id: Q96PC2
gene_symbol: IP6K3
product_type: PROTEIN
status: COMPLETE
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  IP6K3 encodes inositol hexakisphosphate kinase 3, a brain-enriched member of the inositol phosphokinase
  family that phosphorylates soluble inositol polyphosphates. Its core activity converts inositol hexakisphosphate
  (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5) and can also phosphorylate InsP5/inositol
  pyrophosphate substrates. The experimentally supported localization is predominantly cytoplasmic; annotations
  implying protein phosphorylation or phosphatidylinositol-lipid metabolism should be interpreted as misapplied
  to a soluble inositol phosphate kinase.
existing_annotations:
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      Nuclear localization is not the main experimentally supported localization for human IP6K3; the
      original characterization describes IP6K3 as predominantly cytoplasmic.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This orthology/computational nuclear assignment should not be treated as a core human IP6K3 location.
      Cytoplasm/cytosol is the supported annotation.
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
    - reference_id: file:human/IP6K3/IP6K3-deep-research-manual.md
      supporting_text: >-
        PMID:11502751 reports that InsP(6)K3 is enriched in brain and predominates in the cytoplasm,
        whereas InsP(6)K2 is exclusively nuclear and InsP(6)K1 has comparable nuclear and cytosolic densities.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      cytoplasm localization is supported by the original characterization, which reported IP6K3 as predominantly
      cytoplasmic.
    action: ACCEPT
    reason: >-
      Cytoplasmic/cytosolic localization is the experimentally supported cellular component for human
      IP6K3.
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
- term:
    id: GO:0046854
    label: phosphatidylinositol phosphate biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      phosphatidylinositol phosphate biosynthetic process describes phosphatidylinositol lipid metabolism,
      but the evidence for IP6K3 is soluble inositol phosphate/pyrophosphate metabolism.
    action: MODIFY
    reason: >-
      IP6K3 is not primarily a phosphatidylinositol lipid kinase. The supported biological process is
      soluble inositol phosphate biosynthesis/metabolism.
    proposed_replacement_terms:
    - id: GO:0032958
      label: inositol phosphate biosynthetic process
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        We now report the identification, cloning, and characterization of a third InsP(7) forming enzyme
        designated InsP(6)K3.
- term:
    id: GO:0000828
    label: inositol hexakisphosphate kinase activity
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      inositol hexakisphosphate kinase activity fits the characterized IP6K3 catalytic activity toward
      soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
    - reference_id: file:human/IP6K3/IP6K3-deep-research-manual.md
      supporting_text: >-
        UniProt describes the curated function as conversion of InsP6 to InsP7/PP-InsP5, and conversion
        of InsP5 to PP-InsP4.
- term:
    id: GO:0032958
    label: inositol phosphate biosynthetic process
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  review:
    summary: >-
      inositol phosphate biosynthetic process is supported because IP6K3 biosynthesizes/metabolizes soluble
      inositol pyrophosphates from inositol phosphate substrates.
    action: ACCEPT
    reason: >-
      This biological-process term matches the characterized IP6K3 reaction products and Reactome inositol
      phosphate pathway context.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
- term:
    id: GO:0000166
    label: nucleotide binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      nucleotide binding is a broad parent term that does not convey IP6K3 substrate specificity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The annotation should be interpreted through the specific inositol hexakisphosphate/inositol pyrophosphate
      kinase activity terms. Broad kinase, transferase, and nucleotide-binding terms are over-general.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        The curated function identifies IP6K3 as an inositol hexakisphosphate kinase with specific inositol
        polyphosphate substrates.
