Retinoid X receptor alpha

evidence_locator

Figure 2

experimental_model

Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters.

exposure

Receptor coexpression/reconstitution

limitations

Synthetic response elements; not every genomic site.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors

plain_language

Two distinct receptor proteins assemble a DNA-binding complex.

primary_references

[va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

tissue_or_cell_type

Cell-free DNA-binding assay

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1082–1093

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. · source_derived_draft · unverified_draft

### va-sig-rara-rxra-cooperative-binding RXRA associated with RARA and cooperatively bound retinoid response DNA. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Two distinct receptor proteins assemble a DNA-binding complex. organism: Recombinant receptors tissue_or_cell_type: Cell-free DNA-binding assay experimental_model: Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. limitations: Synthetic response elements; not every genomic site. evidence_locator: Figure 2 exposure: Receptor coexpression/reconstitution [va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

evidence_locator

Abstract

experimental_model

Receptor interaction, DNA binding and transfection experiments.

exposure

Receptor cotransfection and RA

limitations

Reporter-system dependence; no nutrient dose response.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Engineered cellular receptor system

plain_language

RXRA can assist RAR signaling without equivalent activation of both partners.

primary_references

[va-zhang-1992] Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors (1992). https://pubmed.ncbi.nlm.nih.gov/1310350/ DOI: 10.1038/355441a0

tissue_or_cell_type

Transfection reporters

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1123–1134

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Receptor interaction, DNA binding and transfection experiments. · source_derived_draft · unverified_draft

### va-sig-rxra-rar-transactivation RXRA enhanced RAR-mediated transcription at RA concentrations insufficient to substantially activate RXRA itself. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RXRA can assist RAR signaling without equivalent activation of both partners. organism: Engineered cellular receptor system tissue_or_cell_type: Transfection reporters experimental_model: Receptor interaction, DNA binding and transfection experiments. limitations: Reporter-system dependence; no nutrient dose response. evidence_locator: Abstract exposure: Receptor cotransfection and RA [va-zhang-1992] Retinoid X receptor is an auxiliary protein for thyroid hormone and retinoic acid receptors (1992). https://pubmed.ncbi.nlm.nih.gov/1310350/ DOI: 10.1038/355441a0

cross_nutrient

Vitamin A-iodine: shared receptor machinery for an iodine-containing hormone; not evidence of iodine repletion.

evidence_locator

Figure 3

experimental_model

Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters.

exposure

Reconstituted TR beta/RXRA

limitations

No iodine nutritional manipulation.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors

plain_language

A receptor used by retinoids also supports thyroid-hormone DNA recognition.

primary_references

[va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

tissue_or_cell_type

Cell-free DNA-binding assay

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1109–1121

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. · source_derived_draft · unverified_draft

### va-sig-rxra-thrb-partnership RXRA complexed with TR beta and enhanced thyroid-response-element binding. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor used by retinoids also supports thyroid-hormone DNA recognition. organism: Recombinant receptors tissue_or_cell_type: Cell-free DNA-binding assay experimental_model: Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. limitations: No iodine nutritional manipulation. evidence_locator: Figure 3 cross_nutrient: Vitamin A-iodine: shared receptor machinery for an iodine-containing hormone; not evidence of iodine repletion. exposure: Reconstituted TR beta/RXRA [va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

cross_nutrient

Vitamin A-vitamin D: shared receptor partner; no supplementation or deficiency rescue tested.

evidence_locator

Figure 3

experimental_model

Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters.

exposure

Reconstituted VDR/RXRA

limitations

Does not prove vitamin A intake enhances calcium absorption.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors

plain_language

Vitamin D signaling shares RXRA receptor machinery with retinoid pathways.

primary_references

[va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

tissue_or_cell_type

Cell-free DNA-binding assay

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1095–1107

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. · source_derived_draft · unverified_draft

### va-sig-rxra-vdr-partnership RXRA formed a VDR complex and enhanced binding to the osteopontin vitamin D response element. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin D signaling shares RXRA receptor machinery with retinoid pathways. organism: Recombinant receptors tissue_or_cell_type: Cell-free DNA-binding assay experimental_model: Recombinant receptors, gel shifts, coimmunoprecipitation and CV-1 reporters. limitations: Does not prove vitamin A intake enhances calcium absorption. evidence_locator: Figure 3 cross_nutrient: Vitamin A-vitamin D: shared receptor partner; no supplementation or deficiency rescue tested. exposure: Reconstituted VDR/RXRA [va-kliewer-1992] Retinoid X receptor interacts with nuclear receptors in retinoic acid, thyroid hormone and vitamin D3 signalling (1992). https://pubmed.ncbi.nlm.nih.gov/1310351/ DOI: 10.1038/355446a0

cross_nutrient

Vitamin D–calcium–phosphate regulation.

