pfkB Family assigned · medium auto-curated

H37Rv Rv2029c · MTBC0 mtbc0_002162 · 339 aa · 2304018–2305037 (-) · RefSeq NP_216545.1

Annotation: from legacy to revised

Legacy (H37Rv / Mycobrowser)6-phosphofructokinase PfkB
MTBC0 PGAP re-annotation1-phosphofructokinase family hexose kinase
Revised (this work)1-phosphofructokinase family hexose kinase. Pfam: PfkB (PF00294.30).

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

Curated reference (UniProt)

UniProt P9WID3 SwissProt · reviewed · Evidence at protein level
UniProt nameATP-dependent 6-phosphofructokinase isozyme 2
EC (curated) EC 2.7.1.11, EC 2.7.1.144
Curated functionCatalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis. Can also catalyze the phosphorylation of tagatose-6-phosphate. The catalytic efficiency with tagatose-6-phosphate is about 1.8 times lower than that with fructose 6-phosphate. Can use phosphate donors other than ATP (GTP and ITP), with lower efficiency. In addition, can catalyze the reverse gluconeogenic reaction, albeit with low efficiency. May support and maintain basic glycolysis and metabolic fluxes during conditions inhibiting PfkA.

Functional vocabulary (eggNOG-mapper, orthology transfer)

COG category H Coenzyme transport and metabolism
Preferred namepfkB
eggNOG descriptionbelongs to the carbohydrate kinase PfkB family
Orthologous groupCOG1105
EC number EC 2.7.1.11, EC 2.7.1.144, EC 2.7.1.56
KEGG orthology K00882, K00917, K16370
KEGG pathways map00010, map00030, map00051, map00052, map00680, map01100, map01110, map01120, map01130, map01200, map01230
KEGG modules M00001, M00345
Gene Ontology (26) GO:0003674, GO:0003824, GO:0005575, GO:0005622, GO:0005623, GO:0005737, GO:0005829, GO:0005975, GO:0006793, GO:0006796, GO:0008150, GO:0008152 +14 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 0.432 · purifying
Polymorphic sites (≥ 0.1% of strains) 5 synonymous, 5 missense, 1 nonsense, 0 frameshift
Disruption 1 distinct premature-stop/frameshift site(s); most common in 0.34% of strains (497) · 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)

PfamAccessioni-EvalueResiduesDescription
PfkBPF00294.30 4.3e-6118–306 pfkB family carbohydrate kinase

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

Closest characterised functional partner: Rv2028c (universal stress protein), high confidence from genomic context alone (score 983 excluding text-mining).

PartnerProductScoreNo text-miningChannels (≥400)
Rv2030c hyp hypothetical protein 996 984 ctx neighborhood:865 coexpression:860 textmining:800
Rv2028c universal stress protein 993 983 ctx neighborhood:882 coexpression:860 textmining:630
Rv1448c tal transaldolase 954 940 coexpression:427 database:900
Rv0363c fba fructose-bisphosphate aldolase 967 939 database:900 textmining:481
Rv3010c pfkA 6-phosphofructokinase 972 920 database:900 textmining:675
Rv0946c pgi glucose-6-phosphate isomerase 954 909 database:900 textmining:518
Rv1449c tkt transketolase 935 907 database:900
Rv3255c manA mannose-6-phosphate isomerase 917 906 database:900
Rv2032 acg NAD(P)H nitroreductase 922 900 ctx neighborhood:470 coexpression:819
Rv1099c glpX fructose 1,6-bisphosphatase 906 900 database:900
Rv2006 otsB1 trehalose-6-phosphate phosphatase OtsB 898 896 ctx neighborhood:460 coexpression:781
Rv1997 ctpF cation transporter ATPase F 908 889 coexpression:860
Rv2625c rip3 zinc metalloprotease Rip3 880 866 coexpression:860
Rv1736c narX nitrate reductase-like protein NarX 888 860 coexpression:860
Rv2624c universal stress protein 857 857 coexpression:855

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: 6-phosphofructokinase PfkB
  • MTBC0 PGAP product: 1-phosphofructokinase family hexose kinase
  • Pfam (hmmscan --cut_ga): PfkB PF00294.30 (E=4e-61)
  • (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_216545.1)
  • Domains: Pfam-A via hmmscan --cut_ga — PfkB (PF00294.30)
  • 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 COG1105
  • Curated reference: UniProt P9WID3 (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 — 101 functional partner(s); context anchor Rv2028c
  • Primary literature: none located yet; annotation rests on the domain/homology sources above.

Ancestral MTBC0 protein sequence

>mtbc0_002162|Rv2029c|pfkB
MTEPAAWDEGKPRIITLTMNPALDITTSVDVVRPTEKMRCGAPRYDPGGGGINVARIVHVLGGCSTALFPAGGSTGSLLMALLGDAGVPFRVIPIAASTRESFTVNESRTAKQYRFVLPGPSLTVAEQEQCLDELRGAAASAAFVVASGSLPPGVAADYYQRVADICRRSSTPLILDTSGGGLQHISSGVFLLKASVRELRECVGSELLTEPEQLAAAHELIDRGRAEVVVVSLGSQGALLATRHASHRFSSIPMTAVSGVGAGDAMVAAITVGLSRGWSLIKSVRLGNAAGAAMLLTPGTAACNRDDVERFFELAAEPTEVGQDQYVWHPIVNPEASP