glpX Resolved · high auto-curated

H37Rv Rv1099c · MTBC0 mtbc0_001182 · 362 aa · 1236036–1237124 (-) · RefSeq NP_215615.3

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)fructose 1,6-bisphosphatase
MTBC0 PGAP re-annotationclass II fructose-bisphosphatase
Revised (this work)Class II fructose-bisphosphatase. Pfam: FBPase_glpX (PF03320.19).

Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.

Curated reference (UniProt)

UniProt P9WN21 SwissProt · reviewed · Evidence at protein level
UniProt nameFructose-1,6-bisphosphatase class 2
EC (curated) EC 3.1.3.11
Curated functionCatalyzes the hydrolysis of fructose 1,6-bisphosphate to fructose 6-phosphate. Seems to be the major FBPase of M.tuberculosis and to play a key role in gluconeogenesis for conversion of lipid carbon into cell wall glycans. Does not display activity against inositol 1-phosphate.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category G Carbohydrate transport and metabolism
Preferred nameglpX
eggNOG descriptionfructose-1,6-bisphosphatase
Orthologous groupCOG1494
EC number EC 3.1.3.11
KEGG orthology K02446
KEGG pathways map00010, map00030, map00051, map00680, map00710, map01100, map01110, map01120, map01130, map01200
KEGG modules M00003, M00165, M00167
Gene Ontology (48) GO:0000287, GO:0003674, GO:0003824, GO:0005488, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005975, GO:0005996, GO:0006006 +36 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 0.114 · 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
FBPase_glpXPF03320.19 4.5e-14331–338 Bacterial fructose-1,6-bisphosphatase, glpX-encoded

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

Closest characterised functional partner: tkt (transketolase), high confidence from genomic context alone (score 945 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv1449c tkt transketolase 974 945 ctx fusion:418 database:900 textmining:562
Rv0363c fba fructose-bisphosphate aldolase 947 915 database:900 textmining:414
Rv1448c tal transaldolase 950 908 database:900 textmining:484
Rv3010c pfkA 6-phosphofructokinase 960 903 database:900 textmining:607
Rv0946c pgi glucose-6-phosphate isomerase 954 903 database:900 textmining:549
Rv3255c manA mannose-6-phosphate isomerase 904 901 database:900
Rv2029c pfkB 6-phosphofructokinase PfkB 906 900 database:900
Rv1098c fum fumarate hydratase 894 856 ctx neighborhood:839
Rv1097c hyp hypothetical protein 821 821 ctx neighborhood:816
Rv1100 hyp hypothetical protein 874 655 ctx neighborhood:655 textmining:652
Rv2299c htpG chaperone protein HtpG 452 452 experimental:444
Rv2773c dapB 4-hydroxy-tetrahydrodipicolinate reductase 570 416 coexpression:416
Rv1416 ribH 6,7-dimethyl-8-ribityllumazine synthase 574 277 textmining:436
Rv1659 argH argininosuccinate lyase 419 275
Rv1240 mdh malate dehydrogenase 466 188

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: fructose 1,6-bisphosphatase
  • MTBC0 PGAP product: class II fructose-bisphosphatase
  • Pfam (hmmscan --cut_ga): FBPase_glpX PF03320.19 (E=5e-143)
  • (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_215615.3)
  • Domains: Pfam-A via hmmscan --cut_ga — FBPase_glpX (PF03320.19)
  • 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 COG1494
  • Curated reference: UniProt P9WN21 (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 — 32 functional partner(s); context anchor tkt
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_001182|Rv1099c|glpX
MTAEGSGSSTAAVASHDPSHTRPSRREAPDRNLAMELVRVTEAGAMAAGRWVGRGDKEGGDGAAVDAMRELVNSVSMRGVVVIGEGEKDHAPMLYNGEEVGNGDGPECDFAVDPIDGTTLMSKGMTNAISVLAVADRGTMFDPSAVFYMNKIAVGPDAAHVLDITAPISENIRAVAKVKDLSVRDMTVCILDRPRHAQLIHDVRATGARIRLITDGDVAGAISACRPHSGTDLLAGIGGTPEGIIAAAAIRCMGGAIQAQLAPRDDAERRKALEAGYDLNQVLTTEDLVSGENVFFCATGVTDGDLLKGVRYYPGGCTTHSIVMRSKSGTVRMIEAYHRLSKLNEYSAIDFTGDSSAVYPLP