Component

Calcineurin

The phosphatase complex that dephosphorylates NFAT.

12 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. Calcineurin binds NFAT1 and supports its reversible dephosphorylated, nuclear-active state during calcium stimulation.

    Calcineurin → NFAT1 / NFATC2 source_derived_draftungraded
    Experimental context and source evidence
    compartment_description
    Cytosol and nucleus
    experimental_model
    Murine T-cell experiments, inhibitor/chelation interventions and protein-binding assays
    limitations
    NFAT1-specific evidence; do not assign this calcium response to all NFAT proteins or NFAT5.
    nutrient_topic
    Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
    organism
    Mus musculus
    plain_language
    Calcineurin connects calcium signaling to NFAT1 activation.
    primary_references
    [ca-loh1996] Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity (1996). https://pubmed.ncbi.nlm.nih.gov/8631904/ DOI: 10.1074/jbc.271.18.10884
    research_relationship_category
    regulation
    tissue_or_cell_type
    T lymphocytes

    Calcium: mechanism-first literature curation (2026-09-17) · lines 425–436

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Murine T-cell experiments, inhibitor/chelation interventions and protein-binding assays · source_derived_draft · unverified_draft

    ### ca-calcineurin-nfat1-regulation Calcineurin binds NFAT1 and supports its reversible dephosphorylated, nuclear-active state during calcium stimulation. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcineurin connects calcium signaling to NFAT1 activation. organism: Mus musculus tissue_or_cell_type: T lymphocytes experimental_model: Murine T-cell experiments, inhibitor/chelation interventions and protein-binding assays limitations: NFAT1-specific evidence; do not assign this calcium response to all NFAT proteins or NFAT5. research_relationship_category: regulation compartment_description: Cytosol and nucleus [ca-loh1996] Calcineurin binds the transcription factor NFAT1 and reversibly regulates its activity (1996). https://pubmed.ncbi.nlm.nih.gov/8631904/ DOI: 10.1074/jbc.271.18.10884
    Complete structured claim and evidence

  2. Calcineurin bound and dephosphorylated TFEB, promoting its nuclear translocation.

    Calcineurin → Human transcription factor EB / TFEB source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Genetic and pharmacological perturbation of the calcineurin–TFEB pathway.
    limitations
    This establishes a regulatory route, not a fixed fasting schedule.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    Removing phosphate marks let a regulator reach the nucleus.
    primary_references
    Lysosomal calcium signalling regulates autophagy through calcineurin and ​TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 336–342

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Genetic and pharmacological perturbation of the calcineurin–TFEB pathway. · source_derived_draft · unverified_draft

    ## fast-tfeb-dephosphorylation Removing phosphate marks let a regulator reach the nucleus. Calcineurin bound and dephosphorylated TFEB, promoting its nuclear translocation. Model: Genetic and pharmacological perturbation of the calcineurin–TFEB pathway. Limitations: This establishes a regulatory route, not a fixed fasting schedule. Evidence access: Primary abstract Lysosomal calcium signalling regulates autophagy through calcineurin and ​TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114
    Complete structured claim and evidence

  3. Calcineurin dephosphorylates NFAT.

    Calcineurin → Dephosphorylated NFAT source_derived_draftsupplied_source_only
    Experimental context and source evidence
    cell_type
    · T cell
    evidence_scope
    Source-derived draft; primary-source verification required
    organism
    · Human

    Selenium in immune cells · lines 30–38

    Selenium immune-cell mechanism draft · supports · Source draft; model details require primary-source verification · source_derived_draft · unverified_draft

    5. TCR → LCK → ZAP70 → LAT → PLCγ1 → PIP₂ → IP₃ + DAG 6. IP₃ → IP3R → ER Ca²⁺ release → store depletion 7. STIM1 oligomerizes → ORAI1 → CRAC channel → sustained Ca²⁺ entry 8. Ca²⁺/calmodulin → CALCINEURIN (PP2B) → dephosphorylates NFAT 9. NFAT → nucleus → partners with AP-1 → IL2, IFNG, CD25 transcription
    Complete structured claim and evidence

What acts on it

  1. Cyclophilin without cyclosporin A bound did not bind or inhibit calcineurin, and neither did FKBP alone, FKBP with rapamycin, or FKBP with the inactive analogue 506BD.

