Component

Regulatory palmitoylated ZDHHC6

ZDHHC6 carrying regulatory C-terminal cysteine S-acylation at C328/C329/C343; distinct from its catalytic DHHC acyl-enzyme intermediate.

5 recorded relationships. Experimental role, claim status and evidence remain attached to each record.

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. C328-palmitoylated ZDHHC6 had higher acyltransferase activity than regulatory-unpalmitoylated forms in the tested system.

    Regulatory palmitoylated ZDHHC6 → ZDHHC6 source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence
    cell_type
    HeLa
    experimental_model
    Cysteine mutants and activity assays
    limitations
    Activity and turnover depend on the full site-occupancy state.
    organism
    human

    Selenium: literature corrections and mechanism additions · lines 906–916

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Cysteine mutants and activity assays · secondary_verified · secondary_verified

    ## zdhhc6-c328-palmitoylation-increases-activity The regulatory lipid state changed ZDHHC6 activity. C328-palmitoylated ZDHHC6 had higher acyltransferase activity than regulatory-unpalmitoylated forms in the tested system. Organism: human Cell type: HeLa Experimental model: Cysteine mutants and activity assays Limitations: Activity and turnover depend on the full site-occupancy state. Primary reference: [Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade](https://elifesciences.org/articles/27826)
    Complete structured claim and evidence

What acts on it

  1. Palmitoylation-deficient APT2-C2S overexpression did not reproduce the significant reduction in ZDHHC6 palmitoylation caused by wild-type APT2.

    Human APT2-C2S overexpression in HeLa → Regulatory palmitoylated ZDHHC6 source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    evidence_cache
    artifacts/discovery-research/round6-sources/zdhhc6-primary-passages.json; SHA256 a02040bb8922a9170e095cdfb5e875a5e7f513b682c0ec69c19feacb3dc191b0
    experimental_model
    Human HeLa; tagged human APT2-C2S and ZDHHC6 constructs
    exposure
    24-hour plasmid expression, then 2-hour tritiated-palmitate labeling; normalized to ZDHHC6 protein; n=6.
    limitations
    These are separate experimental observations, not a demonstrated sulforaphane-GPX4-ZDHHC6 pathway. Sulforaphane-driven APT2 relocalization is not equivalent to genetic depletion or general catalytic inhibition. No dietary, clinical or selenium-repletion effect is inferred. Protein stability, palmitoylation and substrate output remain different measurements. This mutant result supports a role for APT2 palmitoylation in this substrate assay; it is not a sulforaphane experiment.
    organism
    Human experimental cells; construct species unresolved where stated for discussion-only nulls
    primary_locator
    Figure 2E,F; Rapid APT2-mediated ZDHHC6 depalmitoylation
    primary_references
    https://doi.org/10.7554/eLife.27826
    source_access
    Selected primary Results, figure legends and methods via indexed publisher text. No supplement or raw-data reanalysis.
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    APT2: sulforaphane engagement, GPX4 stability and ZDHHC6 turnover · lines 85–93

    Targeted primary-literature curation from recursive ZDHHC6 exploration, 2026-09-20. · supports · Human HeLa; tagged human APT2-C2S and ZDHHC6 constructs · source_derived_draft · unverified_draft

    Palmitoylation-deficient APT2-C2S overexpression did not reproduce the significant reduction in ZDHHC6 palmitoylation caused by wild-type APT2. primary_references: https://doi.org/10.7554/eLife.27826 primary_locator: Figure 2E,F; Rapid APT2-mediated ZDHHC6 depalmitoylation source_access: Selected primary Results, figure legends and methods via indexed publisher text. No supplement or raw-data reanalysis. evidence_cache: artifacts/discovery-research/round6-sources/zdhhc6-primary-passages.json; SHA256 a02040bb8922a9170e095cdfb5e875a5e7f513b682c0ec69c19feacb3dc191b0 experimental_model: Human HeLa; tagged human APT2-C2S and ZDHHC6 constructs organism: Human experimental cells; construct species unresolved where stated for discussion-only nulls exposure: 24-hour plasmid expression, then 2-hour tritiated-palmitate labeling; normalized to ZDHHC6 protein; n=6. limitations: These are separate experimental observations, not a demonstrated sulforaphane-GPX4-ZDHHC6 pathway. Sulforaphane-driven APT2 relocalization is not equivalent to genetic depletion or general catalytic inhibition. No dietary, clinical or selenium-repletion effect is inferred. Protein stability, palmitoylation and substrate output remain different measurements. This mutant result supports a role for APT2 palmitoylation in this substrate assay; it is not a sulforaphane experiment.
    Complete structured claim and evidence

