ACVR2A is a single-pass plasma-membrane type II serine/threonine kinase receptor for activins and several other TGF-beta-superfamily ligands. Its extracellular domain binds ligand, and its intracellular kinase phosphorylates a partner type I receptor, which then activates SMAD-dependent transcriptional responses. With ACVR1B/ALK4 it mediates activin signaling; with appropriate BMP type I receptors it also transduces BMP signals, with ligand and co-receptor context determining receptor utilization. Inhibin binding together with betaglycan can sequester ACVR2A into antagonist complexes that do not recruit the signaling type I receptor. Receptor oligomerization and C-terminal PDZ-adaptor interactions contribute to complex assembly and trafficking. Downstream effects include developmental patterning, erythroid differentiation and context-dependent regulation of osteoblast function.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001649 osteoblast differentiation | IDA PMID:18436533 BMP-2/4 and BMP-6/7 differentially utilize cell surface rece... | KEEP AS NON CORE | Summary: ACVR2A supports BMP-dependent osteoblast differentiation and bone-forming responses. Reason: Primary human mesenchymal-cell experiments couple BMP receptor knockdown to osteogenic marker responses; the study also measures BMP-induced matrix mineralization. These supported physiological outputs are context-dependent and peripheral to the receptor mechanism. They do not contradict the negative effect of activin-ACVR2A signaling on bone mass in mouse osteoblasts. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0001934 positive regulation of protein phosphorylation | IMP PMID:17472960 Repulsive guidance molecule RGMa alters utilization of bone ... | KEEP AS NON CORE | Summary: ACVR2A promotes downstream phosphorylation in an RGMa-dependent BMP context. Reason: The reported receptor requirement supports positive regulation of protein phosphorylation through BMP signal propagation. This precise regulatory outcome is peripheral to the defining ligand-binding receptor kinase activity and does not imply direct phosphorylation of every downstream target. Supporting Evidence: PMID:17472960 These findings suggest that RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and that increased utilization of ActRIIA leads to generation of an enhanced BMP signal. |
| GO:0004672 protein kinase activity | IEA GO_REF:0000002 | MODIFY | Summary: Resolve the broad kinase term into its supported receptor activities. Reason: ACVR2A is a transmembrane serine/threonine kinase used by both activin and BMP ligands. GO:0016362 and GO:0098821 are supported descendants of these kinase terms, already asserted in this review. Retain both ligand-dependent receptor activities rather than selecting only the activin branch. Proposed replacements: activin receptor activity, type II BMP receptor activity Supporting Evidence: PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:8622651 Activation of signalling by the activin receptor complex. | MODIFY | Summary: Resolve the broad kinase term into its supported receptor activities. Reason: ACVR2A is a transmembrane serine/threonine kinase used by both activin and BMP ligands. GO:0016362 and GO:0098821 are supported descendants of these kinase terms, already asserted in this review. Retain both ligand-dependent receptor activities rather than selecting only the activin branch. Proposed replacements: activin receptor activity, type II BMP receptor activity Supporting Evidence: PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0004674 protein serine/threonine kinase activity | EXP PMID:8721982 Formation and activation by phosphorylation of activin recep... | MODIFY | Summary: Resolve the broad kinase term into its supported receptor activities. Reason: ACVR2A is a transmembrane serine/threonine kinase used by both activin and BMP ligands. GO:0016362 and GO:0098821 are supported descendants of these kinase terms, already asserted in this review. Retain both ligand-dependent receptor activities rather than selecting only the activin branch. Proposed replacements: activin receptor activity, type II BMP receptor activity Supporting Evidence: PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0004675 transmembrane receptor protein serine/threonine kinase activity | EXP PMID:25368322 Small molecules dorsomorphin and LDN-193189 inhibit myostati... | MODIFY | Summary: Resolve the broad kinase term into its supported receptor activities. Reason: ACVR2A is a transmembrane serine/threonine kinase used by both activin and BMP ligands. GO:0016362 and GO:0098821 are supported descendants of these kinase terms, already asserted in this review. Retain both ligand-dependent receptor activities rather than selecting only the activin branch. Proposed replacements: activin receptor activity, type II BMP receptor activity Supporting Evidence: PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0004675 transmembrane receptor protein serine/threonine kinase activity | IEA GO_REF:0000120 | MODIFY | Summary: Resolve the broad kinase term into its supported receptor activities. Reason: ACVR2A is a transmembrane serine/threonine kinase used by both activin and BMP ligands. GO:0016362 and GO:0098821 are supported descendants of these kinase terms, already asserted in this review. Retain both ligand-dependent receptor activities rather than selecting only the activin branch. Proposed replacements: activin receptor activity, type II BMP receptor activity Supporting