Component

Endoplasmic reticulum

The organelle containing the calcium store and pathway machinery.

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 acts on it

  1. Tagged human HACL2 colocalized with an ER marker and partitioned into the membrane fraction in HeLa cells.

    Human 2-hydroxyacyl-CoA lyase 2 / HACL2 → Endoplasmic reticulum source_derived_draftungraded
    Experimental context and source evidence
    evidence
    [{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-47", "p-48"], "locator": "HACL2 is an ER membrane protein", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}]
    experimental_model
    Human HACL2 immunofluorescence and fractionation.
    limitations
    Tagged overexpression localization.
    nutrient
    Thiamine (vitamin B1) · Thiamine (vitamin B1)
    nutrient_topic
    Thiamine research collection; topical membership is not evidence of a direct dietary effect. · Thiamine (vitamin B1)
    organism
    Homo sapiens
    plain_language
    This B1-dependent lipid-cleavage protein is associated with ER membranes; its location differs from peroxisomal HACL1.
    primary_references
    [kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
    tissue_or_cell_type
    Transfected HeLa cells

    Thiamine: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 1031–1042

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HACL2 immunofluorescence and fractionation. · source_derived_draft · unverified_draft

    ### b1-hacl2-er-localization Tagged human HACL2 colocalized with an ER marker and partitioned into the membrane fraction in HeLa cells. Condition category: normal nutrient_topic: Thiamine research collection; topical membership is not evidence of a direct dietary effect. plain_language: This B1-dependent lipid-cleavage protein is associated with ER membranes; its location differs from peroxisomal HACL1. organism: Homo sapiens tissue_or_cell_type: Transfected HeLa cells experimental_model: Human HACL2 immunofluorescence and fractionation. limitations: Tagged overexpression localization. evidence: [{"paper_key": "kitamura-2017-hacl2", "source_bundle": "artifacts/thiamine_metabolism_sources.json", "passage_ids": ["p-47", "p-48"], "locator": "HACL2 is an ER membrane protein", "preservation": "Exact text retained in the source bundle; full source document retained when openly retrievable."}] nutrient: Thiamine (vitamin B1) [kitamura-2017-hacl2] Phytosphingosine degradation pathway includes fatty acid α-oxidation reactions in the endoplasmic reticulum (2017). https://pubmed.ncbi.nlm.nih.gov/28289220/ DOI: 10.1073/pnas.1700138114
    Complete structured claim and evidence

  2. Human SLC5A6 R123L-GFP was predominantly retained in the endoplasmic reticulum; ER-marker colocalization supported this localization.

    Human SLC5A6 R123L protein variant → Endoplasmic reticulum source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants
    exposure
    Live-cell confocal imaging 48 hours after transfection; hSMVT-GFP versus R123L-GFP and DsRed-ER.
    limitations
    Some mutant signal remained at the cell surface. Fluorescent-fusion localization does not prove zero residual activity or a dietary treatment response.
    nutrient_topic
    Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. · Pantothenate (vitamin B5)
    organism
    Homo sapiens
    plain_language
    The R123L transporter is largely trapped inside the cell instead of reaching its working surface.
    primary_references
    [b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x
    tissue_or_cell_type
    HuTu-80 and U87 cells; ER-marker colocalization shown in HuTu-80
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Pantothenic acid (vitamin B5): coenzyme A, deficiency and nutrient interactions (2026-09-17) · lines 366–377

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants · source_derived_draft · unverified_draft

    ### b5-trans-r123l-er-retention Human SLC5A6 R123L-GFP was predominantly retained in the endoplasmic reticulum; ER-marker colocalization supported this localization. Condition category: machinery_impairment nutrient_topic: Pantothenic acid (vitamin B5) research collection; topical membership is not evidence of a direct dietary effect. plain_language: The R123L transporter is largely trapped inside the cell instead of reaching its working surface. organism: Homo sapiens tissue_or_cell_type: HuTu-80 and U87 cells; ER-marker colocalization shown in HuTu-80 experimental_model: Human intestinal HuTu-80 and brain-derived U87 cell transfection and live-cell imaging of patient-derived SLC5A6 variants limitations: Some mutant signal remained at the cell surface. Fluorescent-fusion localization does not prove zero residual activity or a dietary treatment response. exposure: Live-cell confocal imaging 48 hours after transfection; hSMVT-GFP versus R123L-GFP and DsRed-ER. cross_nutrient: false [b5-trans-slc5a6-variants2017] Mutations in SLC5A6 associated with brain, immune, bone, and intestinal dysfunction in a young child. (2017). https://pubmed.ncbi.nlm.nih.gov/27904971/ DOI: 10.1007/s00439-016-1751-x
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. ER-store depletion causes STIM1 to redistribute into peripheral puncta through a mechanism requiring its luminal calcium-sensing region.

