TGFBR3 (betaglycan) is a single-pass type I transmembrane proteoglycan and the most abundant TGF-beta binding protein at the cell surface. Its large ectodomain, comprising an endoglin-like N-terminal region and a zona pellucida (ZP) domain and substituted with heparan sulfate and chondroitin sulfate chains, binds all three TGF-beta isoforms (with highest affinity for TGF-beta2), inhibins, and several BMPs and GDF5. Lacking any kinase domain, it acts as a coreceptor: it presents TGF-beta to the type II receptor TGFBR2 and promotes assembly of the TGFBR2-TGFBR1 signaling complex, forms the high-affinity inhibin receptor together with ActRII (allowing inhibin to antagonize activin signaling, e.g. FSH suppression in pituitary gonadotropes), and enhances BMP signaling through ALK3 and ALK6. The short cytoplasmic tail is phosphorylated by TGFBR2 at Thr841, which recruits beta-arrestin 2 to drive endocytosis of TGFBR3 with its partner receptors; a C-terminal class I PDZ motif binds GIPC1, stabilizing TGFBR3 at the surface. Through beta-arrestin 2, TGFBR3 also has ligand-independent activities, activating Cdc42 to restrain epithelial cell migration, inhibiting NF-kappaB signaling and regulating integrin alpha5beta1 trafficking and adhesion to fibronectin. Ectodomain shedding by membrane-type MMPs releases a soluble form into serum and extracellular matrix that sequesters TGF-beta. In mouse, Tgfbr3 is essential for embryonic development, being required in epicardial cells for EMT and invasion that underlie coronary vessel formation. TGFBR3 expression is frequently lost in human cancers, where it behaves as a suppressor of migration and invasion.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0001666 response to hypoxia | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Ensembl Compara transfer from rat betaglycan of a response-to-hypoxia annotation. Reason: Response terms of this kind are typically based on altered expression of the rodent gene under hypoxia; they describe TGFBR3 as a regulated readout rather than a participant in the cellular response. No human evidence for a hypoxia role was found, and it does not reflect the coreceptor function of the protein. |
| GO:0001837 epithelial to mesenchymal transition | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Epithelial to mesenchymal transition (IBA). Betaglycan is required for TGF-beta2- and BMP2-driven endocardial and epicardial EMT and invasion; the IBA comes from PAINT node PTN002678643 (Euteleostomi TGFBR3 clade), seeded by the human IDA. Reason: TGFBR3 does part of the work of EMT in these settings: as the ligand-binding coreceptor that initiates TGF-beta2/BMP2 signaling into the Par6/Smurf1/RhoA pathway, and via its GIPC-binding cytoplasmic tail. EMT is a context-specific cellular outcome (cardiac cushion and epicardium) rather than the core molecular role, so it is retained as non-core. Note that in carcinoma cells TGFBR3 overexpression instead suppresses EMT, reinforcing that the direction is context-dependent. Supporting Evidence: PMID:18184661 BMP-2 specifically stimulates TbetaRIII-mediated epithelial to mesenchymal cell transformation PMID:22033038 the Par6/Smurf1/RhoA pathway is activated downstream of TGFΞ²R3 in epicardial cells PMID:29130787 transfection of a TGFBR3-containing plasmid dramatically inhibited epithelial-to-mesenchymal transition (EMT) and migration in CAL-27 cells |
| GO:0001837 epithelial to mesenchymal transition | IDA PMID:18184661 Bone morphogenetic proteins signal through the transforming ... | KEEP AS NON CORE | Summary: Epithelial to mesenchymal transition (IDA). Betaglycan is required for TGF-beta2- and BMP2-driven endocardial and epicardial EMT and invasion; the IBA comes from PAINT node PTN002678643 (Euteleostomi TGFBR3 clade), seeded by the human IDA. Reason: TGFBR3 does part of the work of EMT in these settings: as the ligand-binding coreceptor that initiates TGF-beta2/BMP2 signaling into the Par6/Smurf1/RhoA pathway, and via its GIPC-binding cytoplasmic tail. EMT is a context-specific cellular outcome (cardiac cushion and epicardium) rather than the core molecular role, so it is retained as non-core. Note that in carcinoma cells TGFBR3 overexpression instead suppresses EMT, reinforcing that the direction is context-dependent. Supporting Evidence: PMID:18184661 BMP-2 specifically stimulates TbetaRIII-mediated epithelial to mesenchymal cell transformation PMID:22033038 the Par6/Smurf1/RhoA pathway is activated downstream of TGFΞ²R3 in epicardial cells PMID:29130787 transfection of a TGFBR3-containing plasmid dramatically inhibited epithelial-to-mesenchymal transition (EMT) and migration in CAL-27 cells |
| GO:0001889 liver development | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of liver development, based on the knockout phenotype. Reason: Tgfbr3-null mouse embryos show hepatocyte apoptosis and liver defects, but this is a downstream organismal phenotype of global loss of a TGF-beta2 coreceptor; no study shows TGFBR3 carrying out a step of liver development. Per the curation rules for this project, knockout phenotypes alone do not establish process participation. Supporting Evidence: PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0003007 heart morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: ISS transfer from chicken TGFBR3 (Q90998) of heart morphogenesis. Reason: The chicken and mouse orthologs (same PANTHER subfamily PTHR14002:SF7 and PAINT clade PTN002678643) mediate TGF-beta2/BMP2 responses in endocardial cushion and epicardial cells that remodel the heart; Tgfbr3-null mice die with heart defects. The protein contributes as the signaling coreceptor in cardiac cell types, so a broad heart-morphogenesis term is defensible as non-core, but it is not a heart-specific function. Supporting Evidence: PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver PMID:21871877 lower rate of epicardial cell proliferation and decreased epicardially derived cell invasion in Tgfbr3(-/-) hearts PMID:18184661 BMP-2 specifically stimulates TbetaRIII-mediated epithelial to mesenchymal cell transformation |
