BMPR2 is a single-pass type-II bone morphogenetic protein receptor with an extracellular ligand-binding domain and an intracellular serine/threonine kinase. At the plasma membrane it participates in BMP ligand/type-I/type-II receptor complexes and phosphorylates type-I receptors, which relay signals to R-SMADs and other effectors. Ligand and receptor composition shape the response, including BMP9/10 signaling in vascular endothelium and BMP-dependent mesenchymal differentiation. These pathways contribute to pulmonary vascular homeostasis, cartilage and bone development, and context-dependent control of proliferation and survival. The canonical 1,038-residue product has a long cytoplasmic tail that binds regulatory proteins; a named 530-residue splice product lacks most of that tail. Activin-A reception is also documented in a defined gonadotrope-like cell context. Disease-associated variants can alter surface trafficking, kinase signaling and endothelial behavior. Some disease-associated mutants produce p38 responses absent from wild-type receptor in the tested cell context.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001558 regulation of cell growth | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BMPR2 signaling influences cell growth in a cell-dependent manner. Reason: The broad ARBA assignment is consistent with BMP-dependent growth control. Endothelial and smooth-muscle responses differ, so this is a contextual consequence of receptor signaling rather than an additional catalytic function. |
| GO:0001568 blood vessel development | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Conserved BMP receptor signaling contributes to vascular development. Reason: The PAINT assertion is a phylogenetic inference, not a count of donor genes. Human pulmonary endothelial signaling and developmental expression support vascular involvement; retain this organismal process outside the minimal receptor-kinase core. Supporting Evidence: |
| GO:0001649 osteoblast differentiation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: BMPR2 supports osteogenic differentiation. Reason: Human adipose-derived mesenchymal-cell BMPR2 RNAi inhibits osteogenic differentiation, corroborating the mouse-based inference as well as the experimental row. This differentiation outcome is mediated by receptor signaling and is not itself a distinct molecular activity. |
| GO:0001649 osteoblast differentiation | IMP PMID:22684006 MicroRNA-100 regulates osteogenic differentiation of human a... | KEEP AS NON CORE | Summary: BMPR2 supports osteogenic differentiation. Reason: Human adipose-derived mesenchymal-cell BMPR2 RNAi inhibits osteogenic differentiation, corroborating the mouse-based inference as well as the experimental row. This differentiation outcome is mediated by receptor signaling and is not itself a distinct molecular activity. |
| GO:0001707 mesoderm formation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Mouse Bmpr2 supports mesoderm induction during gastrulation. Reason: The official primary abstract for the mouse knockout reports arrested epiblast differentiation and failure to form mesoderm. Retain the existing orthology-based developmental assertion as non-core; it is not a human-embryo experiment. The donor reading and its access limits are documented in the notes. Supporting Evidence: GO_REF:0000024 |
| GO:0001935 endothelial cell proliferation | IMP PMID:25187962 Functional changes in pulmonary arterial endothelial cells a... | KEEP AS NON CORE | Summary: BMPR2 affects pulmonary endothelial proliferation in an allele-dependent assay. Reason: In HLMVE cells, Thr268fs, Gln433X and Ser863Asn reduced BrdU incorporation relative to wild-type BMPR2, whereas Tyr67Cys did not. Retain involvement in endothelial proliferation without asserting that all mutants behave alike or that BMPR2 invariably stimulates proliferation in every endothelial context. Supporting Evidence: |
| GO:0001944 vasculature development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BMPR2 contributes to vascular development through BMP signaling. Reason: This broad electronic developmental term agrees with receptor-specific human pulmonary endothelial perturbations and developmental expression; retain it as a contextual process, not an independent biochemical function. Supporting Evidence: |
| GO:0001946 lymphangiogenesis | IEA GO_REF:0000107 | UNDECIDED | Summary: The lymphangiogenesis transfer needs a receptor-specific donor assessment. Reason: The mouse donor annotation is traceable through MGI to the ALK1-pathway study, but its cached abstract does not expose the endogenous BMPR2-specific experiment. Ligand-trapping and type-I receptor inhibition cannot simply be equated with loss of endogenous BMPR2. Preserve the inference without asserting misattribution; the exact donor perturbation and transfer remain unresolved. Supporting Evidence: |
| GO:0001946 lymphangiogenesis | ISS GO_REF:0000024 | UNDECIDED | Summary: The lymphangiogenesis transfer needs a receptor-specific donor assessment. Reason: The mouse donor annotation is traceable through MGI to the ALK1-pathway study, but its cached abstract does not expose the endogenous BMPR2-specific experiment. Ligand-trapping and type-I receptor inhibition cannot simply be equated with loss of endogenous BMPR2. Preserve the inference without asserting misattribution; the exact donor perturbation and transfer remain unresolved. Supporting Evidence: |
| GO:0001974 blood vessel remodeling | IEA GO_REF:0000107 | UNDECIDED | Summary: The blood-vessel-remodeling inference has an unresolved donor experimental boundary. Reason: MGI identifies the mouse pathway study, whose accessible abstract establishes ALK1-pathway involvement. The exact BMPR2 perturbation underlying this remodeling transfer has not been inspected. Broad vascular function is credible, but it does not independently settle this particular donor-derived process. Supporting Evidence: |
| GO:0001974 blood vessel remodeling | ISS GO_REF:0000024 | UNDECIDED | Summary: The blood-vessel-remodeling inference has an unresolved donor experimental boundary. Reason: MGI identifies the mouse pathway study, whose accessible abstract establishes ALK1-pathway involvement. The exact BMPR2 perturbation underlying this remodeling transfer has not been inspected. Broad vascular function is credible, but it does not independently settle this particular donor-derived process. Supporting Evidence: |
| GO:0002063 chondrocyte development | IMP PMID:9442116 Bone morphogenetic protein signaling is required for mainten... | KEEP AS NON CORE | Summary: BMPR2-dependent signaling maintains the differentiated chondrocyte phenotype. Reason: The dominant-negative construct is human BMPR2, while recipient cells are chick sternal chondrocytes. Inhibiting receptor signaling changes differentiation markers and hypertrophy; retain the experimental process with that construct/model boundary rather than treating it as a direct human-tissue assay. Supporting Evidence: |
| GO:0003085 negative regulation of systemic arterial blood pressure | IMP PMID:18364108 A novel mutation in the BMPR2 gene in familial pulmonary art... | UNDECIDED | Summary: Systemic arterial pressure regulation is not resolved by the accessible familial PAH report. Reason: The abstract explicitly concerns pulmonary arterial hypertension and BMPR2 Glu386Val segregation. GO:0003085 concerns systemic arterial pressure. The complete source assay has not been read, so the pulmonary disease association alone is insufficient for this specificity; no wrong-citation or absence conclusion is made. Supporting Evidence: |
| GO:0003148 outflow tract septum morphogenesis | ISS NOT GO_REF:0000024 | UNDECIDED | Summary: Preserve the negated outflow-tract-septum assertion pending resolution of allele and anatomical context. Reason: This is a NOT annotation, not a positive developmental assertion. Mouse hypomorphic and conditional studies distinguish outflow positioning, proximal conotruncal septation and other septal structures. The observed hypomorph septation defect cannot be reconciled with an unrestricted human negative solely from the transferred row; do not silently reverse its polarity or claim universal absence. Supporting Evidence: GO_REF:0000024 |
| GO:0003151 outflow tract morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BMPR2 contributes to positioning and morphogenesis of the cardiac outflow tract. Reason: Official mouse primary abstracts and indexed Results distinguish malpositioned aorta from septation defects. The conserved signaling receptor has a supported developmental role; retain this orthology-based process with the mouse developmental context, not as a separate receptor activity. Supporting Evidence: GO_REF:0000024 |
| GO:0003151 outflow tract morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 contributes to positioning and morphogenesis of the cardiac outflow tract. Reason: Official mouse primary abstracts and indexed Results distinguish malpositioned aorta from septation defects. The conserved signaling receptor has a supported developmental role; retain this orthology-based process with the mouse developmental context, not as a separate receptor activity. Supporting Evidence: GO_REF:0000024 |
| GO:0003176 aortic valve development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BMPR2 signaling contributes to aortic valve development. Reason: Mouse hypomorphic Bmpr2 experiments report failure of semilunar valve formation. The aortic-valve inference is biologically consistent with that phenotype, but describes a developmental deployment of BMP signaling rather than a universal or core biochemical function. Supporting Evidence: GO_REF:0000024 |
| GO:0003176 aortic valve development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 signaling contributes to aortic valve development. Reason: Mouse hypomorphic Bmpr2 experiments report failure of semilunar valve formation. The aortic-valve inference is biologically consistent with that phenotype, but describes a developmental deployment of BMP signaling rather than a universal or core biochemical function. Supporting Evidence: GO_REF:0000024 |
| GO:0003177 pulmonary valve development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BMPR2 signaling contributes to pulmonary valve development. Reason: The mouse hypomorph study reports absent semilunar valves, supporting this developmental transfer. Preserve the pulmonary-valve context and distinguish the phenotype from direct receptor catalysis. Supporting Evidence: GO_REF:0000024 |