evidence_locator

Abstract: reported experimental results

evidence_scope

D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison.

experimental_model

Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays

exposure

Calcitriol-treated cell and reporter systems; dose and time vary by experiment and are not specified in the retrieved abstract.

limitations

Enhancer activation is distinct from a fracture outcome. The human and mouse regulatory landscapes are not asserted to be identical.

nutrient

Vitamin D2 and D3 · Vitamin D2 and D3

nutrient_topic

Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin D2 and D3

organism

Mus musculus

plain_language

Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions.

primary_references

[vdm-meyer2006rankl] Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. (2006). https://pubmed.ncbi.nlm.nih.gov/16914732/ DOI: 10.1128/mcb.00353-06

tissue_or_cell_type

Osteoblastic cell chromatin

Vitamin D2 and D3: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 841–855

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays · source_derived_draft · unverified_draft

### vdm-calcitriol-rankl-distal-enhancer Calcitriol activated mouse Rankl transcription through distal VDR/RXR-associated regulatory regions, including a functional element about 76 kb upstream. Condition category: normal nutrient_topic: Vitamin D2 and D3 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Active vitamin D can induce the osteoclast-development signal RANKL through distant DNA control regions. organism: Mus musculus tissue_or_cell_type: Osteoblastic cell chromatin experimental_model: Mouse osteoblastic cells; VDR/RXR ChIP-chip, reporter mutagenesis and transcriptional assays limitations: Enhancer activation is distinct from a fracture outcome. The human and mouse regulatory landscapes are not asserted to be identical. exposure: Calcitriol-treated cell and reporter systems; dose and time vary by experiment and are not specified in the retrieved abstract. cross_nutrient: Vitamin D–calcium–phosphate regulation. evidence_locator: Abstract: reported experimental results nutrient: Vitamin D2 and D3 evidence_scope: D3 active metabolite or VDR machinery experiment; not a direct D2-versus-D3 comparison. [vdm-meyer2006rankl] Activation of receptor activator of NF-kappaB ligand gene expression by 1,25-dihydroxyvitamin D3 is mediated through multiple long-range enhancers. (2006). https://pubmed.ncbi.nlm.nih.gov/16914732/ DOI: 10.1128/mcb.00353-06

cross_nutrient

An iodine-containing hormone binds THRB in a complex with the retinoid receptor RXRA; no nutritional vitamin A manipulation.

evidence_locator

Figure 2a and Results: structural characterization; Methods: protein production and crystallography

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 2a and Results: structural characterization; Methods: protein production and crystallography", "start_char": 10702, "end_char": 12152}]

experimental_model

Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays

exposure

Human THRB residues 202–461 and RXRA residues 223–462; threefold molar excess of T3 and synthetic HKILHRLL SRC-2 peptide; structure refined at anisotropic 3.2–3.8 angstrom resolution.

limitations

Isolated domains and an eight-residue peptide, not full-length coactivator recruitment in tissue. The structure establishes binding geometry, not a physiological T3 threshold.

nutrient_topic

Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine

organism

Human receptor domains produced in Escherichia coli; synthetic coactivator peptide

plain_language

T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator.

primary_references

[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013

tissue_or_cell_type

Purified receptor-domain complex

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1172–1185

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays · source_derived_draft · unverified_draft

### i-met-t3-thrb-ligand-binding T3 was bound within the human THRB ligand-binding domain in the crystallized THRB–RXRA domain heterodimer, with the THRB activation surface accommodating an SRC-2-derived peptide. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: T3 physically occupies its receptor, which presents a docking surface for a transcription coactivator. organism: Human receptor domains produced in Escherichia coli; synthetic coactivator peptide tissue_or_cell_type: Purified receptor-domain complex experimental_model: Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays limitations: Isolated domains and an eight-residue peptide, not full-length coactivator recruitment in tissue. The structure establishes binding geometry, not a physiological T3 threshold. exposure: Human THRB residues 202–461 and RXRA residues 223–462; threefold molar excess of T3 and synthetic HKILHRLL SRC-2 peptide; structure refined at anisotropic 3.2–3.8 angstrom resolution. cross_nutrient: An iodine-containing hormone binds THRB in a complex with the retinoid receptor RXRA; no nutritional vitamin A manipulation. evidence_locator: Figure 2a and Results: structural characterization; Methods: protein production and crystallography evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 2a and Results: structural characterization; Methods: protein production and crystallography", "start_char": 10702, "end_char": 12152}] [i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013

cross_nutrient

Human thyroid and retinoid receptor machinery jointly support the measured iodine-containing-hormone response; this does not establish dietary vitamin A dependence.

