NAGK

Existing Annotations Review

GO Term	Evidence	Action	Reason
GO:0045127 N-acetylglucosamine kinase activity	IBA GO_REF:0000033	ACCEPT	Summary: Phylogenetic (PAN-GO) inference of the core molecular function. This is the well-established, experimentally confirmed catalytic activity of NAGK (GlcNAc + ATP -> GlcNAc-6-phosphate, EC 2.7.1.59) and is correct. Supporting Evidence: file:human/NAGK/NAGK-uniprot.txt N-acetyl-D-glucosamine + ATP = N-acetyl-D-glucosamine 6-
GO:0006044 N-acetylglucosamine metabolic process	IEA GO_REF:0000117	ACCEPT	Summary: ARBA electronic annotation to the general amino-sugar metabolic process. This is correct and captures the core biological role (GlcNAc salvage into the hexosamine pathway), though it is a broad grouping term; the more specific catabolic/UDP-GlcNAc biosynthetic children are also annotated (IMP, PMID 34844667). Supporting Evidence: file:human/NAGK/NAGK-uniprot.txt Converts endogenous N-acetylglucosamine (GlcNAc), a major
GO:0009384 N-acylmannosamine kinase activity	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic (EC 2.7.1.60 / Rhea) mapping of the N-acetylmannosamine (ManNAc) kinase side activity, which is real (reported biochemically for the recombinant enzyme in PMID 10824116 and captured as a By-similarity catalytic activity in UniProt). ManNAc kinase is a secondary/salvage activity of NAGK rather than its principal in vivo role (canonical ManNAc phosphorylation is via GNE/MNK), so it is not part of the core function. Supporting Evidence: file:human/NAGK/NAGK-uniprot.txt Also has N-acetylmannosamine (ManNAc) kinase
GO:0045127 N-acetylglucosamine kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (EC 2.7.1.59 / Rhea / InterPro) mapping of the core GlcNAc kinase activity. Redundant with the experimental (IDA/IMP) and IBA annotations to the same term but correct. Supporting Evidence: file:human/NAGK/NAGK-uniprot.txt N-acetyl-D-glucosamine + ATP = N-acetyl-D-glucosamine 6-
GO:0005515 protein binding	IPI PMID:16189514 Towards a proteome-scale map of the human protein-protein in...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a large-scale human interactome mapping study (CCSB). Uninformative for molecular function and does not identify a specific binding partner role; not core. Per policy, IPI protein-binding is retained but marked over-annotated rather than removed.
GO:0005515 protein binding	IPI PMID:21516116 Next-generation sequencing to generate interactome datasets.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a high-throughput NGS-based interactome dataset. Uninformative; not core.
GO:0005515 protein binding	IPI PMID:25416956 A proteome-scale map of the human interactome network.	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from the HI-II-14 proteome-scale human interactome map. Uninformative; not core.
GO:0005515 protein binding	IPI PMID:29892012 An interactome perturbation framework prioritizes damaging m...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from an interactome-perturbation framework study. Uninformative; not core.
GO:0005515 protein binding	IPI PMID:31515488 Extensive disruption of protein interactions by genetic vari...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" from a variant-interaction disruption screen. Uninformative; not core.
GO:0005515 protein binding	IPI PMID:37511433 N-Acetylglucosamine Kinase-Small Nuclear Ribonucleoprotein P...	MARK AS OVER ANNOTATED	Summary: Bare "protein binding" (interaction with SNRPN, UniProtKB Q9UJ70/P63164) supporting the kinase-independent, neuron-specific structural role of NAGK in dynein-mediated dendrite branching. The interaction is real and directly demonstrated (His/GST pull-down, Co-IP), but the term is uninformative bare protein binding and the role is a non-core moonlighting function. Retained but marked over-annotated.