| GO:0003177 pulmonary valve development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 signaling contributes to pulmonary valve development. Reason: The mouse hypomorph study reports absent semilunar valves, supporting this developmental transfer. Preserve the pulmonary-valve context and distinguish the phenotype from direct receptor catalysis. Supporting Evidence: GO_REF:0000024 |
| GO:0003181 atrioventricular valve morphogenesis | ISS NOT GO_REF:0000024 | UNDECIDED | Summary: The negated atrioventricular-valve assertion is context-dependent and unresolved. Reason: Preserve NOT. Atrioventricular valves appeared unaffected in the earlier mouse hypomorph, whereas later endocardial conditional deletion produced AV cushion and valve defects. These allele/tissue differences do not justify a universal negative assertion for human BMPR2; the original transfer needs contextual reconciliation. Supporting Evidence: GO_REF:0000024 |
| GO:0003183 mitral valve morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 contributes to mitral-valve morphogenesis in the inferred cardiac context. Reason: The mouse conditional study establishes endocardial BMPRII dependence of AV cushion remodeling and valve formation. Retain the curated mitral-valve transfer as non-core with explicit orthology and tissue limits; the individual human valve phenotype was not tested here. Supporting Evidence: GO_REF:0000024 |
| GO:0003186 tricuspid valve morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 contributes to tricuspid-valve morphogenesis in the inferred cardiac context. Reason: The mouse conditional study establishes an endocardial role in AV cushion remodeling and valve formation. Retain the curated tricuspid-valve transfer as non-core, without claiming a human valve-specific experiment or overriding the separately retained NOT row. Supporting Evidence: GO_REF:0000024 |
| GO:0003197 endocardial cushion development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: Endocardial BMPR2 signaling participates in cushion development and remodeling. Reason: The mouse conditional knockout shows AV cushion defects and thickened valve leaflets. This supports a conserved developmental consequence of receptor signaling; keep it outside the minimal molecular core. Supporting Evidence: GO_REF:0000024 |
| GO:0003197 endocardial cushion development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Endocardial BMPR2 signaling participates in cushion development and remodeling. Reason: The mouse conditional knockout shows AV cushion defects and thickened valve leaflets. This supports a conserved developmental consequence of receptor signaling; keep it outside the minimal molecular core. Supporting Evidence: GO_REF:0000024 |
| GO:0004674 protein serine/threonine kinase activity | IEA GO_REF:0000107 | MODIFY | Summary: BMPR2 is a BMP receptor with transmembrane serine/threonine kinase activity. Reason: The broad kinase activity is correct, but GO:0098821 BMP receptor activity captures the ligand-specific transmembrane receptor mechanism and matches the single molecular core. This term already occurs in the source IEA and ISS rows; the refinement consolidates this broad assertion into existing coverage, rather than adding a new function or an intermediate receptor-kinase term. The original source row is preserved for provenance. BMPR2 phosphorylates type-I receptors, not downstream SMADs directly. Proposed replacements: BMP receptor activity Supporting Evidence: Reactome:R-HSA-201443 |
| GO:0004675 transmembrane receptor protein serine/threonine kinase activity | IEA GO_REF:0000120 | ACCEPT | Summary: BMPR2 phosphorylates type-I receptor components of BMP signaling complexes. Reason: The type-II receptor kinase acts at the plasma membrane upstream of the type-I kinase. The receptor-to-receptor reaction is the catalytic part of the core mechanism; subsequent R-SMAD phosphorylation is performed by the activated type-I receptor. |
| GO:0005024 transforming growth factor beta receptor activity | IBA GO_REF:0000033 | REMOVE | Summary: The TGF-beta-ligand-specific receptor assignment does not describe the established BMP receptor activity. Reason: GO:0005024 requires reception of a TGF-beta ligand; its official comment excludes using receptor-superfamily membership alone. The characterized BMPR2 activity is BMP reception, so this ligand-specificity assignment is retired rather than described as a refinement whose original specificity is sound. GO:0098821 already occurs in the IEA and ISS source rows and in the molecular core, so removing this assertion loses no supported BMP receptor coverage. This is a term-scope judgment based on the receptor mechanism, not a short-donor-list argument or a claim to have reconstructed the PAINT tree/MSA. It does not deny the separately supported contextual activin activity. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:12045205 Functional analysis of bone morphogenetic protein type II re... | MODIFY | Summary: BMPR2 binds the BMP4 ligand; BMP binding describes the interaction more specifically than generic protein binding. Reason: PMID:12045205 explicitly measures reduced 125I-BMP4 binding after cysteine substitutions impair BMPR-II surface trafficking, with wild-type receptor as comparator. This supports ligand binding, not kinase activity toward BMP4. Refine to GO:0036122 BMP binding while preserving the BMP4 partner accession and the original IPI evidence. The abstract does not permit reconstruction of every construct or binding parameter. GO:0036122 already occurs in the source annotation set. This replacement consolidates the generic assertion into that existing function while preserving this row's distinct citation, evidence and partner; it adds no new functional coverage. Proposed replacements: BMP binding Supporting Evidence: PMID:12045205 reduced binding of (125)I-BMP4 |
| GO:0005515 protein binding | IPI PMID:15188402 Proteins associated with type II bone morphogenetic protein ... | UNDECIDED | Summary: The source records association with mouse C4bpa, but the corresponding target-specific proteomic result was not available for inspection. Reason: PMID:15188402 describes GST-BMPR-II cytoplasmic-domain pull-downs from mouse C2C12 extracts followed by two-dimensional gels and mass spectrometry. Its abstract reports 33 interactors but does not identify C4bpa. The supplied UniProt record independently lists P08607 as a xenogeneic C4bpa interactor, which supports curator provenance but does not expose this primary table entry or its domain specificity. P08607 must not be confused with CtBP, a different protein explicitly validated in the abstract. Retain the source assertion as UNDECIDED pending the C4bpa-specific table/assay; no contradiction or incorrect-gene claim is made. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15188402 Proteins associated with type II bone morphogenetic protein ... | MODIFY | Summary: BMPR2 associates with protein kinase C beta, permitting a specific protein kinase C binding refinement. Reason: PMID:15188402 describes the GST-BMPR-II pull-down screen using mouse C2C12 extracts and explicitly states that the PKC beta interaction was confirmed by immunodetection. The supplied UniProt record identifies source partner P68404 as mouse Prkcb. GO:0005080 protein kinase C binding therefore captures the demonstrated partner class. This does not establish that BMPR2 phosphorylates PKC beta, activates it, or uses the same receptor domain in every context. Proposed replacements: protein kinase C binding Supporting Evidence: PMID:15188402 We confirmed interaction of PKC beta and CtBP with BMPR-II using immunodetection. |
| GO:0005515 protein binding | IPI PMID:15657086 Dynamics and interaction of caveolin-1 isoforms with BMP-rec... | KEEP AS NON CORE | Summary: BMPR2 associates with caveolin-1 isoforms in membrane signaling complexes. Reason: PMID:15657086 explicitly reports immunoprecipitation evidence that BRII binds caveolin-1 alpha and beta in transfected COS-7 cells, with confirmation in A431 cells. It also distinguishes isoform-associated membrane redistribution and effects on BMP signaling. Preserve the exact source caveolin isoform accession without converting it into a BMPR2 isoform assertion. This supports a context-dependent interaction, but does not by itself demonstrate a new adaptor or catalytic activity of BMPR2. Under the explicit ClinGen-task instruction, retain the supported generic association as non-core where a defensible more specific term has not been established. The task-specific retention instruction is recorded in projects/CLINGEN_MENDELIAN.md#curation-instructions. It intentionally departs from the informational-exclusion recommendation for this project; an uninformative term is not thereby a biologically false interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:15657086 Dynamics and interaction of caveolin-1 isoforms with BMP-rec... | KEEP AS NON CORE | Summary: BMPR2 associates with caveolin-1 isoforms in membrane signaling complexes. Reason: PMID:15657086 explicitly reports immunoprecipitation evidence that BRII binds caveolin-1 alpha and beta in transfected COS-7 cells, with confirmation in A431 cells. It also distinguishes isoform-associated membrane redistribution and effects on BMP signaling. Preserve the exact source caveolin isoform accession without converting it into a BMPR2 isoform assertion. This supports a context-dependent interaction, but does not by itself demonstrate a new adaptor or catalytic activity of BMPR2. Under the explicit ClinGen-task instruction, retain the supported generic association as non-core where a defensible more specific term has not been established. The task-specific retention instruction is recorded in projects/CLINGEN_MENDELIAN.md#curation-instructions. It intentionally departs from the informational-exclusion recommendation for this project; an uninformative term is not thereby a biologically false interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:19229295 Crystal structure analysis reveals a spring-loaded latch as ... | MODIFY | Summary: The curated GDF5 interaction is more specifically BMP-family ligand binding. Reason: The PMID:19229295 abstract focuses on the GDF5-BMPRIB crystal structure and does not expose a BMPR2-specific binding experiment. This is not evidence of misattribution. Independent PMID:21976273 explicitly tests GDF5 binding to BMPRII and reports impaired binding by the S94N knuckle-epitope mutant; the supplied UniProt record also lists BMPR2-GDF5 interaction. Using that directly relevant corroboration, refine the existing generic interaction to GO:0036122 BMP binding while retaining the original citation, IPI evidence and GDF5 accession. Do not claim that the type-I receptor crystal structure is a BMPR2 structure. GO:0036122 already occurs in the source annotation set. This replacement consolidates the generic assertion into that existing function while preserving this row's distinct citation, evidence and partner; it adds no new functional coverage. Proposed replacements: BMP binding |