Evidence: PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0004675 transmembrane receptor protein serine/threonine kinase activity | TAS PMID:1314589 Molecular cloning and binding properties of the human type I... | MODIFY | Summary: Resolve the broad kinase term into its supported receptor activities. Reason: ACVR2A is a transmembrane serine/threonine kinase used by both activin and BMP ligands. GO:0016362 and GO:0098821 are supported descendants of these kinase terms, already asserted in this review. Retain both ligand-dependent receptor activities rather than selecting only the activin branch. Proposed replacements: activin receptor activity, type II BMP receptor activity Supporting Evidence: PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0005515 protein binding | IPI PMID:10746731 Betaglycan binds inhibin and can mediate functional antagoni... | MODIFY | Summary: Specify inhibin binding instead of generic protein binding. Reason: The crosslinked inhibin-betaglycan-ActRII assembly supports a specific inhibin interaction. Preserve the original contributes_to qualifier for this multicomponent interaction. Proposed replacements: inhibin binding Supporting Evidence: PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII. |
| GO:0005515 protein binding | IPI PMID:11266516 Modulation of activin signal transduction by inhibin B and i... | REMOVE | Summary: Generic protein binding does not specify a distinct molecular activity. Reason: The reported receptor-associated interaction is compatible with receptor complex assembly, but bare protein binding is uninformative under the repository policy. This removal does not reject the interaction or deduplicate evidence; the supported receptor activities and complexes are retained in their specific annotations. Supporting Evidence: PMID:11266516 A recently cloned inhibin-binding protein, InhBP (p120), associates strongly with the type IB activin receptor (Alk4) in a ligand-responsive manner and interacts to a lesser extent with other activin and bone morphogenetic protein (BMP) type I and activin type II receptors. |
| GO:0005515 protein binding | IPI PMID:21791611 TSC-22 promotes transforming growth factor Ξ²-mediated cardia... | UNDECIDED | Summary: The specific ACVR2A interaction needs the full experimental report. Reason: The cached abstract emphasizes TSC22D1 interactions with TGF-beta receptor I and SMAD7. It does not resolve the ACVR2A interaction curated from the full study. This does not show misattribution or absence of the interaction; retain uncertainty until the relevant full-text assay can be examined. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:36115835 Quantitative fragmentomics allow affinity mapping of interac... | MODIFY | Summary: The reported interaction is a PDZ-domain/motif binding assay. Reason: The source quantitatively assays PDZ domains against human protein C-terminal PDZ-binding motifs. The curated ACVR2A interaction belongs to this assay class, and independent ActRIIA C-terminal mapping corroborates PDZ-domain binding. Refine the molecular interaction without treating every fragment hit as an established physiological full-length complex. Supplementary Dataset 1 explicitly includes ACVR2A/P27037 peptide VDFPPKESSL; the PDZ-PBM interactome sheet reports fluorescence-polarization affinities for DLG4_3, SCRIB_1, SNX27 and MAST2, corroborating the assay class. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:36115835 Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer. PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. file:human/ACVR2A/ACVR2A-notes.md The `PDZ-PBM interactome` sheet contains 266 ACVR2A/P27037 rows for the natural and assayed peptide `VDFPPKESSL`. |
| GO:0005515 protein binding | IPI PMID:8242742 Identification of human activin and TGF beta type I receptor... | REMOVE | Summary: Generic protein binding does not specify a distinct molecular activity. Reason: The reported receptor-associated interaction is compatible with receptor complex assembly, but bare protein binding is uninformative under the repository policy. This removal does not reject the interaction or deduplicate evidence; the supported receptor activities and complexes are retained in their specific annotations. Supporting Evidence: PMID:8242742 Transforming growth factor beta (TGF beta) and activin each bind to pairs of membrane proteins, known as receptor types I and II, that associate to form a signaling complex. |
| GO:0005515 protein binding | IPI PMID:8622651 Activation of signalling by the activin receptor complex. | UNDECIDED | Summary: The source-specific ACVR2A interaction remains unresolved from the abstract. Reason: The abstract describes the ActR-IIB/ActR-IB experiment. It does not establish that ActR-IIA was absent from the full study. The general ACVR2A/ACVR1B receptor complex is independently supported, but the exact interaction assay behind this row requires the full text; do not infer a paralog misattribution from the abstract. |
| GO:0005515 protein binding | IPI PMID:9032295 Activin and inhibin have antagonistic effects on ligand-depe... | MODIFY | Summary: Specify the ligand interaction underlying receptor function. Reason: The receptor study distinguishes activin-dependent signaling complex assembly from antagonistic inhibin binding. Refine the generic binding claim to the ligand-specific function represented by this partner. Proposed replacements: inhibin binding Supporting Evidence: PMID:10746731 Inhibins also bind type II activin receptors but do not recruit ALK4, providing a competitive model for the antagonism of activin by inhibin. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. |