- term:
    id: GO:0000827
    label: inositol-1,3,4,5,6-pentakisphosphate kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      inositol-1,3,4,5,6-pentakisphosphate kinase activity fits the characterized IP6K3 catalytic activity
      toward soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0000828
    label: inositol hexakisphosphate kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      inositol hexakisphosphate kinase activity fits the characterized IP6K3 catalytic activity toward
      soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0000829
    label: diphosphoinositol pentakisphosphate kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      diphosphoinositol pentakisphosphate kinase activity fits the characterized IP6K3 catalytic activity
      toward soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0000832
    label: inositol hexakisphosphate 5-kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000116
  review:
    summary: >-
      inositol hexakisphosphate 5-kinase activity fits the characterized IP6K3 catalytic activity toward
      soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0005524
    label: ATP binding
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      ATP binding is required because IP6K3 uses ATP as the phosphate donor for inositol polyphosphate
      kinase reactions.
    action: ACCEPT
    reason: >-
      ATP binding is mechanistically relevant, though less specific than the inositol phosphate kinase
      activity terms.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Catalytic reactions list ATP as substrate and ADP as product for IP6K3 reactions.
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  review:
    summary: >-
      cytoplasm localization is supported by the original characterization, which reported IP6K3 as predominantly
      cytoplasmic.
    action: ACCEPT
    reason: >-
      Cytoplasmic/cytosolic localization is the experimentally supported cellular component for human
      IP6K3.
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
- term:
    id: GO:0016301
    label: kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000120
  review:
    summary: >-
      kinase activity is a broad parent term that does not convey IP6K3 substrate specificity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The annotation should be interpreted through the specific inositol hexakisphosphate/inositol pyrophosphate
      kinase activity terms. Broad kinase, transferase, and nucleotide-binding terms are over-general.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        The curated function identifies IP6K3 as an inositol hexakisphosphate kinase with specific inositol
        polyphosphate substrates.
- term:
    id: GO:0016740
    label: transferase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000043
  review:
    summary: >-
      transferase activity is a broad parent term that does not convey IP6K3 substrate specificity.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The annotation should be interpreted through the specific inositol hexakisphosphate/inositol pyrophosphate
      kinase activity terms. Broad kinase, transferase, and nucleotide-binding terms are over-general.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        The curated function identifies IP6K3 as an inositol hexakisphosphate kinase with specific inositol
        polyphosphate substrates.
- term:
    id: GO:0032958
    label: inositol phosphate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000002
  review:
    summary: >-
      inositol phosphate biosynthetic process is supported because IP6K3 biosynthesizes/metabolizes soluble
      inositol pyrophosphates from inositol phosphate substrates.
    action: ACCEPT
    reason: >-
      This biological-process term matches the characterized IP6K3 reaction products and Reactome inositol
      phosphate pathway context.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
- term:
    id: GO:0043647
    label: inositol phosphate metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      inositol phosphate metabolic process is supported because IP6K3 biosynthesizes/metabolizes soluble
      inositol pyrophosphates from inositol phosphate substrates.
    action: ACCEPT
    reason: >-
      This biological-process term matches the characterized IP6K3 reaction products and Reactome inositol
      phosphate pathway context.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
- term:
    id: GO:0046488
    label: phosphatidylinositol metabolic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      phosphatidylinositol metabolic process describes phosphatidylinositol lipid metabolism, but the
      evidence for IP6K3 is soluble inositol phosphate/pyrophosphate metabolism.
    action: MODIFY
    reason: >-
      IP6K3 is not primarily a phosphatidylinositol lipid kinase. The supported biological process is
      soluble inositol phosphate biosynthesis/metabolism.
    proposed_replacement_terms:
    - id: GO:0032958
      label: inositol phosphate biosynthetic process
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        We now report the identification, cloning, and characterization of a third InsP(7) forming enzyme
        designated InsP(6)K3.
    - reference_id: file:human/IP6K3/IP6K3-deep-research-manual.md
      supporting_text: >-
        The available reviewed function text and the PMID:11502751 abstract support inositol phosphate
        kinase activity rather than direct phosphorylation of protein substrates.