| GO:0003150 muscular septum morphogenesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of muscular septum morphogenesis, derived from Tgfbr3-null embryo cardiac phenotypes. Reason: Tgfbr3-null embryos have thin compact myocardium, reduced proliferation and septal/trabecular abnormalities, but these are secondary consequences of failed epicardial invasion and coronary vessel formation in a global knockout. TGFBR3 acts in epicardial and endocardial cells as a TGF-beta/BMP coreceptor; it is not shown to perform a step of myocardial or septal morphogenesis itself. Fine-grained organismal phenotypes are not transferred as process participation. Supporting Evidence: PMID:17704211 At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0003151 outflow tract morphogenesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of outflow tract morphogenesis, derived from Tgfbr3-null embryo cardiac phenotypes. Reason: Tgfbr3-null embryos have thin compact myocardium, reduced proliferation and septal/trabecular abnormalities, but these are secondary consequences of failed epicardial invasion and coronary vessel formation in a global knockout. TGFBR3 acts in epicardial and endocardial cells as a TGF-beta/BMP coreceptor; it is not shown to perform a step of myocardial or septal morphogenesis itself. Fine-grained organismal phenotypes are not transferred as process participation. Supporting Evidence: PMID:17704211 At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0003223 ventricular compact myocardium morphogenesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of ventricular compact myocardium morphogenesis, derived from Tgfbr3-null embryo cardiac phenotypes. Reason: Tgfbr3-null embryos have thin compact myocardium, reduced proliferation and septal/trabecular abnormalities, but these are secondary consequences of failed epicardial invasion and coronary vessel formation in a global knockout. TGFBR3 acts in epicardial and endocardial cells as a TGF-beta/BMP coreceptor; it is not shown to perform a step of myocardial or septal morphogenesis itself. Fine-grained organismal phenotypes are not transferred as process participation. Supporting Evidence: PMID:17704211 At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0004888 transmembrane signaling receptor activity | IDA PMID:18184661 Bone morphogenetic proteins signal through the transforming ... | MODIFY | Summary: IDA from Kirkbride et al. 2008 showing that betaglycan binds BMPs and enhances BMP signaling. Reason: TGFBR3 has no kinase or other signaling domain of its own; it binds BMPs and enhances ligand binding to the BMP type I receptors, which transduce the signal. This is coreceptor activity rather than an autonomous transmembrane signaling receptor activity, so the more accurate term is coreceptor activity (already carried by IDA for inhibin). Proposed replacements: coreceptor activity Supporting Evidence: PMID:18184661 TbetaRIII directly and specifically binds to multiple members of the BMP subfamily, including BMP-2, BMP-4, BMP-7, and GDF-5 PMID:18184661 TbetaRIII also enhances ligand binding to the BMP type I receptors PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors |
| GO:0005024 transforming growth factor beta receptor activity | IBA GO_REF:0000033 | MODIFY | Summary: TGF-beta receptor activity (IBA). Reason: TGFBR3 binds TGF-beta and presents it to TGFBR2, so the claim is sound, but the GO:0005024 definition specifies signal transmission by serine/threonine kinase catalysis, which betaglycan lacks. Its child GO:0070123 (type III receptor activity: combining with TGF-beta and facilitating ligand binding to type I and II receptors) is the precise description and is already annotated to TGFBR3 by IDA. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: GRANULARITY MISMATCH Sources checked: PANTHER:PTN002678643 SUPPORTS TRANSFER Euteleostomi TGFBR3-clade node; the target sits inside it (PTHR14002:SF7). The ligand-binding receptor claim transfers, but GO:0005024 implies kinase signaling; the type III child GO:0070123 is the correct scope. Proposed replacements: transforming growth factor beta receptor activity, type III Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor |
| GO:0005024 transforming growth factor beta receptor activity | IDA PMID:12958365 Beta-arrestin 2 mediates endocytosis of type III TGF-beta re... | MODIFY | Summary: TGF-beta receptor activity (IDA). Reason: TGFBR3 binds TGF-beta and presents it to TGFBR2, so the claim is sound, but the GO:0005024 definition specifies signal transmission by serine/threonine kinase catalysis, which betaglycan lacks. Its child GO:0070123 (type III receptor activity: combining with TGF-beta and facilitating ligand binding to type I and II receptors) is the precise description and is already annotated to TGFBR3 by IDA. Proposed replacements: transforming growth factor beta receptor activity, type III Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor |
| GO:0005024 transforming growth factor beta receptor activity | IEA GO_REF:0000117 | MODIFY | Summary: TGF-beta receptor activity (IEA). Reason: TGFBR3 binds TGF-beta and presents it to TGFBR2, so the claim is sound, but the GO:0005024 definition specifies signal transmission by serine/threonine kinase catalysis, which betaglycan lacks. Its child GO:0070123 (type III receptor activity: combining with TGF-beta and facilitating ligand binding to type I and II receptors) is the precise description and is already annotated to TGFBR3 by IDA. Proposed replacements: transforming growth factor beta receptor activity, type III Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor |
| GO:0005114 type II transforming growth factor beta receptor binding | IBA GO_REF:0000033 | ACCEPT | Summary: IBA from PAINT node PTN002678643, seeded by human TGFBR3. Reason: The cytoplasmic and extracellular domains of TGFBR3 bind the type II TGF-beta receptor, which phosphorylates the TGFBR3 tail. Direct binding to TGFBR2 is central to the presentation mechanism. Supporting Evidence: PMID:11323414 the cytoplasmic domains of the type III and type II receptors interact specifically in a manner dependent on the kinase activity of the type II receptor PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor |
| GO:0005114 type II transforming growth factor beta receptor binding | IDA PMID:11157754 Type III TGF-beta receptor-independent signalling of TGF-bet... | ACCEPT | Summary: IDA from Rotzer et al. 2001 (EMBO J) on TGF-beta2 receptor complexes. Reason: Binding of betaglycan to TbetaRII is well established (Blobe et al. 2001); the cited paper studied TGF-beta2 binding to type II receptor variants in the presence and absence of TbetaRIII. Accept in line with the curator, who read the full text. Supporting Evidence: PMID:11323414 the cytoplasmic domains of the type III and type II receptors interact specifically in a manner dependent on the kinase activity of the type II receptor |
| GO:0005160 transforming growth factor beta receptor binding | IEA GO_REF:0000107 | MODIFY | Summary: TGF-beta receptor binding transferred from rat betaglycan. Reason: Correct but general. The partner bound is specifically the type II TGF-beta receptor, so the specific child type II TGF-beta receptor binding (GO:0005114), already accepted for TGFBR3, is preferred. Proposed replacements: type II transforming growth factor beta receptor binding Supporting Evidence: PMID:11323414 the cytoplasmic domains of the type III and type II receptors interact specifically in a manner dependent on the kinase activity of the type II receptor |
| GO:0005160 transforming growth factor beta receptor binding | ISS PMID:1333192 Molecular cloning and characterization of the human and porc... | MODIFY | Summary: TGF-beta receptor binding transferred from rat betaglycan. Reason: Correct but general. The partner bound is specifically the type II TGF-beta receptor, so the specific child type II TGF-beta receptor binding (GO:0005114), already accepted for TGFBR3, is preferred. Proposed replacements: type II transforming growth factor beta receptor binding Supporting Evidence: PMID:11323414 the cytoplasmic domains of the type III and type II receptors interact specifically in a manner dependent on the kinase activity of the type II receptor |
| GO:0005515 protein binding | IPI PMID:10746731 Betaglycan binds inhibin and can mediate functional antagoni... | MODIFY | Summary: IPI with inhibin alpha (INHA, P05111) from Lewis et al. 2000, as contributes_to protein binding. Reason: Generic protein binding is uninformative. The paper shows high-affinity binding of the inhibin (alpha-beta dimer) hormone by betaglycan, so the informative term is inhibin complex binding. Proposed replacements: inhibin complex binding Supporting Evidence: PMID:10746731 Betaglycan binds inhibin with high affinity and enhances binding in cells co-expressing ActRII and betaglycan PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII |
| GO:0005515 protein binding | IPI PMID:10746731 Betaglycan binds inhibin and can mediate functional antagoni... | MODIFY | Summary: IPI with a TGF-beta ligand (TGFB1/TGFB2) from PMID:10746731. Reason: Generic protein binding is uninformative. Betaglycan binds TGF-beta isoforms with high affinity (this is the ligand interaction underlying its receptor activity), so the informative term is transforming growth factor beta binding, already accepted for TGFBR3. Proposed replacements: transforming growth factor beta binding Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:23826237 identify a novel major TGF-Ξ²-binding site in TGFR-3 |
| GO:0005515 protein binding | IPI PMID:11157754 Type III TGF-beta receptor-independent signalling of TGF-bet... | MODIFY | Summary: IPI with a TGF-beta ligand (TGFB1/TGFB2) from PMID:11157754. Reason: Generic protein binding is uninformative. Betaglycan binds TGF-beta isoforms with high affinity (this is the ligand interaction underlying its receptor activity), so the informative term is transforming growth factor beta binding, already accepted for TGFBR3. Proposed replacements: transforming growth factor beta binding Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:23826237 identify a novel major TGF-Ξ²-binding site in TGFR-3 |
| GO:0005515 protein binding | IPI PMID:11546783 A novel mechanism for regulating transforming growth factor ... | MODIFY | Summary: IPI with GIPC1 (O14908) from Blobe et al. 2001. Reason: GIPC1 binds via its PDZ domain to the class I PDZ-binding motif at the C-terminus of TGFBR3, which stabilizes TGFBR3 at the cell surface. PDZ domain binding is the informative term. Proposed replacements: PDZ domain binding Supporting Evidence: PMID:11546783 GIPC binds a Class I PDZ binding motif in the cytoplasmic domain of the type III receptor |
| GO:0005515 protein binding | IPI PMID:12958365 Beta-arrestin 2 mediates endocytosis of type III TGF-beta re... | MODIFY | Summary: IPI with beta-arrestin 2 (ARRB2, P32121) from Chen et al. 2003. Reason: Generic protein binding is uninformative. TGFBR2-phosphorylated TGFBR3 (Thr841) recruits beta-arrestin 2, which drives endocytosis of TGFBR3/TGFBR2 and mediates TGFBR3 effects on Cdc42, migration and NF-kappaB. Arrestin family protein binding captures this. Proposed replacements: arrestin family protein binding Supporting Evidence: PMID:12958365 Binding of betaarr2 to TbetaRIII was also triggered by phosphorylation of the receptor on its cytoplasmic domain PMID:12958365 Association with betaarr2 led to internalization of both receptors and down-regulation of TGF-beta signaling |