| GO:0005515 protein binding | IPI PMID:9032295 Activin and inhibin have antagonistic effects on ligand-depe... | MODIFY | Summary: Specify the ligand interaction underlying receptor function. Reason: The receptor study distinguishes activin-dependent signaling complex assembly from antagonistic inhibin binding. Refine the generic binding claim to the ligand-specific function represented by this partner. Proposed replacements: activin binding Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. |
| GO:0005515 protein binding | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | REMOVE | Summary: Generic protein binding does not specify a distinct molecular activity. Reason: The reported receptor-associated interaction is compatible with receptor complex assembly, but bare protein binding is uninformative under the repository policy. This removal does not reject the interaction or deduplicate evidence; the supported receptor activities and complexes are retained in their specific annotations. Supporting Evidence: PMID:9872992 It binds TGF-beta1 and -beta3 by associating with the TGF-beta type II receptor and interacts with activin-A and BMP-7 via activin type II receptors, ActRII and ActRIIB, regardless of which type I receptor partner is coexpressed. |
| GO:0005524 ATP binding | IEA GO_REF:0000002 | ACCEPT | Summary: The intracellular kinase uses an ATP-binding catalytic pocket. Reason: The human ActRIIA kinase structure resolves the ATP pocket occupied by the ATP-competitive inhibitor dorsomorphin. ATP binding is a supported catalytic property rather than a localization or an interaction-screen inference. Supporting Evidence: PMID:25368322 A, overview of the ActRIIA crystal structure showing dorsomorphin bound in the ATP pocket. |
| GO:0005737 cytoplasm | IDA PMID:14738881 Expression of activin subunits and receptors in the developi... | UNDECIDED | Summary: Intracellular ovarian staining cannot be resolved from the available abstract. Reason: PMID:14738881 reports immunohistochemical localization of ActRIIA/ActRIIB in human fetal ovaries, but the cached abstract does not distinguish cytoplasmic staining from membrane receptor signal. A cytoplasmic kinase domain alone does not establish a soluble cytoplasmic pool. Preserve uncertainty pending the relevant full-text images; do not reject an experimental localization on abstract-only evidence. Supporting Evidence: PMID:14738881 Activin subunits and receptors were localised by immunohistochemistry. |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | IEA GO_REF:0000120 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | ISS PMID:25368322 Small molecules dorsomorphin and LDN-193189 inhibit myostati... | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS PMID:1314589 Molecular cloning and binding properties of the human type I... | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1181149 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1181153 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-1549526 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201443 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201453 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201457 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201475 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201476 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201648 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-201821 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-202604 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839405 | ACCEPT | Summary: ACVR2A signals from the plasma membrane. Reason: The cloned human receptor has an extracellular ligand-binding region, one transmembrane segment and an intracellular kinase domain. Functional cell-surface receptor-complex assays and live-cell receptor measurements independently support this localization across the IBA, experimental, similarity and Reactome rows. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0007178 cell surface receptor protein serine/threonine kinase signaling pathway | IEA GO_REF:0000002 | MODIFY | Summary: Specify activin and BMP receptor signaling. Reason: Both GO:0032924 and GO:0030509 are experimentally supported descendants and are already annotated. The generic serine/threonine receptor pathway is correct but unnecessarily broad. Proposed replacements: activin receptor signaling pathway BMP signaling pathway Supporting Evidence: PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0007178 cell surface receptor protein serine/threonine kinase signaling pathway | TAS PMID:1314589 Molecular cloning and binding properties of the human type I... | MODIFY | Summary: Specify activin and BMP receptor signaling. Reason: Both GO:0032924 and GO:0030509 are experimentally supported descendants and are already annotated. The generic serine/threonine receptor pathway is correct but unnecessarily broad. Proposed replacements: activin receptor signaling pathway BMP signaling pathway Supporting Evidence: PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0007389 pattern specification process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Developmental patterning is a conserved downstream role of activin-family type II receptors. Reason: The PAINT annotation reflects ancestral receptor signaling in patterning, not a pairwise donor transfer. Mouse genetic interactions involving Acvr2a and Acvr2b support an early embryonic role. There is no target-specific evidence of loss; retain this precise but peripheral biological role without asserting that all family members specify the same tissue pattern. Supporting Evidence: PMID:10452853 These results provide genetic evidence that type II activin receptors are required for egg cylinder growth, primitive streak formation, and rostral head development in mice. |
