id: Q9Y223
gene_symbol: GNE
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  GNE is the bifunctional UDP-N-acetylglucosamine 2-epimerase / N-acetylmannosamine
  kinase, a cytosolic enzyme that catalyzes the first two committed and rate-limiting
  steps of de novo sialic acid (N-acetylneuraminic acid, Neu5Ac) biosynthesis. Its
  N-terminal epimerase domain converts UDP-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc)
  and water to N-acetyl-D-mannosamine (ManNAc), UDP and a proton (a hydrolyzing
  2-epimerase, EC 3.2.1.183); its C-terminal ROK-family kinase domain then
  phosphorylates ManNAc with ATP to ManNAc-6-phosphate (EC 2.7.1.60). ManNAc-6-P feeds
  the downstream enzymes (NANS, NANP, CMAS) that produce CMP-Neu5Ac, the activated
  sialic-acid donor used by sialyltransferases, so GNE governs overall cell-surface
  sialylation. The epimerase activity is allosterically feedback-inhibited by the
  end product CMP-Neu5Ac, making GNE the rate-controlling step of the pathway. The
  active enzyme is oligomeric (dimer/tetramer/hexamer), requires a divalent cation for
  the kinase reaction, and is expressed most highly in liver and placenta. Loss-of-function
  variants cause the recessive muscle disorder GNE myopathy (Nonaka myopathy / hereditary
  inclusion body myopathy / distal myopathy with rimmed vacuoles) and recessive
  thrombocytopenia, both from muscle or platelet hyposialylation; dominant variants in the
  allosteric site abolish CMP-Neu5Ac feedback and cause sialuria, an overproduction disorder.
alternative_products:
- name: 1 (GNE1)
  id: Q9Y223-1
- name: 2 (GNE2)
  id: Q9Y223-2
  sequence_note: VSP_041027
- name: 3 (GNE3)
  id: Q9Y223-3
  sequence_note: VSP_041028
- name: '4'
  id: Q9Y223-4
  sequence_note: VSP_043474
- name: '5'
  id: Q9Y223-5
  sequence_note: VSP_043975, VSP_043976
existing_annotations:
- term:
    id: GO:0008761
    label: UDP-N-acetylglucosamine 2-epimerase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) assignment of the N-terminal epimerase catalytic activity. This
      is a core molecular function of GNE, extensively supported by direct experimental
      evidence (see the IDA/IMP annotations below). Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/GNE/GNE-uniprot.txt
      supporting_text: "activities, and serves as the initiator of the biosynthetic pathway"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0009384
    label: N-acylmannosamine kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: enables
  review:
    summary: >-
      Phylogenetic (IBA) assignment of the C-terminal ManNAc kinase catalytic activity.
      Core molecular function, supported by direct experimental evidence (EXP PMID:16503651,
      IMP PMID:14707127). Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/GNE/GNE-uniprot.txt
      supporting_text: "RecName: Full=N-acetylmannosamine kinase"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0004553
    label: hydrolase activity, hydrolyzing O-glycosyl compounds
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: enables
  review:
    summary: >-
      InterPro2GO mapping from the UDP-GlcNAc 2-epimerase signature. GNE's epimerase is
      formally a hydrolyzing 2-epimerase (EC 3.2.1.183, releasing UDP), but this broad
      glycosidase term (the O-glycosidase parent) does not describe GNE's actual reaction and
      is misleading as a standalone molecular function. The specific and correct term GO:0008761
      is separately annotated. Over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      Cytosol localization from UniProt Subcellular Location keyword mapping. Consistent with
      the curated location and with IDA/ISS/TAS annotations. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/GNE/GNE-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0006047
    label: UDP-N-acetylglucosamine metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  qualifier: involved_in
  review:
    summary: >-
      InterPro-based process annotation. Accurate but general: GNE consumes UDP-GlcNAc as its
      epimerase substrate, so it participates in UDP-GlcNAc metabolism. Keep as a correct but
      non-core, higher-level process term; the specific pathway role is captured by
      N-acetylneuraminate biosynthetic process.
