Endoglin (CD105) is a disulfide-linked, type I transmembrane glycoprotein that acts as a coreceptor in vascular signaling. Its extracellular orphan region binds BMP9 and BMP10, and its association with signaling receptors supports BMP9βALK1βSMAD responses and context-dependent TGF-beta signaling. Endoglin is prominent on endothelial cell surfaces and contributes to vascular remodeling, vessel-wall maturation and selected cardiac developmental processes. Long and short splice products share the extracellular region but have different cytoplasmic tails; soluble extracellular forms also occur. Heterozygous pathogenic ENG variants cause hereditary hemorrhagic telangiectasia type 1.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001569 branching involved in blood vessel morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endoglin supports vascular branching and organization in developmental models. Reason: The current mouse donor is grounded in PMID10348742: endothelial-marker expression and early primary networks persist, whereas subsequent branching/remodeling and vascular smooth-muscle investment are disrupted. Preserve the transferred developmental context as non-core. This is not a direct human branch-generation assay or proof that ENG catalyzes morphogenesis. |
| GO:0001569 branching involved in blood vessel morphogenesis | ISS PMID:8194490 Molecular characterization and in situ localization of murin... | KEEP AS NON CORE | Summary: Endoglin supports vascular branching and organization in developmental models. Reason: The current mouse donor is grounded in PMID10348742: endothelial-marker expression and early primary networks persist, whereas subsequent branching/remodeling and vascular smooth-muscle investment are disrupted. Preserve the transferred developmental context as non-core. This is not a direct human branch-generation assay or proof that ENG catalyzes morphogenesis. The original cloning source remains literal; its abstract alone is not being presented as the later developmental experiment. |
| GO:0001570 vasculogenesis | IBA GO_REF:0000033 | UNDECIDED | Summary: The PAINT vasculogenesis assertion has a valid ancestry path but unresolved source scope. Reason: Human P17813 lies below PTN007631063 in PTHR14002, with an exact matching IBD and human MSA sequence. Target self-evidence is legitimate and donor count is not a weakness. The current term concerns endothelial differentiation and de novo vessel formation, whereas both inspected mouse originals PMID10348742 and PMID10562296 preserve initial primary networks and distinguish later remodeling defects. The human PMID7894484 operative assay remains unavailable. Preserve the valid phylogenetic source with uncertainty about the specific developmental step, rather than rejecting the clade, guessing a loss or asserting universal absence of ENG participation. Propagation Review Root cause: UNRESOLVED Sources checked: PANTHER:PTN007631063 UNRESOLVED The exact IBD, ancestral node on the human ENG path and 658-residue target MSA match are verified. The unresolved issue is the specific de novo vessel-formation stage in the underlying biological evidence; no node misplacement, target-specific loss, donor-count weakness or self-evidence circularity is asserted. Supporting Evidence: GO_REF:0000033 file:human/ENG/ENG-bioinformatics/RESULTS.md |
| GO:0001570 vasculogenesis | IEA GO_REF:0000107 | UNDECIDED | Summary: The exact de novo vasculogenesis claim remains unresolved across its mouse donor grounding. Reason: The current Q63961 donor query identifies PMID10348742 and PMID10562296. Both inspected originals preserve initial endothelial differentiation and primary plexus formation while describing subsequent branching and remodeling defects. This developmental-stage distinction leaves the specific de novo-formation inference unresolved; it does not establish universal nonparticipation or an incorrect ortholog. Keep all imported source fields unchanged. |
| GO:0001570 vasculogenesis | IMP PMID:7894484 Endoglin, a TGF-beta binding protein of endothelial cells, i... | UNDECIDED | Summary: The human HHT study establishes ENG disease relevance; its source-specific vasculogenesis evidence remains unresolved. Reason: The authentic PMID7894484 abstract identifies pathogenic ENG alterations and vascular disease, but the operative original was not recovered. Neither disease necessity nor the unavailable original establishes which de novo vessel-formation step ENG performs. Preserve the experimental assertion pending its actual assay; no wrong-gene or negative-function inference is made. Supporting Evidence: |
| GO:0001947 heart looping | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Heart-looping defects are a supported developmental consequence of altered endoglin. Reason: Mouse Eng-null studies PMID10348742 and PMID19703439 document incomplete heart-tube rotation or abnormal looping/chamber morphology. These observations support a conserved non-core developmental role, without converting systemic vascular failure or receptor necessity into a separate human molecular activity. |
| GO:0001947 heart looping | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Heart-looping defects are a supported developmental consequence of altered endoglin. Reason: Mouse Eng-null studies PMID10348742 and PMID19703439 document incomplete heart-tube rotation or abnormal looping/chamber morphology. These observations support a conserved non-core developmental role, without converting systemic vascular failure or receptor necessity into a separate human molecular activity. |
| GO:0001947 heart looping | ISS PMID:8194490 Molecular characterization and in situ localization of murin... | KEEP AS NON CORE | Summary: Heart-looping defects are a supported developmental consequence of altered endoglin. Reason: Mouse Eng-null studies PMID10348742 and PMID19703439 document incomplete heart-tube rotation or abnormal looping/chamber morphology. These observations support a conserved non-core developmental role, without converting systemic vascular failure or receptor necessity into a separate human molecular activity. The original cloning source remains literal; its abstract alone is not being presented as the later developmental experiment. |
| GO:0002040 sprouting angiogenesis | ISS NOT GO_REF:0000024 | KEEP AS NON CORE | Summary: The imported negative sprouting result is retained within its early mouse experimental context. Reason: PMID19703439 finds Eng-null cells in sprouts of rescued midgestation chimeras and finds PECAM-positive networks in null embryoid-body cultures. The negative assertion describes those early contexts; it does not exclude non-cell-autonomous vascular remodeling, later or adult angiogenesis, or every possible ENG contribution. Preserve the literal NOT qualifier and donor identity. |
| GO:0003148 outflow tract septum morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: A neural-crest genetic interaction links endoglin dosage to outflow-tract septation. Reason: PMID:17628518 Fig. 4EβH compares wild type, human-ENG overexpression, neural-crest Smad4 loss and the combined manipulation. Persistent truncus arteriosus with failed aortic/pulmonary septation appears in the combined group. This controlled genetic interaction supplies positive evidence for a contextual contribution to septum morphogenesis, supporting retention as non-core. It does not establish normal human dosage requirements or separate ENG action from the Smad4-deficient setting; those attribution limits are retained in this mouse-host human-transgene experiment. |
| GO:0003148 outflow tract septum morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: A neural-crest genetic interaction links endoglin dosage to outflow-tract septation. Reason: PMID:17628518 Fig. 4EβH compares wild type, human-ENG overexpression, neural-crest Smad4 loss and the combined manipulation. Persistent truncus arteriosus with failed aortic/pulmonary septation appears in the combined group. This controlled genetic interaction supplies positive evidence for a contextual contribution to septum morphogenesis, supporting retention as non-core. It does not establish normal human dosage requirements or separate ENG action from the Smad4-deficient setting; those attribution limits are retained in this mouse-host human-transgene experiment. |
