Plasma membrane

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/sodium-research/9109432.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "019508b2d05ec7e21a73ff66bdea9a0b09c6c7e7d8e404de3db49b2a0825ebbe", "start_char": 0, "end_char": 1389, "text_sha256": "019508b2d05ec7e21a73ff66bdea9a0b09c6c7e7d8e404de3db49b2a0825ebbe"}

experimental_model

Human family genetics and transfected COS-cell transport assays

exposure

L243P, T262M and double-mutant constructs

limitations

Family-specific genetic disease; loss of bile-acid transport was tested, whereas individual fat-soluble-vitamin deficiencies were not.

nutrient_topic

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

organism

Human SLC10A2

plain_language

A transporter can reach the right place but still fail to carry its cargo.

primary_references

[sodium-p9109432] Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). (1997). https://pubmed.ncbi.nlm.nih.gov/9109432/ DOI: 10.1172/jci119355

tissue_or_cell_type

Ileal bile-acid transporter

trigger_kind

machinery_impairment Imported condition classification; unverified.

Sodium: gradients, nutrient transport, fluid regulation and loss states (2026-09-17) · lines 655–666

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human family genetics and transfected COS-cell transport assays · source_derived_draft · unverified_draft

### sodium-asbt-trafficking The dysfunctional L243P/T262M constructs retained protein expression and plasma-membrane trafficking. Condition category: machinery_impairment nutrient_topic: Sodium research collection; topical membership is not evidence of a direct dietary effect. plain_language: A transporter can reach the right place but still fail to carry its cargo. organism: Human SLC10A2 tissue_or_cell_type: Ileal bile-acid transporter experimental_model: Human family genetics and transfected COS-cell transport assays limitations: Family-specific genetic disease; loss of bile-acid transport was tested, whereas individual fat-soluble-vitamin deficiencies were not. exposure: L243P, T262M and double-mutant constructs evidence_span: {"source_cache": "artifacts/sodium-research/9109432.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "019508b2d05ec7e21a73ff66bdea9a0b09c6c7e7d8e404de3db49b2a0825ebbe", "start_char": 0, "end_char": 1389, "text_sha256": "019508b2d05ec7e21a73ff66bdea9a0b09c6c7e7d8e404de3db49b2a0825ebbe"} [sodium-p9109432] Primary bile acid malabsorption caused by mutations in the ileal sodium-dependent bile acid transporter gene (SLC10A2). (1997). https://pubmed.ncbi.nlm.nih.gov/9109432/ DOI: 10.1172/jci119355

compartment_description

Extracellular medium to oocyte

experimental_model

Heterologous expression and radiotracer uptake

limitations

Influx in this model does not establish physiological PPi efflux; retain alongside later ATP-release results.

nutrient_topic

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

organism

Mus musculus protein in Xenopus laevis oocytes

plain_language

An earlier assay measured movement into an egg cell, not export from human bone cells.

primary_references

[gurley2006] Biochemical and genetic analysis of ANK in arthritis and bone disease (2006). https://pubmed.ncbi.nlm.nih.gov/17186460/ DOI: 10.1086/509881

tissue_or_cell_type

Oocyte plasma membrane

Calcium: mechanism-first literature curation (2026-09-17) · lines 988–998

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Heterologous expression and radiotracer uptake · source_derived_draft · unverified_draft

### ank-dependent-ppi-uptake-oocytes Mouse ANK expression increased saturable radiolabeled PPi uptake into Xenopus oocytes. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An earlier assay measured movement into an egg cell, not export from human bone cells. organism: Mus musculus protein in Xenopus laevis oocytes tissue_or_cell_type: Oocyte plasma membrane experimental_model: Heterologous expression and radiotracer uptake limitations: Influx in this model does not establish physiological PPi efflux; retain alongside later ATP-release results. compartment_description: Extracellular medium to oocyte [gurley2006] Biochemical and genetic analysis of ANK in arthritis and bone disease (2006). https://pubmed.ncbi.nlm.nih.gov/17186460/ DOI: 10.1086/509881

compartment_description

Cytosol to extracellular medium

experimental_model

ANKH expression with ENPP1 deletion controls

limitations

Cellular export assay; it does not determine purified ANKH transport stoichiometry in every tissue.