| GO:0005515 protein binding | IPI PMID:20856203 Critical role of endoglin in tumor cell plasticity of Ewing ... | MODIFY | Summary: IPI with a TGF-beta ligand (TGFB1/TGFB2) from PMID:20856203. Reason: Generic protein binding is uninformative. Betaglycan binds TGF-beta isoforms with high affinity (this is the ligand interaction underlying its receptor activity), so the informative term is transforming growth factor beta binding, already accepted for TGFBR3. Proposed replacements: transforming growth factor beta binding Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:23826237 identify a novel major TGF-Ξ²-binding site in TGFR-3 |
| GO:0005515 protein binding | IPI PMID:35922511 A physical wiring diagram for the human immune system. | REMOVE | Summary: IPI with FGFR4 from a large-scale immune-system interactome screen. Reason: Bare protein binding from a high-throughput screen is uninformative and there is no follow-up indicating a specific FGFR4-related function for TGFBR3. Removal under the protein-binding policy does not imply the interaction is false. |
| GO:0005539 glycosaminoglycan binding | IBA GO_REF:0000033 | MARK AS OVER ANNOTATED | Summary: Glycosaminoglycan binding (IBA). Reason: Betaglycan is a proteoglycan: its ectodomain is covalently substituted with heparan sulfate and chondroitin sulfate chains. The cited cloning paper only identifies GAG attachment sites. Carrying covalent GAG chains is not the molecular function of binding a glycosaminoglycan; no evidence was found that the core protein binds free GAGs non-covalently as a function. The PAINT node propagated this from rodent annotations, but the underlying observation appears to be GAG substitution rather than binding. Propagation Review Root cause: TERM SCOPING PROBLEM Failure modes: ROLE CONFLATION Sources checked: PANTHER:PTN002678643 UNRESOLVED Target is inside the clade; the node's GAG binding IBD (seeded by rodent annotations) appears to conflate covalent GAG substitution of the proteoglycan with non-covalent GAG binding. Supporting Evidence: PMID:1333192 Potential glycosaminoglycan attachment sites were found in the extracellular domain |
| GO:0005539 glycosaminoglycan binding | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: Glycosaminoglycan binding (ISS). Reason: Betaglycan is a proteoglycan: its ectodomain is covalently substituted with heparan sulfate and chondroitin sulfate chains. The cited cloning paper only identifies GAG attachment sites. Carrying covalent GAG chains is not the molecular function of binding a glycosaminoglycan; no evidence was found that the core protein binds free GAGs non-covalently as a function. The PAINT node propagated this from rodent annotations, but the underlying observation appears to be GAG substitution rather than binding. Supporting Evidence: PMID:1333192 Potential glycosaminoglycan attachment sites were found in the extracellular domain |
| GO:0005539 glycosaminoglycan binding | TAS PMID:1333192 Molecular cloning and characterization of the human and porc... | MARK AS OVER ANNOTATED | Summary: Glycosaminoglycan binding (TAS). Reason: Betaglycan is a proteoglycan: its ectodomain is covalently substituted with heparan sulfate and chondroitin sulfate chains. The cited cloning paper only identifies GAG attachment sites. Carrying covalent GAG chains is not the molecular function of binding a glycosaminoglycan; no evidence was found that the core protein binds free GAGs non-covalently as a function. The PAINT node propagated this from rodent annotations, but the underlying observation appears to be GAG substitution rather than binding. Supporting Evidence: PMID:1333192 Potential glycosaminoglycan attachment sites were found in the extracellular domain |
| GO:0005576 extracellular region | HDA PMID:16502470 Human colostrum: identification of minor proteins in the aqu... | KEEP AS NON CORE | Summary: Extracellular region: soluble betaglycan. Reason: The ectodomain of TGFBR3 is shed by membrane-type MMPs, producing a soluble form found in serum, milk/colostrum and extracellular matrix that sequesters TGF-beta and antagonizes signaling. The extracellular localization is real but secondary to the cell-surface coreceptor role. Supporting Evidence: Reactome:R-HSA-9839367 MT1βMMP and MT3βMMP are responsible for the ectodomain shedding of TGFBR3 Reactome:R-HSA-9839368 Soluble fragments of TGFBR3(1-783) genearted by MMPs maintain their TGFB1/TGFB2 binding ability file:human/TGFBR3/TGFBR3-uniprot.txt as a membrane-bound form and as soluble form in serum and in the |
| GO:0005576 extracellular region | IEA GO_REF:0000120 | KEEP AS NON CORE | Summary: Extracellular region: soluble betaglycan. Reason: The ectodomain of TGFBR3 is shed by membrane-type MMPs, producing a soluble form found in serum, milk/colostrum and extracellular matrix that sequesters TGF-beta and antagonizes signaling. The extracellular localization is real but secondary to the cell-surface coreceptor role. Supporting Evidence: Reactome:R-HSA-9839367 MT1βMMP and MT3βMMP are responsible for the ectodomain shedding of TGFBR3 Reactome:R-HSA-9839368 Soluble fragments of TGFBR3(1-783) genearted by MMPs maintain their TGFB1/TGFB2 binding ability file:human/TGFBR3/TGFBR3-uniprot.txt as a membrane-bound form and as soluble form in serum and in the |