GO:0070434 positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic (ARBA, projected from mouse Q9QZ08) annotation of the NAGK-dependent activation of NOD2 signaling. This is a genuine, experimentally supported role (see the IDA to the same term from PMID 36002575) but is a context-specific innate-immunity moonlight, not the core metabolic function. Supporting Evidence: file:human/NAGK/NAGK-uniprot.txt detection of bacterial peptidoglycan by NOD2: acts by catalyzing
GO:0160047 muramyl dipeptide kinase activity	IEA GO_REF:0000120	ACCEPT	Summary: Electronic (ARBA / Rhea, projected from mouse) mapping of the muramyl dipeptide kinase activity. This is experimentally established (IDA from PMID 36002575, recombinant human NAGK phosphorylates MDP/MurNAc in vitro). Same catalytic chemistry as GlcNAc phosphorylation applied to the MurNAc sugar of MDP; correct. Supporting Evidence: file:human/NAGK/NAGK-uniprot.txt phosphorylation of muramyl dipeptide (MDP), a fragment of bacterial
GO:0019262 N-acetylneuraminate catabolic process	IEA GO_REF:0000120	KEEP AS NON CORE	Summary: Electronic (ARBA / UniPathway UPA00629) annotation to the N-acetylneuraminate (sialic acid) degradation pathway. NAGK contributes to the degradation of the dietary non-human sialic acid Neu5Gc by phosphorylating GlcNAc/GlcNGc (Reactome R-HSA-6803771; PMID 22692205). This is a narrow, context-specific catabolic role, not the core function. Supporting Evidence: file:human/NAGK/NAGK-uniprot.txt Amino-sugar metabolism; N-acetylneuraminate degradation.
GO:0006046 N-acetylglucosamine catabolic process	IMP PMID:34844667 Glutamine deprivation triggers NAGK-dependent hexosamine sal...	ACCEPT	Summary: Experimental (IMP) annotation from the eLife hexosamine-salvage study. NAGK deletion impairs the salvage of free GlcNAc into downstream metabolites, supporting a role in GlcNAc catabolism/utilization. Part of the core amino-sugar salvage function. Supporting Evidence: PMID:34844667 GlcNAc salvage via PMID:34844667 NAGK deletion from PDA cells impairs
GO:0006048 UDP-N-acetylglucosamine biosynthetic process	IMP PMID:34844667 Glutamine deprivation triggers NAGK-dependent hexosamine sal...	ACCEPT	Summary: Experimental (IMP) annotation. Under glutamine limitation, NAGK-mediated GlcNAc salvage feeds the UDP-GlcNAc pool; NAGK deletion reduces salvage-derived UDP-GlcNAc and impairs tumor growth. This is the salvage arm of UDP-GlcNAc biosynthesis and is part of the core biological role. Supporting Evidence: PMID:34844667 N-acetylglucosamine kinase (NAGK) is engaged to feed UDP-GlcNAc pools PMID:34844667 GlcNAc salvage feeds UDP-GlcNAc pools
GO:0045127 N-acetylglucosamine kinase activity	IMP PMID:34844667 Glutamine deprivation triggers NAGK-dependent hexosamine sal...	ACCEPT	Summary: Experimental (IMP) support for the core GlcNAc kinase activity from loss-of-function (NAGK deletion) in the hexosamine-salvage study. Correct core molecular function. Supporting Evidence: PMID:34844667 GlcNAc salvage via
GO:0032495 response to muramyl dipeptide	IDA PMID:36002575 Phosphorylation of muramyl peptides by NAGK is required for ...	KEEP AS NON CORE	Summary: Direct experimental annotation. NAGK is essential for the cellular response to MDP; NAGK-deficient cells and macrophages fail to respond to MDP. Genuine innate-immunity role but non-core relative to the metabolic kinase function. Supporting Evidence: PMID:36002575 completely deficient in MDP sensing
GO:0042742 defense response to bacterium	IDA PMID:36002575 Phosphorylation of muramyl peptides by NAGK is required for ...	KEEP AS NON CORE	Summary: Direct experimental annotation. By generating the NOD2 agonist 6-O-phospho-MDP, NAGK is required for detection of bacterial peptidoglycan and the ensuing pro-inflammatory defense response (loss of response to purified S. aureus and E. coli PGN in NAGK-knockout cells). Genuine but non-core (immunity moonlight). Supporting Evidence: PMID:36002575 constitutes an agonist for NOD2
GO:0070434 positive regulation of nucleotide-binding oligomerization domain containing 2 signaling pathway	IDA PMID:36002575 Phosphorylation of muramyl peptides by NAGK is required for ...	KEEP AS NON CORE	Summary: Direct experimental annotation. NAGK functions upstream of NOD2, and its kinase activity (catalytic-dead D107V fails to rescue) is required for NOD2 activation by MDP. Genuine positive regulation of NOD2 signaling; non-core innate-immunity role. Supporting Evidence: PMID:36002575 did not rescue NOD2 signalling in NAGK-deficient cells