nutrient_topic

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

organism

Homo sapiens

plain_language

ANKH can provide extracellular ATP for subsequent PPi production.

primary_references

[szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528

tissue_or_cell_type

HEK293 cells

Calcium: mechanism-first literature curation (2026-09-17) · lines 1000–1010

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · ANKH expression with ENPP1 deletion controls · source_derived_draft · unverified_draft

### ankh-atp-export ANKH expression drove ATP release from HEK293 cells even when ENPP1 was absent. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ANKH can provide extracellular ATP for subsequent PPi production. organism: Homo sapiens tissue_or_cell_type: HEK293 cells experimental_model: ANKH expression with ENPP1 deletion controls limitations: Cellular export assay; it does not determine purified ANKH transport stoichiometry in every tissue. compartment_description: Cytosol to extracellular medium [szeri2022] The mineralization regulator ANKH mediates cellular efflux of ATP, not pyrophosphate (2022). https://pmc.ncbi.nlm.nih.gov/articles/PMC9098669/ DOI: 10.1002/jbmr.4528

compartment_description

Plasma membrane

experimental_model

Ank genetics and cell PPi measurements

limitations

Historical hypothesis, not a current unconditional transport assignment; later ATP/ENPP1 experiments require qualification.

nutrient_topic

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

organism

Mus musculus protein; cultured mammalian cells

plain_language

An older transport explanation was inferred from changes in PPi distribution.

primary_references

[ho2000] Role of the mouse ank gene in control of tissue calcification and arthritis (2000). https://pubmed.ncbi.nlm.nih.gov/10894769/ DOI: 10.1126/science.289.5477.265

tissue_or_cell_type

Joint-calcification context

Calcium: mechanism-first literature curation (2026-09-17) · lines 976–986

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Ank genetics and cell PPi measurements · source_derived_draft · unverified_draft

### ankh-historical-direct-ppi-export-hypothesis Early ANK-dependent changes in cellular and extracellular PPi motivated a proposal that ANK directly exports PPi. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: An older transport explanation was inferred from changes in PPi distribution. organism: Mus musculus protein; cultured mammalian cells tissue_or_cell_type: Joint-calcification context experimental_model: Ank genetics and cell PPi measurements limitations: Historical hypothesis, not a current unconditional transport assignment; later ATP/ENPP1 experiments require qualification. compartment_description: Plasma membrane [ho2000] Role of the mouse ank gene in control of tissue calcification and arthritis (2000). https://pubmed.ncbi.nlm.nih.gov/10894769/ DOI: 10.1126/science.289.5477.265

compartment_description

Plasma membrane

experimental_model

Human erythrocyte membrane ghosts with purified human or bovine calmodulin

limitations

Membrane ghosts with controlled additions; pump isoforms were not resolved and this is not an intact-cell dose response.

nutrient_topic

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

organism

Homo sapiens

plain_language

Calmodulin makes the red-cell calcium pump respond more strongly to calcium.

primary_references

[ca-roufogalis1980] Regulation by calmodulin of the calcium affinity of the calcium-transport ATPase in human erythrocytes (1980). https://pubmed.ncbi.nlm.nih.gov/6109558/ DOI: 10.1139/o80-126

research_relationship_category

regulation

tissue_or_cell_type

Erythrocyte membranes

Calcium: mechanism-first literature curation (2026-09-17) · lines 612–623

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human erythrocyte membrane ghosts with purified human or bovine calmodulin · source_derived_draft · unverified_draft

### ca-calmodulin-pmca-affinity Calmodulin increases apparent calcium affinity and ATPase activity of the erythrocyte calcium pump. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calmodulin makes the red-cell calcium pump respond more strongly to calcium. organism: Homo sapiens tissue_or_cell_type: Erythrocyte membranes experimental_model: Human erythrocyte membrane ghosts with purified human or bovine calmodulin limitations: Membrane ghosts with controlled additions; pump isoforms were not resolved and this is not an intact-cell dose response. research_relationship_category: regulation compartment_description: Plasma membrane [ca-roufogalis1980] Regulation by calmodulin of the calcium affinity of the calcium-transport ATPase in human erythrocytes (1980). https://pubmed.ncbi.nlm.nih.gov/6109558/ DOI: 10.1139/o80-126

compartment_description

Plasma membrane

experimental_model

Human cardiac NCX1; cryo-EM and functional exchange assays

limitations

Net direction depends on electrochemical gradients and voltage; NCX1 is not an ATP-hydrolyzing pump.