| GO:0005576 extracellular region | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Extracellular region: soluble betaglycan. Reason: The ectodomain of TGFBR3 is shed by membrane-type MMPs, producing a soluble form found in serum, milk/colostrum and extracellular matrix that sequesters TGF-beta and antagonizes signaling. The extracellular localization is real but secondary to the cell-surface coreceptor role. Supporting Evidence: Reactome:R-HSA-9839367 MT1βMMP and MT3βMMP are responsible for the ectodomain shedding of TGFBR3 Reactome:R-HSA-9839368 Soluble fragments of TGFBR3(1-783) genearted by MMPs maintain their TGFB1/TGFB2 binding ability file:human/TGFBR3/TGFBR3-uniprot.txt as a membrane-bound form and as soluble form in serum and in the |
| GO:0005576 extracellular region | TAS PMID:18184661 Bone morphogenetic proteins signal through the transforming ... | KEEP AS NON CORE | Summary: Extracellular region: soluble betaglycan. Reason: The ectodomain of TGFBR3 is shed by membrane-type MMPs, producing a soluble form found in serum, milk/colostrum and extracellular matrix that sequesters TGF-beta and antagonizes signaling. The extracellular localization is real but secondary to the cell-surface coreceptor role. Supporting Evidence: Reactome:R-HSA-9839367 MT1βMMP and MT3βMMP are responsible for the ectodomain shedding of TGFBR3 Reactome:R-HSA-9839368 Soluble fragments of TGFBR3(1-783) genearted by MMPs maintain their TGFB1/TGFB2 binding ability file:human/TGFBR3/TGFBR3-uniprot.txt as a membrane-bound form and as soluble form in serum and in the |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9839367 | KEEP AS NON CORE | Summary: Extracellular region: soluble betaglycan. Reason: The ectodomain of TGFBR3 is shed by membrane-type MMPs, producing a soluble form found in serum, milk/colostrum and extracellular matrix that sequesters TGF-beta and antagonizes signaling. The extracellular localization is real but secondary to the cell-surface coreceptor role. Supporting Evidence: Reactome:R-HSA-9839367 MT1βMMP and MT3βMMP are responsible for the ectodomain shedding of TGFBR3 Reactome:R-HSA-9839368 Soluble fragments of TGFBR3(1-783) genearted by MMPs maintain their TGFB1/TGFB2 binding ability file:human/TGFBR3/TGFBR3-uniprot.txt as a membrane-bound form and as soluble form in serum and in the |
| GO:0005576 extracellular region | TAS Reactome:R-HSA-9839368 | KEEP AS NON CORE | Summary: Extracellular region: soluble betaglycan. Reason: The ectodomain of TGFBR3 is shed by membrane-type MMPs, producing a soluble form found in serum, milk/colostrum and extracellular matrix that sequesters TGF-beta and antagonizes signaling. The extracellular localization is real but secondary to the cell-surface coreceptor role. Supporting Evidence: Reactome:R-HSA-9839367 MT1βMMP and MT3βMMP are responsible for the ectodomain shedding of TGFBR3 Reactome:R-HSA-9839368 Soluble fragments of TGFBR3(1-783) genearted by MMPs maintain their TGFB1/TGFB2 binding ability file:human/TGFBR3/TGFBR3-uniprot.txt as a membrane-bound form and as soluble form in serum and in the |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9839388 | REMOVE | Summary: Reactome TAS to cytosol, from the TGFBR3 translation / plasma-membrane translocation reactions. Reason: TGFBR3 has an N-terminal signal peptide and a single type I transmembrane segment; it is synthesized into the secretory pathway and does not reside in the cytosol. The cytosol compartment is an artifact of how the Reactome reactions model translation and trafficking. Supporting Evidence: file:human/TGFBR3/TGFBR3-uniprot.txt type I membrane protein {ECO:0000255} Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005829 cytosol | TAS Reactome:R-HSA-9839396 | REMOVE | Summary: Reactome TAS to cytosol, from the TGFBR3 translation / plasma-membrane translocation reactions. Reason: TGFBR3 has an N-terminal signal peptide and a single type I transmembrane segment; it is synthesized into the secretory pathway and does not reside in the cytosol. The cytosol compartment is an artifact of how the Reactome reactions model translation and trafficking. Supporting Evidence: file:human/TGFBR3/TGFBR3-uniprot.txt type I membrane protein {ECO:0000255} Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | EXP PMID:19416857 The type III TGF-beta receptor regulates epithelial and canc... | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | EXP PMID:19726563 The transforming growth factor-beta type III receptor mediat... | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | EXP PMID:22562249 TΞ²RIII/Ξ²-arrestin2 regulates integrin Ξ±5Ξ²1 trafficking, func... | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | IBA GO_REF:0000033 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | IEA GO_REF:0000044 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | ISS GO_REF:0000024 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839358 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839363 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839367 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839377 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839378 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839379 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839381 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839384 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839388 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839390 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839401 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839402 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0005886 plasma membrane | TAS Reactome:R-HSA-9839405 | ACCEPT | Summary: Plasma membrane localization. Reason: TGFBR3 is a single-pass type I cell surface proteoglycan; plasma membrane localization is directly shown in human cells and is where it acts as a coreceptor. The IBA (PTN008553354) is consistent. Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles Reactome:R-HSA-9839388 TGFBR3 is a transmembrane glycoprotein which localises to the plasma where it participates in ligand binding and induces signaling |