evidence_locator

Figure 1b and legend; Methods: Cell-based assays

evidence_spans

[{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 1b and legend; Methods: Cell-based assays", "start_char": 45264, "end_char": 46014}]

experimental_model

Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays

exposure

1 micromolar T3 for 24 hours versus vehicle, with THRB/RXRA expression plasmids and a DR4 thyroid-response luciferase reporter; quadruplicate wells and at least two experiments.

limitations

Engineered reporter and receptor overexpression; cannot infer that every endogenous gene is activated by T3 or that dietary iodine or vitamin A improves this signal.

nutrient_topic

Iodine research collection; topical membership is not evidence of a direct dietary effect. · Iodine

organism

Full-length human receptors expressed in African green monkey CV-1 cells

plain_language

Binding of the hormone can be translated into a gene-regulatory signal through its receptor.

primary_references

[i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013

tissue_or_cell_type

CV-1 reporter assay

Iodine: thyroid hormone production, deficiency, excess and nutrient interactions (2026-09-17) · lines 1187–1200

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays · source_derived_draft · unverified_draft

### i-met-t3-thrb-transcription T3 increased thyroid-response-element luciferase activity in CV-1 cells transfected with full-length human THRB and RXRA. Condition category: normal nutrient_topic: Iodine research collection; topical membership is not evidence of a direct dietary effect. plain_language: Binding of the hormone can be translated into a gene-regulatory signal through its receptor. organism: Full-length human receptors expressed in African green monkey CV-1 cells tissue_or_cell_type: CV-1 reporter assay experimental_model: Human TR beta/RXR alpha ligand-binding-domain crystallography; full-length human receptors in CV-1 reporter assays limitations: Engineered reporter and receptor overexpression; cannot infer that every endogenous gene is activated by T3 or that dietary iodine or vitamin A improves this signal. exposure: 1 micromolar T3 for 24 hours versus vehicle, with THRB/RXRA expression plasmids and a DR4 thyroid-response luciferase reporter; quadruplicate wells and at least two experiments. cross_nutrient: Human thyroid and retinoid receptor machinery jointly support the measured iodine-containing-hormone response; this does not establish dietary vitamin A dependence. evidence_locator: Figure 1b and legend; Methods: Cell-based assays evidence_spans: [{"source_document": "artifacts/iodine-metabolism-sources/26289479.txt", "locator": "Figure 1b and legend; Methods: Cell-based assays", "start_char": 45264, "end_char": 46014}] [i-met-26289479] Structural mechanism for signal transduction in RXR nuclear receptor heterodimers. (2015). https://pubmed.ncbi.nlm.nih.gov/26289479/ DOI: 10.1038/ncomms9013

evidence_locator

Abstract

experimental_model

Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters.

exposure

Isomer competition

limitations

Cell metabolism can alter apparent reporter responses.

nutrient_topic

Vitamin A research collection; topical membership is not evidence of a direct dietary effect. · Vitamin A

organism

Recombinant receptors in COS-1 cells

plain_language

RAR and RXR cannot be treated as interchangeable RA receptors.

primary_references

[va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30

tissue_or_cell_type

Nuclear extracts

Vitamin A: forms, mechanisms, deficiency and excess (2026-09-17) · lines 1056–1067

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. · source_derived_draft · unverified_draft

### va-sig-atra-rxr-selectivity All-trans RA did not effectively compete for RXR binding in the tested isomer assay. Condition category: normal nutrient_topic: Vitamin A research collection; topical membership is not evidence of a direct dietary effect. plain_language: RAR and RXR cannot be treated as interchangeable RA receptors. organism: Recombinant receptors in COS-1 cells tissue_or_cell_type: Nuclear extracts experimental_model: Transfected COS-1 nucleosol; ligand competition and chimeric receptor reporters. limitations: Cell metabolism can alter apparent reporter responses. evidence_locator: Abstract exposure: Isomer competition [va-allenby-1993] Retinoic acid receptors and retinoid X receptors: interactions with endogenous retinoic acids (1993). https://pubmed.ncbi.nlm.nih.gov/8380496/ DOI: 10.1073/pnas.90.1.30