nutrient_topic

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

organism

Homo sapiens

plain_language

NCX1 couples calcium movement to sodium moving the other way.

primary_references

[ca-xue2023] Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1 (2023). https://pubmed.ncbi.nlm.nih.gov/37794011/ DOI: 10.1038/s41467-023-41885-4

research_relationship_category

transport

tissue_or_cell_type

Cardiac NCX1 expression system

transport_effect

depends Reversible exchange: forward mode extrudes calcium and reverse mode admits it, which the record states.

transport_or_reaction_direction

Reversible Na+/Ca2+ exchange; forward calcium extrusion or reverse calcium entry

transport_pool

cytosolic calcium Reversible exchange: forward mode extrudes calcium and reverse mode admits it, which the record states.

Calcium: mechanism-first literature curation (2026-09-17) · lines 625–637

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cardiac NCX1; cryo-EM and functional exchange assays · source_derived_draft · unverified_draft

### ca-ncx1-calcium-sodium-exchange Human cardiac NCX1 exchanges calcium and sodium in opposing directions across the membrane. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: NCX1 couples calcium movement to sodium moving the other way. organism: Homo sapiens tissue_or_cell_type: Cardiac NCX1 expression system experimental_model: Human cardiac NCX1; cryo-EM and functional exchange assays limitations: Net direction depends on electrochemical gradients and voltage; NCX1 is not an ATP-hydrolyzing pump. research_relationship_category: transport transport_or_reaction_direction: Reversible Na+/Ca2+ exchange; forward calcium extrusion or reverse calcium entry compartment_description: Plasma membrane [ca-xue2023] Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1 (2023). https://pubmed.ncbi.nlm.nih.gov/37794011/ DOI: 10.1038/s41467-023-41885-4

compartment_description

Cytosolic regulatory domain of plasma-membrane exchanger

experimental_model

Human cardiac NCX1; cryo-EM and functional exchange assays

limitations

Regulatory calcium binding is distinct from calcium being transported; the measured splice form and assay conditions matter.

nutrient_topic

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

organism

Homo sapiens

plain_language

Calcium also regulates NCX1 at a site separate from the transported-ion pathway.

primary_references

[ca-xue2023] Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1 (2023). https://pubmed.ncbi.nlm.nih.gov/37794011/ DOI: 10.1038/s41467-023-41885-4

research_relationship_category

regulation

tissue_or_cell_type

Cardiac NCX1 expression system

Calcium: mechanism-first literature curation (2026-09-17) · lines 639–650

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human cardiac NCX1; cryo-EM and functional exchange assays · source_derived_draft · unverified_draft

### ca-ncx1-regulatory-calcium Calcium binding to the cytosolic CBD2 regulatory domain disrupts an inactive NCX1 assembly and permits exchange. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium also regulates NCX1 at a site separate from the transported-ion pathway. organism: Homo sapiens tissue_or_cell_type: Cardiac NCX1 expression system experimental_model: Human cardiac NCX1; cryo-EM and functional exchange assays limitations: Regulatory calcium binding is distinct from calcium being transported; the measured splice form and assay conditions matter. research_relationship_category: regulation compartment_description: Cytosolic regulatory domain of plasma-membrane exchanger [ca-xue2023] Structural mechanisms of the human cardiac sodium-calcium exchanger NCX1 (2023). https://pubmed.ncbi.nlm.nih.gov/37794011/ DOI: 10.1038/s41467-023-41885-4

compartment_description

Plasma membrane protein complex

experimental_model

Purified human PMCA1-neuroplastin complex; cryo-EM and ATPase assays

limitations

Purified PMCA1 complex; subunit availability and other PMCA isoforms require separate evidence.

