Component

Human amnionless / AMN

Human amnionless / AMN

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

Read recorded mechanisms Open recursive mind map

How nutrients influence it

Every nutrient with a recorded effect on this component, credited to the nutrient that acted rather than the chapter that recorded it. Open a nutrient to see the findings and the conditions they were measured under.

How nutrients reach it in more than one step

Chains of two or more recorded steps that end here, grouped by the nutrient they start from. Each step is a separate finding, so a chain is a route a mechanism could take, not proof that it does.

Tracing routes…

What it does

Every recorded relationship this component is part of, grouped by its role. Plain wording comes first; the technical statement follows.

Recorded relationships

What it acts on

  1. Human AMN coexpressed with rat cubilin 1-1389 enabled IF-B12 internalization in CHO-K1 cells; either intact FXNPXF cytoplasmic motif supported uptake.

    Human amnionless / AMN → Cubam-mediated IF-cobalamin endocytosis source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Human AMN plus rat cubilin minireceptor in CHO-K1 cells
    exposure
    Labeled human/porcine IF-B12 at 37 degrees C over 1-8 hours
    limitations
    Reconstituted mixed-species system. Cell-associated radiolabel includes surface-bound cargo and must not be equated with internalized ligand.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Human AMN; rat cubilin; Chinese hamster host cells; human/porcine IF reagents
    plain_language
    Amnionless supplies signals that bring receptor-bound B12 into cells.
    primary_references
    [pedersen-2010-amn-endocytosis] AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. (2010). https://pubmed.ncbi.nlm.nih.gov/20088845/ DOI: 10.1111/j.1600-0854.2010.01042.x
    tissue_or_cell_type
    Engineered plasma-membrane endocytosis model

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 478–489

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human AMN plus rat cubilin minireceptor in CHO-K1 cells · source_derived_draft · unverified_draft

    ### b12-abs-amn-endocytosis Human AMN coexpressed with rat cubilin 1-1389 enabled IF-B12 internalization in CHO-K1 cells; either intact FXNPXF cytoplasmic motif supported uptake. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Amnionless supplies signals that bring receptor-bound B12 into cells. organism: Human AMN; rat cubilin; Chinese hamster host cells; human/porcine IF reagents tissue_or_cell_type: Engineered plasma-membrane endocytosis model experimental_model: Human AMN plus rat cubilin minireceptor in CHO-K1 cells limitations: Reconstituted mixed-species system. Cell-associated radiolabel includes surface-bound cargo and must not be equated with internalized ligand. exposure: Labeled human/porcine IF-B12 at 37 degrees C over 1-8 hours cross_nutrient: false [pedersen-2010-amn-endocytosis] AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. (2010). https://pubmed.ncbi.nlm.nih.gov/20088845/ DOI: 10.1111/j.1600-0854.2010.01042.x
    Complete structured claim and evidence

  2. Human AMN coexpression allowed rat mini-cubilin to reach the plasma membrane in HEK293T and other tested renal/intestinal cell models, whereas mini-cubilin alone remained intracellular.

    Human amnionless / AMN → Rat N-terminal mini-cubilin construct source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Rat N-terminal mini-cubilin plus human AMN; HEK293T, MDCK, human RPTEC and HCT116
    exposure
    Recombinant coexpression versus single transfection
    limitations
    Mixed-species truncated construct lacks the complete CUB5-8 IF-binding region; surface expression is not direct B12 uptake.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Rattus norvegicus construct; Homo sapiens AMN; human/canine host cells
    plain_language
    Amnionless helped the experimental receptor reach the cell surface.
    primary_references
    [udagawa-2018-glycosylation] Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29402915/ DOI: 10.1038/s41598-018-20731-4
    tissue_or_cell_type
    Cultured renal and colorectal epithelial cells

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 322–333

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat N-terminal mini-cubilin plus human AMN; HEK293T, MDCK, human RPTEC and HCT116 · source_derived_draft · unverified_draft

