Vitamin K-dependent protein gamma-carboxylation

evidence_span

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experimental_model

Genome-wide CRISPR screen and reporter biochemistry

exposure

FSP1 knockout/inhibition and DHODH comparison

limitations

Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human vitamin K-dependent reporter cells

plain_language

Similar antioxidant roles do not make two enzymes interchangeable.

primary_references

[k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8

tissue_or_cell_type

Warfarin-resistant quinone reduction

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 838–849

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide CRISPR screen and reporter biochemistry · source_derived_draft · unverified_draft

### k2-dhodh-not-k-reductase DHODH did not support vitamin K-dependent carboxylation in the tested reporter system despite its separate ubiquinone-associated ferroptosis role. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Similar antioxidant roles do not make two enzymes interchangeable. organism: Human vitamin K-dependent reporter cells tissue_or_cell_type: Warfarin-resistant quinone reduction experimental_model: Genome-wide CRISPR screen and reporter biochemistry limitations: Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function. exposure: FSP1 knockout/inhibition and DHODH comparison evidence_span: {"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"} [k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Metabolic-unit dietary depletion/repletion

exposure

K1 restricted to 18 micrograms/day for 28 days, then stepped repletion

limitations

The measured endpoint is carboxylation, not an observed clinical clotting failure; restricted-K1 exposure does not define isolated K2 deficiency.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

21 women aged 60–80 years

plain_language

A shortfall can appear in protein-modification markers before it is described as a clinical syndrome.

primary_references

[k2-p12888638] Dietary phylloquinone depletion and repletion in older women. (2003). https://pubmed.ncbi.nlm.nih.gov/12888638/ DOI: 10.1093/jn/133.8.2565

tissue_or_cell_type

Hepatic and extrahepatic protein markers

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1007–1018

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-unit dietary depletion/repletion · source_derived_draft · unverified_draft

### k2-dietary-k-prothrombin Dietary K1 restriction reduced prothrombin and osteocalcin gamma-carboxylation and lowered plasma K1 and urinary Gla excretion. Condition category: nutrient_deficiency nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A shortfall can appear in protein-modification markers before it is described as a clinical syndrome. organism: 21 women aged 60–80 years tissue_or_cell_type: Hepatic and extrahepatic protein markers experimental_model: Metabolic-unit dietary depletion/repletion limitations: The measured endpoint is carboxylation, not an observed clinical clotting failure; restricted-K1 exposure does not define isolated K2 deficiency. exposure: K1 restricted to 18 micrograms/day for 28 days, then stepped repletion evidence_span: {"source_cache": "artifacts/k2-research/12888638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874", "start_char": 0, "end_char": 1461, "text_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874"} [k2-p12888638] Dietary phylloquinone depletion and repletion in older women. (2003). https://pubmed.ncbi.nlm.nih.gov/12888638/ DOI: 10.1093/jn/133.8.2565

availability_state

nutrient_deficiency Imported condition classification; unverified.

evidence_span

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experimental_model

Metabolic-unit dietary depletion/repletion

exposure

K1 restricted to 18 micrograms/day for 28 days, then stepped repletion

limitations

K1 restriction probes shared vitamin K status, not an isolated dietary K2 requirement. Biochemical undercarboxylation is not equivalent to clinical bleeding or fractures.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

21 women aged 60–80 years

plain_language

A liver-related marker can recover before an extrahepatic marker.

primary_references

[k2-p12888638] Dietary phylloquinone depletion and repletion in older women. (2003). https://pubmed.ncbi.nlm.nih.gov/12888638/ DOI: 10.1093/jn/133.8.2565

tissue_or_cell_type

Hepatic and extrahepatic protein markers

trigger_kind

nutrient_deficiency Imported condition classification; unverified.

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 1020–1031

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Metabolic-unit dietary depletion/repletion · source_derived_draft · unverified_draft

### k2-different-repletion Prothrombin carboxylation normalized at 200 micrograms/day, whereas other vitamin K markers had not all returned to baseline after short repletion up to 450 micrograms/day. Condition category: nutrient_deficiency nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A liver-related marker can recover before an extrahepatic marker. organism: 21 women aged 60–80 years tissue_or_cell_type: Hepatic and extrahepatic protein markers experimental_model: Metabolic-unit dietary depletion/repletion limitations: K1 restriction probes shared vitamin K status, not an isolated dietary K2 requirement. Biochemical undercarboxylation is not equivalent to clinical bleeding or fractures. exposure: K1 restricted to 18 micrograms/day for 28 days, then stepped repletion evidence_span: {"source_cache": "artifacts/k2-research/12888638.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874", "start_char": 0, "end_char": 1461, "text_sha256": "c57beda0b2c7bdc471fd6f4bfa926e9f12846f040c95689648f599d6cceae874"} [k2-p12888638] Dietary phylloquinone depletion and repletion in older women. (2003). https://pubmed.ncbi.nlm.nih.gov/12888638/ DOI: 10.1093/jn/133.8.2565

evidence_span

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experimental_model

Genome-wide CRISPR screen and reporter biochemistry

exposure

FSP1 knockout/inhibition and DHODH comparison

limitations

Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human vitamin K-dependent reporter cells

plain_language

The antioxidant enzyme also helps supply cofactor for protein modification.

