PDXK

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0008478 pyridoxal kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (PAN-GO/IBA) propagation of the core catalytic function. Correct and strongly supported by direct experimental evidence for the human enzyme. Supporting Evidence: file:human/PDXK/PDXK-uniprot.txt Catalyzes the phosphorylation of the dietary vitamin B6
GO:0005829 cytosol	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetically inferred cytosolic localization, consistent with the UniProt-curated subcellular location and with the enzyme's role in cytosolic B6 salvage. Core location. Supporting Evidence: file:human/PDXK/PDXK-uniprot.txt Cytoplasm, cytosol
GO:0009443 pyridoxal 5'-phosphate salvage	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic propagation of the core biological process (PLP salvage). Correct and corroborated by multiple human experimental annotations.
GO:0005829 cytosol	IEA GO_REF:0000044	ACCEPT	Summary: Electronic annotation from the UniProt Subcellular Location mapping, matching the curated "Cytoplasm, cytosol" location. Correct; core location. Supporting Evidence: file:human/PDXK/PDXK-uniprot.txt Cytoplasm, cytosol
GO:0008478 pyridoxal kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic annotation (InterPro/EC/RHEA to GO) of the core molecular function. Correct and redundant with strong experimental evidence.
GO:0009443 pyridoxal 5'-phosphate salvage	IEA GO_REF:0000002	ACCEPT	Summary: InterPro2GO electronic annotation of the core process. Correct; redundant with experimental annotations.
GO:0042816 vitamin B6 metabolic process	IEA GO_REF:0000117	KEEP AS NON CORE	Summary: ARBA electronic annotation to the broader parent process. Biologically correct (PDXK is central to B6 metabolism) but more general than the specific PLP salvage process; retained as a valid, less specific grouping term.
GO:0005654 nucleoplasm	IDA GO_REF:0000052	MARK AS OVER ANNOTATED	Summary: HPA immunofluorescence localization to nucleoplasm. PDXK is a cytosolic B6 salvage enzyme with no known nuclear function; the physiological location is the cytosol. This IF-based nuclear signal is treated as an over-annotation rather than a core location.
GO:0008478 pyridoxal kinase activity	EXP PMID:19351586 Kinetic and structural studies of the role of the active sit...	ACCEPT	Summary: Direct experimental (kinetic and structural) demonstration of pyridoxal kinase activity, including active-site mutagenesis of the catalytic Asp235. Core molecular function. Supporting Evidence: PMID:19351586 Pyridoxal kinase catalyzes the phosphorylation of pyridoxal (PL) to pyridoxal 5'-phosphate (PLP).
GO:0009443 pyridoxal 5'-phosphate salvage	IDA PMID:10987144 Human pyridoxal kinase: overexpression and properties of the...	ACCEPT	Summary: Direct assay of the recombinant human enzyme phosphorylating pyridoxal, supporting the PLP salvage process. Core process. Supporting Evidence: PMID:10987144 Pyridoxal kinase catalyses the phosphorylation of the vitamin B6.
GO:0009443 pyridoxal 5'-phosphate salvage	IC PMID:17766369 Crystal Structure of human pyridoxal kinase: structural basi...	ACCEPT	Summary: Curator inference (from GO:0008478) that the kinase activity operates in the PLP salvage process. Correct; core process.
GO:0009443 pyridoxal 5'-phosphate salvage	IDA PMID:17766369 Crystal Structure of human pyridoxal kinase: structural basi...	ACCEPT	Summary: Direct kinetic/structural characterization of the human enzyme acting on B6 vitamers, supporting participation in PLP salvage. Core process. Supporting Evidence: PMID:17766369 Pyridoxal kinase catalyzes the transfer of a phosphate group from ATP to the 5' alcohol of pyridoxine, pyridoxamine, and pyridoxal.
GO:0009443 pyridoxal 5'-phosphate salvage	IMP PMID:31187503 PDXK mutations cause polyneuropathy responsive to pyridoxal ...	ACCEPT	Summary: Patient loss-of-function variants reduce PDXK activity and lower cellular PLP, demonstrating the enzyme's requirement for PLP salvage in vivo. Core process. Supporting Evidence: PMID:31187503 Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5'-phosphate (PLP) concentrations.
GO:0009443 pyridoxal 5'-phosphate salvage	IDA PMID:9099727 Human pyridoxal kinase. cDNA cloning, expression, and modula...	ACCEPT	Summary: cDNA cloning and expression confirming the protein is human pyridoxal kinase, the salvage enzyme. Core process. Supporting Evidence: PMID:9099727 Transient expression of the cDNA in human embryonic kidney cells confirmed that it encodes human pyridoxal kinase.