    action: KEEP_AS_NON_CORE
- term:
    id: GO:0009384
    label: N-acylmannosamine kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic (ARBA/RHEA/EC:2.7.1.60) assignment of ManNAc kinase activity. Correct and
      redundant with the experimentally-supported core kinase annotation. Accept.
    action: ACCEPT
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:18560563
  qualifier: enables
  review:
    summary: >-
      IPI to alpha-actinin 1 (ACTN1, P12814). GNE binds alpha-actinin 1 in skeletal muscle,
      shown by SPR biosensor, in vitro binding and co-immunoprecipitation. This is a specific,
      biologically-motivated interaction (a search for muscle-specific GNE partners relevant to
      HIBM pathology), but the GO term used is the uninformative generic protein binding
      (GO:0005515) and no functional consequence for GNE's enzymatic role has been established.
      Keep per policy but mark as over-annotated; not a core function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: PMID:18560563
      supporting_text: "revealed alpha-actinin 1 as a potential interactor of GNE"
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:25416956
  qualifier: enables
  review:
    summary: >-
      IPI from a proteome-scale human interactome (Y2H) screen (Rolland et al.), producing
      generic protein binding annotations to many partners (keratins, keratin-associated
      proteins, SPRY2, GTPBP3, etc.). High-throughput binding with no established functional
      relevance to GNE's sialic-acid function. Uninformative term; over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:31515488
  qualifier: enables
  review:
    summary: >-
      IPI from a systematic interactome variant-disruption study (Fragoza et al.). Generic
      protein binding high-throughput annotation with no established functional consequence
      for GNE. Uninformative term; over-annotation.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0008761
    label: UDP-N-acetylglucosamine 2-epimerase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  qualifier: enables
  review:
    summary: >-
      Electronic (ARBA / mouse ortholog Q91WG8) assignment of the epimerase activity. Correct
      and redundant with the experimentally-supported core epimerase annotation. Accept.
    action: ACCEPT
- term:
    id: GO:0046380
    label: N-acetylneuraminate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  qualifier: involved_in
  review:
    summary: >-
      Orthology-based (Ensembl Compara, mouse Q91WG8) assignment of the sialic acid
      biosynthetic process. This is the core biological process of GNE, also supported by
      IMP (PMID:14707127, PMID:31121216). Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/GNE/GNE-uniprot.txt
      supporting_text: "PATHWAY: Amino-sugar metabolism; N-acetylneuraminate biosynthesis."
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0006045
    label: N-acetylglucosamine biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000041
  qualifier: involved_in
  review:
    summary: >-
      UniPathway (UPA00630) mapping. This term is the wrong direction for GNE: the epimerase
      consumes UDP-GlcNAc, it does not biosynthesize N-acetylglucosamine. The mapping reflects
      the amino-sugar pathway container rather than GNE's actual role, which is ManNAc/Neu5Ac
      production. Over-annotation / misleading.
    action: MARK_AS_OVER_ANNOTATED
- term:
    id: GO:0008761
    label: UDP-N-acetylglucosamine 2-epimerase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4088338
  qualifier: enables
  review:
    summary: >-
      Reactome TAS for the epimerase activity (reaction "Defective GNE does not hydrolyse
      UDP-GlcNAc"). Corroborates the core epimerase function. Accept.
    action: ACCEPT
- term:
    id: GO:0009384
    label: N-acylmannosamine kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4088322
  qualifier: enables
  review:
    summary: >-
      Reactome TAS for the ManNAc kinase activity (reaction "Defective GNE does not
      phosphorylate ManNAc to ManNAc-6-P"). Corroborates the core kinase function. Accept.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: IDA
  original_reference_id: GO_REF:0000052
  qualifier: located_in
  review:
    summary: >-
      Direct immunofluorescence localization (HPA) to cytosol. Consistent with the curated
      subcellular location. Accept as the supported location.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/GNE/GNE-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0009384
    label: N-acylmannosamine kinase activity
  evidence_type: EXP
  original_reference_id: PMID:16503651
  qualifier: enables
  review:
    summary: >-
      Experimental characterization of ManNAc kinase activity: recombinant GNE (and HIBM
      mutants) assayed for both activities in insect cells, each mutant showing reduced
      kinase and epimerase activity. Direct support for the core ManNAc kinase function.
      Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:16503651
      supporting_text: "Each of the mutants that was analyzed displayed a reduction in the two known GNE activities"
- term:
    id: GO:0006055
    label: CMP-N-acetylneuraminate biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:31121216
  qualifier: involved_in
  review:
    summary: >-
      GNE knockout dramatically reduced cellular CMP-sialic acid, placing GNE in CMP-Neu5Ac
      biosynthesis. This is a step downstream of GNE's direct reactions (CMP-Neu5Ac is made by
      CMAS), but GNE is required for it as the pathway-initiating enzyme. Correct and supported;
      keep as a non-core process framing (the direct process is N-acetylneuraminate biosynthesis).
    action: KEEP_AS_NON_CORE
    supported_by:
    - reference_id: PMID:31121216
      supporting_text: "CMP-sialic acid was dramatically reduced in GNE and NANS KO cells"
- term:
    id: GO:0046380
    label: N-acetylneuraminate biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:31121216
  qualifier: involved_in
  review:
    summary: >-
      GNE knockout reduced cell-surface sialylation and CMP-sialic acid, directly demonstrating
      GNE's requirement for de novo sialic acid (N-acetylneuraminate) biosynthesis. Direct
      support for the core biological process. Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:31121216
      supporting_text: "Sialylation of cell surface glycans was reduced by KO of GNE"
- term:
    id: GO:0008761
    label: UDP-N-acetylglucosamine 2-epimerase activity
  evidence_type: IDA
  original_reference_id: PMID:26980148
  qualifier: enables
  review:
    summary: >-
      Direct biochemical/structural characterization of the human UDP-GlcNAc 2-epimerase domain,
      including catalytic-residue mutagenesis (D112A, R113A, S302A) confirming the epimerase
      mechanism, and CMP-Neu5Ac feedback inhibition. Strong direct support for the core epimerase
      function. Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:26980148
      supporting_text: "The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) plays a key role in sialic acid production."
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: ISS
  original_reference_id: GO_REF:0000024
  qualifier: is_active_in
  review:
    summary: >-
      Cytosol (is_active_in) inferred by sequence similarity from the mouse ortholog (O35826).
      Consistent with all other localization evidence and with GNE acting on cytosolic
      nucleotide-sugar substrates. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/GNE/GNE-uniprot.txt
      supporting_text: "SUBCELLULAR LOCATION: Cytoplasm, cytosol"
      reference_section_type: DATABASE_ENTRY
- term:
    id: GO:0008761
    label: UDP-N-acetylglucosamine 2-epimerase activity
  evidence_type: IDA
  original_reference_id: PMID:2808337
  qualifier: enables
  review:
    summary: >-
      Direct assay of the rate-limiting UDP-GlcNAc 2-epimerase activity in cell lysates, which
      identified the sialuria defect as loss of CMP-Neu5Ac feedback inhibition of this enzyme.
