Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Betaglycan binds inhibin and can mediate functional antagonism of activin signalling.
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Inhibin forms complexes with betaglycan and ActRII, antagonizing activin signaling without recruitment of ALK4.
"Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII."
Modulation of activin signal transduction by inhibin B and inhibin-binding protein (INhBP).
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INhBP associates most strongly with ALK4 and more weakly with other activin receptors in the reported receptor-complex experiments.
"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."
Identification of a functional binding site for activin on the type I receptor ALK4.
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ALK4 ligand-binding surface mutagenesis is assessed in complexes containing ActRII; the full assay basis of the ACVR2A positive-regulation annotation remains unresolved.
"Cross-linking studies measuring binding of 125I-activin-A to the ALK4-trunc mutants in the presence of ActRII implicated the same residues."
Molecular cloning and binding properties of the human type II activin receptor.
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Cloned human ACVR2A binds activin A with high affinity and encodes a transmembrane receptor kinase.
"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."
Expression of activin subunits and receptors in the developing human ovary: activin A promotes germ cell survival and proliferation before primordial follicle formation.
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Human fetal ovarian immunohistochemistry localizes activin receptors to germ and somatic cells; the available abstract does not resolve a cytoplasmic compartment annotation.
"Activin subunits and receptors were localised by immunohistochemistry."
Repulsive guidance molecule RGMa alters utilization of bone morphogenetic protein (BMP) type II receptors by BMP2 and BMP4.
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RGMa permits enhanced BMP2/4 signaling through ACVR2A in contexts otherwise favoring BMPRII.
"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."
Hemojuvelin regulates hepcidin expression via a selective subset of BMP ligands and receptors independently of neogenin.
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Hemojuvelin-mediated BMP signaling uses ActRIIA and BMPRII in hepatoma-derived cell systems.
"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."
BMP-2/4 and BMP-6/7 differentially utilize cell surface receptors to induce osteoblastic differentiation of human bone marrow-derived mesenchymal stem cells.
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ACVR2A and BMPR2 mediate BMP-dependent osteogenic signaling in primary human mesenchymal stem cells; BMP6/7 rely more strongly on ACVR2A than BMP2/4.
"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."
Bone morphogenetic protein (BMP) and activin type II receptors balance BMP9 signals mediated by activin receptor-like kinase-1 in human pulmonary artery endothelial cells.
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Human endothelial BMP9 responses include ActR-II-dependent SMAD2 activation alongside SMAD1/5 signaling.
"Conversely, activin receptor type II (ActR-II) contributed more to BMP9-mediated Smad2 activation."
TSC-22 promotes transforming growth factor β-mediated cardiac myofibroblast differentiation by antagonizing Smad7 activity.
Small molecules dorsomorphin and LDN-193189 inhibit myostatin/GDF8 signaling and promote functional myoblast differentiation.
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Human ActRIIA is a type II receptor with a structurally resolved ATP-competitive inhibitor-binding kinase pocket.
"Here, we report that dorsomorphin and LDN-193189 activities, even within the TGF-β family, are not restricted to type I receptors but extend also to the type II receptors ActRIIA and ActRIIB."
Quantitative fragmentomics allow affinity mapping of interactomes.
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Supplementary Dataset 1 identifies human ACVR2A/P27037 peptide VDFPPKESSL in PDZ-domain binding assays; fragment affinities do not establish all endogenous full-length interactions.
"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."
Identification of human activin and TGF beta type I receptors that form heteromeric kinase complexes with type II receptors.
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Type I and type II receptors form diverse heteromeric serine/threonine kinase signaling complexes.
"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."
Activation of signalling by the activin receptor complex.
Formation and activation by phosphorylation of activin receptor complexes.
Activin and inhibin have antagonistic effects on ligand-dependent heteromerization of the type I and type II activin receptors and human erythroid differentiation.
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Activin promotes type I/type II receptor heteromerization and erythroid differentiation in the inducible human K562 model.
"We demonstrate here that activin specifically induces heteromer formation between the type I and type II receptors in a time-dependent manner."
Endoglin is an accessory protein that interacts with the signaling receptor complex of multiple members of the transforming growth factor-beta superfamily.
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Endoglin associates with activin-A and BMP7 through type II activin receptors as an accessory receptor-complex component.
"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."
ACVR2A,B (ActRIIA,B) phosphorylates ACVR1B (ActRIB, ALK4) in response to Activin
Activin A,AB,B binds Activin Receptor ACVR2A,B:ACVR1B
Phosphorylation of SMAD2,3 by Activin:Activin Receptor
Type II receptor phosphorylates type I receptor
Phospho-R-Smad1/5/8 dissociates from the receptor complex
BMP2 binds to the receptor complex
I-Smad competes with R-Smad1/5/8 for type I receptor
Activated type I receptor phosphorylates R-Smad1/5/8 directly
An anchoring protein, Endofin, recruits R-Smad1/5/8
I-Smad binds to type I receptor, preventing Smad1/5/8 from being activated
Formation of a heteromeric BMP receptor complex
InhibinA-TGFBR3 binding to ACVR2A
Characterization of isoforms of activin receptor-interacting protein 2 that augment activin signaling.
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ARIP2 isoforms recognize the ActRIIA C-terminal PDZ-binding motif and differentially regulate receptor internalization and signaling.
"ARIP2, ARIP2b and ARIP2c recognize COOH-terminal residues of ActRIIA that match a PDZ-binding consensus motif."
Activin receptor type 2A (ACVR2A) functions directly in osteoblasts as a negative regulator of bone mass.
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Mouse osteoblast-specific Acvr2a deletion increases differentiation and bone mass, supporting negative regulation in the activin signaling context.
"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."
The Activation of the Fibrodysplasia Ossificans Progressiva-Inducing ALK2-R206H Mutant Depends on the Distinct Homo-Oligomerization Patterns of ACVR2B and ACVR2A.
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Human ACVR2A requires activin A for homodimerization in live-cell receptor measurements, unlike the constitutive homomeric component observed for ACVR2B.
"ACVR2B formed stable homomeric complexes that were enhanced by Activin A (ActA), while ACVR2A required ActA for homodimerization."
Truncated activin type II receptors inhibit bioactivity by the formation of heteromeric complexes with activin type I. receptors.
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Full-length activin type IIA receptors form homomeric complexes in receptor-expression experiments.
"In contrast, homomeric complexes of full-length activin type IIA receptors were detected."
The type II activin receptors are essential for egg cylinder growth, gastrulation, and rostral head development in mice.
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Mouse ActRIIA/ActRIIB genetic interactions establish requirements in primitive streak formation and rostral head development.
"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."
ACVR2A manual review and PDZ supplement inspection notes