GO:0008478 pyridoxal kinase activity	IMP PMID:31187503 PDXK mutations cause polyneuropathy responsive to pyridoxal ...	ACCEPT	Summary: Disease variants (e.g. R220Q, A228T) with decreased pyridoxal kinase activity provide mutational evidence for the core catalytic function. Core molecular function. Supporting Evidence: PMID:31187503 Low PDXK ATP binding resulted in decreased erythrocyte PDXK activity and low pyridoxal 5'-phosphate (PLP) concentrations.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798748	MARK AS OVER ANNOTATED	Summary: Reactome "Exocytosis of secretory granule lumen proteins" (neutrophil degranulation) places PDXK in the extracellular region as part of a bulk secretome pathway. PDXK is a cytosolic enzyme lacking a signal peptide; this is a bystander/secretome annotation, not a functional extracellular location.
GO:0005576 extracellular region	TAS Reactome:R-HSA-6798749	MARK AS OVER ANNOTATED	Summary: Same neutrophil-degranulation secretome context (specific granule variant). Bystander extracellular annotation for a cytosolic enzyme; non-core.
GO:0034774 secretory granule lumen	TAS Reactome:R-HSA-6798748	MARK AS OVER ANNOTATED	Summary: Reactome neutrophil-degranulation secretome mapping. PDXK is cytosolic; its presence in granule-lumen proteomes is incidental and does not reflect a core localization.
GO:0035580 specific granule lumen	TAS Reactome:R-HSA-6798749	MARK AS OVER ANNOTATED	Summary: Reactome neutrophil-degranulation secretome mapping (specific granule). Incidental/bystander localization for a cytosolic enzyme; non-core.
GO:0005634 nucleus	HDA PMID:21630459 Proteomic characterization of the human sperm nucleus.	MARK AS OVER ANNOTATED	Summary: High-throughput MS catalogue of the human sperm nucleus (403 proteins). This is a bulk proteomic detection, not evidence of a functional nuclear role for PDXK; the physiological location is the cytosol. Supporting Evidence: PMID:21630459 403 different proteins have been identified from the isolated sperm nuclei.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	KEEP AS NON CORE	Summary: Detected in an extracellular-vesicle proteome. The protein is plausible EV content, but this is not where it functions. Reason: Cytosolic kinase. Cytosolic protein (UniProt); cytosolic proteins, including abundant enzymes and cytoskeletal proteins, are expected and often promiscuous EV contents (MISEV2018 (PMID:30637094) category 2b). True, but not its core location. (Manual re-review for OMICS_EVIDENCE, 2026-10-10; previous action: MARK_AS_OVER_ANNOTATED.) Supporting Evidence: PMID:19056867 the analysis identified 1132 proteins unambiguously
GO:0005829 cytosol	TAS Reactome:R-HSA-964958	ACCEPT	Summary: Reactome placement of PDXK in the cytosol as part of the B6 activation pathway. Correct; core location.
GO:0005829 cytosol	TAS Reactome:R-HSA-964962	ACCEPT	Summary: Reactome cytosolic placement (B6 activation reaction). Correct; core location.
GO:0005829 cytosol	TAS Reactome:R-HSA-964970	ACCEPT	Summary: Reactome cytosolic placement (B6 activation reaction). Correct; core location.
GO:0005829 cytosol	HDA PMID:16780588 Cell array-based intracellular localization screening reveal...	ACCEPT	Summary: High-throughput chromosome-21 subcellular localization screen; consistent with the curated cytosolic location. Corroborates the core cytosol annotation. Reason: The cached text of this bulk screen names PDXK only in its supplementary table, so the location is corroborated here by the UniProt record, which places PDXK in the cytosol. Supporting Evidence: file:human/PDXK/PDXK-uniprot.txt SUBCELLULAR LOCATION: Cytoplasm, cytosol
GO:0000287 magnesium ion binding	IDA PMID:17766369 Crystal Structure of human pyridoxal kinase: structural basi...	ACCEPT	Summary: Crystal structure of the MgATP complex shows Mg2+ (with Na+) anchoring ATP at the active site. Mg2+ is the physiological divalent cofactor; core supporting molecular function. Supporting Evidence: PMID:17766369 Mg(2+) and Na(+) acting in tandem to anchor the ATP at the active site
GO:0005524 ATP binding	IDA PMID:16600635 Crystal structure of human pyridoxal kinase.	ACCEPT	Summary: Crystal structure of human pyridoxal kinase confirming ATP-dependent phosphotransfer and an ATP-binding pocket. Core supporting molecular function (phosphate donor). Supporting Evidence: PMID:16600635 catalyzes the ATP-dependent phosphorylation reaction of vitamin B6
GO:0005524 ATP binding	IDA PMID:17766369 Crystal Structure of human pyridoxal kinase: structural basi...	ACCEPT	Summary: MgATP complex crystal structure directly demonstrates ATP binding. Core supporting molecular function. Supporting Evidence: PMID:17766369 in complex with MgATP to 2.0 and 2.2 A resolution
GO:0008270 zinc ion binding	IDA PMID:10987144 Human pyridoxal kinase: overexpression and properties of the...	ACCEPT	Summary: Zn2+ is the most effective divalent cation for the human enzyme in vitro; supports metal-ion (Zn2+) binding at the catalytic metal site. Core supporting molecular function (divalent metal cofactor). Supporting Evidence: PMID:10987144 Zn2+ is the most effective divalent cation in the phosphorylation of pyridoxal
