Component

Intestine-specific homeobox protein / ISX

Independent protein identity; organism and experimental state are specified on individual claims.

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

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. ISX recognized upstream BCO1 regulatory motifs and repressed its expression.

    Experimental context and source evidence
    evidence_location
    Abstract
    experimental_model
    Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets.
    exposure
    ISX binding and gene-expression experiments.
    limitations
    Does not establish a fixed carotenoid conversion ratio.
    nutrient_topic
    Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
    organism
    Mus musculus and promoter-binding preparations
    outcome
    ISX recognized upstream BCO1 regulatory motifs and repressed its expression.
    plain_language
    The same feedback factor limits the carotenoid-cleaving enzyme.
    primary_references
    [va-widjajaadhi-2015] A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4424956/ DOI: 10.1093/hmg/ddv072
    tissue_or_cell_type
    Intestinal epithelium

    Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 288–300

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets. · source_derived_draft · unverified_draft

    ### va-isx-bco1-repression ISX recognized upstream BCO1 regulatory motifs and repressed its expression. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The same feedback factor limits the carotenoid-cleaving enzyme. organism: Mus musculus and promoter-binding preparations tissue_or_cell_type: Intestinal epithelium experimental_model: Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets. limitations: Does not establish a fixed carotenoid conversion ratio. exposure: ISX binding and gene-expression experiments. outcome: ISX recognized upstream BCO1 regulatory motifs and repressed its expression. evidence_location: Abstract [va-widjajaadhi-2015] A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4424956/ DOI: 10.1093/hmg/ddv072
    Complete structured claim and evidence
  2. Isx-deficient mice had higher hepatic alpha-tocopherol; the Isx/Bco2 double mutant showed about twice wild-type levels.

    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    Retinoid/ISX control of a shared intestinal transporter affects vitamin E status.
    evidence_location
    Figure 7
    experimental_model
    Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets.
    exposure
    Females; ten weeks of AIN93G with 75 IU vitamin E/kg, with or without 50 mg zeaxanthin/kg.
    limitations
    Accumulation is not a clinical benefit; compound mutants had a larger effect than Isx single mutants.
    nutrient_topic
    Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
    organism
    Mus musculus
    outcome
    Isx-deficient mice had higher hepatic alpha-tocopherol; the Isx/Bco2 double mutant showed about twice wild-type levels.
    plain_language
    Disrupting vitamin A feedback also changed vitamin E accumulation.
    primary_references
    [va-widjajaadhi-2015] A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4424956/ DOI: 10.1093/hmg/ddv072
    tissue_or_cell_type
    Jejunum and liver
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 302–315

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets. · source_derived_draft · unverified_draft

    ### va-isx-loss-tocopherol Isx-deficient mice had higher hepatic alpha-tocopherol; the Isx/Bco2 double mutant showed about twice wild-type levels. Condition category: machinery_impairment nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Disrupting vitamin A feedback also changed vitamin E accumulation. organism: Mus musculus tissue_or_cell_type: Jejunum and liver experimental_model: Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets. limitations: Accumulation is not a clinical benefit; compound mutants had a larger effect than Isx single mutants. exposure: Females; ten weeks of AIN93G with 75 IU vitamin E/kg, with or without 50 mg zeaxanthin/kg. outcome: Isx-deficient mice had higher hepatic alpha-tocopherol; the Isx/Bco2 double mutant showed about twice wild-type levels. evidence_location: Figure 7 cross_nutrient: Retinoid/ISX control of a shared intestinal transporter affects vitamin E status. [va-widjajaadhi-2015] A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4424956/ DOI: 10.1093/hmg/ddv072
    Complete structured claim and evidence
  3. ISX bound upstream SCARB1 regulatory motifs and repressed intestinal SCARB1 expression.

    Experimental context and source evidence
    evidence_location
    Abstract
    experimental_model
    Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets.
    exposure
    Isx genotypes and promoter-binding experiments.
    limitations
    Tissue-specific regulation, not suppression in every organ.
    nutrient_topic
    Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
    organism
    Mus musculus and promoter-binding preparations
    outcome
    ISX bound upstream SCARB1 regulatory motifs and repressed intestinal SCARB1 expression.
    plain_language
    The feedback factor lowers the uptake receptor.
    primary_references
    [va-widjajaadhi-2015] A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4424956/ DOI: 10.1093/hmg/ddv072
    tissue_or_cell_type
    Jejunum and DNA-binding assays

    Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 274–286

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets. · source_derived_draft · unverified_draft

    ### va-isx-scarb1-repression ISX bound upstream SCARB1 regulatory motifs and repressed intestinal SCARB1 expression. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The feedback factor lowers the uptake receptor. organism: Mus musculus and promoter-binding preparations tissue_or_cell_type: Jejunum and DNA-binding assays experimental_model: Isx, Bco1, Bco2 and Scarb1 mouse mutants; promoter binding and controlled diets. limitations: Tissue-specific regulation, not suppression in every organ. exposure: Isx genotypes and promoter-binding experiments. outcome: ISX bound upstream SCARB1 regulatory motifs and repressed intestinal SCARB1 expression. evidence_location: Abstract [va-widjajaadhi-2015] A genetic dissection of intestinal fat-soluble vitamin and carotenoid absorption (2015). https://pmc.ncbi.nlm.nih.gov/articles/PMC4424956/ DOI: 10.1093/hmg/ddv072
    Complete structured claim and evidence

What acts on it

  1. Retinoic-acid receptor signaling increased intestinal ISX expression.

    Experimental context and source evidence
    evidence_location
    Abstract
    experimental_model
    Mouse diet/retinoic-acid interventions and human cell lines.
    exposure
    Retinoic-acid treatment with receptor-dependent tests.
    limitations
    Pharmacological treatment supports feedback circuitry, not a universal dietary threshold.
    nutrient_topic
    Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A
    organism
    Mus musculus and Homo sapiens cell lines
    outcome
    Retinoic-acid receptor signaling increased intestinal ISX expression.
    plain_language
    The active retinoid metabolite induces a brake on further precursor uptake.
    primary_references
    [va-lobo-2010] ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production (2010). https://pubmed.ncbi.nlm.nih.gov/20061533/ DOI: 10.1096/fj.09-150995
    tissue_or_cell_type
    Intestine and cultured cells

    Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 260–272

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse diet/retinoic-acid interventions and human cell lines. · source_derived_draft · unverified_draft

    ### va-retinoic-acid-isx-feedback Retinoic-acid receptor signaling increased intestinal ISX expression. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: The active retinoid metabolite induces a brake on further precursor uptake. organism: Mus musculus and Homo sapiens cell lines tissue_or_cell_type: Intestine and cultured cells experimental_model: Mouse diet/retinoic-acid interventions and human cell lines. limitations: Pharmacological treatment supports feedback circuitry, not a universal dietary threshold. exposure: Retinoic-acid treatment with receptor-dependent tests. outcome: Retinoic-acid receptor signaling increased intestinal ISX expression. evidence_location: Abstract [va-lobo-2010] ISX is a retinoic acid-sensitive gatekeeper that controls intestinal beta,beta-carotene absorption and vitamin A production (2010). https://pubmed.ncbi.nlm.nih.gov/20061533/ DOI: 10.1096/fj.09-150995
    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