| GO:0009986 cell surface | IEA GO_REF:0000107 | ACCEPT | Summary: The ligand-binding receptor is exposed at the cell surface. Reason: Activin binding and cell-surface receptor oligomerization support this specific location. It is compatible with the transmembrane plasma-membrane localization. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0015026 coreceptor activity | IDA PMID:10746731 Betaglycan binds inhibin and can mediate functional antagoni... | KEEP AS NON CORE | Summary: ACVR2A participates in the inhibin-binding receptor assembly with betaglycan. Reason: PMID:10746731 establishes an inhibin-binding complex of ActRII and betaglycan. Betaglycan is the high-affinity accessory co-receptor; ACVR2A supplies the associated inhibin-binding receptor component. Retain the curator-assigned cooperative activity for this inhibitory assembly, distinct from canonical activin kinase signaling, without attributing betaglycan-specific binding enhancement to ACVR2A. Supporting Evidence: PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII. PMID:10746731 Inhibins also bind type II activin receptors but do not recruit ALK4, providing a competitive model for the antagonism of activin by inhibin. |
| GO:0016020 membrane | IEA GO_REF:0000002 | MODIFY | Summary: Specify the plasma membrane. Reason: Membrane is correct but less precise than the experimentally supported plasma-membrane location already annotated to this receptor. Proposed replacements: plasma membrane Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. |
| GO:0016361 activin receptor activity, type I | IDA PMID:25368322 Small molecules dorsomorphin and LDN-193189 inhibit myostati... | MODIFY | Summary: The receptor class should be type II, not type I. Reason: The full text of PMID:25368322 explicitly distinguishes ActRIIA/ActRIIB from type I receptors, expresses the human ActRIIA kinase domain, and solves its inhibitor-bound structure. QuickGO defines type I activity as downstream transduction after association with activin-bound type II receptor; type II activity binds activin and phosphorylates type I receptor. ACVR2A executes the latter. This is a receptor-class correction supported by the actual paper, not an inference from its title. Proposed replacements: activin receptor activity, type II Supporting Evidence: PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. |
| GO:0016362 activin receptor activity, type II | IDA PMID:25368322 Small molecules dorsomorphin and LDN-193189 inhibit myostati... | ACCEPT | Summary: ACVR2A is an activin type II receptor kinase. Reason: Human ACVR2A binds activin and supplies the upstream receptor kinase that activates a type I receptor. This is its defining activin signaling activity. The type II identity is confirmed by direct structural work, independently of the electronic row. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. |
| GO:0016362 activin receptor activity, type II | IEA GO_REF:0000117 | ACCEPT | Summary: ACVR2A is an activin type II receptor kinase. Reason: Human ACVR2A binds activin and supplies the upstream receptor kinase that activates a type I receptor. This is its defining activin signaling activity. The type II identity is confirmed by direct structural work, independently of the electronic row. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. |
| GO:0017002 activin receptor activity | IBA GO_REF:0000033 | MODIFY | Summary: Refine activin receptor activity to the type II activity. Reason: The activity is correct but the already annotated descendant GO:0016362 specifies the experimentally established receptor class. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: activin receptor activity, type II Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. |
| GO:0017002 activin receptor activity | IDA PMID:12665502 Identification of a functional binding site for activin on t... | MODIFY | Summary: Refine activin receptor activity to the type II activity. Reason: The activity is correct but the already annotated descendant GO:0016362 specifies the experimentally established receptor class. Proposed replacements: activin receptor activity, type II Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. |
| GO:0017002 activin receptor activity | IDA PMID:25368322 Small molecules dorsomorphin and LDN-193189 inhibit myostati... | MODIFY | Summary: Refine activin receptor activity to the type II activity. Reason: The activity is correct but the already annotated descendant GO:0016362 specifies the experimentally established receptor class. Proposed replacements: activin receptor activity, type II Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. |
| GO:0017002 activin receptor activity | IEA GO_REF:0000107 | MODIFY | Summary: Refine activin receptor activity to the type II activity. Reason: The activity is correct but the already annotated descendant GO:0016362 specifies the experimentally established receptor class. Proposed replacements: activin receptor activity, type II Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:25368322 Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-Ξ² family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB. |
