id: Q9NPF0
gene_symbol: CD320
product_type: PROTEIN
status: INITIALIZED
taxon:
  id: NCBITaxon:9606
  label: Homo sapiens
description: >-
  CD320 (CD320 antigen; transcobalamin receptor, TCblR; historically the "8D6 antigen"
  or follicular dendritic cell signaling molecule 8D6) is a single-pass type I plasma
  membrane glycoprotein of the low-density lipoprotein receptor (LDLR) family. Its
  extracellular region contains two LDLR class A (LDLR-A) domains, each coordinating a
  central calcium ion, separated by an EGF/complement-like cysteine-rich region. CD320
  is a non-enzymatic cell-surface cargo/endocytic receptor that captures the
  transcobalamin-cobalamin complex (holo-transcobalamin, TC-Cbl) from the circulation
  and internalizes it by receptor-mediated endocytosis, providing the principal route
  for cellular uptake of vitamin B12 (cobalamin) by peripheral tissues. It binds
  transcobalamin with high affinity and specificity (and does not bind haptocorrin);
  ligand binding is calcium-dependent and is released at endosomal low pH, allowing the
  receptor to recycle to the cell surface. CD320 expression is coupled to the cell
  cycle, being highest in actively proliferating cells and upregulated in many cancers.
  Biallelic in-frame variants (most commonly a p.Glu88 deletion in LDLR-A1) reduce
  cobalamin-transport function and cause transient/mild methylmalonic aciduria detected
  on newborn screening (transcobalamin receptor defect, MATR/MMATC), a largely
  asymptomatic condition.
alternative_products:
- name: '1'
  id: Q9NPF0-1
- name: '2'
  id: Q9NPF0-2
  sequence_note: VSP_045368
existing_annotations:
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IBA
  original_reference_id: GO_REF:0000033
  qualifier: is_active_in
  review:
    summary: >-
      Phylogenetic (IBA) inference that CD320 acts at the plasma membrane. This is
      correct and central to its function: CD320 is a single-pass type I cell-surface
      receptor that binds and internalizes the TC-Cbl complex from the extracellular
      space.
    action: ACCEPT
    reason: >-
      Directly supported by experimental subcellular-location data and by the biology
      of the receptor. The plasma membrane is the site where CD320 captures circulating
      holo-transcobalamin.
    supported_by:
    - reference_id: PMID:18779389
      supporting_text: >-
        The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-
        cobalamin (Cbl) and internalizes the complex by endocytosis.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000044
  qualifier: located_in
  review:
    summary: >-
      UniProt subcellular-location keyword mapping to plasma membrane. Consistent with
      the experimentally established cell-membrane localization of CD320.
    action: ACCEPT
    reason: >-
      Redundant with, but consistent with, the experimental plasma membrane annotations
      (PMID:10727470, PMID:18779389). UniProt annotates "Cell membrane; Single-pass type
      I membrane protein".
    supported_by:
    - reference_id: file:human/CD320/CD320-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Cell membrane
- term:
    id: GO:0016020
    label: membrane
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: located_in
  review:
    summary: >-
      ARBA electronic annotation to the generic parent term "membrane". True but far
      less informative than the plasma membrane annotations.
    action: MODIFY
    reason: >-
      CD320 is a single-pass membrane protein, so "membrane" is not wrong, but the more
      specific and better-supported term is plasma membrane. Recommend replacing with
      the specific location.
    proposed_replacement_terms:
    - id: GO:0005886
      label: plasma membrane
    supported_by:
    - reference_id: file:human/CD320/CD320-uniprot.txt
      supporting_text: >-
        Single-pass
- term:
    id: GO:0016192
    label: vesicle-mediated transport
  evidence_type: IEA
  original_reference_id: GO_REF:0000117
  qualifier: involved_in
  review:
    summary: >-
      ARBA electronic annotation to vesicle-mediated transport. CD320 internalizes its
      ligand by receptor-mediated endocytosis, which is a form of vesicle-mediated
      transport, so this is correct but general.
    action: MODIFY
    reason: >-
      The specific mechanism is receptor-mediated endocytosis of the TC-Cbl complex;
      recommend the more precise child term rather than the broad parent.
    proposed_replacement_terms:
    - id: GO:0006898
      label: receptor-mediated endocytosis
    supported_by:
    - reference_id: PMID:27411955
      supporting_text: >-
        transcobalamin (TC)-bound Cbl is transported into cells by receptor-mediated
        endocytosis, which requires Ca2+-dependent complex formation of TC with its
        cognate cell surface receptor CD320
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:27411955
  qualifier: enables
  review:
    summary: >-
      IntAct IPI capturing the physical interaction of CD320 with its physiological
      ligand transcobalamin (TCN2, P20062), shown by crystallography and biochemistry.
      "protein binding" is uninformative on its own; the informative molecular function
      is captured by cargo receptor activity (GO:0038024) and cobalamin binding
      (GO:0031419) in core_functions.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      The interaction is real and important (CD320-TCN2), but the bare "protein binding"
      term does not convey the receptor function. The specific cargo-receptor/cobalamin
      role is captured elsewhere; per curation guidelines the generic term is retained
      but flagged rather than used as a core function.
    supported_by:
    - reference_id: PMID:27411955
      supporting_text: >-
        Cellular uptake of vitamin B12 (cobalamin) requires capture of transcobalamin
    - reference_id: file:human/CD320/CD320-uniprot.txt
      supporting_text: >-
        Interacts (via LDL-receptor class A domains) with TCN2
- term:
    id: GO:0005515
    label: protein binding
  evidence_type: IPI
  original_reference_id: PMID:35922511
  qualifier: enables
  review:
    summary: >-
      IntAct IPI from a large-scale human immune surface-receptor interactome screen,
      recording the CD320-JAML (AMICA1, Q86YT9) interaction; in that study CD320
      contributed to natural killer cell activation. This is a secondary immune
      interaction distinct from the core B12-receptor function.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      A genuine physical interaction from a systematic screen, but "protein binding" is
      uninformative and this immune adhesion/costimulation role is peripheral to the
      core cobalamin-uptake function. Retained but flagged rather than treated as core.
    supported_by:
    - reference_id: PMID:35922511
      supporting_text: >-
        the adhesion proteins CHL1 and CD320 (along with CD58 as previously described31)
        facilitating natural killer (NK) cell activation
- term:
    id: GO:0015889
    label: cobalamin transport
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-9758890
  qualifier: involved_in
  review:
    summary: >-
      Reactome traceable-author-statement annotation placing CD320 in cobalamin
      transport (transport of cobalamins within the body). This is a core biological
      process for CD320: it delivers TC-bound cobalamin into cells.
    action: ACCEPT
    reason: >-
      Well supported by experimental literature (PMID:18779389, PMID:20524213) and by
      the Reactome pathway model of TC-Cbl uptake and distribution.
    supported_by:
    - reference_id: PMID:20524213
      supporting_text: >-
        TCblR expressed on the plasma membrane binds transcobalamin (TC) saturated with
        Cbl (holo-TC) and mediates cellular uptake of Cbl
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: EXP
  original_reference_id: PMID:11418631
  qualifier: located_in
  review:
    summary: >-
      Experimental plasma-membrane localization from the FDC-signaling-molecule 8D6
      characterization (8D6 = CD320). CD320 is detected on follicular dendritic cells at
      the cell surface.
    action: ACCEPT
    reason: >-
      Correct cell-surface localization; consistent with the receptor's function and
      with other experimental and IBA plasma-membrane annotations.
    supported_by:
    - reference_id: PMID:11418631
      supporting_text: >-
        A novel FDC-signaling molecule 8D6 (FDC-SM-8D6) produced by FDC augments PC
        generation in the GC.
- term:
    id: GO:0038024
    label: cargo receptor activity
  evidence_type: EXP
  original_reference_id: PMID:15652495
  qualifier: enables
  review:
    summary: >-
      Experimental molecular-function annotation to cargo receptor activity. This is the
      core molecular function of CD320: it is the plasma-membrane receptor that binds
      the transcobalamin-cobalamin cargo and mediates its endocytic internalization.
    action: ACCEPT
    reason: >-
      Directly supported: the receptor binds holo-TC and internalizes the TC-Cbl complex
      by endocytosis, the defining activity of an endocytic cargo receptor.
    supported_by:
    - reference_id: PMID:15652495
      supporting_text: >-
        is mediated by a receptor
    - reference_id: PMID:15652495
      supporting_text: >-
        internalizes the TC-Cbl by endocytosis
- term:
    id: GO:0005509
    label: calcium ion binding
  evidence_type: IDA
  original_reference_id: PMID:27411955
  qualifier: enables
  review:
    summary: >-
      Direct-assay calcium-ion binding from the crystal structure: each of the two
      LDLR-A domains of CD320 coordinates a central Ca2+ ion. Calcium is required for
      formation of the TC-CD320 complex and hence for ligand capture.
    action: ACCEPT
    reason: >-
      Structurally demonstrated Ca2+ coordination in both LDLR-A domains
      (PDB:4ZRP/4ZRQ); UniProt annotates twelve Ca2+-binding residues across the two
      domains. This is a genuine structural molecular function underpinning ligand
      binding, though secondary to the cargo-receptor function.
    supported_by:
    - reference_id: PMID:27411955
      supporting_text: >-
        Both LDLR-A domains contain central Ca2+ ions bound by four conserved acidic
        residues and two backbone carbonyls in an octahedral coordination.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:10727470
  qualifier: located_in
  review:
    summary: >-
      Direct-assay plasma-membrane localization from the original 8D6/CD320
      identification: the 8D6 antigen (CD320) is expressed abundantly on the surface of
      follicular dendritic cells.
    action: ACCEPT
    reason: >-
      Correct and well supported cell-surface localization consistent with the receptor
      function.
    supported_by:
    - reference_id: PMID:10727470
      supporting_text: >-
        The 8D6 Ag is a novel protein of 282 amino acids that is expressed abundantly on
        FDCs.
- term:
    id: GO:0015889
    label: cobalamin transport
  evidence_type: IMP
  original_reference_id: PMID:18779389
  qualifier: involved_in
  review:
    summary: >-
      Cobalamin transport based on characterization of the purified receptor protein and
      its gene: TCblR/CD320 on the plasma membrane binds holo-TC and internalizes the
      complex by endocytosis, mediating cellular cobalamin uptake. Core biological
      process.
    action: ACCEPT
    reason: >-
      Direct experimental basis for CD320's role in cobalamin transport; the receptor
      was purified and shown to bind and internalize TC-Cbl.
    supported_by:
    - reference_id: PMID:18779389
      supporting_text: >-
        The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-
        cobalamin (Cbl) and internalizes the complex by endocytosis.
- term:
    id: GO:0030890
    label: positive regulation of B cell proliferation
  evidence_type: IMP
  original_reference_id: PMID:10727470
  qualifier: involved_in
  review:
    summary: >-
      Based on the original 8D6/CD320 characterization on follicular dendritic cells:
      CD320 (8D6 antigen) costimulates growth of germinal-center B cells, and blocking
      mAb 8D6 inhibits their proliferation. This is a genuine but tissue/context-specific
      immune role predating the identification of the B12-receptor function.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally supported (IMP with blocking antibody), so retained; but this
      immune costimulatory activity is peripheral to CD320's universal core function as
      the transcobalamin/cobalamin-uptake receptor and is plausibly downstream of
      proliferation-coupled B12 supply. Marked non-core rather than removed, deferring to
      the experimental curation.
    supported_by:
    - reference_id: PMID:10727470
      supporting_text: >-
        Monolayers of COS cells transiently transfected with the 8D6 Ag cDNA stimulate B
        cell growth.
- term:
    id: GO:0031296
    label: B cell costimulation
  evidence_type: IMP
  original_reference_id: PMID:10727470
  qualifier: involved_in
  review:
    summary: >-
      CD320 (8D6 antigen) on follicular dendritic cells provides a costimulatory signal
      for germinal-center B-cell growth and differentiation; blocking mAb 8D6 abolishes
      this costimulation. Genuine but context-specific immune role.
    action: KEEP_AS_NON_CORE
    reason: >-
      Experimentally supported costimulation activity, retained; peripheral to the core
      cobalamin-uptake receptor function and specific to the FDC-B cell context.
    supported_by:
    - reference_id: PMID:10727470
      supporting_text: >-
        The mAb 8D6 blocks the costimulatory function completely.
- term:
    id: GO:0015889
    label: cobalamin transport
  evidence_type: IMP
  original_reference_id: PMID:20524213
  qualifier: involved_in
  review:
    summary: >-
      Cobalamin transport supported by the first disease mutation: an in-frame p.E88del
      in CD320 decreases uptake of holo-TC in patient fibroblasts and causes
      methylmalonic aciduria; reinserting the codon restores receptor function. Core
      biological process.
    action: ACCEPT
    reason: >-
      Genetic loss-of-function evidence (IMP) directly ties CD320 to cobalamin transport,
      the only physiologic route for TC-bound cobalamin into cells.
    supported_by:
    - reference_id: PMID:20524213
      supporting_text: >-
        The only route for physiologic transport of TC-bound Cbl into cells is via TCblR.
    - reference_id: PMID:20524213
      supporting_text: >-
        Inserting the codon by site-directed mutagenesis fully restored TCblR function.
- term:
    id: GO:0016020
    label: membrane
  evidence_type: HDA
  original_reference_id: PMID:19946888
  qualifier: located_in
  review:
    summary: >-
      High-throughput mass-spectrometry detection of CD320 in the membrane proteome of an
      NK-like cell line. Supports membrane localization but at the generic "membrane"
      level.
    action: MODIFY
    reason: >-
      Correct that CD320 is membrane-associated, but this proteomic dataset does not
      distinguish membrane compartments; the specific and better-supported term is
      plasma membrane.
    proposed_replacement_terms:
    - id: GO:0005886
      label: plasma membrane
    supported_by:
    - reference_id: PMID:19946888
      supporting_text: >-
        Mass spectrometric analysis identified 1843 proteins with high confidence scores.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3325546
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS plasma-membrane annotation from the model of defective CD320 failing
      to transport TCII:Cbl to the endosome. Consistent with the receptor's cell-surface
      location.
    action: ACCEPT
    reason: >-
      Correct cell-surface localization, corroborated by experimental data.
    supported_by:
    - reference_id: PMID:18779389
      supporting_text: >-
        The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-
        cobalamin (Cbl) and internalizes the complex by endocytosis.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3000112
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS plasma-membrane annotation from the CD320-mediated TCN2:RCbl uptake
      and lysosomal delivery model, in which CD320 recycles to the plasma membrane after
      internalization.
    action: ACCEPT
    reason: >-
      Correct cell-surface localization; the receptor cycles between the plasma membrane
      and endosomes during ligand uptake.
    supported_by:
    - reference_id: PMID:18779389
      supporting_text: >-
        The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-
        cobalamin (Cbl) and internalizes the complex by endocytosis.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: TAS
  original_reference_id: Reactome:R-HSA-3000122
  qualifier: located_in
  review:
    summary: >-
      Reactome TAS plasma-membrane annotation from the "CD320 binds extracellular
      TCN2:RCbl" reaction. Consistent with the receptor capturing its ligand at the cell
      surface.
    action: ACCEPT
    reason: >-
      Correct cell-surface localization; site of ligand capture.
    supported_by:
    - reference_id: PMID:18779389
      supporting_text: >-
        The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-
        cobalamin (Cbl) and internalizes the complex by endocytosis.