    ### b12-abs-amn-trafficking-rat-construct Human AMN coexpression allowed rat mini-cubilin to reach the plasma membrane in HEK293T and other tested renal/intestinal cell models, whereas mini-cubilin alone remained intracellular. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Amnionless helped the experimental receptor reach the cell surface. organism: Rattus norvegicus construct; Homo sapiens AMN; human/canine host cells tissue_or_cell_type: Cultured renal and colorectal epithelial cells experimental_model: Rat N-terminal mini-cubilin plus human AMN; HEK293T, MDCK, human RPTEC and HCT116 limitations: Mixed-species truncated construct lacks the complete CUB5-8 IF-binding region; surface expression is not direct B12 uptake. exposure: Recombinant coexpression versus single transfection cross_nutrient: false [udagawa-2018-glycosylation] Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29402915/ DOI: 10.1038/s41598-018-20731-4
    Complete structured claim and evidence

  3. Human renal cubilin and AMN copurified and coeluted as a tightly associated complex that required denaturing conditions for separation.

    Human amnionless / AMN → Human cubilin / CUBN source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    false
    experimental_model
    Affinity purification and gel filtration of human kidney membrane proteins
    exposure
    IF-cobalamin affinity chromatography; nondenaturing versus denaturing separation
    limitations
    Native renal purification establishes association; intestinal uptake rate is not measured by this experiment.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Cubilin and amnionless form a stable receptor pair.
    primary_references
    [fyfe-2004-cubam] The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. (2004). https://pubmed.ncbi.nlm.nih.gov/14576052/ DOI: 10.1182/blood-2003-08-2852
    tissue_or_cell_type
    Renal epithelial membranes

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 218–229

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Affinity purification and gel filtration of human kidney membrane proteins · source_derived_draft · unverified_draft

    ### b12-abs-cubam-association Human renal cubilin and AMN copurified and coeluted as a tightly associated complex that required denaturing conditions for separation. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Cubilin and amnionless form a stable receptor pair. organism: Homo sapiens tissue_or_cell_type: Renal epithelial membranes experimental_model: Affinity purification and gel filtration of human kidney membrane proteins limitations: Native renal purification establishes association; intestinal uptake rate is not measured by this experiment. exposure: IF-cobalamin affinity chromatography; nondenaturing versus denaturing separation cross_nutrient: false [fyfe-2004-cubam] The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. (2004). https://pubmed.ncbi.nlm.nih.gov/14576052/ DOI: 10.1182/blood-2003-08-2852
    Complete structured claim and evidence

Where it participates (unsigned role)

  1. Disruption of both human AMN FXNPXF motifs impaired IF-B12 internalization and degradation in CHO-K1 cells despite preserved cubam surface expression.

    Human AMN double FXNPXF-signal mutant → Cubam-mediated IF-cobalamin endocytosis source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Human AMN double-signal mutant plus rat cubilin 1-1389 in CHO-K1 cells
    exposure
    Both cytoplasmic motifs disrupted; wild-type and single-motif mutants as comparators
    limitations
    Engineered trafficking defect, not a patient genotype. Surface binding and intracellular entry are separate readouts.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Human AMN; rat cubilin; Chinese hamster host cells; human/porcine IF reagents
    plain_language
    A receptor can reach the surface yet fail to internalize its cargo.
    primary_references
    [pedersen-2010-amn-endocytosis] AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. (2010). https://pubmed.ncbi.nlm.nih.gov/20088845/ DOI: 10.1111/j.1600-0854.2010.01042.x
    tissue_or_cell_type
    Engineered receptor internalization model
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 491–502

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human AMN double-signal mutant plus rat cubilin 1-1389 in CHO-K1 cells · source_derived_draft · unverified_draft

    ### b12-abs-amn-endocytic-signal-loss Disruption of both human AMN FXNPXF motifs impaired IF-B12 internalization and degradation in CHO-K1 cells despite preserved cubam surface expression. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: A receptor can reach the surface yet fail to internalize its cargo. organism: Human AMN; rat cubilin; Chinese hamster host cells; human/porcine IF reagents tissue_or_cell_type: Engineered receptor internalization model experimental_model: Human AMN double-signal mutant plus rat cubilin 1-1389 in CHO-K1 cells limitations: Engineered trafficking defect, not a patient genotype. Surface binding and intracellular entry are separate readouts. exposure: Both cytoplasmic motifs disrupted; wild-type and single-motif mutants as comparators cross_nutrient: false [pedersen-2010-amn-endocytosis] AMN directs endocytosis of the intrinsic factor-vitamin B(12) receptor cubam by engaging ARH or Dab2. (2010). https://pubmed.ncbi.nlm.nih.gov/20088845/ DOI: 10.1111/j.1600-0854.2010.01042.x
    Complete structured claim and evidence

  2. Two siblings with AMN p.Gln248Ter/c.208-2A>G compound heterozygosity had markedly reduced urinary cubilin receptor activity despite preserved intrinsic-factor binding affinity and no CUBN mutation.