  2. Wild-type APT2 overexpression reduced radiolabeled palmitate incorporation into ZDHHC6 in HeLa cells.

    Human APT2 wild-type overexpression in HeLa → Regulatory palmitoylated ZDHHC6 source_derived_draftungraded
    Experimental context and source evidence
    evidence_cache
    artifacts/discovery-research/round6-sources/zdhhc6-primary-passages.json; SHA256 a02040bb8922a9170e095cdfb5e875a5e7f513b682c0ec69c19feacb3dc191b0
    experimental_model
    Human HeLa; tagged human APT2 and ZDHHC6 constructs
    exposure
    24-hour plasmid expression, then 2-hour tritiated-palmitate labeling; normalized to ZDHHC6 protein; n=6.
    limitations
    These are separate experimental observations, not a demonstrated sulforaphane-GPX4-ZDHHC6 pathway. Sulforaphane-driven APT2 relocalization is not equivalent to genetic depletion or general catalytic inhibition. No dietary, clinical or selenium-repletion effect is inferred. Protein stability, palmitoylation and substrate output remain different measurements.
    organism
    Human experimental cells; construct species unresolved where stated for discussion-only nulls
    primary_locator
    Figure 2E,F; Rapid APT2-mediated ZDHHC6 depalmitoylation
    primary_references
    https://doi.org/10.7554/eLife.27826
    source_access
    Selected primary Results, figure legends and methods via indexed publisher text. No supplement or raw-data reanalysis.

    APT2: sulforaphane engagement, GPX4 stability and ZDHHC6 turnover · lines 74–82

    Targeted primary-literature curation from recursive ZDHHC6 exploration, 2026-09-20. · supports · Human HeLa; tagged human APT2 and ZDHHC6 constructs · source_derived_draft · unverified_draft

    Wild-type APT2 overexpression reduced radiolabeled palmitate incorporation into ZDHHC6 in HeLa cells. primary_references: https://doi.org/10.7554/eLife.27826 primary_locator: Figure 2E,F; Rapid APT2-mediated ZDHHC6 depalmitoylation source_access: Selected primary Results, figure legends and methods via indexed publisher text. No supplement or raw-data reanalysis. evidence_cache: artifacts/discovery-research/round6-sources/zdhhc6-primary-passages.json; SHA256 a02040bb8922a9170e095cdfb5e875a5e7f513b682c0ec69c19feacb3dc191b0 experimental_model: Human HeLa; tagged human APT2 and ZDHHC6 constructs organism: Human experimental cells; construct species unresolved where stated for discussion-only nulls exposure: 24-hour plasmid expression, then 2-hour tritiated-palmitate labeling; normalized to ZDHHC6 protein; n=6. limitations: These are separate experimental observations, not a demonstrated sulforaphane-GPX4-ZDHHC6 pathway. Sulforaphane-driven APT2 relocalization is not equivalent to genetic depletion or general catalytic inhibition. No dietary, clinical or selenium-repletion effect is inferred. Protein stability, palmitoylation and substrate output remain different measurements.
    Complete structured claim and evidence

  3. APT2/LYPLA2 removes regulatory palmitoylation from ZDHHC6, with rapid turnover involving C328.

    LYPLA2 → Regulatory palmitoylated ZDHHC6 source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence
    cell_type
    HeLa
    experimental_model
    Enzyme perturbation and pulse-chase
    limitations
    Not removal of the catalytic acyl intermediate.
    organism
    human

    Selenium: literature corrections and mechanism additions · lines 894–904

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Enzyme perturbation and pulse-chase · secondary_verified · secondary_verified

    ## apt2-depalmitoylates-zdhhc6 APT2 can remove ZDHHC6's regulatory lipid groups. APT2/LYPLA2 removes regulatory palmitoylation from ZDHHC6, with rapid turnover involving C328. Organism: human Cell type: HeLa Experimental model: Enzyme perturbation and pulse-chase Limitations: Not removal of the catalytic acyl intermediate. Primary reference: [Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade](https://elifesciences.org/articles/27826)
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. ZDHHC16 mediates regulatory ZDHHC6 palmitoylation at C328, C329 and C343.

    ZDHHC16 → ZDHHC6 source_derived_draftliterature_reviewed:direct_experimental
    Experimental context and source evidence
    cell_type
    HeLa and HAP1
    experimental_model
    Mutagenesis and enzyme perturbations
    limitations
    Distinct from catalytic DHHC self-acylation.
    organism
    human

    Selenium: literature corrections and mechanism additions · lines 882–892

    Metabolic Ledger literature curation, 17 September 2026; primary papers linked individually · supports · Mutagenesis and enzyme perturbations · secondary_verified · secondary_verified

    ## zdhhc16-palmitoylates-zdhhc6-regulatory-sites Another enzyme adds regulatory lipid groups to ZDHHC6. ZDHHC16 mediates regulatory ZDHHC6 palmitoylation at C328, C329 and C343. Organism: human Cell type: HeLa and HAP1 Experimental model: Mutagenesis and enzyme perturbations Limitations: Distinct from catalytic DHHC self-acylation. Primary reference: [Identification and dynamics of the human ZDHHC16-ZDHHC6 palmitoylation cascade](https://elifesciences.org/articles/27826)
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

    This is a research prototype built from draft material. It is not medical advice, and its statements still await verification against the original studies.

    Evidence, AI assistance and curation standards