- term:
    id: GO:0052836
    label: inositol 5-diphosphate pentakisphosphate 5-kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      inositol 5-diphosphate pentakisphosphate 5-kinase activity fits the characterized IP6K3 catalytic
      activity toward soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0052839
    label: diphosphoinositol tetrakisphosphate kinase activity
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      diphosphoinositol tetrakisphosphate kinase activity fits the characterized IP6K3 catalytic activity
      toward soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0090407
    label: organophosphate biosynthetic process
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  review:
    summary: >-
      Organophosphate biosynthetic process is too broad for IP6K3 when inositol phosphate biosynthetic
      process is already annotated.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The more informative process is soluble inositol phosphate/pyrophosphate biosynthesis. This broad
      parent term obscures the pathway specificity.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        IP6K3 converts inositol hexakisphosphate to diphosphoinositol pentakisphosphate.
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:32296183
  review:
    summary: >-
      Generic protein binding from a high-throughput interactome screen does not describe IP6K3 catalytic
      function.
    action: MARK_AS_OVER_ANNOTATED
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        The curated function describes conversion of inositol phosphate substrates, while listed interactions
        are high-throughput IntAct records.
    reason: >-
      GO:0005515 is uninformative here. The core annotation should focus on inositol phosphate kinase
      activity and inositol phosphate biosynthesis.
- term:
    id: GO:0005634
    label: nucleus
  evidence_type: IEA
  original_reference_id: GO_REF:0000107
  review:
    summary: >-
      Nuclear localization is not the main experimentally supported localization for human IP6K3; the
      original characterization describes IP6K3 as predominantly cytoplasmic.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      This orthology/computational nuclear assignment should not be treated as a core human IP6K3 location.
      Cytoplasm/cytosol is the supported annotation.
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
- term:
    id: GO:0043647
    label: inositol phosphate metabolic process
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855167
  review:
    summary: >-
      inositol phosphate metabolic process is supported because IP6K3 biosynthesizes/metabolizes soluble
      inositol pyrophosphates from inositol phosphate substrates.
    action: ACCEPT
    reason: >-
      This biological-process term matches the characterized IP6K3 reaction products and Reactome inositol
      phosphate pathway context.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
- term:
    id: GO:0000828
    label: inositol hexakisphosphate kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855227
  review:
    summary: >-
      inositol hexakisphosphate kinase activity fits the characterized IP6K3 catalytic activity toward
      soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0000829
    label: diphosphoinositol pentakisphosphate kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855194
  review:
    summary: >-
      diphosphoinositol pentakisphosphate kinase activity fits the characterized IP6K3 catalytic activity
      toward soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0052836
    label: inositol 5-diphosphate pentakisphosphate 5-kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855158
  review:
    summary: >-
      inositol 5-diphosphate pentakisphosphate 5-kinase activity fits the characterized IP6K3 catalytic
      activity toward soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0052839
    label: diphosphoinositol tetrakisphosphate kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855193
  review:
    summary: >-
      diphosphoinositol tetrakisphosphate kinase activity fits the characterized IP6K3 catalytic activity
      toward soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0000827
    label: inositol-1,3,4,5,6-pentakisphosphate kinase activity
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855223
  review:
    summary: >-
      inositol-1,3,4,5,6-pentakisphosphate kinase activity fits the characterized IP6K3 catalytic activity
      toward soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
- term:
    id: GO:0000828
    label: inositol hexakisphosphate kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11502751
  review:
    summary: >-
      inositol hexakisphosphate kinase activity fits the characterized IP6K3 catalytic activity toward
      soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855158
  review:
    summary: >-
      cytosol localization is supported by the original characterization, which reported IP6K3 as predominantly
      cytoplasmic.
    action: ACCEPT
    reason: >-
      Cytoplasmic/cytosolic localization is the experimentally supported cellular component for human
      IP6K3.
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855193
  review:
    summary: >-
      cytosol localization is supported by the original characterization, which reported IP6K3 as predominantly
      cytoplasmic.
    action: ACCEPT
    reason: >-
      Cytoplasmic/cytosolic localization is the experimentally supported cellular component for human
      IP6K3.
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855194
  review:
    summary: >-
      cytosol localization is supported by the original characterization, which reported IP6K3 as predominantly
      cytoplasmic.
    action: ACCEPT
    reason: >-
      Cytoplasmic/cytosolic localization is the experimentally supported cellular component for human
      IP6K3.