| GO:0019838 growth factor binding | IEA GO_REF:0000107 | ACCEPT | Summary: ACVR2A directly binds growth-factor ligands. Reason: Activin A binding is experimentally established. The existing activin-binding term is not an is_a descendant of growth factor binding in the checked ontology, so a descendant refinement would misstate that hierarchy. Retain the supported ligand-binding property. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. |
| GO:0030165 PDZ domain binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: The receptor C terminus binds PDZ-domain adaptors. Reason: The ortholog experiment maps ARIP2 isoform binding to the COOH-terminal PDZ-binding motif of ActRIIA. This supports the transferred specific interaction involved in trafficking and signal modulation. It is peripheral to ligand recognition and receptor kinase catalysis. Supporting Evidence: PMID:16648306 ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif. |
| GO:0030279 negative regulation of ossification | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Activin-ACVR2A signaling can restrain osteoblast bone formation. Reason: Conditional Acvr2a deletion in mouse osteoblasts increases differentiation, mineral deposition and trabecular bone mass (PMID:28659341). This independently supports the conserved, context-specific negative regulatory role behind the similarity annotation. Distinguish this activin context from the positive BMP-driven osteogenic responses observed in human mesenchymal cells. Supporting Evidence: PMID:28659341 Here, we generated mice with conditional deletion of activin receptor (ACVR) type 2A, ACVR2B, or both, in osteoblasts, to determine the contribution of activin receptor signaling in regulating bone mass. PMID:28659341 osteoblasts deficient in ACVR2A exhibited enhanced differentiation indicated by alkaline phosphatase activity, mineral deposition, and transcriptional expression of osterix, osteocalcin, and dentin matrix acidic phosphoprotein 1. |
| GO:0030501 positive regulation of bone mineralization | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ACVR2A supports BMP-dependent osteoblast differentiation and bone-forming responses. Reason: PMID:18436533 measures BMP-induced calcium deposition by Alizarin red staining in Fig. 1. Receptor-specific knockdown establishes ACVR2A dependence through ID1 signaling and osteogenic-marker endpoints (Figs. 4β5), rather than a separate ACVR2A-knockdown calcium-deposition experiment. Together these support the curator-assigned positive bone-mineralization role as a downstream, non-core BMP response. Distinguish it from the activin context in mouse osteoblasts. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| 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: ACVR2A supports BMP-dependent osteoblast differentiation and bone-forming responses. Reason: PMID:18436533 measures BMP-induced calcium deposition by Alizarin red staining in Fig. 1. Receptor-specific knockdown establishes ACVR2A dependence through ID1 signaling and osteogenic-marker endpoints (Figs. 4β5), rather than a separate ACVR2A-knockdown calcium-deposition experiment. Together these support the curator-assigned positive bone-mineralization role as a downstream, non-core BMP response. Distinguish it from the activin context in mouse osteoblasts. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0030509 BMP signaling pathway | IDA PMID:18436533 BMP-2/4 and BMP-6/7 differentially utilize cell surface rece... | ACCEPT | Summary: ACVR2A also functions as a BMP receptor. Reason: Human mesenchymal-cell receptor knockdown establishes ACVR2A-dependent BMP signaling, particularly BMP6/7. RGMa/HJV alter BMP2/4 receptor utilization, and human pulmonary endothelial cells use ActR-II in BMP9 signaling. These direct experiments justify the BMP receptor role without assuming exclusivity for activin. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. PMID:17472960 These findings suggest that RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and that increased utilization of ActRIIA leads to generation of an enhanced BMP signal. PMID:19366699 Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. |
| GO:0030509 BMP signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: ACVR2A also functions as a BMP receptor. Reason: Human mesenchymal-cell receptor knockdown establishes ACVR2A-dependent BMP signaling, particularly BMP6/7. RGMa/HJV alter BMP2/4 receptor utilization, and human pulmonary endothelial cells use ActR-II in BMP9 signaling. These direct experiments justify the BMP receptor role without assuming exclusivity for activin. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. PMID:17472960 These findings suggest that RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and that increased utilization of ActRIIA leads to generation of an enhanced BMP signal. PMID:19366699 Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. |
| GO:0030509 BMP signaling pathway | IMP PMID:17472960 Repulsive guidance molecule RGMa alters utilization of bone ... | ACCEPT | Summary: ACVR2A also functions as a BMP receptor. Reason: Human mesenchymal-cell receptor knockdown establishes ACVR2A-dependent BMP signaling, particularly BMP6/7. RGMa/HJV alter BMP2/4 receptor utilization, and human pulmonary endothelial cells use ActR-II in BMP9 signaling. These direct experiments justify the BMP receptor role without assuming exclusivity for activin. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. PMID:17472960 These findings suggest that RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and that increased utilization of ActRIIA leads to generation of an enhanced BMP signal. PMID:19366699 Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. |