| GO:0005515 protein binding | IPI PMID:19424179 Novel crosstalk to BMP signalling: cGMP-dependent kinase I m... | MODIFY | Summary: BMPR2 binds cGMP-dependent protein kinase I as part of signaling crosstalk. Reason: PMID:19424179 explicitly reports that cGKI interacts with and phosphorylates BMPRII, then dissociates from receptors after BMP2 stimulation. The Q13976 partner is PRKG1 in the supplied UniProt interaction record. GO:0120283 protein serine/threonine kinase binding is a supported refinement. The phosphorylation direction is cGKI toward BMPRII in this experiment; cGKI nuclear redistribution and transcriptional cofactor activity must not be assigned to BMPR2. Proposed replacements: protein serine/threonine kinase binding Supporting Evidence: PMID:19424179 interacts with and phosphorylates the BMP type II receptor (BMPRII). |
| GO:0005515 protein binding | IPI PMID:21791611 TSC-22 promotes transforming growth factor Ξ²-mediated cardia... | KEEP AS NON CORE | Summary: BMPR2 co-immunoprecipitates with TSC22D1/TSC-22 in a receptor-interaction experiment. Reason: Although the canonical PMID:21791611 abstract emphasizes TGF-beta type-I receptor signaling, the authenticated longer record explicitly includes BMPRII among the type-II receptors co-immunoprecipitated with TSC-22 in Figure 2D. That supports the existing interaction. The direct recombinant-protein experiment described for TbetaRI must not be presented as purified direct binding to BMPRII, and the TbetaRI-specific stability/Smad7 mechanism is not automatically a BMPR2 mechanism. Retain the supported association as non-core under the explicit task instruction. The task-specific retention instruction is recorded in projects/CLINGEN_MENDELIAN.md#curation-instructions. It intentionally departs from the informational-exclusion recommendation for this project; an uninformative term is not thereby a biologically false interaction. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:21976273 New insights into the molecular mechanism of multiple synost... | MODIFY | Summary: GDF5 binding to BMPR2 is specifically BMP binding. Reason: PMID:21976273 identifies GDF5 as a BMP-family ligand and reports that its S94N knuckle-epitope variant has impaired binding to BMPRII, with altered downstream signaling. The reported receptor-ligand evidence supports GO:0036122 BMP binding rather than generic protein binding. Keep the GDF5 partner accession and avoid conflating the mutation-dependent noggin resistance with a direct receptor-noggin interaction. GO:0036122 already occurs in the source annotation set. This replacement consolidates the generic assertion into that existing function while preserving this row's distinct citation, evidence and partner; it adds no new functional coverage. Proposed replacements: BMP binding Supporting Evidence: PMID:21976273 GDF5-S94N exhibits impaired binding to BMPRII |
| GO:0005515 protein binding | IPI PMID:21976273 New insights into the molecular mechanism of multiple synost... | UNDECIDED | Summary: The noggin-associated source assertion cannot be resolved from the accessible ligand-competition account. Reason: The PMID:21976273 abstract describes noggin binding GDF5 and covering BMP receptor interaction sites on the ligand, together with altered affinities of the GDF5-S94N mutant. That is not by itself direct evidence of BMPR2 binding the Q13253 partner. The complete relevant receptor/noggin assay or complex record was not inspected. Preserve the original IPI/source partner and use UNDECIDED; neither ligand competition nor an abstract focused on another interaction proves that the curator assertion is false. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:24407287 Promyelocytic leukemia protein interacts with the apoptosis-... | UNDECIDED | Summary: The BMPR2-PYCARD/ASC proteomic assertion remains unresolved because the target-specific table entry is absent from the accessible record. Reason: PMID:24407287 reports ASC immunoprecipitation from THP-1 lysates followed by MALDI-TOF mass spectrometry, then specifically validates PML-ASC. The authenticated longer text preserves the caption of the ASC-associated-proteins table but not its rows; BMPR2 is not identifiable in the inspected prose. Thus the paper can contain the curator evidence even though its abstract and narrative emphasize PML. Do not assert wrong-gene attribution, infer direct BMPR2-ASC binding from the PML validations, or assign inflammasome activity to BMPR2. Keep this source assertion UNDECIDED until its target table row is inspected. Supporting Evidence: |
| GO:0005515 protein binding | IPI PMID:33308444 SCUBE3 loss-of-function causes a recognizable recessive deve... | KEEP AS NON CORE | Summary: BMPR2 associates with the extracellular signaling modulator SCUBE3. Reason: The cached full-text Results of PMID:33308444 report co-immunoprecipitation of SCUBE3 with tagged BMPRII in HEK293T cells. The BMPRII association was ligand independent, whereas the type-I receptor associations were ligand dependent. The final sentence contrasting ligand-inducible interactions must not be read as absence of BMPRII binding. This supports the existing association but does not establish purified binary binding or a new SCUBE3-like co-receptor function for BMPR2. Retain as non-core under the explicit task instruction. The task-specific retention instruction is recorded in projects/CLINGEN_MENDELIAN.md#curation-instructions. It intentionally departs from the informational-exclusion recommendation for this project; an uninformative term is not thereby a biologically false interaction. Supporting Evidence: PMID:33308444 co-immunoprecipitation with BMPRII was ligand independent. |
| GO:0005515 protein binding | IPI PMID:36931259 A central chaperone-like role for 14-3-3 proteins in human c... | UNDECIDED | Summary: The 14-3-3 epsilon screen interaction is curator-supported but its BMPR2-specific result is not exposed in the accessible primary text. Reason: PMID:36931259 reports systematic human 14-3-3 interactome and client-localization analyses, but its canonical abstract does not identify BMPR2 or the individual YWHAE-BMPR2 measurement. The supplied UniProt record lists Q13873-P62258/YWHAE with two experiments, providing curated corroboration rather than direct inspection of the primary target row. Preserve the assertion as UNDECIDED pending that result. The paper-wide chaperone-like role of 14-3-3 proteins is not a chaperone activity of BMPR2. Supporting Evidence: |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: ATP binding supports BMPR2 receptor kinase catalysis. Reason: The ATP-dependent serine/threonine kinase domain and modeled receptor phosphorylation reaction support this auxiliary molecular function. It is retained within the receptor-kinase mechanism rather than synthesized as a redundant separate core function. Supporting Evidence: Reactome:R-HSA-201443 |
| GO:0005576 extracellular region | HDA PMID:22664934 Comparison of tear protein levels in breast cancer patients ... | UNDECIDED | Summary: The extracellular proteomics assignment needs the BMPR2-specific peptide record. Reason: The cached tear-fluid proteomics body does not expose a BMPR2 identifier in the inspected text; the relevant target table/peptide record remains uninspected. An extracellular domain of a membrane receptor is not by itself evidence for a soluble extracellular product, but the HDA assignment is not rejected on that basis. Supporting Evidence: |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: BMPR2 is a plasma-membrane receptor. Reason: Wild-type human BMPR2 is observed at the plasma membrane, consistent with its signal peptide, extracellular ligand-binding region and single transmembrane segment. Retain this location; mutant intracellular retention or nuclear accumulation does not redefine the normal receptor location. |
| GO:0005886 plasma membrane | IDA GO_REF:0000052 | ACCEPT | Summary: BMPR2 is a plasma-membrane receptor. Reason: Wild-type human BMPR2 is observed at the plasma membrane, consistent with its signal peptide, extracellular ligand-binding region and single transmembrane segment. Retain this location; mutant intracellular retention or nuclear accumulation does not redefine the normal receptor location. |
| GO:0005886 plasma membrane | IDA PMID:12045205 Functional analysis of bone morphogenetic protein type II re... | ACCEPT | Summary: BMPR2 is a plasma-membrane receptor. Reason: Wild-type human BMPR2 is observed at the plasma membrane, consistent with its signal peptide, extracellular ligand-binding region and single transmembrane segment. Retain this location; mutant intracellular retention or nuclear accumulation does not redefine the normal receptor location. |
| GO:0005886 plasma membrane | IDA PMID:15657086 Dynamics and interaction of caveolin-1 isoforms with BMP-rec... | ACCEPT | Summary: BMPR2 is a plasma-membrane receptor. Reason: Wild-type human BMPR2 is observed at the plasma membrane, consistent with its signal peptide, extracellular ligand-binding region and single transmembrane segment. Retain this location; mutant intracellular retention or nuclear accumulation does not redefine the normal receptor location. |
