO |
30S ribosomal protein S15 | 782 | 779 | experimental:463 database:573 |
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: nucleotide-sugar epimerase EpiA
- MTBC0 PGAP product: GDP-L-fucose synthase
- Pfam (hmmscan --cut_ga): RmlD_sub_bind PF04321.24 (E=3e-07), Epimerase PF01370.28 (E=1e-60), GDP_Man_Dehyd PF16363.12 (E=1e-15)
- (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_216028.1)
- Domains: Pfam-A via hmmscan --cut_ga — RmlD_sub_bind (PF04321.24), 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
COG0451 - Curated reference: UniProt P71791 (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 —
83 functional partner(s); context anchor
gmdA - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_001619|Rv1512|epiA MNAHTSVGPLDRAARVYIAGHRGLVGSALLRTFAGAGFTNLLVRSRAELDLTDRAATFDFVLESRPQVVIDAAARVGGILANDTYPADFLSENLQIQVNLLDAAVAARVPRLLFLGSSCIYPKLAPQPIPESALLTGPLEPTNDAYAIAKIAGILAVQAVRRQHGLPWISAMPTNLYGPGDNFSPSGSHLLPALIRRYDEAKASGAPNVTNWGTGTPRRELLHVDDLASACLYLLEHFDGPTHVNVGTGIDHTIGEIAEMVASAVGYSGETRWDPSKPDGTPRKLLDVSVLREAGWRPSIALRDGIEATVAWYREHAGTVRQ