pfkA Resolved · high auto-curated
H37Rv Rv3010c · MTBC0 mtbc0_003199 ·
343 aa · 3390132–3391163 (-) ·
RefSeq NP_217526.1
Annotation: from legacy to revised
| Legacy (H37Rv / Mycobrowser) | 6-phosphofructokinase |
|---|---|
| MTBC0 PGAP re-annotation | ATP-dependent 6-phosphofructokinase |
| Revised (this work) | ATP-dependent 6-phosphofructokinase. Pfam: PFK (PF00365.26). |
Auto-curated: this verdict and function were generated by rules from PGAP + Pfam + Foldseek and have not been hand-reviewed.
Curated reference (UniProt)
| UniProt |
P9WID7
SwissProt · reviewed
· Evidence at protein level
|
|---|---|
| UniProt name | ATP-dependent 6-phosphofructokinase |
| EC (curated) |
EC 2.7.1.11, EC 2.7.1.144
|
| Curated function | Catalyzes 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. Both sugar phosphates can function equivalently as substrates. Cannot catalyze the reverse gluconeogenic reaction. |
Functional vocabulary (eggNOG-mapper, orthology transfer)
| COG category |
F Nucleotide transport and metabolism
|
|---|---|
| Preferred name | pfkA |
| eggNOG description | Catalyzes the phosphorylation of D-fructose 6-phosphate to fructose 1,6-bisphosphate by ATP, the first committing step of glycolysis |
| Orthologous group | COG0205 |
| EC number |
EC 2.7.1.11, EC 2.7.1.90
|
| KEGG orthology |
K02351, K07245, K21071
|
| KEGG pathways |
map00010, map00030, map00051, map00052, map00680, map01100, map01110, map01120, map01130
|
| Gene Ontology (8) |
GO:0005575, GO:0005618, GO:0005623, GO:0005886, GO:0016020, GO:0030312, 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 | 0.208 · purifying |
|---|---|
| Polymorphic sites (≥ 0.1% of strains) | 5 synonymous, 3 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 |
|---|---|---|---|---|
PFK | PF00365.26 | 4.0e-106 | 2–298 | Phosphofructokinase |
Functional interaction network (STRING v12, guilt-by-association)
Closest characterised functional partner: gatB (aspartyl/glutamyl-tRNA(Asn/Gln) amidotransferase subunit B), high confidence from genomic context alone (score 801 excluding text-mining).
| Partner | Product | Score | No text-mining | Channels (≥400) |
|---|---|---|---|---|
Rv0946c pgi |
glucose-6-phosphate isomerase | 995 | 981 | coexpression:779 database:900 textmining:748 |
Rv0363c fba |
fructose-bisphosphate aldolase | 977 | 948 | database:900 textmining:595 |
Rv3396c guaA |
GMP synthase | 943 | 923 | coexpression:923 |
Rv2029c pfkB |
6-phosphofructokinase PfkB | 972 | 920 | database:900 textmining:675 |
Rv1449c tkt |
transketolase | 949 | 911 | database:900 textmining:453 |
Rv1448c tal |
transaldolase | 952 | 907 | database:900 textmining:514 |
Rv1099c glpX |
fructose 1,6-bisphosphatase | 960 | 903 | database:900 textmining:607 |
Rv3255c manA |
mannose-6-phosphate isomerase | 916 | 903 | database:900 |
Rv1617 pykA |
pyruvate kinase | 963 | 898 | coexpression:838 textmining:655 |
Rv1438 tpi |
triosephosphate isomerase | 945 | 811 | coexpression:707 textmining:725 |
Rv1023 eno |
enolase | 939 | 801 | coexpression:785 textmining:707 |
Rv3009c gatB |
aspartyl/glutamyl-tRNA(Asn/Gln) amidotransferase subunit B | 881 | 801 ctx | neighborhood:743 textmining:431 |
Rv1436 gap |
glyceraldehyde 3-phosphate dehydrogenase | 903 | 775 | coexpression:648 textmining:590 |
Rv1437 pgk |
phosphoglycerate kinase | 880 | 748 | coexpression:652 textmining:545 |
Rv1328 glgP |
glycogen phosphorylase | 790 | 727 | coexpression:676 |
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
- MTBC0 PGAP product: ATP-dependent 6-phosphofructokinase
- Pfam (hmmscan --cut_ga): PFK PF00365.26 (E=4e-106)
- (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_217526.1)
- Domains: Pfam-A via hmmscan --cut_ga — PFK (PF00365.26)
- 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
COG0205 - Curated reference: UniProt P9WID7 (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 —
86 functional partner(s); context anchor
gatB - Primary literature: none located yet; annotation rests on the domain/homology sources above.
Ancestral MTBC0 protein sequence
>mtbc0_003199|Rv3010c|pfkA MRIGVLTGGGDCPGLNAVIRAVVRTCHARYGSSVVGFQNGFRGLLENRRVQLHNDDRNDRLLAKGGTMLGTARVHPDKLRAGLPQIMQTLDDNGIDVLIPIGGEGTLTAASWLSEENVPVVGVPKTIDNDIDCTDVTFGHDTALTVATEAIDRLHSTAESHERVMLVEVMGRHAGWIALNAGLASGAHMTLIPEQPFDIEEVCRLVKGRFQRGDSHFICVVAEGAKPAPGTIMLREGGLDEFGHERFTGVAAQLAVEVEKRINKDVRVTVLGHIQRGGTPTAYDRVLATRFGVNAADAAHAGEYGQMVTLRGQDIGRVPLADAVRKLKLVPQSRYDDAAAFFG