Uncharacterized sugar kinase belonging to the PfkB/ribokinase carbohydrate kinase family (COG0524). UniProt assigns EC 2.7.1.- indicating it is a phosphotransferase with an alcohol group as acceptor, but the specific sugar substrate is unknown. The protein contains the PfkB domain (Pfam PF00294) and matches InterPro signatures for the ribokinase/fructokinase superfamily (IPR002139, IPR002173, IPR011611). CDD classifies it in the YegV_kinase_like subfamily (cd01944). yegV is transcribed as part of the yegTUV operon (~3.3 kb), which is repressed by the single-target regulator GgaR/YegW and derepressed by ADP-glucose (ADPG). Deletion of ggaR increases yegTUV mRNA ~30-fold and increases glycogen accumulation, linking YegV to carbon/glycogen metabolism. De Crecy-Lagard et al. 2025 (PMID:40703034) highlighted YegV as a case where computational methods (DeepECTF) incorrectly predicted the specific substrate as EC 2.7.1.92 (dehydro-2-deoxygluconokinase), when in fact that activity belongs to KdgK (b3526). This illustrates the challenge of distinguishing substrate specificity among nonisofunctional paralogs within the PfkB superfamily. No experimental characterization of YegV enzymatic activity or substrate has been published to date.
Existing Annotations Review
GO Term
Evidence
Action
Reason
GO:0006796 phosphate-containing compound metabolic process
IEA GO_REF:0000117
ACCEPT
Summary: IEA annotation from ARBA machine learning models mapping YegV to phosphate-containing compound metabolic process. This is a very broad biological process term that encompasses any metabolic process involving phosphate groups. As a predicted kinase (EC 2.7.1.-), YegV would indeed participate in phosphate-containing compound metabolism by catalyzing phosphoryl transfer from ATP to a sugar substrate.
Reason: This is a very general biological process annotation that is consistent with the predicted kinase function of YegV. While broad, it is not incorrect for a member of the PfkB kinase family. The annotation correctly reflects that YegV is involved in some form of phosphorylation, even though the specific substrate and pathway are unknown. For an uncharacterized enzyme, this level of generality is appropriate and avoids over-annotation.
Summary: IEA annotation from InterPro2GO mapping based on InterPro signatures IPR002139 (ribokinase/fructokinase) and IPR002173 (carbohydrate/purine kinase PfkB conserved site). YegV belongs to the PfkB/ribokinase family, and UniProt assigns EC 2.7.1.- (phosphotransferase with OH group as acceptor) based on sequence similarity.
Reason: While kinase activity (GO:0016301) is not wrong, a more informative term is available. YegV is specifically annotated by UniProt as an "uncharacterized sugar kinase" belonging to the PfkB carbohydrate kinase family (Pfam PF00294). CDD classifies it in the YegV_kinase_like subfamily (cd01944). The term GO:0019200 (carbohydrate kinase activity), defined as "catalysis of the transfer of a phosphate group to a carbohydrate", would be more specific and appropriate. This term correctly captures the sugar kinase function predicted from domain architecture without specifying an incorrect substrate. De Crecy-Lagard et al. 2025 (PMID:40703034) specifically noted that while the first three digits of the EC number (2.7.1) are reliably predicted for YegV, the specific substrate (4th digit) is unknown, making GO:0019200 the right level of specificity.
b2100 was annotated as a dehydro-2-deoxygluconokinase (EC 2.7.1.92) using DeepECTF and as an uncharacterized sugar kinase YegV (EC 2.7.1.-) in UniProt (Supplementary Table 1b). These 2 predictions differ by the fourth or last position of the EC number that specifies substrate specificity. This protein is a member of a superfamily of sugar kinases with multiple nonisofunctional paralogous subgroups that phosphorylate different substrates
GO:0016772 transferase activity, transferring phosphorus-containing groups
IEA GO_REF:0000117
ACCEPT
Summary: IEA annotation from ARBA mapping YegV to transferase activity transferring phosphorus-containing groups (GO:0016772). This is the direct parent of kinase activity (GO:0016301) in the GO hierarchy: catalytic activity > transferase activity > transferase activity, transferring phosphorus-containing groups > kinase activity.
Reason: This is a correct but general parent term for kinase activity. As YegV belongs to the PfkB kinase family and UniProt assigns EC 2.7.1.-, it is indeed a transferase that transfers phosphorus-containing groups. While less informative than GO:0016301 (kinase activity) or GO:0019200 (carbohydrate kinase activity), it is not wrong and is acceptable as a broader IEA annotation that is hierarchically consistent with the more specific kinase annotations.
ISS PMID:40703034 Limitations of current machine learning models in predicting...