| GO:0005886 plasma membrane | IDA PMID:25187962 Functional changes in pulmonary arterial endothelial cells a... | ACCEPT | Summary: BMPR2 is a plasma-membrane receptor. Reason: Wild-type human BMPR2 is observed at the plasma membrane, consistent with its signal peptide, extracellular ligand-binding region and single transmembrane segment. Retain this location; mutant intracellular retention or nuclear accumulation does not redefine the normal receptor location. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: BMPR2 is a plasma-membrane receptor. Reason: Wild-type human BMPR2 is observed at the plasma membrane, consistent with its signal peptide, extracellular ligand-binding region and single transmembrane segment. Retain this location; mutant intracellular retention or nuclear accumulation does not redefine the normal receptor location. |
| GO:0005886 plasma membrane | TAS PMID:9442116 Bone morphogenetic protein signaling is required for mainten... | ACCEPT | Summary: BMPR2 is a plasma-membrane receptor. Reason: Wild-type human BMPR2 is observed at the plasma membrane, consistent with its signal peptide, extracellular ligand-binding region and single transmembrane segment. Retain this location; mutant intracellular retention or nuclear accumulation does not redefine the normal receptor location. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201443 | ACCEPT | Summary: BMPR2 is a plasma-membrane component of the BMP receptor system. Reason: This Reactome row models type-II phosphorylation of type-I receptor. Retain the receptor location, without transferring the catalytic activity or subcellular localization of SMADs, endofin or the type-I receptor to BMPR2. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201453 | ACCEPT | Summary: BMPR2 is a plasma-membrane component of the BMP receptor system. Reason: This Reactome row models R-SMAD dissociation. Retain the receptor location, without transferring the catalytic activity or subcellular localization of SMADs, endofin or the type-I receptor to BMPR2. The R-HSA-201453 title/body mismatch is explicitly recorded in the reference and notes; plasma-membrane support here also comes from independent BMPR2 experiments. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201457 | ACCEPT | Summary: BMPR2 is a plasma-membrane component of the BMP receptor system. Reason: This Reactome row models ligand-bound receptor assembly. Retain the receptor location, without transferring the catalytic activity or subcellular localization of SMADs, endofin or the type-I receptor to BMPR2. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201475 | ACCEPT | Summary: BMPR2 is a plasma-membrane component of the BMP receptor system. Reason: This Reactome row models inhibitory-SMAD competition. Retain the receptor location, without transferring the catalytic activity or subcellular localization of SMADs, endofin or the type-I receptor to BMPR2. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201476 | ACCEPT | Summary: BMPR2 is a plasma-membrane component of the BMP receptor system. Reason: This Reactome row models type-I-mediated R-SMAD phosphorylation. Retain the receptor location, without transferring the catalytic activity or subcellular localization of SMADs, endofin or the type-I receptor to BMPR2. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201648 | ACCEPT | Summary: BMPR2 is a plasma-membrane component of the BMP receptor system. Reason: This Reactome row models endofin-associated signaling. Retain the receptor location, without transferring the catalytic activity or subcellular localization of SMADs, endofin or the type-I receptor to BMPR2. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201821 | ACCEPT | Summary: BMPR2 is a plasma-membrane component of the BMP receptor system. Reason: This Reactome row models inhibitory-SMAD recruitment. Retain the receptor location, without transferring the catalytic activity or subcellular localization of SMADs, endofin or the type-I receptor to BMPR2. Supporting Evidence: |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202604 | ACCEPT | Summary: BMPR2 is a plasma-membrane component of the BMP receptor system. Reason: This Reactome row models heteromeric receptor assembly. Retain the receptor location, without transferring the catalytic activity or subcellular localization of SMADs, endofin or the type-I receptor to BMPR2. Supporting Evidence: |
| GO:0005901 caveola | IMP PMID:15657086 Dynamics and interaction of caveolin-1 isoforms with BMP-rec... | KEEP AS NON CORE | Summary: BMPR2 associates with caveolin-containing membrane compartments. Reason: The source reports caveolin/receptor localization and interaction, with isoform-dependent effects. Caveolar organization is a signaling/trafficking context, not an exclusive residence or distinct core catalytic activity. Supporting Evidence: |
| GO:0005905 clathrin-coated pit | IEA GO_REF:0000107 | UNDECIDED | Summary: The clathrin-coated-pit transfer requires its exact donor localization assay. Reason: The mouse donor and MGI source record were identified, but the target-specific trafficking experiment was not accessed. General receptor endocytosis does not establish this precise compartment; preserve the existing inference as unresolved. Supporting Evidence: GO_REF:0000107 |
| GO:0005912 adherens junction | IDA PMID:25468996 E-cadherin interactome complexity and robustness resolved by... | UNDECIDED | Summary: The adherens-junction proteomic assignment requires the target-level source record. Reason: The available canonical text describes an E-cadherin proximity/interactome experiment, but its BMPR2-specific table entry was not inspected. Independent VE-cadherin co-complex evidence makes junctional association plausible but does not certify this particular spatial assay. |
| GO:0007178 cell surface receptor protein serine/threonine kinase signaling pathway | IDA PMID:12045205 Functional analysis of bone morphogenetic protein type II re... | ACCEPT | Summary: BMPR2 transduces extracellular BMP signals through a receptor kinase complex. Reason: Receptor-mutant signaling assays and the established type-II-to-type-I kinase reaction support this core process. The broader signaling category is valid; mutant-specific p38 gain of function is not assigned as the normal mechanism. |
| GO:0007178 cell surface receptor protein serine/threonine kinase signaling pathway | IEA GO_REF:0000002 | ACCEPT | Summary: BMPR2 transduces extracellular BMP signals through a receptor kinase complex. Reason: Receptor-mutant signaling assays and the established type-II-to-type-I kinase reaction support this core process. The broader signaling category is valid; mutant-specific p38 gain of function is not assigned as the normal mechanism. |
| GO:0008285 negative regulation of cell population proliferation | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: BMPR2 can restrain cell proliferation in defined vascular settings. Reason: Human BMP9/BMPRII endothelial experiments and BMP2/BMPRII smooth-muscle experiments support anti-mitogenic signaling. Retain the broad mouse-derived process as contextual: other ligand/cell combinations promote endothelial proliferation. |
| GO:0008285 negative regulation of cell population proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 can restrain cell proliferation in defined vascular settings. Reason: Human BMP9/BMPRII endothelial experiments and BMP2/BMPRII smooth-muscle experiments support anti-mitogenic signaling. Retain the broad mouse-derived process as contextual: other ligand/cell combinations promote endothelial proliferation. |
| GO:0009267 cellular response to starvation | IEP PMID:15657086 Dynamics and interaction of caveolin-1 isoforms with BMP-rec... | UNDECIDED | Summary: The starvation-response expression annotation is not resolved by the cached abstract. Reason: The accessible caveolin study does not expose the starvation-specific expression comparison. IEP is an expression-based observation, not proof of a dedicated nutrient-sensing function. Preserve the row pending inspection of that condition-specific experiment. Supporting Evidence: |
| GO:0009888 tissue development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BMPR2 signaling contributes broadly to tissue development. Reason: This electronic umbrella process is consistent with experimentally supported chondrocyte and vascular developmental roles. It is retained as a broad contextual description, not promoted to an additional core function. |
| GO:0009952 anterior/posterior pattern specification | ISS GO_REF:0000024 | UNDECIDED | Summary: The anterior/posterior-pattern transfer needs its donor-specific genetic context. Reason: MGI traces mouse evidence to early embryo and Btg2/BMP pathway experiments. The precise patterning readout and genetic interaction underlying transfer were not fully inspected; mesoderm failure alone does not settle this directional patterning term. Supporting Evidence: GO_REF:0000024 |
| GO:0009986 cell surface | IEA GO_REF:0000107 | ACCEPT | Summary: BMPR2 exposes its ligand-binding domain at the cell surface. Reason: Independent human wild-type receptor localization supports the surface location and corroborates the mouse-based electronic inference. Cell-surface residence is compatible with receptor internalization and does not imply every disease mutant reaches the membrane. Supporting Evidence: |
| GO:0010628 positive regulation of gene expression | IMP PMID:22684006 MicroRNA-100 regulates osteogenic differentiation of human a... | KEEP AS NON CORE | Summary: BMPR2 signaling supports differentiation-associated gene expression. Reason: The source identifies BMPR2 as a miR-100 RNA target and shows that receptor RNAi inhibits osteogenesis. Retain the curator-assigned expression-regulation outcome in that cellular context; BMPR2 protein is neither the microRNA nor a DNA-binding transcription factor. The complete gene-expression panel was not independently read. Supporting Evidence: |
| GO:0010634 positive regulation of epithelial cell migration | IDA PMID:12819188 The mature bone morphogenetic protein-2 is aberrantly expres... | UNDECIDED | Summary: The BMPR2-specific epithelial migration assay is not accessible in the abstract. Reason: The abstract establishes BMP2 ligand effects in lung cancer cells, but does not expose the receptor-specific experiment behind this IDA row. Do not label it a wrong-gene assignment or infer receptor activity solely from ligand treatment. Supporting Evidence: |