| GO:0003198 epithelial to mesenchymal transition involved in endocardial cushion formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endoglin contributes to endocardial-cushion transition in the examined developmental model. Reason: PMID19703439 shows poor Eng-null contribution to cushion mesenchyme in rescued chimeras and delayed transformation/invasion of AVC explants. Residual mesenchymal cells at 48 hours mean the transition is impaired rather than absolutely impossible. Preserve the original tissue/species context and distinguish receptor-mediated developmental participation from direct execution of every EMT step. |
| GO:0003198 epithelial to mesenchymal transition involved in endocardial cushion formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Endoglin contributes to endocardial-cushion transition in the examined developmental model. Reason: PMID19703439 shows poor Eng-null contribution to cushion mesenchyme in rescued chimeras and delayed transformation/invasion of AVC explants. Residual mesenchymal cells at 48 hours mean the transition is impaired rather than absolutely impossible. Preserve the original tissue/species context and distinguish receptor-mediated developmental participation from direct execution of every EMT step. |
| GO:0003203 endocardial cushion morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endocardial-cushion morphogenesis is a supported contextual role. Reason: The directly assessed PMID19703439 chimera and AVC-explant experiments support abnormal cushion formation and patterning in Eng-deficient mice. The separate PMID12941632 donor remains abstract-only, so its precise assay is not claimed independently read. Preserve the imported sources, including the two raw contexts collapsed into row 14, without adding a second annotation or assigning a new molecular activity. |
| GO:0003203 endocardial cushion morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Endocardial-cushion morphogenesis is a supported contextual role. Reason: The directly assessed PMID19703439 chimera and AVC-explant experiments support abnormal cushion formation and patterning in Eng-deficient mice. The separate PMID12941632 donor remains abstract-only, so its precise assay is not claimed independently read. Preserve the imported sources, including the two raw contexts collapsed into row 14, without adding a second annotation or assigning a new molecular activity. |
| GO:0003208 cardiac ventricle morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiac-ventricle morphogenesis is retained as a developmental context. Reason: PMID19703439 compares somite-matched mouse embryos and reports ventricular/chamber and AVC morphology changes in Eng-null hearts. The organismal and tissue interaction context is retained as non-core; the evidence does not identify an isolated ENG ventricular-patterning enzyme or establish a direct human assay. |
| GO:0003208 cardiac ventricle morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiac-ventricle morphogenesis is retained as a developmental context. Reason: PMID19703439 compares somite-matched mouse embryos and reports ventricular/chamber and AVC morphology changes in Eng-null hearts. The organismal and tissue interaction context is retained as non-core; the evidence does not identify an isolated ENG ventricular-patterning enzyme or establish a direct human assay. |
| GO:0003209 cardiac atrium morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Cardiac-atrium morphogenesis is retained as a developmental context. Reason: PMID19703439 reports atrial/chamber size and AV-boundary abnormalities in matched Eng-null mouse embryos. These findings support the inherited contextual role, without implying that altered atrial morphology identifies a distinct molecular activity of ENG or demonstrates equivalence of the human natural products. |
| GO:0003209 cardiac atrium morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cardiac-atrium morphogenesis is retained as a developmental context. Reason: PMID19703439 reports atrial/chamber size and AV-boundary abnormalities in matched Eng-null mouse embryos. These findings support the inherited contextual role, without implying that altered atrial morphology identifies a distinct molecular activity of ENG or demonstrates equivalence of the human natural products. |
| GO:0003222 ventricular trabecula myocardium morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Eng-deficient embryos and severely affected chimeras have reduced ventricular trabeculation. Reason: PMID:19703439 Figs. 4EβF and 6IβJ document reduced ventricular trabeculation in Eng-null embryos and affected chimeras. The same study detects hypoxia-response transcripts (Fig. 7) and explicitly allows circulatory insufficiency and hypoxia to contribute to the morphology. Retain the experimental developmental association as non-core, with this systemic mediation unresolved. The finding does not establish a myocardium-autonomous role or an exclusive local trabeculation mechanism, and these limits are not interpreted as proof that the curated developmental involvement is false. |
| GO:0003222 ventricular trabecula myocardium morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Eng-deficient embryos and severely affected chimeras have reduced ventricular trabeculation. Reason: PMID:19703439 Figs. 4EβF and 6IβJ document reduced ventricular trabeculation in Eng-null embryos and affected chimeras. The same study detects hypoxia-response transcripts (Fig. 7) and explicitly allows circulatory insufficiency and hypoxia to contribute to the morphology. Retain the experimental developmental association as non-core, with this systemic mediation unresolved. The finding does not establish a myocardium-autonomous role or an exclusive local trabeculation mechanism, and these limits are not interpreted as proof that the curated developmental involvement is false. |
| GO:0004888 transmembrane signaling receptor activity | NAS PMID:18974388 S-endoglin expression is induced in senescent endothelial ce... | MODIFY | Summary: Endoglin is an auxiliary signaling coreceptor rather than an independently catalytic receptor. Reason: PMID18974388 describes long and short endoglin as auxiliary TGF-beta receptors and reports receptor interactions and different signaling responses. Its full Methods remain unavailable here. Independently inspected human-domain association and reporter experiments in PMID12015308, together with the BMP9 structural and signaling evidence, establish cooperation with signaling receptors. GO:0015026 captures that role more specifically than generic transmembrane signaling receptor activity without assigning kinase activity or equal activity to both natural products. Proposed replacements: coreceptor activity |
| GO:0005114 type II transforming growth factor beta receptor binding | IPI PMID:12015308 Extracellular and cytoplasmic domains of endoglin interact w... | ACCEPT | Summary: Human endoglin associates with the type II TGF-beta receptor. Reason: PMID12015308 maps association with TGFBR2 through human endoglin extracellular and cytoplasmic constructs by coimmunoprecipitation. COS-7 and rat L6E9 host experiments are distinct from the human ENG construct. Domain association supports receptor binding without an isolated-interface affinity claim or kinase activity. Supporting Evidence: |
| GO:0005114 type II transforming growth factor beta receptor binding | ISS PMID:8294451 Endoglin forms a heteromeric complex with the signaling rece... | ACCEPT | Summary: Type II receptor association is supported in the porcine donor and independently in human endoglin. Reason: PMID8294451 uses native porcine aortic endothelial cells, radioligand crosslinking and receptor/endoglin immunoprecipitation to support a heteromeric TGF-beta receptor complex. Preserve the literal P37176 transfer and historical 643-residue clone rather than equating it to the current 653-residue donor or either human product. Human endoglinβTGFBR2 association in PMID12015308 independently supports conservation. |
| GO:0005515 protein binding | IPI PMID:15702480 Interaction and functional interplay between endoglin and AL... | MODIFY | Summary: Human endoglin association with TGFBR1/ALK5 supports the specific receptor-binding term. Reason: The imported P36897 partner is TGFBR1/ALK5. PMID:15702480 remains unavailable beyond its abstract, so its exact assay is not claimed as inspected. Independent PMID:12015308 Results and receptor-domain coimmunoprecipitation experiments establish association of human endoglin with this receptor in COS-7 cells, supporting GO:0034713 in place of generic protein binding. This is receptor association in the tested cellular system, not an isolated binary affinity or evidence of ENG kinase activity. Preserve the original reference, partner and qualifier. Proposed replacements: type I transforming growth factor beta receptor binding |