      Direct support for the core epimerase function (and its feedback regulation). Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:2808337
      supporting_text: "the activity of the rate-limiting enzyme in the biosynthesis of sialic acid has been measured directly in whole cell lysates"
- term:
    id: GO:0008761
    label: UDP-N-acetylglucosamine 2-epimerase activity
  evidence_type: IMP
  original_reference_id: PMID:14707127
  qualifier: enables
  review:
    summary: >-
      Mutational analysis (DMRV/HIBM patient variants) showing reduced epimerase activity in an
      in vitro expression assay. Supports the core epimerase function. Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:14707127
      supporting_text: "the bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase, which"
- term:
    id: GO:0009384
    label: N-acylmannosamine kinase activity
  evidence_type: IMP
  original_reference_id: PMID:14707127
  qualifier: enables
  review:
    summary: >-
      Mutational analysis showing reduced ManNAc kinase activity for patient variants in an
      in vitro expression assay. Supports the core kinase function. Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:14707127
      supporting_text: "which catalyzes the initial two steps in the biosynthesis of sialic acid"
- term:
    id: GO:0046380
    label: N-acetylneuraminate biosynthetic process
  evidence_type: IMP
  original_reference_id: PMID:14707127
  qualifier: involved_in
  review:
    summary: >-
      Reduced GNE enzymatic activity in DMRV patients was accompanied by reduced muscle
      sialylation, linking GNE to sialic acid (N-acetylneuraminate) biosynthesis in vivo.
      Direct support for the core biological process. Accept as core.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:14707127
      supporting_text: "the levels of sialic acid in muscle and primary cultured cells from DMRV patients were reduced to 60-75% of control"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4088322
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS cytosol location, associated with the ManNAc kinase reaction. Consistent
      with the curated location. Accept.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4088338
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS cytosol location, associated with the epimerase reaction. Consistent with the
      curated location. Accept.
    action: ACCEPT
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4085021
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS cytosol location (reaction: GNE hydrolyzes and epimerises UDP-GlcNAc to ManNAc
      and UDP). Consistent with the curated location. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: Reactome:R-HSA-4085021
      supporting_text: "(GNE) is a bifunctional enzyme in the cytosol"
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-4085028
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS cytosol location (reaction: GNE phosphorylates ManNAc to ManNAc-6-P).
      Consistent with the curated location. Accept.
    action: ACCEPT
    supported_by:
    - reference_id: Reactome:R-HSA-4085028
      supporting_text: "(GNE) is a bifunctional enzyme in the cytosol"
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO
    terms
  findings: []
- id: GO_REF:0000024
  title: Manual transfer of experimentally-verified manual GO annotation data to orthologs
    by curator judgment of sequence similarity
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000041
  title: Gene Ontology annotation based on UniPathway vocabulary mapping
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000052
  title: Gene Ontology annotation based on curation of immunofluorescence data
  findings: []
- id: GO_REF:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to
    orthologs using Ensembl Compara
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:14707127
  title: Reduction of UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase
    activity and sialylation in distal myopathy with rimmed vacuoles.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Identified pathogenic GNE mutations in distal myopathy with rimmed vacuoles and showed
      reduced epimerase and kinase activities and reduced muscle sialylation; source of the
      core MF (both activities) and BP (sialic acid biosynthesis) IMP annotations. Abstract-only
      in cache; claims verified against the abstract and UniProt.
- id: PMID:16503651
  title: Influence of UDP-GlcNAc 2-epimerase/ManNAc kinase mutant proteins on hereditary
    inclusion body myopathy.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Recombinant expression and enzymatic assay of GNE HIBM mutants; each mutant reduced both
      GNE activities. Supports the core ManNAc kinase (EXP) function. Abstract-only in cache.
- id: PMID:18560563
  title: 'UDP-N-acetylglucosamine 2-epimerase/N-acetylmannosamine kinase (GNE) binds
    to alpha-actinin 1: novel pathways in skeletal muscle?'
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Full text available. Demonstrates a specific GNE-alpha-actinin 1 (ACTN1) interaction in
      skeletal muscle by SPR, in vitro binding and co-IP. Supports the ACTN1 IPI, but only via
      the uninformative protein binding term; no functional consequence for GNE catalysis
      established, so annotation is marked over-annotated.
- id: PMID:25416956
  title: A proteome-scale map of the human interactome network.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput Y2H interactome map (Rolland et al.); source of multiple generic protein
      binding IPI annotations with no established functional relevance to GNE. Correctly cited
      but low informativeness for GNE function.
