galE3 Resolved · high auto-curated

H37Rv Rv0536 · MTBC0 - · 346 aa · 627248–628288 (+) · RefSeq YP_177737.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)UDP-glucose 4-epimerase GalE
MTBC0 PGAP re-annotation
Revised (this work)UDP-glucose 4-epimerase GalE. Pfam: GDP_Man_Dehyd (PF16363.12), Epimerase (PF01370.28).

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 L7N670 TrEMBL · unreviewed · Evidence at protein level
UniProt nameProbable UDP-glucose 4-epimerase GalE3

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
M Cell wall / membrane / envelope biogenesis
Preferred namegalE3
eggNOG descriptiondehydratase
Orthologous groupCOG0451
EC number EC 5.1.3.25
KEGG orthology K17947
KEGG pathways map00523, map01130

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 0.285 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 4 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)

PfamAccessioni-EvalueResiduesDescription
GDP_Man_DehydPF16363.12 1.2e-15164–339 GDP-mannose 4,6 dehydratase
EpimerasePF01370.28 2.8e-23165–266 NAD dependent epimerase/dehydratase family

Functional interaction network (STRING v12, guilt-by-association)

Closest characterised functional partner: pnp (5'-methylthioadenosine phosphorylase), high confidence from genomic context alone (score 934 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv3266c rmlD dTDP-4-dehydrorhamnose reductase 944 941 database:900
Rv0535 pnp 5'-methylthioadenosine phosphorylase 991 934 ctx neighborhood:882 cooccurence:441 textmining:875
Rv3465 rmlC dTDP-4-dehydrorhamnose 3,5-epimerase 887 881 coexpression:409 database:800
Rv3784 dTDP-glucose 4,6-dehydratase 858 852 database:800
Rv0539 dolichyl-phosphate sugar synthase 978 835 ctx cooccurence:771 textmining:874
Rv3464 rmlB dTDP-glucose 4,6-dehydratase 829 822 database:800
Rv0540 hyp hypothetical protein 975 817 ctx cooccurence:770 textmining:870
Rv0705 rpsS 30S ribosomal protein S19 816 816 experimental:463 database:574
Rv0541c integral membrane protein 974 809 ctx cooccurence:767 textmining:870
Rv0682 rpsL 30S ribosomal protein S12 813 805 experimental:463 database:573
Rv0218 transmembrane protein 804 805 ctx cooccurence:769
Rv0710 rpsQ 30S ribosomal protein S17 803 797 experimental:463 database:578
Rv0707 rpsC 30S ribosomal protein S3 802 795 experimental:463 database:578
Rv0534c menA 1,4-dihydroxy-2-naphthoate octaprenyltransferase 792 792 ctx neighborhood:791
Rv0721 rpsE 30S ribosomal protein S5 796 789 experimental:463 database:575

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): UDP-glucose 4-epimerase GalE
  • Pfam (hmmscan --cut_ga): GDP_Man_Dehyd PF16363.12 (E=1e-15), Epimerase PF01370.28 (E=3e-23)
  • (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_177737.1)
  • Domains: Pfam-A via hmmscan --cut_ga — GDP_Man_Dehyd (PF16363.12), Epimerase (PF01370.28)
  • 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 L7N670 (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 — 91 functional partner(s); context anchor pnp
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>H37Rv|Rv0536|galE3
MRVLLTGAAGFIGSRVDAALRAAGHDVVGVDALLPAAHGPNPVLPPGCQRVDVRDASALAPLLAGVDLVCHQAAMVGAGVNAADAPAYGGHNDFATTVLLAQMFAAGVRRLVLASSMVVYGQGRYDCPQHGPVDPLPRRRADLDNGVFEHRCPGCGEPVIWQLVDEDAPLRPRSLYAASKTAQEHYALAWSEASGGSVVALRYHNVYGPGMPRDTPYSGVAAIFRSAVEKGKPPKVFEDGGQMRDFVHVDDVAAANLAAVHLGEADRDGFTAVNVCSGRPISILQVATAICDARGGSMSPAITGHYRSGDVRHIVADPARAARVLGFRAAVDPGEGLREFAFAPLR