| GO:0030509 BMP signaling pathway | IMP PMID:19366699 Bone morphogenetic protein (BMP) and activin type II recepto... | ACCEPT | Summary: ACVR2A also functions as a BMP receptor. Reason: Human mesenchymal-cell receptor knockdown establishes ACVR2A-dependent BMP signaling, particularly BMP6/7. RGMa/HJV alter BMP2/4 receptor utilization, and human pulmonary endothelial cells use ActR-II in BMP9 signaling. These direct experiments justify the BMP receptor role without assuming exclusivity for activin. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. PMID:17472960 These findings suggest that RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and that increased utilization of ActRIIA leads to generation of an enhanced BMP signal. PMID:19366699 Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. |
| GO:0032502 developmental process | IEA GO_REF:0000117 | MODIFY | Summary: Replace the generic developmental process with supported developmental descendants. Reason: Osteoblast differentiation and pattern specification are already annotated, supported descendants of developmental process. These retain the known breadth without leaving an uninformative umbrella annotation. Proposed replacements: osteoblast differentiation pattern specification process Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. PMID:10452853 These results provide genetic evidence that type II activin receptors are required for egg cylinder growth, primitive streak formation, and rostral head development in mice. |
| GO:0032924 activin receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: ACVR2A directly participates in activin receptor signaling. Reason: The receptor binds activin, assembles with a type I receptor and supplies receptor kinase activity. It performs signal-transduction chemistry rather than merely serving as a downstream readout. The function is supported independently of any one row or donor list. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. |
| GO:0032924 activin receptor signaling pathway | IMP PMID:12665502 Identification of a functional binding site for activin on t... | ACCEPT | Summary: ACVR2A directly participates in activin receptor signaling. Reason: The receptor binds activin, assembles with a type I receptor and supplies receptor kinase activity. It performs signal-transduction chemistry rather than merely serving as a downstream readout. The function is supported independently of any one row or donor list. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. |
| GO:0032924 activin receptor signaling pathway | IMP PMID:18326817 Hemojuvelin regulates hepcidin expression via a selective su... | ACCEPT | Summary: ACVR2A directly participates in activin receptor signaling. Reason: The receptor binds activin, assembles with a type I receptor and supplies receptor kinase activity. It performs signal-transduction chemistry rather than merely serving as a downstream readout. The function is supported independently of any one row or donor list. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. |
| GO:0032927 positive regulation of activin receptor signaling pathway | IDA PMID:12665502 Identification of a functional binding site for activin on t... | UNDECIDED | Summary: The positive-regulatory interpretation requires the full assay context. Reason: PMID:12665502 establishes ligand-dependent receptor-complex signaling in its abstract, but the available text does not resolve the experimental basis of this positive-regulation annotation. GO:0032927 denotes increased pathway frequency, rate or extent; it does not require a separate molecular mechanism. Do not downgrade the experimental claim merely because receptor participation is independently established. Both rows remain unresolved pending the relevant full-text assays. Supporting Evidence: PMID:12665502 Cross-linking studies measuring binding of 125I-activin-A to the ALK4-trunc mutants in the presence of ActRII implicated the same residues. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. |
| GO:0032927 positive regulation of activin receptor signaling pathway | IEA GO_REF:0000117 | UNDECIDED | Summary: The positive-regulatory interpretation requires the full assay context. Reason: PMID:12665502 establishes ligand-dependent receptor-complex signaling in its abstract, but the available text does not resolve the experimental basis of this positive-regulation annotation. GO:0032927 denotes increased pathway frequency, rate or extent; it does not require a separate molecular mechanism. Do not downgrade the experimental claim merely because receptor participation is independently established. Both rows remain unresolved pending the relevant full-text assays. Supporting Evidence: PMID:12665502 Cross-linking studies measuring binding of 125I-activin-A to the ALK4-trunc mutants in the presence of ActRII implicated the same residues. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. |