| GO:0005515 protein binding | IPI PMID:15702480 Interaction and functional interplay between endoglin and AL... | KEEP AS NON CORE | Summary: The reported endoglin association with ACVRL1/ALK1 is retained as generic non-core binding. Reason: PMID15702480 reports endoglin receptor association and functional interplay, but operative full text was not recovered. The literal partner is ACVRL1/ALK1; independently inspected receptor-complex evidence supports the pair class without replacing this source with a more specific native molecular function. Preserve generic binding, source identity and the access boundary; receptor activity is assessed separately. |
| GO:0005515 protein binding | IPI PMID:15702480 Interaction and functional interplay between endoglin and AL... | MODIFY | Summary: Human endoglin association with TGFBR2 supports the specific receptor-binding term. Reason: The imported P37173 partner is TGFBR2. PMID:15702480 remains unavailable beyond its abstract, so its exact assay is not claimed as inspected. Independent PMID:12015308 Results and receptor-domain coimmunoprecipitation experiments establish association of human endoglin with this receptor in COS-7 cells, supporting GO:0005114 in place of generic protein binding. The evidence establishes receptor association without requiring an isolated-interface affinity measurement or assigning receptor kinase activity to ENG. Preserve the original reference, partner and qualifier. Proposed replacements: type II transforming growth factor beta receptor binding |
| GO:0005515 protein binding | IPI PMID:20856203 Critical role of endoglin in tumor cell plasticity of Ewing ... | KEEP AS NON CORE | Summary: The source-reported TGFB1 association is retained as generic non-core binding. Reason: The inspected PMID20856203 main text includes TGF-beta affinity labeling and endoglin perturbation in human Ewing-sarcoma and melanoma cells, but the relevant supplementary affinity-labeling panel was not recovered. Its BMP/TGF-beta signaling experiments do not establish a purified TGFB1 interface. Independent human cell-surface ligand evidence in PMID1326540 supports the literal TGFB1 association; retain the source pair without claiming that all original assay details were verified. |
| GO:0005515 protein binding | IPI PMID:22940691 Endoglin mediates fibronectin/Ξ±5Ξ²1 integrin and TGF-Ξ² pathwa... | KEEP AS NON CORE | Summary: EndoglinβITGB1 association is supported in the tested receptor-complex context. Reason: PMID22940691 reports reciprocal transfected and endogenous coimmunoprecipitation with alpha5/beta1 integrin, separately supported by proximity and internalization experiments. Human endothelial cells, mouse endothelial cells and COS-7 expression assays are distinguished. Retain the positive generic association without inferring an autonomous adhesion activity or direct binary interface from proximity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:22940691 Endoglin mediates fibronectin/Ξ±5Ξ²1 integrin and TGF-Ξ² pathwa... | KEEP AS NON CORE | Summary: EndoglinβITGA5 association is supported in the tested receptor-complex context. Reason: PMID22940691 reports reciprocal transfected and endogenous coimmunoprecipitation with alpha5/beta1 integrin, separately supported by proximity and internalization experiments. Human endothelial cells, mouse endothelial cells and COS-7 expression assays are distinguished. Retain the positive generic association without inferring an autonomous adhesion activity or direct binary interface from proximity alone. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:23868260 LRG1 promotes angiogenesis by modulating endothelial TGF-Ξ² s... | KEEP AS NON CORE | Summary: LRG1 association with endoglin is supported in receptor-complex and soluble-domain assays. Reason: PMID23868260 reports human endothelial coimmunoprecipitation, soluble extracellular-domain association and an SPR interaction. The Methods contain an insert-name inconsistency between the stated LRG1 cloning sequence and the GST-ENG reagent used subsequently; exact insert identity is therefore not claimed independently verified. Positive association is retained without equating it to a new ENG catalytic or regulatory molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:28564608 Structural Basis of the Human Endoglin-BMP9 Interaction: Ins... | MODIFY | Summary: Direct human endoglin recognition of BMP9 supports BMP binding. Reason: PMID:28564608 Fig. 2 and Table 1 resolve a human endoglin orphan-regionβBMP9 complex and test interface mutations with secretion/folding controls and binding assays. PMID:21737454 Fig. 2 and Table 1 independently measure human soluble endoglin binding to BMP9 and BMP10; PMID:22347366 Fig. 2/Table 1 corroborates BMP9 recognition with separately prepared human constructs. Replace generic protein binding with GO:0036122 while retaining the imported mature BMP9 partner and enables qualifier. Construct-dependent affinities are not assigned universally to natural products, and shared extracellular recognition does not establish equivalent cytoplasmic-tail signaling. Proposed replacements: BMP binding |
| GO:0005515 protein binding | IPI PMID:31540324 Endoglin Protein Interactome Profiling Identifies TRIM21 and... | KEEP AS NON CORE | Summary: Galectin-3 binds the extracellular region of endoglin in the tested assays. Reason: PMID31540324 reports array screening followed by coimmunoprecipitation and purified-protein BLI using soluble human ENG26β586 and galectin-3 reagents. Galectin-3 recognizes glycan-bearing endoglin; this does not make ENG a lectin. Retain the positive pair without an additional molecular-function refinement. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:31540324 Endoglin Protein Interactome Profiling Identifies TRIM21 and... | KEEP AS NON CORE | Summary: TRIM21 association with endoglin is supported in the studied preparations. Reason: PMID31540324 reports endogenous and transfected coimmunoprecipitation, ectodomain constructs and BLI with recombinant TRIM21. The endogenous reciprocal direction was not uniformly positive, and the authors describe a possible degradation mechanism as future work. Generic binding is retained without assigning ubiquitin-ligase activity or demonstrated TRIM21-mediated ENG degradation. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | KEEP AS NON CORE | Summary: The source-supported INHBA/activin A association is retained as non-core binding. Reason: PMID9872992 uses radioligand affinity labeling, chemical crosslinking and immunoprecipitation in receptor-expression systems. Endoglin ligand association depends on a suitable ligand-binding receptor; receptor association and ligand binding are not interchangeable isolated-binary assays. The literal partner/source and positive receptor-system context are retained, without inventing an additional native molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | KEEP AS NON CORE | Summary: The source-supported BMP7 association is retained as non-core binding. Reason: PMID9872992 uses radioligand affinity labeling, chemical crosslinking and immunoprecipitation in receptor-expression systems. Endoglin ligand association depends on a suitable ligand-binding receptor; receptor association and ligand binding are not interchangeable isolated-binary assays. The literal partner/source and positive receptor-system context are retained, without inventing an additional native molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | KEEP AS NON CORE | Summary: The source-supported ACVR2A association is retained as non-core binding. Reason: PMID9872992 uses radioligand affinity labeling, chemical crosslinking and immunoprecipitation in receptor-expression systems. Endoglin ligand association depends on a suitable ligand-binding receptor; receptor association and ligand binding are not interchangeable isolated-binary assays. The literal partner/source and positive receptor-system context are retained, without inventing an additional native molecular function. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | KEEP AS NON CORE | Summary: The source-supported ACVR2B association is retained as non-core binding. Reason: PMID9872992 uses radioligand affinity labeling, chemical crosslinking and immunoprecipitation in receptor-expression systems. Endoglin ligand association depends on a suitable ligand-binding receptor; receptor association and ligand binding are not interchangeable isolated-binary assays. The literal partner/source and positive receptor-system context are retained, without inventing an additional native molecular function. Supporting Evidence: |