GO:0008478 pyridoxal kinase activity	IDA PMID:10987144 Human pyridoxal kinase: overexpression and properties of the...	ACCEPT	Summary: Direct assay of the purified recombinant human enzyme (Km for PL and ATP determined). Core molecular function. Supporting Evidence: PMID:10987144 Pyridoxal kinase catalyses the phosphorylation of the vitamin B6.
GO:0008478 pyridoxal kinase activity	IDA PMID:17766369 Crystal Structure of human pyridoxal kinase: structural basi...	ACCEPT	Summary: Direct kinetic characterization of human pyridoxal kinase acting on the B6 vitamers. Core molecular function. Supporting Evidence: PMID:17766369 Pyridoxal kinase catalyzes the transfer of a phosphate group from ATP to the 5' alcohol of pyridoxine, pyridoxamine, and pyridoxal.
GO:0008478 pyridoxal kinase activity	IDA PMID:9099727 Human pyridoxal kinase. cDNA cloning, expression, and modula...	ACCEPT	Summary: cDNA expression in HEK cells confirming the protein is human pyridoxal kinase, with kinetic characterization (Km 3.3 uM for pyridoxal). Core molecular function. Supporting Evidence: PMID:9099727 confirmed that it encodes human pyridoxal kinase
GO:0030170 pyridoxal phosphate binding	IDA PMID:16600635 Crystal structure of human pyridoxal kinase.	MARK AS OVER ANNOTATED	Summary: PLP is the reaction product and is observed bound in product-complex crystal structures; the annotation captures product binding at the active site rather than a PLP-cofactor role (PDXK does not use PLP as a cofactor). Retained as a real but non-core binding property; risks implying a cofactor function.
GO:0030955 potassium ion binding	IDA PMID:17766369 Crystal Structure of human pyridoxal kinase: structural basi...	KEEP AS NON CORE	Summary: K+ binds the monovalent-cation site and activates the enzyme (increases affinity for substrates and Vmax). A genuine regulatory/activation property but not the core catalytic function; retained as non-core. Supporting Evidence: PMID:17766369 hPLK affinity for ATP and PL is increased manyfold in the presence of K(+)
GO:0030955 potassium ion binding	IDA PMID:9252787 Kinetic studies of the effects of K+, Na+ and Li+ on the cat...	KEEP AS NON CORE	Summary: Erythrocyte pyridoxal kinase kinetics show K+ is the most effective monovalent activator. Real regulatory property; non-core. Supporting Evidence: PMID:9252787 K+ is the most effective, improving both PK affinity for the substrates and maximal velocity
GO:0031402 sodium ion binding	IDA PMID:17766369 Crystal Structure of human pyridoxal kinase: structural basi...	KEEP AS NON CORE	Summary: Na+ occupies the monovalent-cation site in crystal structures (with Mg2+ anchoring ATP) and activates the enzyme. Genuine regulatory/structural property; non-core relative to the catalytic function. Supporting Evidence: PMID:17766369 Mg(2+) and Na(+) acting in tandem to anchor the ATP at the active site
GO:0031402 sodium ion binding	IDA PMID:9252787 Kinetic studies of the effects of K+, Na+ and Li+ on the cat...	KEEP AS NON CORE	Summary: Erythrocyte enzyme kinetics show Na+ is an activator (increases Vmax and ATP affinity). Real regulatory property; non-core. Supporting Evidence: PMID:9252787 Na+ increases maximal velocity and PK affinity for ATP
GO:0031403 lithium ion binding	IDA PMID:9252787 Kinetic studies of the effects of K+, Na+ and Li+ on the cat...	MARK AS OVER ANNOTATED	Summary: Li+ is described as a poor activator that binds a distinct site and can alter the kinetic mechanism; it is not a physiological cofactor. This is an over-annotation of a minor, non-physiological in vitro cation effect. Supporting Evidence: PMID:9252787 Li+ is a poor activator
GO:0042803 protein homodimerization activity	IDA PMID:16600635 Crystal structure of human pyridoxal kinase.	KEEP AS NON CORE	Summary: The crystal structure is a homodimer, consistent with the curated homodimeric quaternary structure. However, a recombinant monomeric form retains catalytic activity, so dimerization is not required for the core function; retained as a genuine but non-core property. Supporting Evidence: PMID:16600635 the structure in dimeric form was well refined
GO:0042803 protein homodimerization activity	IDA PMID:17766369 Crystal Structure of human pyridoxal kinase: structural basi...	KEEP AS NON CORE	Summary: Structural evidence for the homodimer. Real but non-core (dimerization not required for catalysis).

Gene Description

Existing Annotations Review

Core Functions

ATP binding: PDXK binds ATP as the phosphate donor for the kinase reaction; the MgATP complex is coordinated at the active site by Mg2+ and a monovalent cation.

Divalent metal ion binding: PDXK requires a divalent metal cofactor at the active site. Mg2+ coordinates ATP in crystal structures and is the physiological cofactor; Zn2+ is the most effective divalent cation in vitro.

References

📚 Additional Documentation

Notes

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