| GO:0034673 inhibin-betaglycan-ActRII complex | IDA PMID:10746731 Betaglycan binds inhibin and can mediate functional antagoni... | KEEP AS NON CORE | Summary: ACVR2A occurs in the inhibin-betaglycan-ActRII complex. Reason: Crosslinking directly supports membership in this inhibitory ligand-receptor assembly. Inhibin-bound complexes fail to recruit the signaling type I receptor, so this complex is distinct from the active activin receptor complex. Supporting Evidence: PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII. PMID:10746731 Inhibins also bind type II activin receptors but do not recruit ALK4, providing a competitive model for the antagonism of activin by inhibin. |
| GO:0034711 inhibin binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: ACVR2A binds inhibin in an antagonist receptor complex. Reason: Inhibin binding is experimentally supported and mediates antagonism of activin receptor assembly. It is a specific inhibitory interaction, not evidence that inhibin activates the canonical ACVR1B-SMAD branch. Supporting Evidence: PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII. PMID:10746731 Inhibins also bind type II activin receptors but do not recruit ALK4, providing a competitive model for the antagonism of activin by inhibin. |
| GO:0042802 identical protein binding | IEA GO_REF:0000107 | ACCEPT | Summary: ACVR2A undergoes ligand-associated homomeric assembly. Reason: Earlier full-length receptor coimmunoprecipitation and later live-cell measurements support homomeric interactions. The human receptor study resolves activin-dependent ACVR2A homodimerization; do not describe the receptor as constitutively dimeric by analogy to ACVR2B. Supporting Evidence: PMID:8612709 In contrast, homomeric complexes of full-length activin type IIA receptors were detected. PMID:38334613 ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization. |
| GO:0043235 signaling receptor complex | IEA GO_REF:0000117 | MODIFY | Summary: Specify both established receptor complexes. Reason: The generic receptor-complex term can be refined to the already annotated activin receptor complex and inhibin-betaglycan-ActRII complex. These correspond to active signaling and antagonist-bound assemblies, respectively. Proposed replacements: activin receptor complex inhibin-betaglycan-ActRII complex Supporting Evidence: PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII. |
| GO:0043235 signaling receptor complex | IPI PMID:9872992 Endoglin is an accessory protein that interacts with the sig... | MODIFY | Summary: Specify both established receptor complexes. Reason: The generic receptor-complex term can be refined to the already annotated activin receptor complex and inhibin-betaglycan-ActRII complex. These correspond to active signaling and antagonist-bound assemblies, respectively. Proposed replacements: activin receptor complex inhibin-betaglycan-ActRII complex Supporting Evidence: PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII. |
| GO:0045648 positive regulation of erythrocyte differentiation | IDA PMID:9032295 Activin and inhibin have antagonistic effects on ligand-depe... | KEEP AS NON CORE | Summary: Activin receptor signaling promotes erythroid differentiation in the tested human cell model. Reason: PMID:9032295 uses inducible receptor expression in K562 human erythroleukemia cells and measures increased hemoglobin with reduced proliferation. This is a supported cell-context response, not a defining receptor activity across tissues. Supporting Evidence: PMID:9032295 Our results indicate that activin signal transduction mediated through its type I and type II receptors results in an increase in the hemoglobin content of the cells and limits their proliferation. |
| GO:0045669 positive regulation of osteoblast differentiation | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ACVR2A supports BMP-dependent osteoblast differentiation and bone-forming responses. Reason: Primary human mesenchymal-cell experiments couple BMP receptor knockdown to osteogenic marker responses; the study also measures BMP-induced matrix mineralization. These supported physiological outputs are context-dependent and peripheral to the receptor mechanism. They do not contradict the negative effect of activin-ACVR2A signaling on bone mass in mouse osteoblasts. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| 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: ACVR2A supports BMP-dependent osteoblast differentiation and bone-forming responses. Reason: Primary human mesenchymal-cell experiments couple BMP receptor knockdown to osteogenic marker responses; the study also measures BMP-induced matrix mineralization. These supported physiological outputs are context-dependent and peripheral to the receptor mechanism. They do not contradict the negative effect of activin-ACVR2A signaling on bone mass in mouse osteoblasts. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| 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: ACVR2A-dependent BMP signaling promotes transcriptional output. Reason: The hemojuvelin study links ACVR2A-containing BMP receptor complexes to hepcidin expression. Retain this downstream transcriptional regulation as non-core; ACVR2A is a membrane kinase and is not itself a DNA-binding transcription factor. Supporting Evidence: PMID:18326817 We demonstrate in vitro that HJV selectively uses the BMP type II receptors ActRIIA and BMPRII, but not ActRIIB, and HJV enhances utilization of ActRIIA by BMP-2 and BMP-4. |