| GO:0014069 postsynaptic density | IEA GO_REF:0000107 | UNDECIDED | Summary: The postsynaptic-density transfer needs its target phosphoproteomic evidence. Reason: The mouse source is a large synaptosomal phosphoproteomic study; its abstract does not identify the BMPR2 peptide, fraction or target localization. Preserve the inference as unresolved rather than interpreting broad brain expression as postsynaptic-density proof. Supporting Evidence: |
| GO:0014916 regulation of lung blood pressure | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: BMPR2 contributes to pulmonary blood-pressure homeostasis. Reason: Familial pulmonary arterial hypertension associated with BMPR2 dysfunction supports the pulmonary context, together with vascular receptor biology. Retain this physiological consequence as non-core, distinct from a direct systemic-pressure assay or an intrinsic vasodilator activity. |
| GO:0014916 regulation of lung blood pressure | IMP PMID:18364108 A novel mutation in the BMPR2 gene in familial pulmonary art... | KEEP AS NON CORE | Summary: BMPR2 contributes to pulmonary blood-pressure homeostasis. Reason: Familial pulmonary arterial hypertension associated with BMPR2 dysfunction supports the pulmonary context, together with vascular receptor biology. Retain this physiological consequence as non-core, distinct from a direct systemic-pressure assay or an intrinsic vasodilator activity. |
| GO:0014916 regulation of lung blood pressure | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 contributes to pulmonary blood-pressure homeostasis. Reason: Familial pulmonary arterial hypertension associated with BMPR2 dysfunction supports the pulmonary context, together with vascular receptor biology. Retain this physiological consequence as non-core, distinct from a direct systemic-pressure assay or an intrinsic vasodilator activity. |
| GO:0016020 membrane | IEA GO_REF:0000002 | ACCEPT | Summary: BMPR2 is an integral single-pass membrane receptor. Reason: Its transmembrane topology and independent wild-type surface localization support the broad membrane annotation. The more specific plasma-membrane rows are retained separately without manufacturing another molecular activity. Supporting Evidence: |
| GO:0016362 activin receptor activity, type II | IDA PMID:19366699 Bone morphogenetic protein (BMP) and activin type II recepto... | KEEP AS NON CORE | Summary: BMPR2 can act as an activin type-II receptor in a defined experimental context. Reason: The original BMP9 paper and BMP Reactome event do not themselves demonstrate activin-ligand reception. The immutable UniProt record independently documents activin-A binding and signaling. Retain that contextual activity as non-core without asserting universal receptor usage. Additional primary-paper interpretation and its access limits are documented in BMPR2-notes.md under Activin evidence and unavailable optional sources; no uncached paper-specific assay claim or cached quotation is made here. Supporting Evidence: file:human/BMPR2/BMPR2-uniprot.txt Promotes signaling also by binding to activin A/INHBA |
| GO:0016362 activin receptor activity, type II | TAS Reactome:R-HSA-201443 | KEEP AS NON CORE | Summary: BMPR2 can act as an activin type-II receptor in a defined experimental context. Reason: The original BMP9 paper and BMP Reactome event do not themselves demonstrate activin-ligand reception. The immutable UniProt record independently documents activin-A binding and signaling. Retain that contextual activity as non-core without asserting universal receptor usage. Additional primary-paper interpretation and its access limits are documented in BMPR2-notes.md under Activin evidence and unavailable optional sources; no uncached paper-specific assay claim or cached quotation is made here. Supporting Evidence: file:human/BMPR2/BMPR2-uniprot.txt |
| GO:0030054 cell junction | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BMPR2 can associate with endothelial junctional receptor complexes. Reason: Endogenous BMPRII/VE-cadherin association supports a junction-associated signaling context. Retain the broad electronic component term as non-core; the interaction does not establish BMPR2 as a structural cadherin or an obligatory component of every junction. Supporting Evidence: |
| GO:0030154 cell differentiation | IDA PMID:22684006 MicroRNA-100 regulates osteogenic differentiation of human a... | MODIFY | Summary: The demonstrated differentiation outcome is osteogenic. Reason: BMPR2 RNAi in human adipose-derived mesenchymal cells inhibits osteogenic differentiation. Refine the generic differentiation annotation to osteoblast differentiation without claiming BMPR2 directly makes bone matrix. GO:0001649 is already represented by source annotations retained as non-core. This is a source-specific refinement into existing coverage, not a new differentiation function; the original evidence row remains available for provenance. Proposed replacements: osteoblast differentiation Supporting Evidence: |
| GO:0030166 proteoglycan biosynthetic process | ISS GO_REF:0000024 | MODIFY | Summary: BMPR2 signaling positively regulates proteoglycan synthesis. Reason: The human dominant-negative receptor reduces chondrocyte glycosaminoglycan accumulation and aggrecan expression in the chick assay. The receptor supplies signaling, not the proteoglycan-biosynthetic chemistry; the positive regulatory process states its demonstrated role more accurately. Preserve the original chicken donor ID and inference. Proposed replacements: positive regulation of proteoglycan biosynthetic process Supporting Evidence: |
| GO:0030308 negative regulation of cell growth | IDA PMID:12819188 The mature bone morphogenetic protein-2 is aberrantly expres... | UNDECIDED | Summary: The receptor-specific negative-growth experiment remains unverified. Reason: The cached abstract focuses on BMP2-driven tumor-cell migration and growth. Without the full BMPR2-specific experiment, neither the sign nor the receptor attribution can be independently adjudicated. Preserve the experimental row as unresolved rather than reversing it from the abstract. Supporting Evidence: |
| GO:0030324 lung development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BMPR2 contributes to lung development through vascular BMP signaling. Reason: Human developmental localization and receptor-perturbation experiments support pulmonary vascular deployment of BMPR2 signaling. Retain this broad developmental term as non-core; it does not establish each epithelial or alveolar subprogram. Supporting Evidence: |
| GO:0030424 axon | IEA GO_REF:0000107 | UNDECIDED | Summary: The neuron-compartment transfer requires the original mouse localization evidence. Reason: MGI identifies a mouse Bmpr2 neuronal localization study, but its exact axon, dendrite and cell-body assays were not accessed here. General neuronal BMP signaling is insufficient to independently verify this compartment-specific transfer. Preserve the donor and do not infer absence. Supporting Evidence: GO_REF:0000107 |
| GO:0030425 dendrite | IEA GO_REF:0000107 | UNDECIDED | Summary: The neuron-compartment transfer requires the original mouse localization evidence. Reason: MGI identifies a mouse Bmpr2 neuronal localization study, but its exact axon, dendrite and cell-body assays were not accessed here. General neuronal BMP signaling is insufficient to independently verify this compartment-specific transfer. Preserve the donor and do not infer absence. Supporting Evidence: GO_REF:0000107 |
| GO:0030501 positive regulation of bone mineralization | IMP PMID:18436533 BMP-2/4 and BMP-6/7 differentially utilize cell surface rece... | KEEP AS NON CORE | Summary: BMPR2-dependent osteogenic signaling supports mineralization-related differentiation. Reason: The human mesenchymal-cell study combines BMP-induced mineralization with receptor-specific knockdown of osteogenic signaling. Retain the curator-assigned positive mineralization process as a downstream differentiation outcome, not a direct mineral-deposition activity of the receptor. Supporting Evidence: |
| GO:0030509 BMP signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: BMPR2 is a conserved signaling receptor in the BMP pathway. Reason: The PAINT ancestral assertion agrees with direct human receptor evidence. BMPR2 appearing among descendant evidence is legitimate target experimental grounding, not circularity; no donor-count argument is used. |
| GO:0030509 BMP signaling pathway | IDA PMID:18436533 BMP-2/4 and BMP-6/7 differentially utilize cell surface rece... | ACCEPT | Summary: Human BMPR2 mediates BMP-dependent signaling in mesenchymal cells. Reason: BMPR2 RNAi reduces BMP2/4 and BMP6/7 induction of ID1, with ligand-dependent receptor usage and partial compensation by ACVR2A. This directly supports the central signaling role without equating BMPR2 with the type-I receptor BRET dimers. Supporting Evidence: PMID:18436533 A greater reliance on BMPR2 was observed for BMP-2/4 relative to BMP-6/7 |
| GO:0030509 BMP signaling pathway | IEA GO_REF:0000120 | ACCEPT | Summary: BMPR2 is a BMP pathway receptor kinase. Reason: The integrated electronic assignment agrees with human ligand-binding, receptor-perturbation and signaling-complex evidence. The core reaction activates a type-I receptor rather than directly phosphorylating every downstream effector. |
| GO:0030509 BMP signaling pathway | IGI PMID:18382765 An antiproliferative BMP-2/PPARgamma/apoE axis in human and ... | ACCEPT | Summary: BMP2 signals through BMPR2 in pulmonary smooth-muscle cells. Reason: The primary abstract reports BMPRII-dependent BMP2 anti-proliferative signaling, supported by human shRNA and patient-derived mutant cells. Preserve BMP2 as the source interaction partner; downstream PPARgamma DNA binding belongs to PPARgamma. Supporting Evidence: |
| GO:0030509 BMP signaling pathway | IMP PMID:12045205 Functional analysis of bone morphogenetic protein type II re... | ACCEPT | Summary: BMPR2 function is required for normal BMP4-dependent signaling. Reason: Wild-type versus mutant receptor experiments support BMP reception and downstream signaling. Some mutant receptors gained p38-dependent proliferative responses; that mutation-specific observation is not a normal BMPR2 core activity. Supporting Evidence: |
| GO:0030509 BMP signaling pathway | IMP PMID:17992660 Regulation of bone morphogenetic protein signalling in human... | ACCEPT | Summary: BMPR2 mediates BMP responses in pulmonary endothelial cells. Reason: Kinase-deficient BMPRII and receptor siRNA inhibit BMP4-dependent SMAD signaling and proliferation in the cited human pulmonary endothelial study. Retain the core receptor-pathway assertion with the assay context. Supporting Evidence: |