    Human AMN p.Gln248Ter / c.208-2A>G compound genotype → Urinary cubilin intrinsic factor-binding activity source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Two affected siblings and family carriers; urinary receptor characterization
    exposure
    Inherited compound AMN nonsense/splice genotype
    limitations
    Urinary receptor activity is a localization-related readout; it is not direct intestinal flux. Heterozygous relatives were unaffected.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Faulty amnionless reduced available receptor without changing its affinity.
    primary_references
    [namour-2011-amn] Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7. (2011). https://pubmed.ncbi.nlm.nih.gov/21750092/ DOI: 10.3324/haematol.2011.043984
    tissue_or_cell_type
    Renal epithelial receptor expression
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 296–307

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Two affected siblings and family carriers; urinary receptor characterization · source_derived_draft · unverified_draft

    ### b12-abs-amn-human-receptor Two siblings with AMN p.Gln248Ter/c.208-2A>G compound heterozygosity had markedly reduced urinary cubilin receptor activity despite preserved intrinsic-factor binding affinity and no CUBN mutation. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Faulty amnionless reduced available receptor without changing its affinity. organism: Homo sapiens tissue_or_cell_type: Renal epithelial receptor expression experimental_model: Two affected siblings and family carriers; urinary receptor characterization limitations: Urinary receptor activity is a localization-related readout; it is not direct intestinal flux. Heterozygous relatives were unaffected. exposure: Inherited compound AMN nonsense/splice genotype cross_nutrient: false [namour-2011-amn] Luminal expression of cubilin is impaired in Imerslund-Grasbeck syndrome with compound AMN mutations in intron 3 and exon 7. (2011). https://pubmed.ncbi.nlm.nih.gov/21750092/ DOI: 10.3324/haematol.2011.043984
    Complete structured claim and evidence

  3. Human renal cubilin and AMN remained associated during coelution in EDTA, indicating that their mutual association did not require calcium under these conditions.

    Calcium ion → Human cubilin-amnionless complex source_derived_draftungraded
    Experimental context and source evidence
    cross_nutrient
    true
    experimental_model
    Human kidney cubilin-AMN purification with chelation
    exposure
    EDTA present during coelution
    limitations
    Chelation result concerns CUBN-AMN association, not IF-cobalamin docking or whole-body calcium deficiency.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    Calcium dependence concerns ligand binding, not every receptor interaction.
    primary_references
    [fyfe-2004-cubam] The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. (2004). https://pubmed.ncbi.nlm.nih.gov/14576052/ DOI: 10.1182/blood-2003-08-2852
    tissue_or_cell_type
    Renal epithelial receptor complex

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 231–242

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Human kidney cubilin-AMN purification with chelation · source_derived_draft · unverified_draft

    ### b12-abs-cubam-association-calcium Human renal cubilin and AMN remained associated during coelution in EDTA, indicating that their mutual association did not require calcium under these conditions. Condition category: normal nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Calcium dependence concerns ligand binding, not every receptor interaction. organism: Homo sapiens tissue_or_cell_type: Renal epithelial receptor complex experimental_model: Human kidney cubilin-AMN purification with chelation limitations: Chelation result concerns CUBN-AMN association, not IF-cobalamin docking or whole-body calcium deficiency. exposure: EDTA present during coelution cross_nutrient: true [fyfe-2004-cubam] The functional cobalamin (vitamin B12)-intrinsic factor receptor is a novel complex of cubilin and amnionless. (2004). https://pubmed.ncbi.nlm.nih.gov/14576052/ DOI: 10.1182/blood-2003-08-2852
    Complete structured claim and evidence

  4. Combined N711D/N749D/N781D/N857D substitutions in rat mini-cubilin abolished mature glycosylation and surface targeting with human AMN; the tested smaller combinations did not.