    Human cyclophilin A / PPIA → Calcineurin source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not stated here
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Purified mammalian proteins
    exposure
    Free cyclophilin; free FKBP; FKBP-rapamycin; FKBP-506BD
    limitations
    This is the control set that makes the complex the active species. It is recorded as a measured null rather than as an absence of evidence.
    organism
    Purified mammalian proteins
    plain_language
    Cyclophilin without cyclosporin A bound did not bind or inhibit calcineurin, and neither did FKBP alone, FKBP with rapamycin, or FKBP with the inactive analogue 506BD.
    primary_references
    Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. (1991). https://pubmed.ncbi.nlm.nih.gov/1715244/ DOI: 10.1016/0092-8674(91)90124-h
    route
    In vitro
    tissue
    Calcineurin phosphatase activity

    Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 58–58

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Purified mammalian proteins · source_derived_draft · unverified_draft

    Cyclophilin without cyclosporin A bound did not bind or inhibit calcineurin, and neither did FKBP alone, FKBP with rapamycin, or FKBP with the inactive analogue 506BD.
    Complete structured claim and evidence

  2. In the 2.8-angstrom crystal structure the cyclophilin A-cyclosporin A complex binds a composite surface formed by the catalytic and regulatory subunits of calcineurin, and unlike FKBP-FK506 it also interacts with Arg-122 at the calcineurin active site.

    Cyclophilin A-cyclosporine complex → Calcineurin source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not applicable
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Recombinant human proteins in crystal
    exposure
    Cyclophilin A with cyclosporin A bound
    limitations
    A structure shows contact, not rate. The authors read the active-site contact as implying direct involvement in regulating catalysis, which is an interpretation and is recorded as one. No direction is recorded for this claim, because a binding geometry is not itself an increase or a decrease.
    organism
    Recombinant human proteins in crystal
    plain_language
    In the 2.8-angstrom crystal structure the cyclophilin A-cyclosporin A complex binds a composite surface formed by the catalytic and regulatory subunits of calcineurin, and unlike FKBP-FK506 it also interacts with Arg-122 at the calcineurin active site.
    primary_references
    Crystal structure of calcineurin-cyclophilin-cyclosporin shows common but distinct recognition of immunophilin-drug complexes. (2002). https://pubmed.ncbi.nlm.nih.gov/12218175/ DOI: 10.1073/pnas.192206699
    route
    In vitro
    tissue
    Calcineurin catalytic and regulatory subunit interface

    Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 91–91

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Recombinant human proteins in crystal · source_derived_draft · unverified_draft

    In the 2.8-angstrom crystal structure the cyclophilin A-cyclosporin A complex binds a composite surface formed by the catalytic and regulatory subunits of calcineurin, and unlike FKBP-FK506 it also interacts with Arg-122 at the calcineurin active site.
    Complete structured claim and evidence

  3. The cyclophilin-cyclosporin A complex competitively binds and inhibits the calcium- and calmodulin-dependent phosphatase calcineurin.

    Cyclophilin A-cyclosporine complex → Calcineurin source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not stated here
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Purified mammalian proteins
    exposure
    Cyclophilin complexed with cyclosporin A
    limitations
    Binding and inhibition of calcineurin did not require calmodulin in this report. The inhibitor is the complex, not the drug, so this arrow must not be redrawn from cyclosporine directly to calcineurin.
    organism
    Purified mammalian proteins
    plain_language
    The cyclophilin-cyclosporin A complex competitively binds and inhibits the calcium- and calmodulin-dependent phosphatase calcineurin.
    primary_references
    Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. (1991). https://pubmed.ncbi.nlm.nih.gov/1715244/ DOI: 10.1016/0092-8674(91)90124-h
    route
    In vitro
    tissue
    Calcineurin phosphatase activity

    Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 47–47

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Purified mammalian proteins · source_derived_draft · unverified_draft

    The cyclophilin-cyclosporin A complex competitively binds and inhibits the calcium- and calmodulin-dependent phosphatase calcineurin.
    Complete structured claim and evidence

  4. The FKBP-FK506 complex also competitively binds and inhibits calcineurin, making calcineurin the common target of two structurally unrelated immunophilin-drug complexes.

    FKBP-FK506 complex → Calcineurin source_derived_draftungraded
    Experimental context and source evidence
    duration
    Not stated here
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    experimental_model
    Purified mammalian proteins
    exposure
    FKBP complexed with FK506 (tacrolimus)
    limitations
    Convergence on one target does not make the two drugs interchangeable; their immunophilins, their tissue distribution and their other complexes differ, and none of that is measured here.
    organism
    Purified mammalian proteins
    plain_language
    The FKBP-FK506 complex also competitively binds and inhibits calcineurin, making calcineurin the common target of two structurally unrelated immunophilin-drug complexes.
    primary_references
    Calcineurin is a common target of cyclophilin-cyclosporin A and FKBP-FK506 complexes. (1991). https://pubmed.ncbi.nlm.nih.gov/1715244/ DOI: 10.1016/0092-8674(91)90124-h
    route
    In vitro
    tissue
    Calcineurin phosphatase activity