| GO:0030509 BMP signaling pathway | IMP PMID:19366699 Bone morphogenetic protein (BMP) and activin type II recepto... | ACCEPT | Summary: BMPR2 participates in BMP9 signaling through endothelial ALK1 complexes. Reason: BMPRII perturbation distinguishes BMP9 outputs and reveals compensation by ActRII for selected SMAD1/5 and ID responses. This supports BMP signaling, not an activin-ligand assay merely because ActRII appears in the title. Supporting Evidence: |
| GO:0030509 BMP signaling pathway | IMP PMID:9442116 Bone morphogenetic protein signaling is required for mainten... | ACCEPT | Summary: Human BMPR2 constructs perturb BMP signaling in chick chondrocytes. Reason: The human dominant-negative receptor abolishes BMP2 responses in a chick chondrocyte system. Retain BMP-pathway involvement while explicitly preserving the recipient-organism and engineered-construct boundaries. Supporting Evidence: |
| GO:0030509 BMP signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: BMPR2 is an upstream BMP receptor kinase. Reason: The orthology and pathway assertions are corroborated by direct human BMP ligand binding and receptor perturbation. Type-II kinase activates the type-I receptor, which then phosphorylates R-SMADs. |
| GO:0030509 BMP signaling pathway | TAS Reactome:R-HSA-201451 | ACCEPT | Summary: BMPR2 is an upstream BMP receptor kinase. Reason: The orthology and pathway assertions are corroborated by direct human BMP ligand binding and receptor perturbation. Type-II kinase activates the type-I receptor, which then phosphorylates R-SMADs. |
| GO:0032924 activin receptor signaling pathway | IEA GO_REF:0000108 | KEEP AS NON CORE | Summary: BMPR2 can contribute to activin signaling in defined receptor contexts. Reason: The electronic inference from activin receptor activity agrees with the immutable UniProt activin-A statement. Retain the contextual signaling function as non-core without treating it as universal BMPR2 pathway usage. Additional primary-paper interpretation and its access limits are documented in BMPR2-notes.md under Activin evidence and unavailable optional sources; no uncached paper-specific assay claim or cached quotation is made here. Supporting Evidence: file:human/BMPR2/BMPR2-uniprot.txt |
| GO:0036122 BMP binding | IEA GO_REF:0000120 | ACCEPT | Summary: BMPR2 directly binds BMP-family ligands. Reason: Purified human BMPRII extracellular-domain/BMP10 structures establish direct ligand contact at the knuckle epitope. This validates the integrated binding assignment as part of the receptor mechanism; ligand affinity depends on receptor-complex context. Supporting Evidence: |
| GO:0036122 BMP binding | IPI PMID:21976273 New insights into the molecular mechanism of multiple synost... | ACCEPT | Summary: BMPR2 binds BMP-family ligands; the preserved source partner is a type-I receptor, not a BMP ligand. Reason: GO:0036122 means binding to a member of the BMP family. PMID:21976273 explicitly reports GDF5-BMPRII binding and the impairment caused by the GDF5-S94N variant, so the biological BMP-binding assertion is supported. The source WITH/FROM accession O00238/BMPR1B is a receptor partner and must not be described as the bound BMP. The precise role of that source partner in the curator's assay or complex evidence is not recoverable from the abstract; preserve it without relabeling or inventing a direct ligand identity. Acceptance concerns the independently supported BMPR2 ligand-binding function, not a claim that this receptor accession encodes a BMP. Supporting Evidence: |
| GO:0036122 BMP binding | IPI PMID:21976273 New insights into the molecular mechanism of multiple synost... | ACCEPT | Summary: BMPR2 binds BMP-family ligands; the preserved source partner is a type-I receptor, not a BMP ligand. Reason: GO:0036122 means binding to a member of the BMP family. PMID:21976273 explicitly reports GDF5-BMPRII binding and the impairment caused by the GDF5-S94N variant, so the biological BMP-binding assertion is supported. The source WITH/FROM accession P36894/BMPR1A is a receptor partner and must not be described as the bound BMP. The precise role of that source partner in the curator's assay or complex evidence is not recoverable from the abstract; preserve it without relabeling or inventing a direct ligand identity. Acceptance concerns the independently supported BMPR2 ligand-binding function, not a claim that this receptor accession encodes a BMP. Supporting Evidence: |
| GO:0040017 positive regulation of locomotion | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BMPR2 signaling can regulate cell movement in vascular contexts. Reason: Human pulmonary endothelial studies link BMP/BMPRII signaling with migratory responses. Retain this broad electronic movement-regulation term as contextual; it is not a direct motor activity or a claim of identical behavior in all cell types. Supporting Evidence: |
| GO:0042127 regulation of cell population proliferation | IMP PMID:11502704 Altered growth responses of pulmonary artery smooth muscle c... | KEEP AS NON CORE | Summary: BMPR2-associated vascular signaling influences smooth-muscle proliferation. Reason: The source compares patient pulmonary-artery smooth-muscle isolates and their BMP/TGF-beta growth responses; only a subset carried detected BMPR2 mutations. Retain the curator-assigned proliferation regulation with disease-cell and genotype limits, not as proof that all observed differences are receptor-autonomous. Supporting Evidence: |
| GO:0043235 signaling receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: BMPR2 functions within heteromeric signaling-receptor complexes. Reason: Structures and signaling experiments support ligand/type-I/type-II assemblies. Complex membership does not require direct extracellular ALK1-BMPRII contact: that contact is absent in the BMP10 ternary crystal structure. Supporting Evidence: |
| GO:0044297 cell body | IEA GO_REF:0000107 | UNDECIDED | Summary: The neuron-compartment transfer requires the original mouse localization evidence. Reason: MGI identifies a mouse Bmpr2 neuronal localization study, but its exact axon, dendrite and cell-body assays were not accessed here. General neuronal BMP signaling is insufficient to independently verify this compartment-specific transfer. Preserve the donor and do not infer absence. Supporting Evidence: GO_REF:0000107 |
| GO:0045296 cadherin binding | IPI PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeab... | KEEP AS NON CORE | Summary: BMPR2 associates with VE-cadherin in endothelial BMP receptor complexes. Reason: The full-text Results and Figure5 of PMID:26598555 report endogenous VE-cadherin/BMPRII co-immunoprecipitation in HUVECs, increased association after BMP6, and additional overexpression and proximity-ligation evidence. These support cadherin binding in a defined endothelial context. Retain as non-core rather than treating all BMPR2 activity as cell-cell adhesion; co-IP/PLA do not alone establish purified direct binary binding or that BMPR2 itself provides cadherin adhesion. Supporting Evidence: |
| GO:0045597 positive regulation of cell differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BMPR2 signaling promotes differentiation in selected mesenchymal contexts. Reason: Human receptor RNAi inhibits osteogenic differentiation, supporting this broad positive-regulatory process. It is retained as a contextual outcome rather than as direct transcription-factor or matrix-synthesis activity. Supporting Evidence: |
| GO:0045669 positive regulation of osteoblast differentiation | IMP PMID:18436533 BMP-2/4 and BMP-6/7 differentially utilize cell surface rece... | KEEP AS NON CORE | Summary: BMPR2 signaling supports osteoblast differentiation in human mesenchymal cells. Reason: Receptor-specific knockdown reduces osteoinductive BMP signaling. Preserve the ligand-dependent use of BMPR2 versus ACVR2A and classify the differentiation endpoint as non-core. Supporting Evidence: |
| GO:0045778 positive regulation of ossification | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: BMPR2 signaling supports ossification-related differentiation. Reason: Human osteogenic and chondrocyte experiments corroborate the broad bone-formation context of the mouse-derived inference. The receptor regulates differentiation; it does not itself deposit mineral or synthesize the bone matrix. |
| GO:0045778 positive regulation of ossification | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 signaling supports ossification-related differentiation. Reason: Human osteogenic and chondrocyte experiments corroborate the broad bone-formation context of the mouse-derived inference. The receptor regulates differentiation; it does not itself deposit mineral or synthesize the bone matrix. |
| GO:0045906 negative regulation of vasoconstriction | IEA GO_REF:0000107 | UNDECIDED | Summary: The specific negative-vasoconstriction transfer remains unresolved. Reason: Pulmonary vascular disease and altered endothelial mediators make this plausible, but they are not a direct vessel-contraction assay. The exact mouse donor experiment was not accessible, so retain the transferred row as unresolved rather than inferring regulatory sign from PAH alone. Supporting Evidence: GO_REF:0000024 |
| GO:0045906 negative regulation of vasoconstriction | ISS GO_REF:0000024 | UNDECIDED | Summary: The specific negative-vasoconstriction transfer remains unresolved. Reason: Pulmonary vascular disease and altered endothelial mediators make this plausible, but they are not a direct vessel-contraction assay. The exact mouse donor experiment was not accessible, so retain the transferred row as unresolved rather than inferring regulatory sign from PAH alone. Supporting Evidence: GO_REF:0000024 |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: BMPR2 signaling can increase RNA-polymerase-II-dependent transcription. Reason: BMP receptor kinase signaling changes transcription through downstream SMAD/cofactor complexes. Regulation of transcription does not require BMPR2 to bind DNA or be part of the polymerase; retain this electronic downstream process as non-core. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:12045205 Functional analysis of bone morphogenetic protein type II re... | KEEP AS NON CORE | Summary: Wild-type receptor signaling supports transcriptional reporter activation. Reason: The receptor-mutant study tests BMP/TGF-beta-responsive transcriptional reporters. Retain positive regulation of transcription as a signaling consequence; distinguish normal receptor signaling from mutant-specific p38 gain of function and do not claim direct receptor DNA binding. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | IMP PMID:18326817 Hemojuvelin regulates hepcidin expression via a selective su... | KEEP AS NON CORE | Summary: BMPR2 contributes to hepcidin-promoter regulation through BMP signaling. Reason: The HJV study identifies BMPRII and ActRIIA receptor use upstream of hepcidin transcription. The receptor performs signaling that regulates transcription; the term does not assert that BMPR2 itself transcribes DNA or binds the promoter. Supporting Evidence: |