    STIM1 → Calcium ion source_derived_draftungraded
    Experimental context and source evidence
    compartment_description
    ER lumen and ER-plasma-membrane junctions
    experimental_model
    Human HeLa cells; RNA interference screen, calcium imaging and STIM1 EF-hand mutagenesis
    limitations
    Local store depletion is a cellular signal, not evidence of dietary calcium deficiency.
    nutrient_topic
    Calcium research collection; topical membership is not evidence of a direct dietary effect. · Calcium
    organism
    Homo sapiens
    plain_language
    STIM1 detects falling calcium inside the ER.
    primary_references
    [ca-liou2005] STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx (2005). https://pubmed.ncbi.nlm.nih.gov/16005298/ DOI: 10.1016/j.cub.2005.05.055
    research_relationship_category
    regulation
    tissue_or_cell_type
    HeLa cells

    Calcium: mechanism-first literature curation (2026-09-17) · lines 505–516

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HeLa cells; RNA interference screen, calcium imaging and STIM1 EF-hand mutagenesis · source_derived_draft · unverified_draft

    ### ca-stim1-store-sensing ER-store depletion causes STIM1 to redistribute into peripheral puncta through a mechanism requiring its luminal calcium-sensing region. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: STIM1 detects falling calcium inside the ER. organism: Homo sapiens tissue_or_cell_type: HeLa cells experimental_model: Human HeLa cells; RNA interference screen, calcium imaging and STIM1 EF-hand mutagenesis limitations: Local store depletion is a cellular signal, not evidence of dietary calcium deficiency. research_relationship_category: regulation compartment_description: ER lumen and ER-plasma-membrane junctions [ca-liou2005] STIM is a Ca2+ sensor essential for Ca2+-store-depletion-triggered Ca2+ influx (2005). https://pubmed.ncbi.nlm.nih.gov/16005298/ DOI: 10.1016/j.cub.2005.05.055
    Complete structured claim and evidence

  2. In HuH7 cells expressing human ABCD4-HA, adding LMBD1-GFP shifted ABCD4 from an ER-like distribution toward LAMP1-positive lysosomes.

    Human LMBD1 lysosomal membrane protein → Human ABCD4 lysosomal cobalamin transporter source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    evidence_location
    Results: Figures 1, 6, 7; Methods: cell lines and CRISPR
    experimental_model
    Human HuH7 tagged-protein localization
    exposure
    ABCD4-HA stable expression and transient LMBD1-GFP
    limitations
    Tagged overexpression; colocalization does not measure cobalamin flux.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    LMBD1 helped the B12 transporter reach lysosomes.
    primary_references
    [kawaguchi-2016-lmbd1-escort] Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1 (2016). https://pubmed.ncbi.nlm.nih.gov/27456980/ DOI: 10.1038/srep30183
    tissue_or_cell_type
    Hepatoma cell line

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 571–583

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HuH7 tagged-protein localization · source_derived_draft · unverified_draft

    ### b12-lmbrd1-escort-huh7 In HuH7 cells expressing human ABCD4-HA, adding LMBD1-GFP shifted ABCD4 from an ER-like distribution toward LAMP1-positive lysosomes. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: LMBD1 helped the B12 transporter reach lysosomes. organism: Homo sapiens tissue_or_cell_type: Hepatoma cell line experimental_model: Human HuH7 tagged-protein localization limitations: Tagged overexpression; colocalization does not measure cobalamin flux. exposure: ABCD4-HA stable expression and transient LMBD1-GFP cross_nutrient: false evidence_location: Results: Figures 1, 6, 7; Methods: cell lines and CRISPR [kawaguchi-2016-lmbd1-escort] Translocation of the ABC transporter ABCD4 from the endoplasmic reticulum to lysosomes requires the escort protein LMBD1 (2016). https://pubmed.ncbi.nlm.nih.gov/27456980/ DOI: 10.1038/srep30183
    Complete structured claim and evidence

  3. Functional IP3R enables release of calcium from the ER.

    Stable functional IP3R → ER calcium release 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

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