    Cyclosporine: the complex that inhibits calcineurin, a second cyclophilin, and the transport step that decides exposure (2026-09-23) · lines 69–69

    Original AI-assisted curation of seven primary studies resolved by PubMed title search, with every abstract read and all DOIs cross-checked against live PubMed metadata on 2026-09-23. No reference carries a recorded retraction, erratum or expression of concern. Each of the seven is a separate laboratory and each carries its own lineage key, so none of them can be counted twice as independent support. Study-specific concentrations, kinetic constants and limitations retained. Not publisher full text. · supports · Purified mammalian proteins · source_derived_draft · unverified_draft

    The FKBP-FK506 complex also competitively binds and inhibits calcineurin, making calcineurin the common target of two structurally unrelated immunophilin-drug complexes.
    Complete structured claim and evidence

  5. Calcium/calmodulin binding folds the human calcineurin regulatory region and supports displacement of autoinhibition.

    Calcium/calmodulin → Calcineurin source_derived_draftungraded
    Experimental context and source evidence
    compartment_description
    Cytosol
    experimental_model
    Recombinant human alpha-calcineurin, regulatory fragments and calmodulin; spectroscopy and exchange mass spectrometry
    limitations
    Fragment and biochemical data support a regulatory mechanism; not tissue-level output.
    nutrient_topic
    Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
    organism
    Homo sapiens
    plain_language
    Calcium-bound calmodulin helps switch on calcineurin.
    primary_references
    [ca-rumimasante2012] Structural basis for activation of calcineurin by calmodulin (2012). https://pubmed.ncbi.nlm.nih.gov/22100452/ DOI: 10.1016/j.jmb.2011.11.008
    research_relationship_category
    regulation
    tissue_or_cell_type
    Recombinant signaling proteins

    Calcium: mechanism-first literature curation (2026-09-17) · lines 412–423

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant human alpha-calcineurin, regulatory fragments and calmodulin; spectroscopy and exchange mass spectrometry · source_derived_draft · unverified_draft

    ### ca-calmodulin-calcineurin-activation Calcium/calmodulin binding folds the human calcineurin regulatory region and supports displacement of autoinhibition. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium-bound calmodulin helps switch on calcineurin. organism: Homo sapiens tissue_or_cell_type: Recombinant signaling proteins experimental_model: Recombinant human alpha-calcineurin, regulatory fragments and calmodulin; spectroscopy and exchange mass spectrometry limitations: Fragment and biochemical data support a regulatory mechanism; not tissue-level output. research_relationship_category: regulation compartment_description: Cytosol [ca-rumimasante2012] Structural basis for activation of calcineurin by calmodulin (2012). https://pubmed.ncbi.nlm.nih.gov/22100452/ DOI: 10.1016/j.jmb.2011.11.008
    Complete structured claim and evidence

  6. Calcium/calmodulin activates calcineurin.

    Calcium/calmodulin → Calcineurin source_derived_draftsupplied_source_only
    Experimental context and source evidence
    cell_type
    · T cell
    evidence_scope
    Source-derived draft; primary-source verification required
    organism
    · Human

    Selenium in immune cells · lines 30–38

    Selenium immune-cell mechanism draft · supports · Source draft; model details require primary-source verification · source_derived_draft · unverified_draft

    5. TCR → LCK → ZAP70 → LAT → PLCγ1 → PIP₂ → IP₃ + DAG 6. IP₃ → IP3R → ER Ca²⁺ release → store depletion 7. STIM1 oligomerizes → ORAI1 → CRAC channel → sustained Ca²⁺ entry 8. Ca²⁺/calmodulin → CALCINEURIN (PP2B) → dephosphorylates NFAT 9. NFAT → nucleus → partners with AP-1 → IL2, IFNG, CD25 transcription
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Repeated capsaicin activation caused calcium-dependent TRPV1 desensitization regulated in part by calcineurin and PKA at Thr370.

