galE1 Resolved · high auto-curated

H37Rv Rv3634c · MTBC0 mtbc0_003851 · 314 aa · 4096371–4097315 (-) · RefSeq NP_215015.2

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)UDP-glucose 4-epimerase
MTBC0 PGAP re-annotationUDP-glucose 4-epimerase
Revised (this work)UDP-glucose 4-epimerase. 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_10 (PF13460.13), 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 P9WN67 SwissProt · reviewed · Evidence at protein level
UniProt nameUDP-glucose 4-epimerase
EC (curated) EC 5.1.3.2
Curated functionInvolved in the metabolism of galactose. Catalyzes the conversion of UDP-galactose (UDP-Gal) to UDP-glucose (UDP-Glc) through a mechanism involving the transient reduction of NAD (By similarity).

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category M Cell wall / membrane / envelope biogenesis
Preferred namegalE1
eggNOG descriptionUDP-glucose 4-epimerase
Orthologous groupCOG0451
EC number EC 4.2.1.46, EC 5.1.3.2
KEGG orthology K01710, K01784
KEGG pathways map00052, map00520, map00521, map00523, map00525, map01055, map01100, map01130
KEGG modules M00361, M00362, M00632, M00793
Gene Ontology (8) GO:0005575, GO:0005623, GO:0005886, GO:0008150, GO:0016020, GO:0040007, GO:0044464, GO:0071944

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 0.119 · strong purifying
Polymorphic sites (≥ 0.1% of strains) 3 synonymous, 1 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
RmlD_sub_bindPF04321.24 1.1e-151–156 RmlD substrate binding domain
EpimerasePF01370.28 6.6e-603–241 NAD dependent epimerase/dehydratase family
GDP_Man_DehydPF16363.12 5.6e-574–304 GDP-mannose 4,6 dehydratase
3Beta_HSDPF01073.26 1.2e-164–226 3-beta hydroxysteroid dehydrogenase/isomerase family
Polysacc_synt_2PF02719.22 4.7e-104–121 Polysaccharide biosynthesis protein
NAD_binding_10PF13460.13 2.3e-087–132 NAD(P)H-binding
NAD_binding_4PF07993.19 1.8e-0572–224 Male sterility protein

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

Closest characterised functional partner: Rv3635 (transmembrane protein), high confidence from genomic context alone (score 795 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv0322 udgA UDP-glucose 6-dehydrogenase UdgA 969 967 coexpression:412 database:900
Rv3468c dTDP-glucose 4,6-dehydratase 991 935 database:900 textmining:870
Rv3809c glf UDP-galactopyranose mutase 969 927 database:900 textmining:600
Rv0993 galU UTP--glucose-1-phosphate uridylyltransferase 934 922 database:900
Rv0501 galE2 UDP-glucose 4-epimerase GalE 920 921 database:900
Rv0618 galTa Rv0618, (MTCY19H5.03c), len: 231 aa (probable partial CDS). Probable galTa, first part of galactose-1-phosphate uridylyltransferase, highly 907 903 database:900
Rv0705 rpsS 30S ribosomal protein S19 823 824 experimental:463 database:574
Rv0682 rpsL 30S ribosomal protein S12 818 810 experimental:463 database:573
Rv0710 rpsQ 30S ribosomal protein S17 808 803 experimental:463 database:578
Rv0707 rpsC 30S ribosomal protein S3 808 801 experimental:463 database:578
Rv0721 rpsE 30S ribosomal protein S5 806 799 experimental:463 database:575
Rv0718 rpsH 30S ribosomal protein S8 802 795 experimental:463 database:578
Rv3635 transmembrane protein 796 795 ctx neighborhood:790
Rv0700 rpsJ 30S ribosomal protein S10 798 794 experimental:463 database:557
Rv0717 rpsN1 30S ribosomal protein S14 793 793 experimental:436 database:548

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: UDP-glucose 4-epimerase
  • MTBC0 PGAP product: UDP-glucose 4-epimerase
  • Pfam (hmmscan --cut_ga): RmlD_sub_bind PF04321.24 (E=1e-15), Epimerase PF01370.28 (E=7e-60), GDP_Man_Dehyd PF16363.12 (E=6e-57), 3Beta_HSD PF01073.26 (E=1e-16), Polysacc_synt_2 PF02719.22 (E=5e-10), NAD_binding_10 PF13460.13 (E=2e-08), NAD_binding_4 PF07993.19 (E=2e-05)
  • (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_215015.2)
  • 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_10 (PF13460.13), 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 COG0451
  • Curated reference: UniProt P9WN67 (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 — 104 functional partner(s); context anchor Rv3635
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_003851|Rv3634c|galE1
MRALVTGAAGFIGSTLVDRLLADGHSVVGLDNFATGRATNLEHLADNSAHVFVEADIVTADLHAILEQHRPEVVFHLAAQIDVRRSVADPQFDAAVNVIGTVRLAEAARQTGVRKIVHTSSGGSIYGTPPEYPTPETAPTDPASPYAAGKVAGEIYLNTFRHLYGLDCSHIAPANVYGPRQDPHGEAGVVAIFAQALLSGKPTRVFGDGTNTRDYVFVDDVVDAFVRVSADVGGGLRFNIGTGKETSDRQLHSAVAAAVGGPDDPEFHPPRLGDLKRSCLDIGLAERVLGWRPQIELADGVRRTVEYFRHKHTD