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855223
  review:
    summary: >-
      cytosol localization is supported by the original characterization, which reported IP6K3 as predominantly
      cytoplasmic.
    action: ACCEPT
    reason: >-
      Cytoplasmic/cytosolic localization is the experimentally supported cellular component for human
      IP6K3.
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
- term:
    id: GO:0005829
    label: cytosol
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-1855227
  review:
    summary: >-
      cytosol localization is supported by the original characterization, which reported IP6K3 as predominantly
      cytoplasmic.
    action: ACCEPT
    reason: >-
      Cytoplasmic/cytosolic localization is the experimentally supported cellular component for human
      IP6K3.
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
- term:
    id: GO:0000831
    label: inositol hexakisphosphate 6-kinase activity
  evidence_type: IDA
  original_reference_id: PMID:11502751
  review:
    summary: >-
      inositol hexakisphosphate 6-kinase activity fits the characterized IP6K3 catalytic activity toward
      soluble inositol polyphosphate and inositol pyrophosphate substrates.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
        Converts 1,3,4,5,6-pentakisphosphate (InsP5) to PP-InsP4.
    reason: >-
      This is the specific molecular-function space for IP6K3. The PMID:11502751 characterization and
      UniProt catalytic activities support conversion of InsP6 to PP-InsP5/InsP7 and related inositol
      polyphosphate kinase reactions.
- term:
    id: GO:0032958
    label: inositol phosphate biosynthetic process
  evidence_type: IDA
  original_reference_id: PMID:11502751
  review:
    summary: >-
      inositol phosphate biosynthetic process is supported because IP6K3 biosynthesizes/metabolizes soluble
      inositol pyrophosphates from inositol phosphate substrates.
    action: ACCEPT
    supported_by:
    - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
      supporting_text: >-
        Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
    reason: >-
      This biological-process term matches the characterized IP6K3 reaction products and Reactome inositol
      phosphate pathway context.
- term:
    id: GO:0006468
    label: protein phosphorylation
  evidence_type: IDA
  original_reference_id: PMID:11502751
  review:
    summary: >-
      IP6K3 is an inositol polyphosphate kinase, not a protein kinase. The characterized substrates are
      InsP6, InsP5, and related inositol pyrophosphates.
    action: REMOVE
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        We now report the identification, cloning, and characterization of a third InsP(7) forming enzyme
        designated InsP(6)K3.
    reason: >-
      The evidence supports phosphorylation of soluble inositol phosphate substrates, not protein phosphorylation.
      This row should not remain as a protein phosphorylation BP annotation.
- term:
    id: GO:0046488
    label: phosphatidylinositol metabolic process
  evidence_type: IDA
  original_reference_id: PMID:11502751
  review:
    summary: >-
      phosphatidylinositol metabolic process describes phosphatidylinositol lipid metabolism, but the
      evidence for IP6K3 is soluble inositol phosphate/pyrophosphate metabolism.
    action: MODIFY
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        We now report the identification, cloning, and characterization of a third InsP(7) forming enzyme
        designated InsP(6)K3.
    reason: >-
      IP6K3 is not primarily a phosphatidylinositol lipid kinase. The supported biological process is
      soluble inositol phosphate biosynthesis/metabolism.
    proposed_replacement_terms:
    - id: GO:0032958
      label: inositol phosphate biosynthetic process
- term:
    id: GO:0005737
    label: cytoplasm
  evidence_type: IDA
  original_reference_id: PMID:11502751
  review:
    summary: >-
      cytoplasm localization is supported by the original characterization, which reported IP6K3 as predominantly
      cytoplasmic.
    action: ACCEPT
    supported_by:
    - reference_id: PMID:11502751
      supporting_text: >-
        Intracellular disposition discriminates the three enzymes with InsP(6)K2 being exclusively nuclear,
        InsP(6)K3 predominating in the cytoplasm, and InsP(6)K1 displaying comparable nuclear and cytosolic
        densities.
    reason: >-
      Cytoplasmic/cytosolic localization is the experimentally supported cellular component for human
      IP6K3.