    Capsaicin → TRPV1 calcium-dependent desensitization source_derived_draftungraded
    Experimental context and source evidence
    dose
    Repeated capsaicin; calcineurin inhibitor, forskolin and point mutants
    duration
    Acute repeated activation
    evidence_access
    Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    evidence_scope
    literature_reviewed; model-specific source-derived curation
    experimental_model
    TRPV1-transfected HEK293T or HeLa cells
    limitations
    Kinase and phosphatase manipulations identify regulatory machinery in engineered cells, not a dietary calcium threshold.
    nutrient_topic
    Capsaicin chapter; interacting nutrients, drugs, peptides and proteins retain their experimental settings. · Capsaicin
    organism
    TRPV1-transfected HEK293T or HeLa cells
    plain_language
    Repeated capsaicin activation caused calcium-dependent TRPV1 desensitization regulated in part by calcineurin and PKA at Thr370.
    primary_references
    Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase. (2005). https://pubmed.ncbi.nlm.nih.gov/15691846/ DOI: 10.1074/jbc.M410917200
    route
    In vitro
    tissue
    Whole-cell capsaicin currents

    Capsaicin: mechanism of action and interactions (2026-09-20) · lines 33–42

    Original AI-assisted source-specific curation with primary-study citations, model, exposure, route, duration, negative findings and limitations preserved. Not publisher full text. · supports · TRPV1-transfected HEK293T or HeLa cells · source_derived_draft · unverified_draft

    ## capsaicin-calcineurin-desensitization Repeated capsaicin activation caused calcium-dependent TRPV1 desensitization regulated in part by calcineurin and PKA at Thr370. Model/species: TRPV1-transfected HEK293T or HeLa cells Tissue/system: Whole-cell capsaicin currents Exposure: Repeated capsaicin; calcineurin inhibitor, forskolin and point mutants Route: In vitro Duration: Acute repeated activation Limits: Kinase and phosphatase manipulations identify regulatory machinery in engineered cells, not a dietary calcium threshold. Primary reference: Regulation of Ca2+-dependent desensitization in the vanilloid receptor TRPV1 by calcineurin and cAMP-dependent protein kinase. (2005). https://pubmed.ncbi.nlm.nih.gov/15691846/ DOI: 10.1074/jbc.M410917200 Access: Primary PubMed abstract and indexed metadata reviewed. Full-text method details not stated here remain unresolved.
    Complete structured claim and evidence

  2. MCOLN1-dependent lysosomal calcium release activated calcineurin.

    Human mucolipin-1 / MCOLN1 → Lysosomal calcium release source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Lysosomal signaling and starvation experiments in cultured cells.
    limitations
    Local calcium release is not equivalent to blood calcium or taking calcium.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    A local calcium signal linked the lysosome to a phosphatase.
    primary_references
    Lysosomal calcium signalling regulates autophagy through calcineurin and ​TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 328–334

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Lysosomal signaling and starvation experiments in cultured cells. · source_derived_draft · unverified_draft

    ## fast-lysosomal-calcium A local calcium signal linked the lysosome to a phosphatase. MCOLN1-dependent lysosomal calcium release activated calcineurin. Model: Lysosomal signaling and starvation experiments in cultured cells. Limitations: Local calcium release is not equivalent to blood calcium or taking calcium. Evidence access: Primary abstract Lysosomal calcium signalling regulates autophagy through calcineurin and ​TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114
    Complete structured claim and evidence

  3. Autophagy and lysosomal biogenesis through TFEB required MCOLN1-mediated calcineurin activation.

    Human transcription factor EB / TFEB → Lysosomal biogenesis source_derived_draftungraded
    Experimental context and source evidence
    evidence_access
    Primary abstract
    experimental_model
    Cellular starvation and mouse exercise experiments.
    limitations
    Lysosome abundance alone is not proof of increased degradation flux.
    nutrient_topic
    Fasting physiological-state collection; human protocols, cellular deprivation and refeeding are distinguished. · Fasting / abstention from energy intake
    plain_language
    The signal helped build the cell’s recycling capacity.
    primary_references
    Lysosomal calcium signalling regulates autophagy through calcineurin and ​TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114

    Fasting: fuel switching, nutrient sensing, ketone signaling, nutrient dependencies and refeeding (2026-09-18) · lines 344–350

    AI-assisted research curation; primary-abstract references and experimental limitations individually identified. Not publisher full text. · supports · Cellular starvation and mouse exercise experiments. · source_derived_draft · unverified_draft

    ## fast-tfeb-biogenesis The signal helped build the cell’s recycling capacity. Autophagy and lysosomal biogenesis through TFEB required MCOLN1-mediated calcineurin activation. Model: Cellular starvation and mouse exercise experiments. Limitations: Lysosome abundance alone is not proof of increased degradation flux. Evidence access: Primary abstract Lysosomal calcium signalling regulates autophagy through calcineurin and ​TFEB. · 2015 · https://pubmed.ncbi.nlm.nih.gov/25720963/ · DOI 10.1038/ncb3114
    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