nutrient_topic

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

organism

Homo sapiens

plain_language

Neuroplastin helps PMCA1 function.

primary_references

[ca-gong2018] Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin (2018). https://pubmed.ncbi.nlm.nih.gov/30190470/ DOI: 10.1038/s41467-018-06075-7

research_relationship_category

regulation

tissue_or_cell_type

Purified recombinant proteins

Calcium: mechanism-first literature curation (2026-09-17) · lines 599–610

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human PMCA1-neuroplastin complex; cryo-EM and ATPase assays · source_derived_draft · unverified_draft

### ca-neuroplastin-pmca1-support Neuroplastin binds the transmembrane region of human PMCA1 and supports pump ATPase activity. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Neuroplastin helps PMCA1 function. organism: Homo sapiens tissue_or_cell_type: Purified recombinant proteins experimental_model: Purified human PMCA1-neuroplastin complex; cryo-EM and ATPase assays limitations: Purified PMCA1 complex; subunit availability and other PMCA isoforms require separate evidence. research_relationship_category: regulation compartment_description: Plasma membrane protein complex [ca-gong2018] Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin (2018). https://pubmed.ncbi.nlm.nih.gov/30190470/ DOI: 10.1038/s41467-018-06075-7

compartment_description

Plasma membrane

experimental_model

Human ORAI1 mutagenesis and membrane-current/selectivity measurements

limitations

Pore evidence does not specify channel stoichiometry or all tissue contributions.

nutrient_topic

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

organism

Homo sapiens

plain_language

ORAI1 forms the pore through which store-operated calcium enters.

primary_references

[ca-prakriya2006] Orai1 is an essential pore subunit of the CRAC channel (2006). https://www.nature.com/articles/nature05122 DOI: 10.1038/nature05122

research_relationship_category

transport

tissue_or_cell_type

Recombinant channel assays

transport_effect

raises The CRAC pore carries calcium from extracellular fluid to cytosol.

transport_or_reaction_direction

Extracellular fluid to cytosol

transport_pool

cytosolic calcium The CRAC pore carries calcium from extracellular fluid to cytosol.

Calcium: mechanism-first literature curation (2026-09-17) · lines 544–556

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human ORAI1 mutagenesis and membrane-current/selectivity measurements · source_derived_draft · unverified_draft

### ca-orai1-calcium-permeation ORAI1 supplies the calcium-selective CRAC pore; transmembrane substitutions alter calcium and monovalent-ion permeability. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: ORAI1 forms the pore through which store-operated calcium enters. organism: Homo sapiens tissue_or_cell_type: Recombinant channel assays experimental_model: Human ORAI1 mutagenesis and membrane-current/selectivity measurements limitations: Pore evidence does not specify channel stoichiometry or all tissue contributions. research_relationship_category: transport transport_or_reaction_direction: Extracellular fluid to cytosol compartment_description: Plasma membrane [ca-prakriya2006] Orai1 is an essential pore subunit of the CRAC channel (2006). https://www.nature.com/articles/nature05122 DOI: 10.1038/nature05122

availability_state

machinery_impairment Imported condition classification; unverified.

compartment_description

Plasma membrane

experimental_model

Human inherited immune deficiency, patient T-cell rescue and functional channel assays

limitations

A rare channelopathy, not nutritional calcium deficiency; the evidence concerns the studied variant.

nutrient_topic

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

organism

Homo sapiens

plain_language

This inherited channel defect interrupts calcium entry into T cells.

primary_references

[ca-feske2006] A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function (2006). https://pubmed.ncbi.nlm.nih.gov/16582901/ DOI: 10.1038/nature04702

research_relationship_category

loss_of_function

tissue_or_cell_type

Patient T lymphocytes

trigger_kind

machinery_impairment Imported condition classification; unverified.