primary_references

[k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8

tissue_or_cell_type

Warfarin-resistant quinone reduction

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 825–836

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Genome-wide CRISPR screen and reporter biochemistry · source_derived_draft · unverified_draft

### k2-fsp1-carboxylation A CRISPR screen independently identified FSP1 as the warfarin-resistant vitamin K reductase; FSP1 inhibition impaired vitamin K-dependent carboxylation. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The antioxidant enzyme also helps supply cofactor for protein modification. organism: Human vitamin K-dependent reporter cells tissue_or_cell_type: Warfarin-resistant quinone reduction experimental_model: Genome-wide CRISPR screen and reporter biochemistry limitations: Supports cycle biochemistry; a different ferroptosis defense enzyme need not share the same vitamin K function. exposure: FSP1 knockout/inhibition and DHODH comparison evidence_span: {"source_cache": "artifacts/k2-research/36788244.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93", "start_char": 0, "end_char": 1359, "text_sha256": "5fda09197d386351a1b1d261c9b385db36e02eab0c238bf18599d7086b501f93"} [k2-p36788244] A genome-wide CRISPR-Cas9 knockout screen identifies FSP1 as the warfarin-resistant vitamin K reductase. (2023). https://pubmed.ncbi.nlm.nih.gov/36788244/ DOI: 10.1038/s41467-023-36446-8

evidence_span

{"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"}

experimental_model

Cryo-EM, mutagenesis and molecular dynamics

exposure

GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin

limitations

Structural and biochemical model; the proposed bicarbonate proton relay is not a demonstrated benefit of bicarbonate ingestion.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human GGCX

plain_language

The enzyme can modify several sites on the same protein during one encounter.

primary_references

[k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3

tissue_or_cell_type

Substrate recognition and carbon-dioxide capture

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 409–420

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM, mutagenesis and molecular dynamics · source_derived_draft · unverified_draft

### k2-ggcx-processivity A conserved dipeptide-anchoring mechanism supports repeated glutamate carboxylation while a substrate remains associated with GGCX. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The enzyme can modify several sites on the same protein during one encounter. organism: Human GGCX tissue_or_cell_type: Substrate recognition and carbon-dioxide capture experimental_model: Cryo-EM, mutagenesis and molecular dynamics limitations: Structural and biochemical model; the proposed bicarbonate proton relay is not a demonstrated benefit of bicarbonate ingestion. exposure: GGCX complexes with vitamin K, clotting-factor substrates and osteocalcin evidence_span: {"source_cache": "artifacts/k2-research/41290650.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc", "start_char": 0, "end_char": 1177, "text_sha256": "0ea90e4c1af519fa0fc3645f4a4f8f0721924797e0eaa44569ff445c4afe19bc"} [k2-p41290650] Structural insight into bicarbonate-mediated carboxylation by human vitamin K-dependent carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/41290650/ DOI: 10.1038/s41467-025-65488-3

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/k2-research/34813684.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206", "start_char": 0, "end_char": 1777, "text_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206"}

experimental_model

CRISPR reporter cells with UBIAD1 variants

exposure

UBIAD1 N102S, G186R and other variants

limitations

Cell-specific residual activity differs between variants; a UBIAD1 mutation is not automatically global vitamin K failure.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human HEK293 reporter cells

plain_language

A different variant impaired both supply and use in the same assay.

primary_references

[k2-p34813684] Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation. (2022). https://pubmed.ncbi.nlm.nih.gov/34813684/ DOI: 10.1111/febs.16291

tissue_or_cell_type

MK-4 production and protein carboxylation

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 253–264

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR reporter cells with UBIAD1 variants · source_derived_draft · unverified_draft