| GO:0006955 immune response | IMP PMID:16886151 Association of polymorphisms of IGF1R and genes in the trans... | REMOVE | Summary: IMP from a candidate-gene SNP association study of bacteremia in sickle cell anemia. Reason: A genetic association between TGFBR3 polymorphisms and bacteremia risk does not show that TGFBR3 participates in an immune response; the abstract only suggests a possible role. IMP is not an appropriate reading of an association study. Supporting Evidence: PMID:16886151 We found significant associations with SNPs in IGF1R and genes of the TGF-beta /BMP pathway (BMP6, TGFBR3, BMPR1A, SMAD6 and SMAD3) |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: TGF-beta receptor signaling pathway. Reason: TGFBR3 binds TGF-beta (especially TGF-beta2), presents it to TGFBR2 and promotes formation of the TGFBR2/TGFBR1 signaling complex; increased TGFBR3 enhances TGF-beta responses and its loss reduces TGF-beta2 sensitivity. This is a core process for the gene, consistent with the IBA from PTN002678643. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex PMID:11546783 increased expression of the type III receptor is sufficient to enhance TGF-beta signaling PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:12958365 Beta-arrestin 2 mediates endocytosis of type III TGF-beta re... | ACCEPT | Summary: TGF-beta receptor signaling pathway. Reason: TGFBR3 binds TGF-beta (especially TGF-beta2), presents it to TGFBR2 and promotes formation of the TGFBR2/TGFBR1 signaling complex; increased TGFBR3 enhances TGF-beta responses and its loss reduces TGF-beta2 sensitivity. This is a core process for the gene, consistent with the IBA from PTN002678643. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex PMID:11546783 increased expression of the type III receptor is sufficient to enhance TGF-beta signaling PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IDA PMID:29130787 miR-19a and miR-424 target TGFBR3 to promote epithelial-to-m... | ACCEPT | Summary: TGF-beta receptor signaling pathway. Reason: TGFBR3 binds TGF-beta (especially TGF-beta2), presents it to TGFBR2 and promotes formation of the TGFBR2/TGFBR1 signaling complex; increased TGFBR3 enhances TGF-beta responses and its loss reduces TGF-beta2 sensitivity. This is a core process for the gene, consistent with the IBA from PTN002678643. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex PMID:11546783 increased expression of the type III receptor is sufficient to enhance TGF-beta signaling PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000117 | ACCEPT | Summary: TGF-beta receptor signaling pathway. Reason: TGFBR3 binds TGF-beta (especially TGF-beta2), presents it to TGFBR2 and promotes formation of the TGFBR2/TGFBR1 signaling complex; increased TGFBR3 enhances TGF-beta responses and its loss reduces TGF-beta2 sensitivity. This is a core process for the gene, consistent with the IBA from PTN002678643. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex PMID:11546783 increased expression of the type III receptor is sufficient to enhance TGF-beta signaling PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IMP PMID:11157754 Type III TGF-beta receptor-independent signalling of TGF-bet... | ACCEPT | Summary: TGF-beta receptor signaling pathway. Reason: TGFBR3 binds TGF-beta (especially TGF-beta2), presents it to TGFBR2 and promotes formation of the TGFBR2/TGFBR1 signaling complex; increased TGFBR3 enhances TGF-beta responses and its loss reduces TGF-beta2 sensitivity. This is a core process for the gene, consistent with the IBA from PTN002678643. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex PMID:11546783 increased expression of the type III receptor is sufficient to enhance TGF-beta signaling PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0007179 transforming growth factor beta receptor signaling pathway | IMP PMID:30467960 MicroRNA let-7a regulates angiogenesis by targeting TGFBR3 m... | ACCEPT | Summary: TGF-beta receptor signaling pathway. Reason: TGFBR3 binds TGF-beta (especially TGF-beta2), presents it to TGFBR2 and promotes formation of the TGFBR2/TGFBR1 signaling complex; increased TGFBR3 enhances TGF-beta responses and its loss reduces TGF-beta2 sensitivity. This is a core process for the gene, consistent with the IBA from PTN002678643. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex PMID:11546783 increased expression of the type III receptor is sufficient to enhance TGF-beta signaling PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0007179 transforming growth factor beta receptor signaling pathway | ISS GO_REF:0000024 | ACCEPT | Summary: TGF-beta receptor signaling pathway. Reason: TGFBR3 binds TGF-beta (especially TGF-beta2), presents it to TGFBR2 and promotes formation of the TGFBR2/TGFBR1 signaling complex; increased TGFBR3 enhances TGF-beta responses and its loss reduces TGF-beta2 sensitivity. This is a core process for the gene, consistent with the IBA from PTN002678643. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex PMID:11546783 increased expression of the type III receptor is sufficient to enhance TGF-beta signaling PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0007181 transforming growth factor beta receptor complex assembly | IEA GO_REF:0000107 | ACCEPT | Summary: TGF-beta receptor complex assembly (IEA from rat). Reason: Via its cytoplasmic domain, TGFBR3 selectively binds autophosphorylated TGFBR2 and promotes complex formation between TGFBR2 and TGFBR1 before dissociating, i.e. it does part of the work of assembling the active receptor complex. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex |
| GO:0008201 heparin binding | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Heparin binding transferred from rat betaglycan. Reason: As for glycosaminoglycan binding, the relevant property of betaglycan is covalent substitution with heparan sulfate chains (which bind FGF2), not binding of heparin by the core protein. No human evidence supports heparin binding as a function. Supporting Evidence: PMID:1333192 Potential glycosaminoglycan attachment sites were found in the extracellular domain |
| GO:0008201 heparin binding | ISS PMID:1333192 Molecular cloning and characterization of the human and porc... | MARK AS OVER ANNOTATED | Summary: Heparin binding transferred from rat betaglycan. Reason: As for glycosaminoglycan binding, the relevant property of betaglycan is covalent substitution with heparan sulfate chains (which bind FGF2), not binding of heparin by the core protein. No human evidence supports heparin binding as a function. Supporting Evidence: PMID:1333192 Potential glycosaminoglycan attachment sites were found in the extracellular domain |
| GO:0009897 external side of plasma membrane | IDA PMID:12958365 Beta-arrestin 2 mediates endocytosis of type III TGF-beta re... | ACCEPT | Summary: External side of plasma membrane (IDA). Reason: The large ligand-binding ectodomain (residues 21-787) is extracellular and binds TGF-beta at the cell surface. Supporting Evidence: file:human/TGFBR3/TGFBR3-uniprot.txt type I membrane protein {ECO:0000255} PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized |
| GO:0009986 cell surface | ISS GO_REF:0000024 | ACCEPT | Summary: Cell surface (ISS from mouse). Reason: TGFBR3 is an abundant cell surface proteoglycan; supported directly in human cells. Supporting Evidence: PMID:18184661 an abundant cell surface proteoglycan that has been well characterized as a TGF-beta and inhibin receptor PMID:22562249 In MCF10A cells endogenous TΞ²RIII and integrin Ξ±5 co-localized both at the plasma membrane and in intracellular vesicles |
| GO:0010628 positive regulation of gene expression | IMP PMID:30467960 MicroRNA let-7a regulates angiogenesis by targeting TGFBR3 m... | MARK AS OVER ANNOTATED | Summary: IMP from siRNA knockdown of TGFBR3 in HUVECs reducing VEGFC and MMP9 mRNA. Reason: Reduced expression of two downstream genes after partial knockdown is an indirect consequence of altered TGF-beta superfamily signaling; TGFBR3 does not itself regulate gene expression. Positive regulation of gene expression is an uninformative over-interpretation. Supporting Evidence: PMID:30467960 only VEGFC and MMP9 mRNA levels significantly decreased, whereas mRNA levels of ID1 and PROX1 remained unchanged |
| GO:0015026 coreceptor activity | IDA PMID:10746731 Betaglycan binds inhibin and can mediate functional antagoni... | ACCEPT | Summary: Coreceptor activity (IDA, Lewis et al. 2000). Reason: Betaglycan binds inhibin and, together with ActRII, forms the high-affinity inhibin receptor complex, conferring inhibin responsiveness. It acts likewise for TGF-beta2 and BMPs. This is the core molecular function. Supporting Evidence: PMID:10746731 betaglycan, can function as an inhibin co-receptor with ActRII PMID:10746731 Betaglycan binds inhibin with high affinity and enhances binding in cells co-expressing ActRII and betaglycan PMID:10746731 betaglycan confers inhibin sensitivity to cell lines that otherwise respond poorly to this hormone PMID:30364975 TGFBR3 (betaglycan) functions as an inhibin A, but not an inhibin B, coreceptor in gonadotrope cells in vivo |
| GO:0016020 membrane | IEA GO_REF:0000107 | MODIFY | Summary: Membrane (IEA). Reason: Correct but general; TGFBR3 is a plasma membrane protein, a term already accepted for it. Proposed replacements: plasma membrane Supporting Evidence: PMID:19726563 TΞ²RIII expression alone in HEK293 cells was predominantly plasma membrane-localized |
| GO:0016323 basolateral plasma membrane | TAS Reactome:R-HSA-9839367 | MARK AS OVER ANNOTATED | Summary: Reactome TAS to basolateral plasma membrane, from MMP-shedding and gamma-secretase reactions. Reason: The Reactome summaries describe ectodomain shedding and intramembrane cleavage but give no evidence for polarized basolateral localization of TGFBR3. The plasma-membrane localization is supported; the basolateral restriction is not. Supporting Evidence: Reactome:R-HSA-9839367 MT1βMMP and MT3βMMP are responsible for the ectodomain shedding of TGFBR3 |
| GO:0016323 basolateral plasma membrane | TAS Reactome:R-HSA-9839376 | MARK AS OVER ANNOTATED | Summary: Reactome TAS to basolateral plasma membrane, from MMP-shedding and gamma-secretase reactions. Reason: The Reactome summaries describe ectodomain shedding and intramembrane cleavage but give no evidence for polarized basolateral localization of TGFBR3. The plasma-membrane localization is supported; the basolateral restriction is not. Supporting Evidence: Reactome:R-HSA-9839367 MT1βMMP and MT3βMMP are responsible for the ectodomain shedding of TGFBR3 |
| GO:0016477 cell migration | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: Cell migration (IBA; donor chicken Q90998). Reason: TGFBR3 contributes to migration/invasion of cardiac mesenchymal and epicardial cells (via GIPC binding and the Par6/Smurf1/RhoA pathway), and in epithelial cells it restrains random migration via beta-arrestin2/Cdc42. Its role is regulatory and context-specific rather than a core migratory machinery role, so non-core. Supporting Evidence: PMID:21871877 Expression of TGFΞ²R3 missing the 3 C-terminal amino acids that are required to interact with the scaffolding protein GIPC1 did not rescue any of the deficits PMID:22237159 Tgfbr3(-/-) cells show decreased invasion in response to BMP2 and overexpression of TGFΞ²R3 in Tgfbr3(-/-) cells rescued invasion PMID:19416857 TbetaRIII through its interaction with the scaffolding protein beta-arrestin2, activates Cdc42 and inhibits migration |