| GO:0045944 positive regulation of transcription by RNA polymerase II | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Conserved BMPR2 signaling supports positive transcriptional regulation. Reason: The mouse-derived inference is corroborated by human receptor-dependent transcriptional responses. Retain this downstream regulatory process as non-core without asserting a transcription-factor molecular function. |
| GO:0048286 lung alveolus development | IEA GO_REF:0000107 | UNDECIDED | Summary: The lung-alveolus developmental transfer needs the exact donor assay. Reason: Human pulmonary vascular expression and endothelial signaling do not by themselves establish alveolar morphogenesis. The mouse donor source for this more specific process was not recovered in accessible primary evidence; preserve the inference as unresolved. Supporting Evidence: GO_REF:0000024 |
| GO:0048286 lung alveolus development | ISS GO_REF:0000024 | UNDECIDED | Summary: The lung-alveolus developmental transfer needs the exact donor assay. Reason: Human pulmonary vascular expression and endothelial signaling do not by themselves establish alveolar morphogenesis. The mouse donor source for this more specific process was not recovered in accessible primary evidence; preserve the inference as unresolved. Supporting Evidence: GO_REF:0000024 |
| GO:0048662 negative regulation of smooth muscle cell proliferation | IMP PMID:18382765 An antiproliferative BMP-2/PPARgamma/apoE axis in human and ... | KEEP AS NON CORE | Summary: BMP2/BMPR2 signaling can inhibit pulmonary smooth-muscle proliferation. Reason: The source uses human receptor shRNA and mutant PASMCs to support receptor-dependent anti-proliferative signaling via PPARgamma/apoE. This cell-specific outcome is retained outside the molecular core; downstream PPARgamma DNA binding and apoE secretion are not BMPR2 activities. Supporting Evidence: PMID:18382765 the antiproliferative effect of BMP-2 was BMP-RII, PPARgamma, and apoE dependent. |
| GO:0048738 cardiac muscle tissue development | ISS NOT GO_REF:0000024 | UNDECIDED | Summary: Preserve the NOT cardiac-muscle-development transfer with conditional-knockout limits. Reason: Mouse myocardial deletion experiments report normal myocardial development and possible compensation by other type-II receptors. That conditional dispensability is not proof of universal nonparticipation by human BMPR2. Preserve the original negation, but leave the cross-species unrestricted negative unresolved. Supporting Evidence: GO_REF:0000024 |
| GO:0048842 positive regulation of axon extension involved in axon guidance | IEA GO_REF:0000107 | UNDECIDED | Summary: The axon-guidance transfer needs its neuronal donor mechanism. Reason: The exact mouse source assay and receptor-tail/SMAD dependence were not inspected. BMPR2-associated actin signaling is plausible, but general cytoskeletal regulation does not establish this specific axon-extension-in-guidance process. Supporting Evidence: GO_REF:0000107 |
| GO:0048863 stem cell differentiation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 contributes to differentiation of early developmental cells. Reason: Official mouse knockout evidence describes an undifferentiated epiblast and failed mesoderm induction, and human BMPR2 perturbation supports mesenchymal differentiation. Retain the broad MGI-derived stem-cell differentiation process as non-core with organism and developmental-context limits. |
| GO:0060350 endochondral bone morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 signaling contributes to the chondrocyte program used in endochondral bone formation. Reason: The human dominant-negative receptor in chick sternal chondrocytes disrupts hypertrophic markers and differentiation. Retain the curated chicken-based developmental transfer as non-core; the culture experiment does not directly measure whole-bone morphogenesis. Supporting Evidence: |
| GO:0060391 positive regulation of SMAD protein signal transduction | IGI PMID:18382765 An antiproliferative BMP-2/PPARgamma/apoE axis in human and ... | UNDECIDED | Summary: This source-specific SMAD-regulation assertion requires its actual experiment. Reason: The accessible abstract establishes BMPRII-dependent antiproliferative signaling but explicitly describes the PPARgamma effect as independent of SMAD1/5/8 phosphorylation. The full source could contain a separate SMAD experiment; do not refute it from the abstract, but do not treat the anti-proliferative assay as direct support for this particular row. Supporting Evidence: |
| GO:0060391 positive regulation of SMAD protein signal transduction | IMP PMID:17992660 Regulation of bone morphogenetic protein signalling in human... | KEEP AS NON CORE | Summary: BMPR2 positively regulates downstream SMAD signaling through type-I receptors. Reason: BMPRII perturbation reduces BMP-dependent SMAD signaling in pulmonary endothelial experiments, with ligand/receptor compensation differing between studies. Retain the causal regulatory process; BMPR2 does not thereby become the direct SMAD kinase. |
| GO:0060391 positive regulation of SMAD protein signal transduction | IMP PMID:19366699 Bone morphogenetic protein (BMP) and activin type II recepto... | KEEP AS NON CORE | Summary: BMPR2 positively regulates downstream SMAD signaling through type-I receptors. Reason: BMPRII perturbation reduces BMP-dependent SMAD signaling in pulmonary endothelial experiments, with ligand/receptor compensation differing between studies. Retain the causal regulatory process; BMPR2 does not thereby become the direct SMAD kinase. |
| GO:0060412 ventricular septum morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BMPR2-dependent endocardial signaling supports ventricular septal development. Reason: Mouse conditional deletion produces membranous ventricular-septal and AV cushion defects. Retain this developmental transfer as non-core, distinguishing septal morphogenesis from myocardial differentiation and preserving the separate negated muscle-development row. Supporting Evidence: GO_REF:0000024 |
| GO:0060412 ventricular septum morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2-dependent endocardial signaling supports ventricular septal development. Reason: Mouse conditional deletion produces membranous ventricular-septal and AV cushion defects. Retain this developmental transfer as non-core, distinguishing septal morphogenesis from myocardial differentiation and preserving the separate negated muscle-development row. Supporting Evidence: GO_REF:0000024 |
| GO:0060413 atrial septum morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BMPR2-dependent endocardial signaling supports atrial septal development. Reason: Mouse endocardial conditional deletion produces atrial septal defects with AV cushion abnormalities. Retain the curated inference as a tissue-specific developmental role rather than a distinct molecular activity. Supporting Evidence: GO_REF:0000024 |
| GO:0060413 atrial septum morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2-dependent endocardial signaling supports atrial septal development. Reason: Mouse endocardial conditional deletion produces atrial septal defects with AV cushion abnormalities. Retain the curated inference as a tissue-specific developmental role rather than a distinct molecular activity. Supporting Evidence: GO_REF:0000024 |
| GO:0060426 lung vasculature development | IMP PMID:17992660 Regulation of bone morphogenetic protein signalling in human... | KEEP AS NON CORE | Summary: BMPR2 signaling contributes to pulmonary vascular development. Reason: Human embryonic/fetal localization is combined with mutant-receptor and siRNA endothelial assays. This supports the developmental signaling role, while not converting expression correlation alone into a human in-vivo loss-of-function experiment. Supporting Evidence: |
| GO:0060836 lymphatic endothelial cell differentiation | IEA GO_REF:0000107 | UNDECIDED | Summary: The lymphatic-endothelial differentiation transfer requires its BMPR2-specific donor assay. Reason: The traced ALK1-pathway study supports lymphatic differentiation at pathway level, but its cached abstract does not resolve the endogenous type-II receptor contribution. Preserve the inference; no wrong-gene conclusion follows from the paper title. Supporting Evidence: |
| GO:0060836 lymphatic endothelial cell differentiation | ISS GO_REF:0000024 | UNDECIDED | Summary: The lymphatic-endothelial differentiation transfer requires its BMPR2-specific donor assay. Reason: The traced ALK1-pathway study supports lymphatic differentiation at pathway level, but its cached abstract does not resolve the endogenous type-II receptor contribution. Preserve the inference; no wrong-gene conclusion follows from the paper title. Supporting Evidence: |
| GO:0060840 artery development | IEA GO_REF:0000107 | UNDECIDED | Summary: The artery-development transfer has an unresolved receptor-specific source boundary. Reason: The mouse donor maps to an ALK1-pathway/vascular study, but the precise BMPR2 perturbation and artery-specific outcome were not inspected. Broad human vascular function does not certify every inferred vascular subprogram. Supporting Evidence: |
| GO:0060840 artery development | ISS GO_REF:0000024 | UNDECIDED | Summary: The artery-development transfer has an unresolved receptor-specific source boundary. Reason: The mouse donor maps to an ALK1-pathway/vascular study, but the precise BMPR2 perturbation and artery-specific outcome were not inspected. Broad human vascular function does not certify every inferred vascular subprogram. Supporting Evidence: |