- id: PMID:26980148
  title: Mechanism and inhibition of human UDP-GlcNAc 2-epimerase, the key enzyme
    in sialic acid biosynthesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Full text available. Crystal structure of the human epimerase domain with UDP and
      CMP-Neu5Ac plus catalytic-residue mutagenesis; establishes the epimerase mechanism and the
      CMP-Neu5Ac feedback-inhibition / sialuria basis. Primary support for the core epimerase MF
      (IDA).
- id: PMID:2808337
  title: Identification of the metabolic defect in sialuria.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Direct assay of the rate-limiting UDP-GlcNAc 2-epimerase; identified the sialuria defect as
      loss of CMP-Neu5Ac feedback inhibition. Supports the core epimerase MF and its allosteric
      regulation. Abstract-only in cache; claims verified against abstract and UniProt.
- id: PMID:31121216
  title: Activity of N-acylneuraminate-9-phosphatase (NANP) is not essential for de
    novo sialic acid biosynthesis.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      GNE knockout cell lines show reduced cell-surface sialylation and dramatically reduced
      CMP-sialic acid, directly demonstrating GNE's requirement for de novo sialic acid
      biosynthesis. Supports the BP (IMP) annotations. Abstract-only in cache.
- id: PMID:31515488
  title: Extensive disruption of protein interactions by genetic variants across the
    allele frequency spectrum in human populations.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Systematic interactome variant-disruption study; source of a generic protein binding IPI
      with no established functional relevance to GNE's sialic-acid function.
- id: Reactome:R-HSA-4085021
  title: GNE hydrolyzes and epimerises UDP-GlcNAc to ManNAc and UDP
  findings: []
- id: Reactome:R-HSA-4085028
  title: GNE phosphorylates ManNAc to ManNAc-6-P
  findings: []
- id: Reactome:R-HSA-4088322
  title: Defective GNE does not phosphorylate ManNAc to ManNAc-6-P
  findings: []
- id: Reactome:R-HSA-4088338
  title: Defective GNE does not hydrolyse UDP-GlcNAc
  findings: []
core_functions:
- description: >-
    UDP-N-acetylglucosamine 2-epimerase activity of the N-terminal domain, converting
    UDP-N-acetyl-alpha-D-glucosamine (UDP-GlcNAc) and water to N-acetyl-D-mannosamine (ManNAc),
    UDP and a proton (a hydrolyzing 2-epimerase, EC 3.2.1.183); the first and rate-limiting step
    of sialic acid biosynthesis, allosterically feedback-inhibited by the pathway end product
    CMP-Neu5Ac.
  molecular_function:
    id: GO:0008761
    label: UDP-N-acetylglucosamine 2-epimerase activity
  supported_by:
  - reference_id: PMID:26980148
    supporting_text: "The bifunctional enzyme UDP-GlcNAc 2-epimerase/ManNAc kinase (GNE) plays a key role in sialic acid production."
  - reference_id: PMID:2808337
    supporting_text: "the activity of the rate-limiting enzyme in the biosynthesis of sialic acid has been measured directly in whole cell lysates"
  directly_involved_in:
  - id: GO:0046380
    label: N-acetylneuraminate biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
- description: >-
    N-acetylmannosamine kinase activity of the C-terminal ROK-family domain, phosphorylating
    N-acetyl-D-mannosamine (ManNAc) with ATP to ManNAc-6-phosphate (EC 2.7.1.60); the second
    committed step of sialic acid biosynthesis, requiring a divalent metal ion.
  molecular_function:
    id: GO:0009384
    label: N-acylmannosamine kinase activity
  supported_by:
  - reference_id: PMID:16503651
    supporting_text: "Each of the mutants that was analyzed displayed a reduction in the two known GNE activities"
  - reference_id: PMID:14707127
    supporting_text: "which catalyzes the initial two steps in the biosynthesis of sialic acid"
  directly_involved_in:
  - id: GO:0046380
    label: N-acetylneuraminate biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol