ANTXR1 (TEM8) is a cell-surface receptor whose transmembrane forms couple extracellular attachment to the actin cytoskeleton. Its extracellular von Willebrand factor A domain supports ligand recognition, while the cytoplasmic tail binds actin and contributes to adhesion-dependent cell spreading and organization of membrane protrusions. Direct collagen-I recognition and receptor-dependent collagen uptake support a role in extracellular-matrix handling; collagen-VI recognition remains experimentally contested. In specific cellular settings ANTXR1 binds urokinase plasminogen activator and promotes EGFR signaling. It also binds anthrax protective antigen. Biallelic loss of ANTXR1 causes GAPO syndrome.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0004888 transmembrane signaling receptor activity | IBA GO_REF:0000033 | ACCEPT | Summary: Transmembrane receptor activity is supported by direct human studies. Reason: Human receptor activity is experimentally established. PAINT is a node-based inference; self-inclusion is valid experimental grounding. The complete PTN000412053 tree and alignment have not been independently audited, and no donor-count or circularity objection is made. Supporting Evidence: PMID:16762926 the extracellular and transmembrane domains of TEM8 were sufficient to provide cell attachment, the intracellular domain was critical for spreading. file:human/ANTXR1/ANTXR1-notes.md |
| GO:0004888 transmembrane signaling receptor activity | IDA PMID:16762926 Anthrax toxin receptor 1/tumor endothelium marker 8 mediates... | MODIFY | Summary: Cell-adhesion receptor activity specifies the attachment-to-actin mechanism. Reason: The original full primary paper demonstrates tail-dependent spreading after extracellular attachment and coupling to actin. Cell adhesion receptor activity specifies this supported receptor role; the claim does not require intrinsic kinase activity. Collagen binding has independent later support, while collagen-VI specificity remains contested. Proposed replacements: cell adhesion receptor activity Supporting Evidence: PMID:16762926 the extracellular and transmembrane domains of TEM8 were sufficient to provide cell attachment, the intracellular domain was critical for spreading. file:human/ANTXR1/ANTXR1-notes.md |
| GO:0005515 protein binding | IPI PMID:16564009 The LDL receptor-related protein LRP6 mediates internalizati... | MODIFY | Summary: LRP6 association supports signaling receptor binding. Reason: Reciprocal cellular co-immunoprecipitation associates TEM8 with full-length LRP6 and its extracellular region. LRP6 is a signaling receptor, so signaling receptor binding is more informative than generic protein binding. The current GO definition is not restricted to a ligand occupying an agonist site; it includes receptor-associated interactions. This source IPI supports coassociation, without establishing a purified binary interface, an agonist binding site or universal LRP6 necessity for toxin entry. Proposed replacements: signaling receptor binding Supporting Evidence: PMID:16564009 by interacting at the cell surface with PA receptors TEM8/ATR and/or CMG2 file:human/ANTXR1/ANTXR1-notes.md |
| GO:0005515 protein binding | IPI PMID:16762926 Anthrax toxin receptor 1/tumor endothelium marker 8 mediates... | MODIFY | Summary: Anthrax-toxin recognition occurs through its protective-antigen receptor-binding component. Reason: TEM8 binds protective antigen, the receptor-binding component of anthrax toxin. In the original study, PA-dependent attachment accompanies TEM8-dependent susceptibility to LF plus PA. This supports toxic substance binding through the PA moiety of the toxin. The term does not require each bound component to be independently poisonous. This refinement does not assert that isolated PA is toxic, that TEM8 binds isolated LF or EF, or that TEM8 has antitoxin activity. The pathogen interaction remains outside the physiological core. Proposed replacements: toxic substance binding Supporting Evidence: PMID:16762926 acts as a receptor for Protective Antigen (PA), the cell-binding component of the anthrax toxin determinant for toxin entrance into cells. file:human/ANTXR1/ANTXR1-notes.md |
| GO:0005518 collagen binding | IDA PMID:16762926 Anthrax toxin receptor 1/tumor endothelium marker 8 mediates... | ACCEPT | Summary: Collagen binding is supported, with collagen-VI specificity unresolved. Reason: The original 2006 evidence is cell attachment/spreading, with direct collagen binding left open. Later PMID:36400786 supplies purified fusion binding with MIDAS controls and an explicitly human TEM8 mutant series supporting collagen I. Its purification Methods cover mouse or human AP fusions, so species is not assigned to every unlabelled collagen-VI panel. PMID:36185380 reports contrary collagen-VI/C5 results using murine receptors, both human and murine C5 ligands, and distinct collagen preparations. Broad collagen binding remains supported through collagen I; collagen-VI specificity remains contested. The later binding experiments are not attributed to the original attachment study. Supporting Evidence: PMID:16762926 the extracellular and transmembrane domains of TEM8 were sufficient to provide cell attachment, the intracellular domain was critical for spreading. file:human/ANTXR1/ANTXR1-notes.md PMID:36400786 WT TEM8-AP, but not TEM8-D150A-AP or AP alone, robustly bound PA and collagen I PMID:36185380 overexpression of the two anthrax toxin receptors did not increase the interaction of collagen VI with the cells. |
| GO:0005886 plasma membrane | EXP PMID:16762926 Anthrax toxin receptor 1/tumor endothelium marker 8 mediates... | ACCEPT | Summary: The receptor localizes to the plasma membrane. Reason: Original full Results and Figure 6 directly place TEM8 at the plasma membrane, with additional punctate intracellular signal. Membrane localization is core receptor architecture. Supporting Evidence: PMID:21129411 Immunofluorescence staining using anti-FLAG mAbs revealed FLAG-TEM8 on the cell surface of non-permeabilized 293/FlagT8 cells immediately following transfection file:human/ANTXR1/ANTXR1-notes.md |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT plasma-membrane inference agrees with human target evidence. Reason: The PAINT membrane inference is compatible with human topology and direct surface assays. The phylogenetic node was not independently reconstructed; self-inclusion and donor count are not defects. The original is_active_in qualifier is preserved and assessed as the ordinary localization assertion. Supporting Evidence: PMID:21129411 Immunofluorescence staining using anti-FLAG mAbs revealed FLAG-TEM8 on the cell surface of non-permeabilized 293/FlagT8 cells immediately following transfection file:human/ANTXR1/ANTXR1-notes.md |
| GO:0005886 plasma membrane | IDA PMID:30241478 TEM8 functions as a receptor for uPA and mediates uPA-stimul... | ACCEPT | Summary: Human receptor assays support the plasma-membrane location. Reason: Human HepG2 receptor context and tagged-receptor cell assays in PMID:30241478 support the plasma membrane site. uPA/EGFR response does not imply intrinsic receptor kinase activity. Supporting Evidence: PMID:21129411 Immunofluorescence staining using anti-FLAG mAbs revealed FLAG-TEM8 on the cell surface of non-permeabilized 293/FlagT8 cells immediately following transfection file:human/ANTXR1/ANTXR1-notes.md |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The subcellular mapping agrees with direct membrane assays. Reason: UniProt subcellular-location mapping is supported by direct membrane and extracellular epitope evidence; preserve the original mapping and qualifier. Supporting Evidence: PMID:21129411 Immunofluorescence staining using anti-FLAG mAbs revealed FLAG-TEM8 on the cell surface of non-permeabilized 293/FlagT8 cells immediately following transfection file:human/ANTXR1/ANTXR1-notes.md |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5210909 | ACCEPT | Summary: Receptor-bound toxin assembly occurs at the plasma membrane. Reason: Receptor-bound PA oligomer assembly occurs at the target-cell plasma membrane. Full normal Reactome summary read. Supporting Evidence: Reactome:R-HSA-5210909 ANTXR1 (Anthrax Receptor 1)-bound pagA(197-794) (protective antigen, large fragment) forms oligomers in the target cell plasma membrane. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5210921 | ACCEPT | Summary: ANTXR1 binds protective antigen at the target-cell plasma membrane. Reason: The curated reaction places PA binding to human ANTXR1 at the plasma membrane; its older physiological-ligand uncertainty is updated only in review findings, never the cache. Full normal Reactome summary read. Supporting Evidence: Reactome:R-HSA-5210921 Extracellular pagA (also known as PA83 - full length Protective Antigen - Petosa et al. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5210923 | ACCEPT | Summary: The receptor-bound PA complex is on the cell surface. Reason: The reaction positions the receptor-bound PA complex on the cell surface. Toxin enzymes bind PA, not necessarily ANTXR1 directly. Full normal Reactome summary read. Supporting Evidence: Reactome:R-HSA-5210923 The enzyme components of anthrax toxins cya (also known as EF, Edema Factor - Robertson et al. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5210935 | ACCEPT | Summary: Furin processes receptor-bound PA at the cell surface. Reason: Furin cleaves receptor-bound PA at the surface; ANTXR1 is the membrane receptor, not the protease. Full normal Reactome summary read. Supporting Evidence: Reactome:R-HSA-5210935 Furin or a related protease at the cell surface cleaves ANTXR1-bound pagA (Anthrax Protective Antigen, full-length). |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-5210944 | ACCEPT | Summary: The endocytic reaction begins at the plasma membrane. Reason: The endocytic reaction starts with receptor-bound toxin at the plasma membrane, supporting the location independently of the later destination. Full normal Reactome summary read. Supporting Evidence: Reactome:R-HSA-5210944 cya (Anthrax EF, edema factor) and lef (LF, lethal factor) toxins bound to pagA(197-794):ANTXR1 (protective antigen, large fragment:Anthrax receptor 1) oligomer on the plasma membrane of the target cell, are localized into clathrin coated vesicles and transported to endosomes. |
| GO:0009897 external side of plasma membrane | IDA PMID:21129411 The cell surface structure of tumor endothelial marker 8 (TE... | ACCEPT | Summary: Externally exposed receptor epitopes support this membrane compartment. Reason: The official term includes proteins embedded in the outer leaflet, not only extrinsic proteins. Nonpermeabilized external FLAG/epitope assays and surface biotinylation of explicitly human TEM8 in PMID:21129411 support this location. Supporting Evidence: PMID:21129411 Immunofluorescence staining using anti-FLAG mAbs revealed FLAG-TEM8 on the cell surface of non-permeabilized 293/FlagT8 cells immediately following transfection file:human/ANTXR1/ANTXR1-notes.md |
| GO:0009986 cell surface | HDA PMID:19581412 Quantitative proteomics identifies a Dab2/integrin module re... | ACCEPT | Summary: The curated surface-proteomics assertion agrees with independent target assays. Reason: The source uses surface-labeling quantitative proteomics in HeLa cells. Its ANTXR1-specific supplementary row has not been independently inspected; the HDA assertion is retained with curator deference and strong independent human surface evidence from PMID:21129411, without claiming the pair table was read. Supporting Evidence: PMID:21129411 Immunofluorescence staining using anti-FLAG mAbs revealed FLAG-TEM8 on the cell surface of non-permeabilized 293/FlagT8 cells immediately following transfection file:human/ANTXR1/ANTXR1-notes.md |
| GO:0009986 cell surface | IBA GO_REF:0000033 | ACCEPT | Summary: The PAINT cell-surface inference is consistent with human experiments. Reason: Human cell-surface receptor evidence supports this PAINT inference. No phylogenetic misplacement is established; target self-inclusion is legitimate, and the tree/MSA boundary remains explicit. Supporting Evidence: PMID:21129411 Immunofluorescence staining using anti-FLAG mAbs revealed FLAG-TEM8 on the cell surface of non-permeabilized 293/FlagT8 cells immediately following transfection file:human/ANTXR1/ANTXR1-notes.md |
| GO:0009986 cell surface | IDA PMID:21129411 The cell surface structure of tumor endothelial marker 8 (TE... | ACCEPT | Summary: Human TEM8 is accessible at the cell surface. Reason: PMID:21129411 cell-surface assays use human TEM8 AF279145; masking of a subset of antibody epitopes does not establish absence from the surface. Supporting Evidence: PMID:21129411 Immunofluorescence staining using anti-FLAG mAbs revealed FLAG-TEM8 on the cell surface of non-permeabilized 293/FlagT8 cells immediately following transfection file:human/ANTXR1/ANTXR1-notes.md |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-5210944 | KEEP AS NON CORE | Summary: The endosomal receptor pool is retained in the toxin-uptake context. Reason: The full curated reaction transports receptor-bound toxin into endosomal membranes. Retain the trafficking location, with the toxin-context boundary; neither catalytic proteolysis nor membrane-pore activity is assigned to the receptor. Supporting Evidence: Reactome:R-HSA-5210944 cya (Anthrax EF, edema factor) and lef (LF, lethal factor) toxins bound to pagA(197-794):ANTXR1 (protective antigen, large fragment:Anthrax receptor 1) oligomer on the plasma membrane of the target cell, are localized into clathrin coated vesicles and transported to endosomes. |
| GO:0010008 endosome membrane | TAS Reactome:R-HSA-5210947 | KEEP AS NON CORE | Summary: The endosomal location is distinct from the PA translocation pore. Reason: The curated late step retains endosomal receptor context, while PA dissociates and supplies the translocation pore. The location is valid; the pore-forming activity belongs to PA. Supporting Evidence: Reactome:R-HSA-5210947 Through the action of vacuolar ATPase the pH of the target cell early endosome is lowered. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: Membrane mapping agrees with receptor architecture. Reason: Broad InterPro membrane mapping agrees with the receptor transmembrane architecture and direct surface assays. Broad location is correct and preserved alongside more informative locations. Supporting Evidence: PMID:21129411 Immunofluorescence staining using anti-FLAG mAbs revealed FLAG-TEM8 on the cell surface of non-permeabilized 293/FlagT8 cells immediately following transfection file:human/ANTXR1/ANTXR1-notes.md |
| GO:0030036 actin cytoskeleton organization | IDA PMID:16762926 Anthrax toxin receptor 1/tumor endothelium marker 8 mediates... | ACCEPT | Summary: The receptor tail structurally couples adhesion to actin organization. Reason: Original receptor/tail experiments couple adhesion to actin-dependent spreading and peripheral cytoskeletal organization. Later PMID:19817382 directly shows human-tail binding and bundling of preformed F-actin; this is structural participation, not merely necessity. No actin-polymerization claim is made. Supporting Evidence: PMID:16762926 cytoplasmic domain mediated linkage with the actin cytoskeleton file:human/ANTXR1/ANTXR1-notes.md PMID:19817382 We observed that TAIL360-420, but not TAIL360-420(Y383A), bound actin PMID:19817382 These data suggest this region of the cytoplasmic tail of ANTXR1 bundles filamentous actin. |
| GO:0031258 lamellipodium membrane | IDA PMID:16762926 Anthrax toxin receptor 1/tumor endothelium marker 8 mediates... | ACCEPT | Summary: Imaging supports a lamellipodial membrane pool. Reason: Original full Figure 6 and Results localize receptor to actin-rich lamellipodial membrane in the tested cell system. Do not generalize every receptor isoform or every membrane pool. The specific original Results passage adjoining Figure 6 is transcribed and linked in the notes. The abstract-only cache does not contain that localization passage. Supporting Evidence: file:human/ANTXR1/ANTXR1-notes.md TEM8 was localized at the tip of actin-rich filopodia and was enriched at the membrane of lamellipodia. |
| GO:0031258 lamellipodium membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The electronic lamellipodial mapping agrees with direct imaging. Reason: The subcellular-location mapping is supported by the original direct lamellipodial localization; preserve electronic-source fields and tested-context limits. The specific original Results passage adjoining Figure 6 is transcribed and linked in the notes. The abstract-only cache does not contain that localization passage. Supporting Evidence: file:human/ANTXR1/ANTXR1-notes.md TEM8 was localized at the tip of actin-rich filopodia and was enriched at the membrane of lamellipodia. |
| GO:0031527 filopodium membrane | IDA PMID:16762926 Anthrax toxin receptor 1/tumor endothelium marker 8 mediates... | ACCEPT | Summary: Imaging supports receptor localization in filopodial membrane. Reason: Original Figure 6 and Results show receptor at filopodial tips and membrane aligned with peripheral actin. This supports a protrusive membrane pool without requiring focal-adhesion membership. The specific original Results passage adjoining Figure 6 is transcribed and linked in the notes. The abstract-only cache does not contain that localization passage. Supporting Evidence: file:human/ANTXR1/ANTXR1-notes.md TEM8 was localized at the tip of actin-rich filopodia and was enriched at the membrane of lamellipodia. |
| GO:0031527 filopodium membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The filopodial mapping agrees with direct target evidence. Reason: The electronic filopodial membrane mapping agrees with original direct imaging; retain source fields and avoid claiming exclusive localization. The specific original Results passage adjoining Figure 6 is transcribed and linked in the notes. The abstract-only cache does not contain that localization passage. Supporting Evidence: file:human/ANTXR1/ANTXR1-notes.md TEM8 was localized at the tip of actin-rich filopodia and was enriched at the membrane of lamellipodia. |
| GO:0034446 substrate adhesion-dependent cell spreading | IDA PMID:16762926 Anthrax toxin receptor 1/tumor endothelium marker 8 mediates... | ACCEPT | Summary: The receptor contributes attachment and actin coupling during spreading. Reason: The receptor supplies extracellular attachment and intracellular actin coupling needed for spreading; the original IL2R-tail chimera/domain studies address mechanistic participation. This is an existing annotation, not a new necessity-only process. Supporting Evidence: PMID:16762926 the extracellular and transmembrane domains of TEM8 were sufficient to provide cell attachment, the intracellular domain was critical for spreading. file:human/ANTXR1/ANTXR1-notes.md |
| GO:0038023 signaling receptor activity | IDA PMID:30241478 TEM8 functions as a receptor for uPA and mediates uPA-stimul... | MODIFY | Summary: uPA receptor activity specifies the experimentally tested ligand. Reason: PMID:30241478 shows uPA binding by the TEM8 extracellular region and uPA-dependent cellular signaling. Urokinase plasminogen activator receptor activity specifies the ligand. The receptor does not enhance uPA catalytic activity in the reported enzyme assay. Proposed replacements: urokinase plasminogen activator receptor activity Supporting Evidence: PMID:30241478 Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. file:human/ANTXR1/ANTXR1-notes.md |
| GO:0038023 signaling receptor activity | IEA GO_REF:0000002 | ACCEPT | Summary: Broad signaling-receptor activity is consistent with direct target assays. Reason: Broad family-based signaling receptor activity is consistent with direct target receptor assays; preserve the InterPro inference without inventing an ancestral ligand-specific claim. Supporting Evidence: PMID:16762926 the extracellular and transmembrane domains of TEM8 were sufficient to provide cell attachment, the intracellular domain was critical for spreading. file:human/ANTXR1/ANTXR1-notes.md |
| GO:0045742 positive regulation of epidermal growth factor receptor signaling pathway | IDA PMID:30241478 TEM8 functions as a receptor for uPA and mediates uPA-stimul... | KEEP AS NON CORE | Summary: uPA-dependent EGFR regulation is a contextual signaling response. Reason: Actual human HepG2 LMW-uPA experiments show TEM8-associated EGFR phosphorylation and inhibition by TEM8-Fc; this is contextual receptor cross-talk, not intrinsic kinase activity or a universal basal function. Supporting Evidence: PMID:30241478 Binding of uPA stimulated the phosphorylation of TEM8 and augmented phosphorylation of EGFR and ERK1/2. file:human/ANTXR1/ANTXR1-notes.md |
| GO:0051015 actin filament binding | IDA PMID:16762926 Anthrax toxin receptor 1/tumor endothelium marker 8 mediates... | ACCEPT | Summary: The cytoplasmic tail binds actin filaments. Reason: The original 2006 receptor-tail/cytoskeleton observations are strengthened by later PMID:19817382 direct binding of a synthetic human tail segment to purified human beta-actin and bundling of preformed filaments. That later purified assay is distinct from the earlier co-IP. Historical sv1 constructs are not assigned a current isoform ID without sequence reconciliation. Supporting Evidence: PMID:16762926 cytoplasmic domain mediated linkage with the actin cytoskeleton file:human/ANTXR1/ANTXR1-notes.md PMID:19817382 We observed that TAIL360-420, but not TAIL360-420(Y383A), bound actin PMID:19817382 These data suggest this region of the cytoplasmic tail of ANTXR1 bundles filamentous actin. |
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Download this section (compressed HTML)Q: Which receptor species, construct states and collagen preparations explain the conflicting collagen-VI/C5 binding results, and which interactions occur at endogenous receptor abundance?
Q: Which coat-adaptor interactions link ANTXR1-bound collagen to endocytic carriers, and do they support a specific cargo-receptor activity?
Q: How do the historical sv1 constructs align with the six current human alternative products, and which preserve the extracellular adhesion and actin-binding modules?
Q: Does TEM8 form a direct functional receptor complex with LRP6 in a defined physiological context, beyond the reported toxin-associated coassociation?
Suggested experts: Receptor trafficking and structural biology researchers
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