### k2-ubiad1-g186r UBIAD1 G186R significantly impaired both MK-4 biosynthesis and vitamin K-dependent reporter carboxylation. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A different variant impaired both supply and use in the same assay. organism: Human HEK293 reporter cells tissue_or_cell_type: MK-4 production and protein carboxylation experimental_model: CRISPR reporter cells with UBIAD1 variants limitations: Cell-specific residual activity differs between variants; a UBIAD1 mutation is not automatically global vitamin K failure. exposure: UBIAD1 N102S, G186R and other variants evidence_span: {"source_cache": "artifacts/k2-research/34813684.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206", "start_char": 0, "end_char": 1777, "text_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206"} [k2-p34813684] Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation. (2022). https://pubmed.ncbi.nlm.nih.gov/34813684/ DOI: 10.1111/febs.16291

availability_state

machinery_impairment Imported condition classification; unverified.

evidence_span

{"source_cache": "artifacts/k2-research/34813684.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206", "start_char": 0, "end_char": 1777, "text_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206"}

experimental_model

CRISPR reporter cells with UBIAD1 variants

exposure

UBIAD1 N102S, G186R and other variants

limitations

Cell-specific residual activity differs between variants; a UBIAD1 mutation is not automatically global vitamin K failure.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human HEK293 reporter cells

plain_language

A partial synthesis change did not automatically disable the downstream reaction.

primary_references

[k2-p34813684] Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation. (2022). https://pubmed.ncbi.nlm.nih.gov/34813684/ DOI: 10.1111/febs.16291

tissue_or_cell_type

MK-4 production and protein carboxylation

trigger_kind

machinery_impairment Imported condition classification; unverified.

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 240–251

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · CRISPR reporter cells with UBIAD1 variants · source_derived_draft · unverified_draft

### k2-ubiad1-n102s UBIAD1 N102S retained about 82% of MK-4 biosynthetic activity and did not impair reporter carboxylation. Condition category: machinery_impairment nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A partial synthesis change did not automatically disable the downstream reaction. organism: Human HEK293 reporter cells tissue_or_cell_type: MK-4 production and protein carboxylation experimental_model: CRISPR reporter cells with UBIAD1 variants limitations: Cell-specific residual activity differs between variants; a UBIAD1 mutation is not automatically global vitamin K failure. exposure: UBIAD1 N102S, G186R and other variants evidence_span: {"source_cache": "artifacts/k2-research/34813684.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206", "start_char": 0, "end_char": 1777, "text_sha256": "f533947abd5f26101d1bf1e2548d37b98d16bb72c470dcdfaf2b2f2625c5e206"} [k2-p34813684] Naturally occurring UBIAD1 mutations differentially affect menaquinone biosynthesis and vitamin K-dependent carboxylation. (2022). https://pubmed.ncbi.nlm.nih.gov/34813684/ DOI: 10.1111/febs.16291

evidence_span

{"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"}

experimental_model

Cryo-EM, binding, cell assays and molecular dynamics

exposure

Apo, osteocalcin-bound and vitamin-K-bound structures

limitations

Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone.

nutrient_topic

Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin K2 / menaquinone family

organism

Human GGCX

plain_language

Vitamin K helps an enzyme modify selected proteins; it does not carry calcium into bone itself.

primary_references

[k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9

tissue_or_cell_type

Endoplasmic-reticulum membrane enzyme

Vitamin K2: menaquinone forms, carboxylation, recycling and nutrient interactions (2026-09-17) · lines 370–381

AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Cryo-EM, binding, cell assays and molecular dynamics · source_derived_draft · unverified_draft

### k2-ggcx-cofactor GGCX couples oxidation of reduced vitamin K to conversion of protein-bound glutamate into gamma-carboxyglutamate. Condition category: normal nutrient_topic: Vitamin K2 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Vitamin K helps an enzyme modify selected proteins; it does not carry calcium into bone itself. organism: Human GGCX tissue_or_cell_type: Endoplasmic-reticulum membrane enzyme experimental_model: Cryo-EM, binding, cell assays and molecular dynamics limitations: Shared vitamin K chemistry; the abstract does not establish K2 exclusivity or identical kinetics for every menaquinone. exposure: Apo, osteocalcin-bound and vitamin-K-bound structures evidence_span: {"source_cache": "artifacts/k2-research/39880952.abstract.txt", "locator": "Exact primary indexed abstract; zero-based, end-exclusive Unicode character offsets", "file_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653", "start_char": 0, "end_char": 1230, "text_sha256": "eb8e6d00eecd7c5c780921cae3f804fab60e919301eeb16e9909f36293aaa653"} [k2-p39880952] Structure and mechanism of vitamin-K-dependent γ-glutamyl carboxylase. (2025). https://pubmed.ncbi.nlm.nih.gov/39880952/ DOI: 10.1038/s41586-024-08484-9