Calcium: mechanism-first literature curation (2026-09-17) · lines 558–569

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human inherited immune deficiency, patient T-cell rescue and functional channel assays · source_derived_draft · unverified_draft

### ca-orai1-inherited-loss-influx Homozygous ORAI1 R91W loss of function abolishes CRAC activity in patient T cells; wild-type ORAI1 restores influx. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: This inherited channel defect interrupts calcium entry into T cells. organism: Homo sapiens tissue_or_cell_type: Patient T lymphocytes experimental_model: Human inherited immune deficiency, patient T-cell rescue and functional channel assays limitations: A rare channelopathy, not nutritional calcium deficiency; the evidence concerns the studied variant. research_relationship_category: loss_of_function compartment_description: Plasma membrane [ca-feske2006] A mutation in Orai1 causes immune deficiency by abrogating CRAC channel function (2006). https://pubmed.ncbi.nlm.nih.gov/16582901/ DOI: 10.1038/nature04702

compartment_description

Plasma membrane

experimental_model

Purified human PMCA1-neuroplastin complex; cryo-EM and ATPase assays

limitations

This study combines structure and ATPase assays; it does not quantify whole-tissue extrusion flux.

nutrient_topic

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

organism

Homo sapiens

plain_language

PMCA1 uses ATP to clear calcium from the cytosol.

primary_references

[ca-gong2018] Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin (2018). https://pubmed.ncbi.nlm.nih.gov/30190470/ DOI: 10.1038/s41467-018-06075-7

research_relationship_category

transport

tissue_or_cell_type

Purified recombinant pump

transport_effect

lowers Recorded as an ATP-driven plasma-membrane calcium extrusion pump.

transport_or_reaction_direction

Cytosol to extracellular fluid

transport_pool

cytosolic calcium Recorded as an ATP-driven plasma-membrane calcium extrusion pump.

Calcium: mechanism-first literature curation (2026-09-17) · lines 585–597

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Purified human PMCA1-neuroplastin complex; cryo-EM and ATPase assays · source_derived_draft · unverified_draft

### ca-pmca1-extrusion Human PMCA1 is an ATP-driven plasma-membrane calcium extrusion pump characterized structurally with neuroplastin. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: PMCA1 uses ATP to clear calcium from the cytosol. organism: Homo sapiens tissue_or_cell_type: Purified recombinant pump experimental_model: Purified human PMCA1-neuroplastin complex; cryo-EM and ATPase assays limitations: This study combines structure and ATPase assays; it does not quantify whole-tissue extrusion flux. research_relationship_category: transport transport_or_reaction_direction: Cytosol to extracellular fluid compartment_description: Plasma membrane [ca-gong2018] Structure of the human plasma membrane Ca2+-ATPase 1 in complex with its obligatory subunit neuroplastin (2018). https://pubmed.ncbi.nlm.nih.gov/30190470/ DOI: 10.1038/s41467-018-06075-7

compartment_description

ER-plasma-membrane junctions

experimental_model

Human HEK293/HEK293T expression, electrophysiology and purified protein-binding assays

limitations

Domain-expression experiments isolate coupling; physiological amplitude depends on cellular context.

nutrient_topic

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

organism

Homo sapiens

plain_language

STIM1 directly opens the ORAI1 calcium-entry pathway.

primary_references

[ca-park2009] STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1 (2009). https://pubmed.ncbi.nlm.nih.gov/19249086/ DOI: 10.1016/j.cell.2009.02.014

research_relationship_category

regulation

tissue_or_cell_type

HEK293 expression system and purified proteins

Calcium: mechanism-first literature curation (2026-09-17) · lines 531–542

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human HEK293/HEK293T expression, electrophysiology and purified protein-binding assays · source_derived_draft · unverified_draft

### ca-stim1-direct-orai1-gating The cytosolic CRAC-activation domain of STIM1 binds ORAI1 directly and activates its calcium current. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: STIM1 directly opens the ORAI1 calcium-entry pathway. organism: Homo sapiens tissue_or_cell_type: HEK293 expression system and purified proteins experimental_model: Human HEK293/HEK293T expression, electrophysiology and purified protein-binding assays limitations: Domain-expression experiments isolate coupling; physiological amplitude depends on cellular context. research_relationship_category: regulation compartment_description: ER-plasma-membrane junctions [ca-park2009] STIM1 clusters and activates CRAC channels via direct binding of a cytosolic domain to Orai1 (2009). https://pubmed.ncbi.nlm.nih.gov/19249086/ DOI: 10.1016/j.cell.2009.02.014

availability_state

machinery_impairment Imported condition classification; unverified.

compartment_description

ER-plasma-membrane signaling junction

experimental_model

Human HeLa cells; RNA interference screen, calcium imaging and STIM1 EF-hand mutagenesis

limitations

RNA interference perturbs signaling machinery; it does not model low calcium intake.

nutrient_topic

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

organism

Homo sapiens

plain_language

Reducing STIM1 weakens calcium entry after stores empty.