NEW
Summary: New annotation proposed based on domain architecture and family membership. YegV is a member of the PfkB/ribokinase carbohydrate kinase family (COG0524, Pfam PF00294). UniProt names it "uncharacterized sugar kinase YegV" with EC 2.7.1.- (phosphotransferase with OH acceptor, substrate unknown). CDD assigns it to the YegV_kinase_like subfamily (cd01944). De Crecy-Lagard et al. 2025 (PMID:40703034) confirmed the first three EC digits (2.7.1) are reliable for this protein, placing it firmly in the carbohydrate kinase class, while noting the specific substrate remains unknown.
Reason: GO:0019200 (carbohydrate kinase activity) is the most informative molecular function term that can be applied without over-specifying the substrate. This term captures the sugar kinase function predicted from multiple independent lines of evidence: PfkB domain (Pfam PF00294), InterPro ribokinase/fructokinase signatures (IPR002139), COG0524 membership, CDD YegV_kinase_like classification (cd01944), and UniProt naming as "uncharacterized sugar kinase." It avoids the error of specifying a particular sugar substrate, which PMID:40703034 demonstrated leads to incorrect annotations due to paralog confusion within this large superfamily.
This protein is a member of a superfamily of sugar kinases with multiple nonisofunctional paralogous subgroups that phosphorylate different substrates (Supplementary Table 1d, bottom). The dehydro-2-deoxygluconokinase (EC 2.7.1.92) activity is encoded by another member of this superfamily KdgK/b3526 (Supplementary Table 1d, bottom). Here, DeepECTF predicted correctly the first 3 digits of the EC number but not the last, making an overpropagation mistake
file:ECOLI/yegV/yegV-deep-research-falcon.md
Falcon deep research confirms yegV as a putative sugar kinase in the yegTUV operon regulated by GgaR/YegW in response to ADPG, linking it to glycogen metabolism. No direct enzymology for YegV exists; the carbohydrate kinase annotation is the most specific term supported by domain architecture.
Core Functions
Predicted carbohydrate kinase activity - YegV is an uncharacterized member of the PfkB/ribokinase carbohydrate kinase family that likely catalyzes phosphorylation of an unknown sugar substrate using ATP as the phosphoryl donor. The specific sugar substrate has not been experimentally determined.
Q: What is the specific sugar substrate of YegV? Metabolomic profiling of yegV knockout strains under various carbon sources could reveal accumulated substrates.
Suggested experts: de Crecy-Lagard V
Q: Is there a specific growth condition or carbon source where yegV expression is induced, which would provide clues to its physiological substrate?
Suggested experts: Mori H
Suggested Experiments
Experiment: Express and purify recombinant YegV, then screen for kinase activity against a panel of monosaccharides and sugar derivatives (including ribose, fructose, galactose, gluconate derivatives, and other PfkB family substrates) using a coupled enzyme assay that monitors ADP production. Include divalent cations (Mg2+, Mn2+) and monovalent cations (K+) as the PfkB family typically requires these for activity.
Hypothesis: YegV phosphorylates a specific monosaccharide or sugar derivative that can be identified through substrate screening
Type: In vitro substrate screening with coupled enzyme assay
Experiment: Perform growth phenotyping of a yegV deletion strain on a diverse panel of carbon sources (Biolog phenotype microarray) to identify conditions where YegV is required for growth, thereby providing clues to its substrate and metabolic pathway.
Hypothesis: Deletion of yegV causes a growth defect under specific nutrient conditions that reveal its physiological role
Type: Phenotype microarray carbon source screen
External Prediction Reviews
These computational predictions are reviewed separately from the GOA annotation set used for this review. The assessments below are from this project and do not constitute official GO annotations or endorsement by GO/UniProt. They are not included in the existing annotation review above.
YegV DeepECTF prediction review. The DeepECTF prediction of dehydro-2-deoxygluconokinase (EC 2.7.1.92) is a paralog overannotation error. YegV is correctly identified as a sugar kinase (first 3 EC digits correct) but the specific substrate assignment is wrong - that activity belongs to KdgK/b3526. YegV's substrate specificity remains unknown.
Review score: 2 = concordant with evidence; 1 = uncertain; 0 = discordant with evidence. This is an assessment score, not a model probability.
Review rationale: Paralog incorrect. YegV is annotated as an uncharacterized sugar kinase (EC 2.7.1.-) in UniProt, so DeepECTF correctly predicted the first 3 digits of the EC number but assigned the wrong substrate specificity. The dehydro-2-deoxygluconokinase (EC 2.7.1.92) activity is already encoded by KdgK/b3526, a different member of the same sugar kinase superfamily. This is a classic overpropagation mistake (error type 6) - failing to distinguish nonisofunctional paralogous subgroups within the superfamily.
Supporting Evidence:
PMID:40703034: "b2100 was annotated as a dehydro-2-deoxygluconokinase (EC 2.7.1.92) using DeepECTF...The dehydro-2-deoxygluconokinase (EC 2.7.1.92) activity is encoded by another member of this superfamily KdgK/b3526"
PMID:40703034: "Here, DeepECTF predicted correctly the first 3 digits of the EC number but not the last, making an overpropagation mistake"