    Rat mini-cubilin N711D/N749D/N781D/N857D construct → Surface expression of rat mini-cubilin source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    Rat mini-cubilin 4567ND versus wild type in HEK293T cells coexpressing human AMN
    exposure
    Four Asn-to-Asp substitutions; Figure 6 and Supplementary Figure 11
    limitations
    Engineered combined construct; does not show that every single site is individually indispensable. B12 absorption itself was not measured.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Rattus norvegicus construct; Homo sapiens AMN and host cells
    plain_language
    Several glycosylation sites jointly support receptor maturation.
    primary_references
    [udagawa-2018-glycosylation] Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29402915/ DOI: 10.1038/s41598-018-20731-4
    tissue_or_cell_type
    HEK293T biosynthetic trafficking
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 335–346

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · Rat mini-cubilin 4567ND versus wild type in HEK293T cells coexpressing human AMN · source_derived_draft · unverified_draft

    ### b12-abs-glycosylation-quadruple-mutant Combined N711D/N749D/N781D/N857D substitutions in rat mini-cubilin abolished mature glycosylation and surface targeting with human AMN; the tested smaller combinations did not. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: Several glycosylation sites jointly support receptor maturation. organism: Rattus norvegicus construct; Homo sapiens AMN and host cells tissue_or_cell_type: HEK293T biosynthetic trafficking experimental_model: Rat mini-cubilin 4567ND versus wild type in HEK293T cells coexpressing human AMN limitations: Engineered combined construct; does not show that every single site is individually indispensable. B12 absorption itself was not measured. exposure: Four Asn-to-Asp substitutions; Figure 6 and Supplementary Figure 11 cross_nutrient: false [udagawa-2018-glycosylation] Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29402915/ DOI: 10.1038/s41598-018-20731-4
    Complete structured claim and evidence

  5. In the renal biopsy of the studied patient carrying CUBN G653R, cubilin and AMN localized with the ER marker instead of normal brush-border localization.

    Human cubilin G653R variant → Human cubilin-amnionless retention in endoplasmic reticulum source_derived_draftungraded
    Experimental context and source evidence
    availability_state
    machinery_impairment Imported condition classification; unverified.
    cross_nutrient
    false
    experimental_model
    One IGS patient renal biopsy compared with a control biopsy
    exposure
    Patient CUBN G653R; co-occurring AMN P295S also reported
    limitations
    One patient; AMN P295S contribution was inconclusive. This tissue observation alone cannot assign all disease causality to G653R.
    nutrient_topic
    Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. · Vitamin B12 (cobalamins)
    organism
    Homo sapiens
    plain_language
    The patient receptor proteins accumulated inside kidney cells.
    primary_references
    [udagawa-2018-glycosylation] Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29402915/ DOI: 10.1038/s41598-018-20731-4
    tissue_or_cell_type
    Human renal proximal tubular epithelium
    trigger_kind
    machinery_impairment Imported condition classification; unverified.

    Vitamin B12: mechanisms, deficiency and nutrient interactions (2026-09-17) · lines 348–359

    AI-assisted literature curation; primary study URLs and scope retained in the document and extraction. Not publisher full text. · supports · One IGS patient renal biopsy compared with a control biopsy · source_derived_draft · unverified_draft

    ### b12-abs-human-g653r-er In the renal biopsy of the studied patient carrying CUBN G653R, cubilin and AMN localized with the ER marker instead of normal brush-border localization. Condition category: machinery_impairment nutrient_topic: Vitamin B12 research collection; topical membership is not evidence of a direct dietary effect. plain_language: The patient receptor proteins accumulated inside kidney cells. organism: Homo sapiens tissue_or_cell_type: Human renal proximal tubular epithelium experimental_model: One IGS patient renal biopsy compared with a control biopsy limitations: One patient; AMN P295S contribution was inconclusive. This tissue observation alone cannot assign all disease causality to G653R. exposure: Patient CUBN G653R; co-occurring AMN P295S also reported cross_nutrient: false [udagawa-2018-glycosylation] Amnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells. (2018). https://pubmed.ncbi.nlm.nih.gov/29402915/ DOI: 10.1038/s41598-018-20731-4
    Complete structured claim and evidence

In the sources

Preserved passages that mention this component, quoted exactly. Open one to read it in context.

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