GO:0160047 muramyl dipeptide kinase activity	IDA PMID:36002575 Phosphorylation of muramyl peptides by NAGK is required for ...	ACCEPT	Summary: Direct experimental demonstration that recombinant human NAGK phosphorylates muramyl dipeptide (and MurNAc) in vitro, at the MurNAc C6 hydroxyl, yielding 6-O-phospho-MDP. This is a distinct, well-supported catalytic activity mechanistically identical to GlcNAc-6-OH phosphorylation. Correct. Supporting Evidence: PMID:36002575 NAGK readily phosphorylated MDP and the related molecule N-acetylmuramic acid PMID:36002575 in an in vitro kinase assay with various substrates
GO:0005829 cytosol	TAS Reactome:R-HSA-6803771	ACCEPT	Summary: NAGK is a soluble cytosolic enzyme (Reactome, consistent with its role in cytosolic amino-sugar salvage and with cytosolic activity in the Neu5Gc study). Correct core localization.
GO:0070062 extracellular exosome	HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos...	MARK AS OVER ANNOTATED	Summary: High-throughput mass-spectrometric detection of NAGK in urinary exosomes. Abundant cytosolic enzymes are commonly detected in exosome/secretome proteomics; this does not reflect a functional extracellular localization and is not core. Supporting Evidence: PMID:19056867 urinary exosomes
GO:0019262 N-acetylneuraminate catabolic process	TAS PMID:22692205 Metabolism of vertebrate amino sugars with N-glycolyl groups...	KEEP AS NON CORE	Summary: Author-asserted (TAS) role in the degradation of the dietary non-human sialic acid Neu5Gc, where NAGK phosphorylates GlcNAc/GlcNGc to their 6-phosphates. A narrow, context-specific catabolic role; genuine but non-core. Supporting Evidence: file:human/NAGK/NAGK-uniprot.txt Amino-sugar metabolism; N-acetylneuraminate degradation.
GO:0045127 N-acetylglucosamine kinase activity	IDA PMID:22692205 Metabolism of vertebrate amino sugars with N-glycolyl groups...	ACCEPT	Summary: Direct experimental demonstration of GlcNAc kinase activity by recombinant human NAGK (also the basis for the UniProt EC 2.7.1.59 experimental assignment, ECO 0000269 / PubMed 22692205). Core molecular function. Supporting Evidence: file:human/NAGK/NAGK-uniprot.txt N-acetyl-D-glucosamine + ATP = N-acetyl-D-glucosamine 6-
GO:0006044 N-acetylglucosamine metabolic process	TAS PMID:10824116 Molecular cloning and characterization of murine and human N...	ACCEPT	Summary: Author-asserted role from the original cloning/characterization paper, which established that GlcNAc enters amino-sugar metabolism through the action of NAGK. Correct core biological process (broad grouping term). Supporting Evidence: PMID:10824116 pathways of aminosugar metabolism by the action of N-acetylglucosamine kinase
GO:0006051 N-acetylmannosamine metabolic process	TAS PMID:10824116 Molecular cloning and characterization of murine and human N...	KEEP AS NON CORE	Summary: Author-asserted BP reflecting the ManNAc kinase side activity reported for the recombinant enzyme in the same paper. A secondary/salvage activity (canonical ManNAc phosphorylation is via GNE/MNK), so non-core. Supporting Evidence: PMID:10824116 N-acetylglucosamine kinase activity as well as N-acetylmannosamine

Gene Description

Existing Annotations Review

Core Functions

ATP-dependent phosphorylation of free N-acetyl-D-glucosamine (GlcNAc) to GlcNAc 6-phosphate, the salvage entry point of amino-sugar/hexosamine metabolism that recycles GlcNAc into the UDP-GlcNAc pool.

Uses ATP as phosphate donor for its sugar-kinase reactions.

Phosphorylation of the N-acetylmuramic acid C6 hydroxyl of bacterial muramyl dipeptide (MDP) to generate 6-O-phospho-MDP, the agonist that activates NOD2 in innate immune sensing of peptidoglycan.

References

📚 Additional Documentation

Notes

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