| GO:0005534 galactose binding | IDA PMID:3262645 Biochemical characterization of the 44G4 antigen from the HO... | MARK AS OVER ANNOTATED | Summary: The cited lectin experiment characterizes galactose carried by endoglin, not galactose recognition by ENG. Reason: In PMID3262645, purified human HOON-cell 44G4 antigen binds Ricinus communis agglutinin; free galactose competes with that lectin interaction, and glycosidase treatment characterizes the antigen carbohydrate groups. The lectin is the galactose-recognizing entity. These positive results do not establish GO:0005534 activity by ENG. This source-specific overannotation judgment preserves the glycosylation findings and makes no universal claim that ENG cannot bind sugars. Supporting Evidence: |
| GO:0005539 glycosaminoglycan binding | IDA PMID:3262645 Biochemical characterization of the 44G4 antigen from the HO... | MARK AS OVER ANNOTATED | Summary: The inspected source does not establish glycosaminoglycan recognition as an ENG molecular function. Reason: PMID3262645 characterizes lectin affinity, N- and O-linked carbohydrate removal, disulfide-linked antigen structure and antibody recognition. ENG is the glycosylated antigen in those assays; the current GO:0005539 definition requires binding a glycosaminoglycan. No separate ENGβglycosaminoglycan recognition experiment was identified in the inspected operative Methods, Results and Discussion. Retain the positive biochemical findings while flagging this narrower functional interpretation as overannotated, not proven universal nonbinding. Supporting Evidence: |
| GO:0005539 glycosaminoglycan binding | ISS PMID:8294451 Endoglin forms a heteromeric complex with the signaling rece... | UNDECIDED | Summary: The porcine donor glycosaminoglycan-binding assertion remains unresolved. Reason: The actual PMID8294451 material inspected supports porcine endoglin association with TGF-beta receptors, ligand crosslinking, dimerization and phosphorylation. It does not independently resolve the specific glycosaminoglycan-binding assay behind the P37176 donor assertion. The donor identity is correct; the source is not rejected because it concerns pig, and receptor association or glycosylation is not substituted for glycosaminoglycan binding. Supporting Evidence: |
| GO:0005576 extracellular region | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: An extracellular endoglin pool is supported, with the conserved PAINT placement preserved. Reason: The exact extracellular-region IBD is on ancestral PTN007631115 along the human ENG lineage; its source list matches the imported assertion. Human extracellular sample detection and soluble ectodomain ligand experiments independently support an external pool. The is_active_in source is preserved; neither the whole transmembrane protein nor all natural products are asserted to be exclusively extracellular. Supporting Evidence: GO_REF:0000033 file:human/ENG/ENG-bioinformatics/RESULTS.md |
| GO:0005576 extracellular region | IDA PMID:19004009 Endoglin (CD105) as a urinary and serum marker of prostate c... | KEEP AS NON CORE | Summary: Endoglin is detected in extracellular clinical samples. Reason: PMID19004009 measures endoglin by ELISA in human post-DRE urine supernatants and serum. This directly supports extracellular occurrence, but does not identify the exact cleaved species, tissue of origin or extracellular activity. Retain as a non-core localization context without adding a tumor-related process. Supporting Evidence: |
| GO:0005886 plasma membrane | EXP PMID:10545596 Expression analysis of four endoglin missense mutations sugg... | ACCEPT | Summary: Plasma-membrane localization of normal human endoglin is supported. Reason: The authentic PMID10545596 abstract explicitly describes human patient HUVEC/monocyte protein analysis and surface biotinylation of transfectants, distinguishing normal surface protein from intracellular missense mutants. Its full operative original was not recovered; independent human cell-surface and current HPA evidence supports the location. No mutant trafficking result is generalized to wild-type ENG. |
| GO:0005886 plasma membrane | EXP PMID:1326540 Endoglin is a component of the transforming growth factor-be... | ACCEPT | Summary: Endogenous human and transfected human endoglin occur at the cell surface. Reason: The independent PMID1326540 original assessment verifies HUVEC and human-ENG COS-M6 cell-surface affinity labeling and immunoprecipitation. This supports plasma-membrane localization without sequence-level equivalence of the historical insert to either current product or a claim of exclusive localization. Supporting Evidence: |
| GO:0005886 plasma membrane | EXP PMID:1692830 Primary structure of endoglin, an RGD-containing glycoprotei... | ACCEPT | Summary: Human endoglin is a type I plasma-membrane protein. Reason: The authentic PMID1692830 abstract links human endothelial cDNA to the N-terminal sequence of placental endoglin and identifies extracellular, membrane-spanning and cytoplasmic regions. Historical partial-signal sequence numbering is not forced onto the current precursor. Independent cell-surface experiments and official topology support the plasma-membrane claim; no RGD-dependent adhesion function is inferred from sequence alone. |
| GO:0005886 plasma membrane | EXP PMID:17540773 The interaction of endoglin with beta-arrestin2 regulates tr... | ACCEPT | Summary: Plasma-membrane endoglin can undergo regulated internalization. Reason: The authentic PMID17540773 abstract reports endoglinβbeta-arrestin2 association and internalization into endocytic vesicles. Full operative Methods were not recovered, so exact preparation details are not claimed. Independent human cell-surface experiments support the imported plasma-membrane location; internalization does not invalidate that location or imply constitutive vesicle residence. |
| GO:0005886 plasma membrane | EXP PMID:8370410 Identification and expression of two forms of the human tran... | ACCEPT | Summary: The human long and short constructs support membrane endoglin localization. Reason: The authentic PMID8370410 abstract reports separate human long and short cDNAs expressed in mouse fibroblasts and positive TGFB1 binding and disulfide-linked dimers. Operative localization Methods remain inaccessible. Independent human surface evidence supports the membrane claim, while exact inserts, kinetic equivalence and equal native functions of the two products remain unverified. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: Official HPA evidence supports plasma-membrane endoglin. Reason: The target-matched HPA ENSG00000106991 XML gives supported main plasma-membrane localization in its ICC/IF summary. The XML evidence is read; image pixels are not. This agrees with independent human surface labeling, without elevating secondary cell-line observations into new locations or claiming exclusive plasma-membrane residence. |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: The UniProt cell-membrane mapping is consistent with endoglin topology and experiments. Reason: The official SL-0039 mapping is explicitly GO:0005886. Frozen human ENG has extracellular, transmembrane and cytoplasmic regions, and human surface-labeling experiments independently establish membrane occurrence. This is a verified mapping rather than a localization inferred solely from a generic family name. Supporting Evidence: GO_REF:0000044 file:human/ENG/ENG-bioinformatics/RESULTS.md |
| GO:0005925 focal adhesion | HDA PMID:21423176 Analysis of the myosin-II-responsive focal adhesion proteome... | KEEP AS NON CORE | Summary: Endoglin was detected in a human focal-adhesion-enriched proteomic fraction. Reason: The genuine PMID21423176 workbook identifies ENG/endoglin in reproducible HFF1 substrate-bound fractions and reports peptide evidence under IPI00017567.3. The preparation retains stress-fiber fragments and may contain nonadhesion material; no ENG-specific validation row was found in its validation sheets. This supports the HDA fraction-localization context, not an autonomous adhesion mechanism or natural-product-specific localization. Supporting Evidence: |
| GO:0006355 regulation of DNA-templated transcription | IMP PMID:15702480 Interaction and functional interplay between endoglin and AL... | KEEP AS NON CORE | Summary: Endoglin modulates ligand-dependent transcriptional reporter output through receptor signaling. Reason: PMID:15702480 remains abstract-only. Independent PMID:12015308 Fig. 9CβD tests human ENG expression in rat L6E9 cells and shows dose-dependent enhancement of TGF-beta responsiveness of the mix.2-derived pARE reporter, while basal reporter activity differs. This is positive evidence for contextual regulation of transcription through the receptorβSMAD pathway. GO:0006355 describes regulation and does not require ENG to bind DNA or catalyze transcription. Retain as non-core without generalizing the response across promoters, ligands, cell types or natural products. |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:12015308 Extracellular and cytoplasmic domains of endoglin interact w... | ACCEPT | Summary: Endoglin participates in TGF-beta receptor signaling as a receptor-associated coreceptor. Reason: PMID12015308 reports receptor-domain associations, receptor-mediated phosphorylation of ENG and altered Smad2 reporter responses in defined expression systems. The signaling kinases are the type I/II receptors, not ENG. The evidence supports direct receptor-system participation while retaining cell, ligand and construct dependence. Supporting Evidence: |
| GO:0009897 external side of plasma membrane | IDA PMID:1537377 Regulated expression on human macrophages of endoglin, an Ar... | ACCEPT | Summary: Human macrophage surface expression supports the external plasma-membrane context. Reason: The authentic PMID1537377 abstract describes endoglin-specific flow cytometry of differentiated human monocytes and surface expression associated with differentiation, plus tissue immunostaining. Full operative Methods were not recovered. The independent type I membrane topology and cell-surface evidence support an externally exposed ENG pool, without implying that every residue of this transmembrane protein lies outside the cell. |
| GO:0009986 cell surface | IBA GO_REF:0000033 | ACCEPT | Summary: Cell-surface activity is consistent with the exact PAINT ancestry and human evidence. Reason: The GO:0009986 IBD at PTN007631115 is on the human ENG path, with the exact imported node/donor set and matching human sequence. Human endothelial affinity-labeling and receptor-coreceptor assays support the cell-surface pool. Self-WITH evidence is expected, not circular; no target-specific loss is inferred from donor count. Supporting Evidence: GO_REF:0000033 file:human/ENG/ENG-bioinformatics/RESULTS.md |
| GO:0010629 negative regulation of gene expression | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific transferred negative gene-expression context remains unresolved. Reason: The current mouse GO:0010629 donor is PMID12941632, with the recorded Q64314 input and dorsal-aortic context. Its authentic abstract does not disclose the precise repression assay, and operative original text was not recovered. Other ENG-dependent expression changes do not verify that exact donor mechanism. Preserve the source and uncertainty without asserting a wrong gene, a transcription-factor activity, or universal failure to repress expression. |
| GO:0010629 negative regulation of gene expression | ISS GO_REF:0000024 | UNDECIDED | Summary: The specific transferred negative gene-expression context remains unresolved. Reason: The current mouse GO:0010629 donor is PMID12941632, with the recorded Q64314 input and dorsal-aortic context. Its authentic abstract does not disclose the precise repression assay, and operative original text was not recovered. Other ENG-dependent expression changes do not verify that exact donor mechanism. Preserve the source and uncertainty without asserting a wrong gene, a transcription-factor activity, or universal failure to repress expression. |
| GO:0010665 regulation of cardiac muscle cell apoptotic process | ISS NOT GO_REF:0000024 | KEEP AS NON CORE | Summary: The imported negative cardiac apoptosis result is retained as a limited gain-of-function observation. Reason: PMID17628518 reports no increased TUNEL signal in the examined E12.5 human-ENG-overexpressing mouse heart context, with data not shown. This does not establish universal absence of ENG regulation, identify every stained cell as a cardiomyocyte, or substitute for a loss-of-function apoptosis assay. Retain the literal NOT source as non-core with those scope limits. |
| GO:0015026 coreceptor activity | IPI PMID:12015308 Extracellular and cytoplasmic domains of endoglin interact w... | ACCEPT | Summary: Endoglin acts as a coreceptor for signaling receptors. Reason: Human ENG association with type I/II receptors and modulation of ligand-driven reporter activity in PMID12015308 establish cooperation with signaling receptors. BMP9 binding and signaling evidence independently corroborate the coreceptor role. No autonomous receptor kinase, obligatory direct binary affinity assay or all-product functional equivalence is asserted. |
| GO:0017015 regulation of transforming growth factor beta receptor signaling pathway | IDA PMID:15702480 Interaction and functional interplay between endoglin and AL... | ACCEPT | Summary: Endoglin regulates TGF-beta receptor signaling in a context-dependent manner. Reason: The authentic PMID15702480 abstract reports ALK1/ALK5 functional interplay, with its full operative text unavailable. Independent human receptor-domain and reporter experiments in PMID12015308 and ENG knockdown signaling in PMID23300529 substantiate regulation. This broad regulatory term is retained without generalizing one positive or negative branch response to every cell, ligand or product. |
| GO:0022009 central nervous system vasculogenesis | IMP PMID:7894484 Endoglin, a TGF-beta binding protein of endothelial cells, i... | UNDECIDED | Summary: The source-specific central nervous system vasculogenesis claim remains unresolved. Reason: PMID7894484 establishes human ENG-related vascular disease, but its operative original was not recovered through the inspected routes. Clinical vascular lesions and necessity alone cannot distinguish de novo CNS vessel formation from later remodeling or maintenance. Preserve the imported experimental assertion pending its actual evidence; no wrong-reference or wrong-gene claim is made. Supporting Evidence: |
| GO:0030336 negative regulation of cell migration | IDA PMID:19736306 Endoglin phosphorylation by ALK2 contributes to the regulati... | KEEP AS NON CORE | Summary: Endoglin inhibits migration in the studied prostate-cancer cell context. Reason: PMID19736306 directly compares human long-endoglin and cytoplasmic mutants in PC3/PC3-M migration assays. Wild-type ENG inhibits migration, whereas receptor phosphorylation and cytoplasmic changes modify that effect; TGF-beta can counter it. Retain this non-core, context-specific regulatory process without a universal antimigratory sign or extension to the short natural product. Supporting Evidence: |
| GO:0030509 BMP signaling pathway | TAS PMID:11382917 Endoglin: An accessory component of the TGF-beta-binding rec... | ACCEPT | Summary: Endoglin is a participant in BMP receptor signaling. Reason: The cited PMID11382917 is an accessory-receptor review whose full body was not recovered. Independently inspected human ENG/BMP9 receptor-system experiments in PMID17068149 and PMID23300529, plus ligand binding in PMID28564608, substantiate the broad BMP signaling claim. This does not imply that ENG is the catalytic receptor or that every BMP behaves identically. |
| GO:0030513 positive regulation of BMP signaling pathway | IDA PMID:17068149 Identification of BMP9 and BMP10 as functional activators of... | ACCEPT | Summary: Human endoglin potentiates BMP9 signaling in the tested receptor system. Reason: PMID17068149 Methods identify human ENG expression plasmids; Results and Figure4 caption show increased BMP9-driven BRE reporter activity with ENG and ALK1 in NIH-3T3 cells. The effect is observed at low BMP9 and was not significant for BMP2 in the same comparison. Preserve human construct versus mouse host and ligand specificity; no direct ENG kinase or exact current-product insert assignment is made. Supporting Evidence: |
| GO:0030546 signaling receptor activator activity | IDA PMID:12015308 Extracellular and cytoplasmic domains of endoglin interact w... | ACCEPT | Summary: Endoglin enhances signaling-receptor activity through coreceptor interactions. Reason: GO:0030546 includes direct or indirect interaction that increases the active receptor fraction. PMID12015308 receptor associations and ligand-dependent reporter enhancement support this regulatory activity in the tested context, while basal or alternative pathway responses differ. No autonomous ENG catalytic step or uniform positive effect on every receptor branch is inferred. Supporting Evidence: |
| GO:0034713 type I transforming growth factor beta receptor binding | IPI PMID:12015308 Extracellular and cytoplasmic domains of endoglin interact w... | ACCEPT | Summary: Human endoglin associates with type I TGF-beta receptors. Reason: PMID12015308 uses coimmunoprecipitation and human ENG domain constructs to map association with type I receptor ALK5/TGFBR1. This supports receptor binding in the experimental system; the receptor phosphorylates ENG, not the reverse, and isolated-fragment activity is not equated with a natural product. Supporting Evidence: |
| GO:0034713 type I transforming growth factor beta receptor binding | ISS PMID:8294451 Endoglin forms a heteromeric complex with the signaling rece... | ACCEPT | Summary: Type I receptor association is supported by the porcine donor and human receptor evidence. Reason: PMID8294451 uses porcine aortic endothelial-cell ligand crosslinking and immunoprecipitation to support a heteromeric endoglin/type I/type II receptor system. Preserve the P37176 transfer and the lack of an isolated binary-interface assay. Human domain-based receptor association in PMID12015308 independently supports conservation. |
| GO:0035912 dorsal aorta morphogenesis | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific dorsal-aorta donor assertion remains unverified. Reason: The current same-term mouse donor points to PMID12941632. Its abstract describes vascular boundary/hematopoietic effects but does not resolve the dorsal-aorta morphogenesis assay, and the operative original was unavailable. Other inspected studies show dorsal-aortic vascular abnormalities, but they do not establish the exact assertion behind this transfer. Preserve the source and qualifier without using the article title or ontology wording as evidence of a wrong organism. |
| GO:0035912 dorsal aorta morphogenesis | ISS GO_REF:0000024 | UNDECIDED | Summary: The specific dorsal-aorta donor assertion remains unverified. Reason: The current same-term mouse donor points to PMID12941632. Its abstract describes vascular boundary/hematopoietic effects but does not resolve the dorsal-aorta morphogenesis assay, and the operative original was unavailable. Other inspected studies show dorsal-aortic vascular abnormalities, but they do not establish the exact assertion behind this transfer. Preserve the source and qualifier without using the article title or ontology wording as evidence of a wrong organism. |
| GO:0036122 BMP binding | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | KEEP AS NON CORE | Summary: Endoglin contributes to BMP7 binding within a receptor system. Reason: PMID9872992 reports BMP7 association in suitable activin-receptor expression contexts. The imported contributes_to relation is essential: the assay does not establish autonomous ENGβBMP7 binding independently of ligand-binding receptors. Retain this contextual ligand-recognition contribution separately from the better-defined BMP9 mechanism. Supporting Evidence: |
| GO:0042802 identical protein binding | IPI PMID:28564608 Structural Basis of the Human Endoglin-BMP9 Interaction: Ins... | ACCEPT | Summary: Endoglin self-association is supported by extracellular dimer evidence. Reason: The independently inspected PMID28564608 original distinguishes monomeric orphan region from covalent ZP-region/ectodomain dimers and tests the relevant cysteines. Human ectodomain association supports the self-binding assertion. Historical C350 truncation inferences are not substituted for the later C350βC382 intramolecular bond evidence; exact full-length natural-product equivalence is not assumed. Supporting Evidence: |
| GO:0042803 protein homodimerization activity | IEA GO_REF:0000107 | ACCEPT | Summary: Endoglin homodimerization is supported by conserved and direct human evidence. Reason: The current Q63961 donor is the homodimerization experiment associated with PMID8194490; its authentic abstract reports a disulfide-linked murine homodimer. Independently assessed human ectodomain/ZP experiments in PMID28564608 directly support dimerization and distinguish it from the monomeric orphan region. This does not assign every recombinant truncation to a natural product or conflate intramolecular and intermolecular cysteines. |
| GO:0043235 signaling receptor complex | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | ACCEPT | Summary: Endoglin occurs in a receptor complex involving ACVR2A. Reason: PMID9872992 receptor-expression, affinity-labeling and immunoprecipitation experiments place ENG in ligand-binding receptor complexes. Retain the literal part_of source and partner. The experiments do not establish a fixed native stoichiometry, constitutive assembly in every cell, or autonomous ENG receptor catalysis. Supporting Evidence: |
| GO:0043235 signaling receptor complex | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | ACCEPT | Summary: Endoglin occurs in a receptor complex involving ACVR2B. Reason: PMID9872992 receptor-expression, affinity-labeling and immunoprecipitation experiments place ENG in ligand-binding receptor complexes. Retain the literal part_of source and partner. The experiments do not establish a fixed native stoichiometry, constitutive assembly in every cell, or autonomous ENG receptor catalysis. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endoglin-dependent cardiac signaling supports developmental transcriptional activation in the assessed mouse context. Reason: PMID:19703439 Fig. 5H and Fig. 6 report reduced Snai1 and BMP2 expression, loss of Tbx2 expression and altered chamber-expression domains in Eng-null mouse hearts. These spatial and expression findings support a contextual upstream regulatory contribution to developmental transcription. GO:0045944 covers processes increasing Pol II transcription and does not require ENG itself to bind DNA or act as polymerase. Retain the inherited annotation as non-core; altered tissue patterning and systemic physiology constrain causal attribution, and nascent transcription or promoter occupancy by ENG was not measured. The two original tissue/input contexts collapsed in source index 74 remain documented. |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Endoglin-dependent cardiac signaling supports developmental transcriptional activation in the assessed mouse context. Reason: PMID:19703439 Fig. 5H and Fig. 6 report reduced Snai1 and BMP2 expression, loss of Tbx2 expression and altered chamber-expression domains in Eng-null mouse hearts. These spatial and expression findings support a contextual upstream regulatory contribution to developmental transcription. GO:0045944 covers processes increasing Pol II transcription and does not require ENG itself to bind DNA or act as polymerase. Retain the inherited annotation as non-core; altered tissue patterning and systemic physiology constrain causal attribution, and nascent transcription or promoter occupancy by ENG was not measured. The two original tissue/input contexts collapsed in source index 74 remain documented. |
| GO:0048185 activin binding | TAS PMID:11382917 Endoglin: An accessory component of the TGF-beta-binding rec... | KEEP AS NON CORE | Summary: Endoglin-associated receptor systems can bind activin. Reason: The cited PMID11382917 review body is unavailable, but the inspected PMID9872992 original reports activin A association with ENG in the presence of appropriate activin receptors. Retain the contextual binding term without converting it into purified autonomous ENGβactivin affinity or the principal BMP9 core mechanism. |
| GO:0048745 smooth muscle tissue development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endoglin supports vascular smooth-muscle development in developmental models. Reason: PMID10348742 shows impaired smooth-muscle investment and marker expression that precede overt endothelial remodeling failure in Eng-null embryos/yolk sacs. The later PMID17628518 differentiation experiments independently support this developmental context. Retain as non-core without treating ENG as a structural smooth-muscle component or assigning exact human-product activity. |