| GO:0060841 venous blood vessel development | IEA GO_REF:0000107 | UNDECIDED | Summary: The venous-vessel developmental transfer needs exact donor evidence. Reason: The accessible vascular source material does not independently establish the BMPR2-specific venous developmental assay. Keep the donor-based annotation unresolved rather than infer venous specificity from general BMP endothelial signaling. Supporting Evidence: GO_REF:0000024 |
| GO:0060841 venous blood vessel development | ISS GO_REF:0000024 | UNDECIDED | Summary: The venous-vessel developmental transfer needs exact donor evidence. Reason: The accessible vascular source material does not independently establish the BMPR2-specific venous developmental assay. Keep the donor-based annotation unresolved rather than infer venous specificity from general BMP endothelial signaling. Supporting Evidence: GO_REF:0000024 |
| GO:0061036 positive regulation of cartilage development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 signaling supports maintenance and maturation of cartilage cells. Reason: Dominant-negative human BMPR2 in chick chondrocytes impairs differentiated and hypertrophic phenotypes. This provides receptor-specific signaling evidence consistent with the curated chicken-based positive cartilage-development transfer; it is a developmental regulatory outcome. Supporting Evidence: |
| GO:0061298 retina vasculature development in camera-type eye | IEA GO_REF:0000107 | UNDECIDED | Summary: The retinal-vasculature inference requires the exact BMPR2 donor experiment. Reason: MGI traces this mouse annotation to the ALK1-pathway study. Its accessible abstract does not expose the target-specific receptor perturbation or retinal assay, so the precise transfer remains unresolved despite well-supported general BMP vascular signaling. Supporting Evidence: |
| GO:0061298 retina vasculature development in camera-type eye | ISS GO_REF:0000024 | UNDECIDED | Summary: The retinal-vasculature inference requires the exact BMPR2 donor experiment. Reason: MGI traces this mouse annotation to the ALK1-pathway study. Its accessible abstract does not expose the target-specific receptor perturbation or retinal assay, so the precise transfer remains unresolved despite well-supported general BMP vascular signaling. Supporting Evidence: |
| GO:0061626 pharyngeal arch artery morphogenesis | ISS NOT GO_REF:0000024 | UNDECIDED | Summary: Preserve the NOT pharyngeal-arch-artery assertion pending donor-context clarification. Reason: This is a negated transfer. Mouse hypomorphic and conditional receptor phenotypes differ with allele and tissue, and an aortic-arch abnormality is not automatically the same developmental event as pharyngeal-arch-artery morphogenesis. The exact negative donor observation has not been resolved; do not change polarity or assert universal absence. Supporting Evidence: GO_REF:0000024 |
| GO:0071363 cellular response to growth factor stimulus | IBA GO_REF:0000033 | ACCEPT | Summary: BMPR2 detects extracellular BMP-family growth factors and initiates signaling. Reason: The PAINT assignment agrees with direct ligand-binding and functional receptor studies. This is the growth-factor-response context of the core receptor activity; downstream outputs remain cell- and ligand-dependent. Supporting Evidence: |
| GO:0071773 cellular response to BMP stimulus | IMP PMID:18326817 Hemojuvelin regulates hepcidin expression via a selective su... | ACCEPT | Summary: BMPR2 participates directly in cellular responses to BMP ligands. Reason: The HJV/hepcidin study places BMPRII in the responsive receptor system. Receptor signaling is a direct contribution to BMP response, even though the measured hepcidin transcription occurs downstream. Supporting Evidence: |
| GO:0072577 endothelial cell apoptotic process | IMP PMID:25187962 Functional changes in pulmonary arterial endothelial cells a... | KEEP AS NON CORE | Summary: BMPR2 dysfunction affects endothelial apoptosis in a variant-dependent context. Reason: TUNEL measurements increased for Thr268fs, Gln433X and Ser863Asn relative to wild-type BMPR2; Tyr67Cys did not show that effect. Retain involvement in the apoptotic process without presenting normal BMPR2 as a constitutive pro-apoptotic receptor or generalizing across variants. Supporting Evidence: |
| GO:0098821 BMP receptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: BMPR2 binds BMP ligands and transmits signals through a receptor kinase complex. Reason: Purified human BMP10/BMPRII structures and cellular receptor-perturbation experiments establish BMP receptor activity and corroborate these electronic/orthology assignments. The type-II kinase activates the type-I receptor; no independent direct SMAD-kinase claim is required. |
| GO:0098821 BMP receptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: BMPR2 binds BMP ligands and transmits signals through a receptor kinase complex. Reason: Purified human BMP10/BMPRII structures and cellular receptor-perturbation experiments establish BMP receptor activity and corroborate these electronic/orthology assignments. The type-II kinase activates the type-I receptor; no independent direct SMAD-kinase claim is required. |
| GO:1902731 negative regulation of chondrocyte proliferation | IMP PMID:9442116 Bone morphogenetic protein signaling is required for mainten... | KEEP AS NON CORE | Summary: BMPR2-dependent signaling restrains chondrocyte proliferation in the tested system. Reason: Chick sternal cultures expressing human dominant-negative BMPR2 proliferate more strongly than controls. The anchorage/medium context and engineered inhibition are explicit; retain this non-core negative-regulatory outcome without claiming it applies to every proliferating cell. Supporting Evidence: |
| GO:1905314 semi-lunar valve development | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: BMPR2 signaling contributes to semilunar-valve development. Reason: Mouse hypomorphic and conditional studies support semilunar-valve formation/remodeling phenotypes. Retain this conserved developmental role as non-core; normal AV valves in one hypomorph are not a general statement about every valve or allele. Supporting Evidence: GO_REF:0000024 |
| GO:1905314 semi-lunar valve development | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: BMPR2 signaling contributes to semilunar-valve development. Reason: Mouse hypomorphic and conditional studies support semilunar-valve formation/remodeling phenotypes. Retain this conserved developmental role as non-core; normal AV valves in one hypomorph are not a general statement about every valve or allele. Supporting Evidence: GO_REF:0000024 |
| GO:1990782 protein tyrosine kinase binding | IPI PMID:26598555 VE-cadherin facilitates BMP-induced endothelial cell permeab... | KEEP AS NON CORE | Summary: BMPR2 associates with the protein tyrosine kinase SRC in endothelial BMP signaling. Reason: The full-text Results and Figure3E of PMID:26598555 show endogenous BMPRII and c-Src co-immunoprecipitation in HUVECs, with overexpression corroboration in HEK293T cells. This supports protein tyrosine kinase binding. The paper distinguishes context-dependent Src regulation and does not make binding equivalent to BMPR2 directly phosphorylating SRC; preserve this as a non-core signaling interaction. Supporting Evidence: |
| GO:2000026 regulation of multicellular organismal development | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: BMPR2 regulates developmental programs through BMP receptor signaling. Reason: Human chondrocyte and pulmonary endothelial experiments support developmental deployment of the receptor pathway. The broad electronic regulatory term is retained as non-core rather than expanded into untested developmental subprograms. |
| GO:2000137 negative regulation of cell proliferation involved in heart morphogenesis | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The existing mouse-derived inference supports a contextual role in restraining proliferation during heart morphogenesis. Reason: Retain the existing mouse-to-human inference as non-core with its donor and developmental-context limits. The primary-paper interpretation supporting this disposition, including the tissue/stage distinction and access limits, is documented in BMPR2-notes.md under Developmental transfers and four NOT assertions. No uncached paper-specific experimental result is asserted here, and this transfer is not a direct human assay or a universal effect on cardiomyocyte proliferation. Supporting Evidence: GO_REF:0000024 |
| GO:2000137 negative regulation of cell proliferation involved in heart morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: The existing mouse-derived inference supports a contextual role in restraining proliferation during heart morphogenesis. Reason: Retain the existing mouse-to-human inference as non-core with its donor and developmental-context limits. The primary-paper interpretation supporting this disposition, including the tissue/stage distinction and access limits, is documented in BMPR2-notes.md under Developmental transfers and four NOT assertions. No uncached paper-specific experimental result is asserted here, and this transfer is not a direct human assay or a universal effect on cardiomyocyte proliferation. Supporting Evidence: GO_REF:0000024 |
Loading supporting contentβ¦
Download this section (compressed HTML)Q: Which exact mouse allele, tissue, developmental stage and anatomical readout justify each of the four transferred NOT developmental annotations?
Q: Do the ALK1-pathway donor experiments establish an endogenous BMPR2 requirement for each lymphatic, arterial and retinal process, or a broader ligand/receptor-pathway requirement?
Q: How broadly does the demonstrated activin-A/BMPR2/ALK4 pathway operate outside the gonadotrope-like cell system?
Q: Which phenotypes and interactions distinguish the natural short BMPR2 splice product from engineered kinase/tail truncations and disease alleles?
Q: Can the original C4bpa, ASC and YWHAE screen entries, the noggin-specific assay and the compartment-specific proteomic records be recovered to resolve the remaining target-level evidence gaps?
Loading supporting contentβ¦
Download this section (compressed HTML)Loading supporting contentβ¦
Download this section (compressed HTML)