- term:
    id: GO:0005886
    label: plasma membrane
  evidence_type: IDA
  original_reference_id: PMID:18779389
  qualifier: located_in
  review:
    summary: >-
      MGI-assigned direct-assay plasma-membrane localization from characterization of the
      purified receptor. The receptor is a plasma-membrane protein that binds and
      internalizes TC-Cbl.
    action: ACCEPT
    reason: >-
      Directly supported cell-surface localization consistent with all other localization
      evidence.
    supported_by:
    - reference_id: PMID:18779389
      supporting_text: >-
        The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-
        cobalamin (Cbl) and internalizes the complex by endocytosis.
- term:
    id: GO:0031419
    label: cobalamin binding
  evidence_type: IDA
  original_reference_id: PMID:18779389
  qualifier: enables
  review:
    summary: >-
      Direct-assay cobalamin binding: CD320 binds cobalamin in the form of the
      transcobalamin-cobalamin complex (holo-TC), the ligand it captures at the cell
      surface. Core molecular function alongside cargo receptor activity.
    action: ACCEPT
    reason: >-
      The purified receptor binds holo-TC (TC saturated with Cbl); recognition of the
      cobalamin-loaded ligand is central to its function. LDLR-family; binds TC-Cbl with
      high affinity.
    supported_by:
    - reference_id: PMID:18779389
      supporting_text: >-
        The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-
        cobalamin (Cbl) and internalizes the complex by endocytosis.
    - reference_id: PMID:18779389
      supporting_text: >-
        TCblR belongs to the low-density lipoprotein receptor family
- term:
    id: GO:0005783
    label: endoplasmic reticulum
  evidence_type: IDA
  original_reference_id: GO_REF:0000054
  qualifier: located_in
  review:
    summary: >-
      LIFEdb annotation from imaging of an overexpressed GFP/epitope-tagged fusion
      protein. ER signal for a plasma-membrane receptor most likely reflects the
      biosynthetic/secretory pathway of an overexpressed membrane protein rather than a
      functional ER localization.
    action: MARK_AS_OVER_ANNOTATED
    reason: >-
      CD320 is a single-pass plasma-membrane receptor; like all such proteins it transits
      the ER during biosynthesis, but its functional compartment is the cell surface (and
      endosomes during uptake). ER localization from a single high-throughput
      overexpressed-fusion assay is not a core function and is an over-annotation of the
      functional site.
    supported_by:
    - reference_id: file:human/CD320/CD320-uniprot.txt
      supporting_text: >-
        SUBCELLULAR LOCATION: Cell membrane
core_functions:
- description: >-
    Cell-surface cargo/endocytic receptor that captures the transcobalamin-cobalamin
    complex (holo-TC) from plasma and mediates its uptake by receptor-mediated
    endocytosis, delivering vitamin B12 (cobalamin) into cells.
  molecular_function:
    id: GO:0038024
    label: cargo receptor activity
  directly_involved_in:
  - id: GO:0015889
    label: cobalamin transport
  locations:
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: PMID:18779389
    supporting_text: >-
      The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-
      cobalamin (Cbl) and internalizes the complex by endocytosis.
  - reference_id: PMID:15652495
    supporting_text: >-
      internalizes the TC-Cbl by endocytosis
- description: >-
    Internalization of the bound transcobalamin-cobalamin ligand from the plasma membrane
    via receptor-mediated endocytosis; ligand is released at endosomal low pH and the
    receptor recycles to the cell surface.
  molecular_function:
    id: GO:0038024
    label: cargo receptor activity
  directly_involved_in:
  - id: GO:0006898
    label: receptor-mediated endocytosis
  locations:
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: PMID:27411955
    supporting_text: >-
      transcobalamin (TC)-bound Cbl is transported into cells by receptor-mediated
      endocytosis, which requires Ca2+-dependent complex formation of TC with its
      cognate cell surface receptor CD320
- description: >-
    Recognition and binding of cobalamin in the form of the transcobalamin-cobalamin
    (holo-TC) complex, the ligand captured by CD320 at the cell surface.