| GO:0048745 smooth muscle tissue development | ISS PMID:8194490 Molecular characterization and in situ localization of murin... | KEEP AS NON CORE | Summary: Endoglin supports vascular smooth-muscle development in developmental models. Reason: PMID10348742 shows impaired smooth-muscle investment and marker expression that precede overt endothelial remodeling failure in Eng-null embryos/yolk sacs. The later PMID17628518 differentiation experiments independently support this developmental context. Retain as non-core without treating ENG as a structural smooth-muscle component or assigning exact human-product activity. The original cloning source remains literal; its abstract alone is not being presented as the later developmental experiment. |
| GO:0048844 artery morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Arterial morphogenesis is a supported developmental context for endoglin. Reason: The inspected PMID10348742 mouse original documents disorganized dorsal aortae, branchial arches and carotid arteries with defective smooth-muscle investment. This supports the contextual arterial role while preserving the developmental stage and systemic vascular setting; no direct human arterial-patterning experiment is claimed. |
| GO:0048844 artery morphogenesis | ISS PMID:8194490 Molecular characterization and in situ localization of murin... | KEEP AS NON CORE | Summary: Arterial morphogenesis is a supported developmental context for endoglin. Reason: The inspected PMID10348742 mouse original documents disorganized dorsal aortae, branchial arches and carotid arteries with defective smooth-muscle investment. This supports the contextual arterial role while preserving the developmental stage and systemic vascular setting; no direct human arterial-patterning experiment is claimed. The original cloning source remains literal; its abstract alone is not being presented as the later developmental experiment. |
| GO:0048845 venous blood vessel morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Venous morphogenesis is retained in the broader vascular-development context. Reason: The current same-term mouse donor links PMID10348742 to disturbed vascular organization, whose strongest inspected evidence concerns remodeling and smooth-muscle investment. Independently inspected PMID10562296 Results describe a dilated umbilical vein and embryonic vascular fragility. Together these support a contextual venous-development role, without a vein-specific isolated ENG activity or direct human assay. The original cloning source, where present, is not claimed to contain the later developmental experiment. |
| GO:0048845 venous blood vessel morphogenesis | ISS PMID:8194490 Molecular characterization and in situ localization of murin... | KEEP AS NON CORE | Summary: Venous morphogenesis is retained in the broader vascular-development context. Reason: The current same-term mouse donor links PMID10348742 to disturbed vascular organization, whose strongest inspected evidence concerns remodeling and smooth-muscle investment. Independently inspected PMID10562296 Results describe a dilated umbilical vein and embryonic vascular fragility. Together these support a contextual venous-development role, without a vein-specific isolated ENG activity or direct human assay. The original cloning source, where present, is not claimed to contain the later developmental experiment. |
| GO:0050431 transforming growth factor beta binding | IEA GO_REF:0000120 | ACCEPT | Summary: The rule-based TGF-beta-binding claim is supported by a matching rule clause and human receptor evidence. Reason: ARBA00090009 contains a sufficient positive OR clause requiring IPR058899, PTHR14002 and Euarchontoglires; all three premises match the frozen human UniProt record. The rule outputs GO:0050431, also grounded by the current mouse binding record and independently assessed human TGFB1/TGFB3 receptor-system experiments. Other OR clauses are not claimed to match, and the broad peptide-binding term does not encode the erroneous TGFB2/TGFB3 wording in the separate UniProt SUBUNIT comment. Supporting Evidence: GO_REF:0000120 file:human/ENG/ENG-bioinformatics/RESULTS.md |
| GO:0050431 transforming growth factor beta binding | IPI PMID:1326540 Endoglin is a component of the transforming growth factor-be... | ACCEPT | Summary: The human cell-surface receptor system supports endoglin association with TGFB1. Reason: The independently assessed PMID1326540 original uses radiolabeled ligand, chemical crosslinking, anti-endoglin immunoprecipitation and competition in HUVEC and human-ENG COS-M6 cells. It supports TGFB1/TGFB3 positivity, with TGFB3 tested as competitor; it is not a purified binary-binding assay. The frozen UniProt prose inversion of TGFB2/TGFB3 is a separate record-text issue and does not invalidate this correct imported partner. Supporting Evidence: |
| GO:0050431 transforming growth factor beta binding | IPI PMID:1326540 Endoglin is a component of the transforming growth factor-be... | ACCEPT | Summary: The human cell-surface receptor system supports endoglin association with TGFB3. Reason: The independently assessed PMID1326540 original uses radiolabeled ligand, chemical crosslinking, anti-endoglin immunoprecipitation and competition in HUVEC and human-ENG COS-M6 cells. It supports TGFB1/TGFB3 positivity, with TGFB3 tested as competitor; it is not a purified binary-binding assay. The frozen UniProt prose inversion of TGFB2/TGFB3 is a separate record-text issue and does not invalidate this correct imported partner. Supporting Evidence: |
| GO:0050431 transforming growth factor beta binding | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | ACCEPT | Summary: Endoglin contributes to TGFB1 binding in a TGF-beta receptor system. Reason: PMID9872992 tests ligand binding in receptor-expression systems and shows the requirement for appropriate ligand-binding receptors. The imported contributes_to qualifier is preserved and fits a receptor-complex contribution; it is not judged against an autonomous purified-binding requirement. The ligand-specific source context is retained without kinase activity or fixed complex stoichiometry. Supporting Evidence: |
| GO:0050431 transforming growth factor beta binding | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | ACCEPT | Summary: Endoglin contributes to TGFB3 binding in a TGF-beta receptor system. Reason: PMID9872992 tests ligand binding in receptor-expression systems and shows the requirement for appropriate ligand-binding receptors. The imported contributes_to qualifier is preserved and fits a receptor-complex contribution; it is not judged against an autonomous purified-binding requirement. The ligand-specific source context is retained without kinase activity or fixed complex stoichiometry. Supporting Evidence: |
| GO:0051897 positive regulation of phosphatidylinositol 3-kinase/protein kinase B signal transduction | IGI PMID:26857067 miR-342-5p Is a Notch Downstream Molecule and Regulates Mult... | KEEP AS NON CORE | Summary: Endoglin supports Akt pathway output in the tested endothelial signaling context. Reason: PMID26857067 shows miR-342-5p targeting the human ENG 3-prime UTR and reducing ENG and Akt phosphorylation in HUVECs; ENG expression rescues the Akt readout. Methods identify the rescue as murine Eng cDNA, so this is not an isolated human-protein rescue or kinase assay. Retain contextual positive PI3K/Akt signal regulation with the literal genetic-interaction source, without assigning ENG catalytic activity or attributing all miRNA effects solely to ENG. Supporting Evidence: |
| GO:0055009 atrial cardiac muscle tissue morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Atrial cardiac-muscle morphology is affected in the examined endoglin gain-of-function model. Reason: PMID17628518 reports atrial-wall thinning and hemorrhage after human ENG overexpression in mouse neural crest-derived cells. This supports a contextual developmental phenotype rather than a new ENG muscle contractile activity. It does not show a normal human cardiac isoform-specific function or make apoptosis the demonstrated cause. |
| GO:0055009 atrial cardiac muscle tissue morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Atrial cardiac-muscle morphology is affected in the examined endoglin gain-of-function model. Reason: PMID17628518 reports atrial-wall thinning and hemorrhage after human ENG overexpression in mouse neural crest-derived cells. This supports a contextual developmental phenotype rather than a new ENG muscle contractile activity. It does not show a normal human cardiac isoform-specific function or make apoptosis the demonstrated cause. |