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

loss_of_function

tissue_or_cell_type

HeLa cells

trigger_kind

machinery_impairment Imported condition classification; unverified.

Calcium: mechanism-first literature curation (2026-09-17) · lines 518–529

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-knockdown-influx STIM1 knockdown suppresses store-depletion-triggered calcium influx in HeLa cells. Condition category: machinery_impairment nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Reducing STIM1 weakens calcium entry after stores empty. 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: RNA interference perturbs signaling machinery; it does not model low calcium intake. research_relationship_category: loss_of_function compartment_description: ER-plasma-membrane signaling junction [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

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

compartment_description

Presynaptic vesicle-plasma-membrane interface

experimental_model

Mouse synaptotagmin-1 knock-in and cultured neuronal release measurements

limitations

SYT1-dependent evoked release; does not establish the sensor for every secretory cell or all release modes.

nutrient_topic

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

organism

Mus musculus

plain_language

Synaptotagmin 1 helps convert a calcium signal into vesicle release.

primary_references

[ca-fernandezchacon2001] Synaptotagmin I functions as a calcium regulator of release probability (2001). https://pubmed.ncbi.nlm.nih.gov/11242035/ DOI: 10.1038/35065004

research_relationship_category

regulation

tissue_or_cell_type

Cultured neurons

Calcium: mechanism-first literature curation (2026-09-17) · lines 783–794

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Mouse synaptotagmin-1 knock-in and cultured neuronal release measurements · source_derived_draft · unverified_draft

### ca-synaptotagmin-calcium-release Calcium binding to synaptotagmin 1 participates in triggering evoked neurotransmitter release at mouse synapses. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Synaptotagmin 1 helps convert a calcium signal into vesicle release. organism: Mus musculus tissue_or_cell_type: Cultured neurons experimental_model: Mouse synaptotagmin-1 knock-in and cultured neuronal release measurements limitations: SYT1-dependent evoked release; does not establish the sensor for every secretory cell or all release modes. research_relationship_category: regulation compartment_description: Presynaptic vesicle-plasma-membrane interface [ca-fernandezchacon2001] Synaptotagmin I functions as a calcium regulator of release probability (2001). https://pubmed.ncbi.nlm.nih.gov/11242035/ DOI: 10.1038/35065004

compartment_description

Extracellular protein-membrane interface

experimental_model

X-ray crystallography and NMR with lysophosphatidylserine

limitations

The carboxylated Gla domain is a vitamin-K-dependent protein state; calcium binding does not perform gamma-carboxylation.

nutrient_topic

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

organism

Bos taurus

plain_language

Protein-bound calcium helps a clotting protein recognize a membrane lipid headgroup.

primary_references

[huang2003] Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins (2003). https://www.nature.com/articles/nsb971 DOI: 10.1038/nsb971

tissue_or_cell_type

Purified prothrombin fragment; blood-protein context

Calcium: mechanism-first literature curation (2026-09-17) · lines 1104–1114

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · X-ray crystallography and NMR with lysophosphatidylserine · source_derived_draft · unverified_draft

### calcium-gla-phosphatidylserine-binding In the bovine prothrombin Gla-domain structure, the lysophosphatidylserine headgroup contacted domain-bound Ca2+ and gamma-carboxyglutamate residues. Condition category: normal nutrient_topic: Calcium research collection; topical membership is not evidence of a direct dietary effect. plain_language: Protein-bound calcium helps a clotting protein recognize a membrane lipid headgroup. organism: Bos taurus tissue_or_cell_type: Purified prothrombin fragment; blood-protein context experimental_model: X-ray crystallography and NMR with lysophosphatidylserine limitations: The carboxylated Gla domain is a vitamin-K-dependent protein state; calcium binding does not perform gamma-carboxylation. compartment_description: Extracellular protein-membrane interface [huang2003] Structural basis of membrane binding by Gla domains of vitamin K-dependent proteins (2003). https://www.nature.com/articles/nsb971 DOI: 10.1038/nsb971

cross_nutrient

true

evidence_location

Figure 1a–b

experimental_model

Laser wounding and time-resolved dye exclusion

exposure

200 µM racemic alpha-tocopherol (96% pure) for 18 h, washed; 1.2 mM extracellular calcium.