references:
- id: GO_REF:0000002
  title: Gene Ontology annotation through association of InterPro records with GO terms
  findings: []
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000043
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot keyword 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:0000107
  title: Automatic transfer of experimentally verified manual GO annotation data to orthologs using
    Ensembl Compara
  findings: []
- id: GO_REF:0000116
  title: Automatic Gene Ontology annotation based on Rhea mapping
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: GO_REF:0000120
  title: Combined Automated Annotation using Multiple IEA Methods
  findings: []
- id: PMID:11502751
  title: Identification and characterization of a novel inositol hexakisphosphate kinase.
  findings: []
- id: PMID:32296183
  title: A reference map of the human binary protein interactome.
  findings: []
- id: Reactome:R-HSA-1855158
  title: 5-PP-IP5 is phosphorylated to 5-PPP-IP5 by IP6K1/3 in the cytosol
  findings: []
- id: Reactome:R-HSA-1855167
  title: Synthesis of pyrophosphates in the cytosol
  findings: []
- id: Reactome:R-HSA-1855193
  title: 1-PP-IP4 is phosphorylated to 1,5-(PP)2-IP3 by IP6K1/3 in the cytosol
  findings: []
- id: Reactome:R-HSA-1855194
  title: 1-PP-IP5 is phosphorylated to 1,5-(PP)2-IP4 by IP6K1/3 in the cytosol
  findings: []
- id: Reactome:R-HSA-1855223
  title: I(1,3,4,5,6)P5 is phosphorylated to 5-PP-IP4 by IP6K1/3 in the cytosol
  findings: []
- id: Reactome:R-HSA-1855227
  title: IP6 is phosphorylated to 5-PP-IP5 by IP6K1/3 in the cytosol
  findings: []
- id: file:human/IP6K3/IP6K3-uniprot.txt
  title: UniProt record for human IP6K3
  findings: []
- id: file:human/IP6K3/IP6K3-deep-research-manual.md
  title: Manual deep research on IP6K3 function
  findings: []
core_functions:
- description: >-
    Phosphorylates soluble inositol polyphosphates, especially converting InsP6 to diphosphoinositol pentakisphosphate/InsP7
    and supporting inositol pyrophosphate biosynthesis in the cytoplasm.
  molecular_function:
    id: GO:0000828
    label: inositol hexakisphosphate kinase activity
  directly_involved_in:
  - id: GO:0032958
    label: inositol phosphate biosynthetic process
  locations:
  - id: GO:0005829
    label: cytosol
  - id: GO:0005737
    label: cytoplasm
  substrates:
  - id: CHEBI:58130
    label: 1D-myo-inositol hexakisphosphate
  supported_by:
  - reference_id: file:human/IP6K3/IP6K3-uniprot.txt
    supporting_text: >-
      Converts inositol hexakisphosphate (InsP6) to diphosphoinositol pentakisphosphate (InsP7/PP-InsP5).
  - reference_id: file:human/IP6K3/IP6K3-deep-research-manual.md
    supporting_text: >-
      Reactome R-HSA-1855227 describes IP6K1 and IP6K3 phosphorylating IP6 to 5-PP-IP5 in the cytosol.
proposed_new_terms: []
suggested_questions:
- question: What fraction of endogenous IP6K3 is nuclear in human neurons compared with the
    predominant cytoplasmic pool?
  experts:
  - inositol phosphate biochemists
  - neurocell biologists
- question: Which inositol pyrophosphate products are generated by IP6K3 in brain tissue under
    physiological conditions?
  experts:
  - metabolomics experts
  - neurochemists
suggested_experiments:
- experiment_type: Targeted metabolomics
  description: Quantify inositol pyrophosphate species in IP6K3 knockout and rescue neuronal models.
  hypothesis: IP6K3 loss reduces specific InsP7/PP-InsP products in brain-derived cells.
- experiment_type: Endogenous localization
  description: Use validated IP6K3 antibodies or tagged knock-in alleles to measure cytoplasmic
    versus nuclear localization in neuronal cells.
  hypothesis: Endogenous IP6K3 is predominantly cytoplasmic, consistent with the original
    characterization.