| GO:0060391 positive regulation of SMAD protein signal transduction | IDA PMID:12015308 Extracellular and cytoplasmic domains of endoglin interact w... | ACCEPT | Summary: Endoglin can positively modulate SMAD signaling through receptor complexes. Reason: PMID12015308 reports enhanced ligand-driven Smad2-responsive transcription and complex receptor-domain interactions, while different basal or receptor contexts can behave differently. Independent ENG-dependent BMP9/SMAD1 evidence supports the broader positive signaling role. The product acts through receptor cooperation rather than directly phosphorylating SMADs. |
| GO:0072563 endothelial microparticle | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endoglin is present in a mouse endothelial-microparticle preparation. Reason: PMID20978343 directly detects CD105 in blood-derived microparticle pellets after FeCl3 injury using staining/confocal analysis and dot immunoblot. Its CD36-focused title does not invalidate the ENG observation. Retain transferred fraction localization with the preparation limit; no human-specific isoform, exosome identity or ENG microparticle-biogenesis function is inferred. |
| GO:0090500 endocardial cushion to mesenchymal transition | ISS NOT GO_REF:0000024 | UNDECIDED | Summary: The precise negative endocardial-cushion transition assertion remains unresolved. Reason: The current mouse NOT donor is PMID12941632, whose operative original was not recovered. The authentic abstract does not disclose the specific negative transition assay. GO:0090500 and the positive GO:0003198 name related but differently specified starting-cell processes; a later positive EMT study is not mechanically treated as the literal inverse of this source. Preserve the imported NOT qualifier and uncertainty. |
| GO:0097084 vascular associated smooth muscle cell development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endoglin contributes to development of vascular-associated smooth-muscle cells. Reason: PMID17628518 separates human-ENG neural-crest gain of function in mice from mouse-null and rat NCSC differentiation assays. Increased/disorganized smooth-muscle markers, reduced null-cell myogenic potential and reconstitution support this non-core developmental context. Exact retroviral insert identity is not inferred from the separate human transgene, and necessity is not mislabeled as an ENG catalytic reaction. |
| GO:0097084 vascular associated smooth muscle cell development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Endoglin contributes to development of vascular-associated smooth-muscle cells. Reason: PMID17628518 separates human-ENG neural-crest gain of function in mice from mouse-null and rat NCSC differentiation assays. Increased/disorganized smooth-muscle markers, reduced null-cell myogenic potential and reconstitution support this non-core developmental context. Exact retroviral insert identity is not inferred from the separate human transgene, and necessity is not mislabeled as an ENG catalytic reaction. |
| GO:1905007 positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endoglin positively influences cushion-forming EMT in the examined mouse model. Reason: PMID19703439 finds poor Eng-null contribution to cushion mesenchyme and delayed AVC-explant transformation/invasion, with residual activity at 48 hours. Those experiments support positive contextual regulation rather than an absolute on/off requirement or direct execution of every EMT step. The imported source and tissue boundaries are retained. |
| GO:1905007 positive regulation of epithelial to mesenchymal transition involved in endocardial cushion formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Endoglin positively influences cushion-forming EMT in the examined mouse model. Reason: PMID19703439 finds poor Eng-null contribution to cushion mesenchyme and delayed AVC-explant transformation/invasion, with residual activity at 48 hours. Those experiments support positive contextual regulation rather than an absolute on/off requirement or direct execution of every EMT step. The imported source and tissue boundaries are retained. |
| GO:1905065 positive regulation of vascular associated smooth muscle cell differentiation | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endoglin positively influences vascular smooth-muscle differentiation in the tested progenitors. Reason: PMID17628518 reports reduced myogenic potential in mouse Eng-null and rat CD105-low NCSCs, with reconstitution and ligand-response comparisons. These are actual differentiation readouts, distinct from counts alone. The human overexpression experiment and rodent culture preparations remain separate; no exact current human-product equivalence is inferred. |
| GO:1905065 positive regulation of vascular associated smooth muscle cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Endoglin positively influences vascular smooth-muscle differentiation in the tested progenitors. Reason: PMID17628518 reports reduced myogenic potential in mouse Eng-null and rat CD105-low NCSCs, with reconstitution and ligand-response comparisons. These are actual differentiation readouts, distinct from counts alone. The human overexpression experiment and rodent culture preparations remain separate; no exact current human-product equivalence is inferred. |
| GO:1905222 atrioventricular canal morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Atrioventricular-canal morphogenesis is a supported developmental context. Reason: PMID19703439 reports abnormal AV constriction, chamber boundaries and regional expression in somite-matched Eng-null mouse embryos, with cushion-explant evidence. Retain this tissue-level consequence of receptor-system function as non-core, without assigning ENG a new autonomous patterning activity. |
| GO:1905222 atrioventricular canal morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Atrioventricular-canal morphogenesis is a supported developmental context. Reason: PMID19703439 reports abnormal AV constriction, chamber boundaries and regional expression in somite-matched Eng-null mouse embryos, with cushion-explant evidence. Retain this tissue-level consequence of receptor-system function as non-core, without assigning ENG a new autonomous patterning activity. |
| GO:1905310 regulation of cardiac neural crest cell migration involved in outflow tract morphogenesis | ISS NOT GO_REF:0000024 | KEEP AS NON CORE | Summary: The imported negative migration result is retained within the examined lineage-tracing context. Reason: PMID17628518 finds similar neural-crest-derived cell contribution around the E12.5 heart/vessels after human ENG overexpression. This argues against impaired migration as the explanation of that phenotype, but is not time-resolved cell-motility measurement or universal absence of migration regulation. Preserve the original NOT qualifier and context. |
| GO:2000136 regulation of cell proliferation involved in heart morphogenesis | ISS NOT GO_REF:0000024 | KEEP AS NON CORE | Summary: The imported negative proliferation result is retained within the examined gain-of-function context. Reason: PMID17628518 reports no phosphohistone-H3 difference in the examined heart and surrounding vasculature, with data not shown. The finding is a context-specific negative after human ENG overexpression in mouse neural crest, not proof that ENG cannot regulate proliferation in another cell, stage or ligand setting. Preserve the literal NOT source as non-core. |
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Download this section (compressed HTML)Q: Which stage- and cell-type-resolved experiments distinguish endoglin participation in initial de novo vasculogenesis from its established roles in later vascular remodeling and smooth-muscle investment? How should that distinction constrain the inherited general and CNS vasculogenesis annotations?
Q: Which original porcine endoglin assay supports glycosaminoglycan recognition underlying the PMID:8294451 transfer? Can direct ENG binding be distinguished from recognition of ENG-associated glycans by another assay component?
Q: What precise developmental stages, target cells and readouts support the PMID:12941632 negative endocardial-cushion transition, negative gene-expression and dorsal-aorta assertions? How do the transition conditions compare with the later positive cushion-formation experiments in PMID:19703439?
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