| GO:0048179 activin receptor complex | IBA GO_REF:0000033 | ACCEPT | Summary: ACVR2A is the type II component of activin receptor complexes. Reason: Activin-induced type I/type II heteromer formation and receptor activation directly support complex membership. The IBA is corroborated by biochemical evidence and is not evaluated by donor count. Supporting Evidence: PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. PMID:8721982 Phosphorylation of the GS domain was dependent upon a functional ActRII. |
| GO:0048185 activin binding | IEA GO_REF:0000107 | ACCEPT | Summary: Activin binding is a direct receptor property. Reason: Human receptor cloning and binding measurements demonstrate high-affinity activin A binding, and activin-dependent receptor heteromerization supports its signaling role. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. |
| GO:0048185 activin binding | IPI PMID:9032295 Activin and inhibin have antagonistic effects on ligand-depe... | ACCEPT | Summary: Activin binding is a direct receptor property. Reason: Human receptor cloning and binding measurements demonstrate high-affinity activin A binding, and activin-dependent receptor heteromerization supports its signaling role. Supporting Evidence: PMID:1314589 The type II human activin receptor consists of an extracellular domain that specifically binds activin A with a Kd of 360 pM, a single-membrane spanning domain, and an intracellular kinase domain with predicted serine/threonine specificity. PMID:9032295 We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner. |
| 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: ACVR2A promotes BMP9-induced SMAD signaling in human endothelial cells. Reason: PMID:19366699 explicitly finds that ActR-II contributes to BMP9-mediated SMAD2 activation. Retain the downstream regulatory effect without assigning direct SMAD phosphorylation to the type II receptor. Supporting Evidence: PMID:19366699 Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. |
| GO:0071363 cellular response to growth factor stimulus | IBA GO_REF:0000033 | MODIFY | Summary: Specify the experimentally established BMP signaling response. Reason: QuickGO places BMP signaling (GO:0030509) under cellular response to growth factor stimulus. This supported descendant provides a mechanistic refinement; activin signaling is retained separately in its own annotation. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Proposed replacements: BMP signaling pathway Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. |
| GO:0071773 cellular response to BMP stimulus | IMP PMID:18326817 Hemojuvelin regulates hepcidin expression via a selective su... | MODIFY | Summary: Refine the BMP response to the receptor signaling pathway. Reason: ACVR2A executes the receptor step of BMP signaling. GO:0030509 is an already annotated descendant of cellular response to BMP stimulus and specifies this direct mechanism. Proposed replacements: BMP signaling pathway Supporting Evidence: PMID:18326817 We demonstrate in vitro that HJV selectively uses the BMP type II receptors ActRIIA and BMPRII, but not ActRIIB, and HJV enhances utilization of ActRIIA by BMP-2 and BMP-4. PMID:19366699 Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. |
| GO:0071773 cellular response to BMP stimulus | IMP PMID:19366699 Bone morphogenetic protein (BMP) and activin type II recepto... | MODIFY | Summary: Refine the BMP response to the receptor signaling pathway. Reason: ACVR2A executes the receptor step of BMP signaling. GO:0030509 is an already annotated descendant of cellular response to BMP stimulus and specifies this direct mechanism. Proposed replacements: BMP signaling pathway Supporting Evidence: PMID:18326817 We demonstrate in vitro that HJV selectively uses the BMP type II receptors ActRIIA and BMPRII, but not ActRIIB, and HJV enhances utilization of ActRIIA by BMP-2 and BMP-4. PMID:19366699 Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. |
| GO:0098821 BMP receptor activity | IEA GO_REF:0000107 | ACCEPT | Summary: ACVR2A also functions as a BMP receptor. Reason: Human mesenchymal-cell receptor knockdown establishes ACVR2A-dependent BMP signaling, particularly BMP6/7. RGMa/HJV alter BMP2/4 receptor utilization, and human pulmonary endothelial cells use ActR-II in BMP9 signaling. These direct experiments justify the BMP receptor role without assuming exclusivity for activin. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. PMID:17472960 These findings suggest that RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and that increased utilization of ActRIIA leads to generation of an enhanced BMP signal. PMID:19366699 Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. |
| GO:0098821 BMP receptor activity | ISS GO_REF:0000024 | ACCEPT | Summary: ACVR2A also functions as a BMP receptor. Reason: Human mesenchymal-cell receptor knockdown establishes ACVR2A-dependent BMP signaling, particularly BMP6/7. RGMa/HJV alter BMP2/4 receptor utilization, and human pulmonary endothelial cells use ActR-II in BMP9 signaling. These direct experiments justify the BMP receptor role without assuming exclusivity for activin. Supporting Evidence: PMID:18436533 RNA interference-mediated gene knockdown revealed that osteoinductive BMP activities in hMSC are elicited through the type I receptors ACVR1A and BMPR1A and the type II receptors ACVR2A and BMPR2. PMID:17472960 These findings suggest that RGMa facilitates the use of ActRIIA by endogenous BMP2 and BMP4 ligands that otherwise prefer signaling via BMPRII and that increased utilization of ActRIIA leads to generation of an enhanced BMP signal. PMID:19366699 Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation. |
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