limitations

Pharmacologic cell loading; not a dietary intake equivalent.

nutrient_topic

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

organism

Mus musculus

plain_language

Vitamin E loading helped cultured muscle-line cells close laser-induced membrane wounds.

primary_references

[ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594

tissue_or_cell_type

C2C12 myoblasts

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 662–674

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Laser wounding and time-resolved dye exclusion · source_derived_draft · unverified_draft

### ver-c2c12-membrane-repair Loading C2C12 cells with 200 µM alpha-tocopherol for 18 hours reduced FM1-43 entry after laser injury in calcium-containing buffer, consistent with faster membrane resealing. Condition category: normal nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin E loading helped cultured muscle-line cells close laser-induced membrane wounds. organism: Mus musculus tissue_or_cell_type: C2C12 myoblasts experimental_model: Laser wounding and time-resolved dye exclusion limitations: Pharmacologic cell loading; not a dietary intake equivalent. exposure: 200 µM racemic alpha-tocopherol (96% pure) for 18 h, washed; 1.2 mM extracellular calcium. cross_nutrient: true evidence_location: Figure 1a–b [ver-howard2011] Promotion of plasma membrane repair by vitamin E. (2011). https://pubmed.ncbi.nlm.nih.gov/22186893/ DOI: 10.1038/ncomms1594

availability_state

nutrient_deficiency Imported condition classification; unverified.

cross_nutrient

false

evidence_location

Methods; Figure 3

experimental_model

Dietary depletion with chow and add-back controls; laser assay

exposure

Male Sprague-Dawley rats started diets at 4 weeks; assay at 11-month diet interval.

limitations

Long-term rat dietary deprivation and controlled wound assays; not evidence that ordinary supplementation improves muscle performance in replete people.

nutrient_topic

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

organism

Rattus norvegicus

plain_language

Long-term vitamin E deprivation impaired muscle-fiber wound repair in rats.

primary_references

[ver-labazi2015] The antioxidant requirement for plasma membrane repair in skeletal muscle. (2015). https://pubmed.ncbi.nlm.nih.gov/25843658/ DOI: 10.1016/j.freeradbiomed.2015.03.016

tissue_or_cell_type

Flexor digitorum brevis muscle

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin E: transport, membrane protection and nutrient interactions (2026-09-17) · lines 704–716

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Dietary depletion with chow and add-back controls; laser assay · source_derived_draft · unverified_draft

### ver-diet-e-muscle-repair-failure Following 11 months on vitamin E-stripped chow, rat flexor digitorum brevis fibers displayed continued dye influx after controlled laser injury; normal chow and alpha-tocopherol-add-back controls resealed more effectively. Condition category: nutrient_deficiency nutrient_topic: Vitamin E research collection; topical membership is not evidence of a direct dietary effect. plain_language: Long-term vitamin E deprivation impaired muscle-fiber wound repair in rats. organism: Rattus norvegicus tissue_or_cell_type: Flexor digitorum brevis muscle experimental_model: Dietary depletion with chow and add-back controls; laser assay limitations: Long-term rat dietary deprivation and controlled wound assays; not evidence that ordinary supplementation improves muscle performance in replete people. exposure: Male Sprague-Dawley rats started diets at 4 weeks; assay at 11-month diet interval. cross_nutrient: false evidence_location: Methods; Figure 3 [ver-labazi2015] The antioxidant requirement for plasma membrane repair in skeletal muscle. (2015). https://pubmed.ncbi.nlm.nih.gov/25843658/ DOI: 10.1016/j.freeradbiomed.2015.03.016