  molecular_function:
    id: GO:0031419
    label: cobalamin binding
  directly_involved_in:
  - id: GO:0015889
    label: cobalamin transport
  locations:
  - id: GO:0005886
    label: plasma membrane
  supported_by:
  - reference_id: PMID:18779389
    supporting_text: >-
      The transcobalamin (TC, TCII) receptor (TCblR) on the plasma membrane binds TC-
      cobalamin (Cbl) and internalizes the complex by endocytosis.
references:
- id: GO_REF:0000033
  title: Annotation inferences using phylogenetic trees
  findings: []
- id: GO_REF:0000044
  title: Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location
    vocabulary mapping, accompanied by conservative changes to GO terms applied by
    UniProt
  findings: []
- id: GO_REF:0000054
  title: Gene Ontology annotation based on curation of intracellular localizations
    of expressed fusion proteins in living cells
  findings: []
- id: GO_REF:0000117
  title: Electronic Gene Ontology annotations created by ARBA machine learning models
  findings: []
- id: file:human/CD320/CD320-uniprot.txt
  title: UniProtKB entry Q9NPF0 (CD320_HUMAN)
  findings: []
- id: PMID:10727470
  title: Identification of a human follicular dendritic cell molecule that stimulates
    germinal center B cell growth.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Original cloning of CD320 as the FDC "8D6 antigen"; establishes plasma-membrane
      localization and B-cell costimulation. Immune role predates the B12-receptor
      identification and is treated as non-core.
- id: PMID:11418631
  title: The distinct roles of T cell-derived cytokines and a novel follicular dendritic
    cell-signaling molecule 8D6 in germinal center-B cell differentiation.
  findings: []
  reference_review:
    relevance: MEDIUM
    correctness: VERIFIED
    review_notes: >-
      Characterizes FDC-SM-8D6 (CD320) in germinal-center B cell differentiation;
      supports plasma-membrane location and the non-core immune costimulation role.
- id: PMID:15652495
  title: The binding properties of the human receptor for the cellular uptake of vitamin
    B12.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Establishes the receptor binds holo-TC and internalizes TC-Cbl by endocytosis;
      supports cargo receptor activity.
- id: PMID:18779389
  title: The protein and the gene encoding the receptor for the cellular uptake of
    transcobalamin-bound cobalamin.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Purification and gene identification of TCblR/CD320; core evidence for
      plasma-membrane localization, cobalamin binding (as holo-TC) and cobalamin
      transport.
- id: PMID:19946888
  title: Defining the membrane proteome of NK cells.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      High-throughput proteomic detection in an NK-like line; supports generic membrane
      localization only.
- id: PMID:20524213
  title: Positive newborn screen for methylmalonic aciduria identifies the first mutation
    in TCblR/CD320, the gene for cellular uptake of transcobalamin-bound vitamin B(12).
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      First CD320 disease mutation (p.E88del) causing transient/mild methylmalonic
      aciduria on newborn screening; loss-of-function evidence for cobalamin transport.
- id: PMID:27411955
  title: Structural basis of transcobalamin recognition by human CD320 receptor.
  findings: []
  reference_review:
    relevance: HIGH
    correctness: VERIFIED
    review_notes: >-
      Crystal structure of holo-TC bound to the CD320 ectodomain; supports Ca2+ binding
      by the LDLR-A domains, Ca2+-dependent receptor-mediated endocytosis, and TCN2
      interaction.
- id: PMID:35922511
  title: A physical wiring diagram for the human immune system.
  findings: []
  reference_review:
    relevance: LOW
    correctness: VERIFIED
    review_notes: >-
      Systematic immune surface-interactome screen; records CD320-JAML interaction and a
      role in NK-cell activation. Peripheral immune interaction, not core function.
- id: Reactome:R-HSA-3000112
  title: CD320-mediated TCN2:RCbl uptake and delivery to lysosome
  findings: []
- id: Reactome:R-HSA-3000122
  title: CD320 binds extracellular TCN2:RCbl
  findings: []
- id: Reactome:R-HSA-3325546
  title: Defective CD320 does not transport extracellular TCII:Cbl to endosome
  findings: []
- id: Reactome:R-HSA-9758890
  title: Transport of RCbl within the body
  findings: []