| GO:0016477 cell migration | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Cell migration (ISS; donor chicken Q90998). Reason: TGFBR3 contributes to migration/invasion of cardiac mesenchymal and epicardial cells (via GIPC binding and the Par6/Smurf1/RhoA pathway), and in epithelial cells it restrains random migration via beta-arrestin2/Cdc42. Its role is regulatory and context-specific rather than a core migratory machinery role, so non-core. Supporting Evidence: PMID:21871877 Expression of TGFΞ²R3 missing the 3 C-terminal amino acids that are required to interact with the scaffolding protein GIPC1 did not rescue any of the deficits PMID:22237159 Tgfbr3(-/-) cells show decreased invasion in response to BMP2 and overexpression of TGFΞ²R3 in Tgfbr3(-/-) cells rescued invasion PMID:19416857 TbetaRIII through its interaction with the scaffolding protein beta-arrestin2, activates Cdc42 and inhibits migration |
| GO:0017015 regulation of transforming growth factor beta receptor signaling pathway | IBA GO_REF:0000033 | ACCEPT | Summary: Regulation of TGF-beta receptor signaling pathway (IBA from PTN002678643). Reason: TGFBR3 both enhances (ligand presentation, GIPC-stabilized surface expression) and attenuates (beta-arrestin2 endocytosis, soluble ectodomain sequestration) TGF-beta signaling. The neutral regulation term at the PAINT node is a good summary. Supporting Evidence: PMID:11546783 increased expression of the type III receptor is sufficient to enhance TGF-beta signaling PMID:12958365 Association with betaarr2 led to internalization of both receptors and down-regulation of TGF-beta signaling |
| GO:0017134 fibroblast growth factor binding | IEA GO_REF:0000107 | KEEP AS NON CORE | Summary: FGF binding (IEA from rat). Reason: Betaglycan binds FGF2 through its heparan sulfate chains and TGFBR3 loss reduces FGF2 responsiveness of epicardial cells; Reactome also models FGF2:TGFBR3 binding. Real but peripheral to the TGF-beta superfamily coreceptor role. Supporting Evidence: PMID:21871877 Unexpectedly, loss of TGFΞ²R3 also decreases responsiveness to two other important regulators of epicardial cell behavior, FGF2 and HMW-HA |
| GO:0030165 PDZ domain binding | ISS GO_REF:0000024 | ACCEPT | Summary: PDZ domain binding (ISS from mouse). Reason: Directly supported in human: the C-terminal class I PDZ motif of TGFBR3 binds the PDZ domain of GIPC1, regulating its surface level and signaling; the same interaction is required for TGFBR3 function in mouse epicardial cells. Supporting Evidence: PMID:11546783 GIPC binds a Class I PDZ binding motif in the cytoplasmic domain of the type III receptor PMID:21871877 Expression of TGFΞ²R3 missing the 3 C-terminal amino acids that are required to interact with the scaffolding protein GIPC1 did not rescue any of the deficits |
| GO:0030336 negative regulation of cell migration | IDA PMID:29130787 miR-19a and miR-424 target TGFBR3 to promote epithelial-to-m... | ACCEPT | Summary: Negative regulation of cell migration (IDA, overexpression in tongue carcinoma cells). Reason: Well supported in human epithelial and cancer cells: TGFBR3, through beta-arrestin2, activates Cdc42 and inhibits random migration, a TGF-beta-independent activity. A genuine, TGF-beta-independent function of the beta-arrestin2-binding cytoplasmic tail. Supporting Evidence: PMID:29130787 transfection of a TGFBR3-containing plasmid dramatically inhibited epithelial-to-mesenchymal transition (EMT) and migration in CAL-27 cells PMID:19416857 TbetaRIII through its interaction with the scaffolding protein beta-arrestin2, activates Cdc42 and inhibits migration PMID:19416857 reducing directional persistence to inhibit random migration of both cancer and normal epithelial cells |
| GO:0030509 BMP signaling pathway | IDA PMID:18184661 Bone morphogenetic proteins signal through the transforming ... | ACCEPT | Summary: BMP signaling pathway (IDA). Reason: TGFBR3 binds BMP2/4/7 and GDF5, enhances ligand binding to BMP type I receptors and is required for full BMP-induced Smad1 phosphorylation; it differentially regulates ALK3 and ALK6 signaling. Supporting Evidence: PMID:18184661 TbetaRIII directly and specifically binds to multiple members of the BMP subfamily, including BMP-2, BMP-4, BMP-7, and GDF-5 PMID:18184661 short hairpin RNA-mediated silencing of endogenous TbetaRIII attenuates BMP-mediated Smad1 phosphorylation PMID:19726563 TbetaRIII associated with ALK3 primarily through their extracellular domains |
| GO:0030511 positive regulation of transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Positive regulation of TGF-beta receptor signaling (IEA from rat). Reason: Increased TGFBR3 expression is sufficient to enhance TGF-beta signaling, and loss reduces TGF-beta2 responses. Supporting Evidence: PMID:11546783 increased expression of the type III receptor is sufficient to enhance TGF-beta signaling PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0030512 negative regulation of transforming growth factor beta receptor signaling pathway | IEA GO_REF:0000107 | ACCEPT | Summary: Negative regulation of TGF-beta receptor signaling (IEA from rat). Reason: beta-arrestin2-mediated internalization of TGFBR3 with TGFBR2 down-regulates TGF-beta signaling, and the shed soluble ectodomain sequesters TGF-beta. The bidirectional regulation is context-dependent rather than contradictory. Supporting Evidence: PMID:12958365 Association with betaarr2 led to internalization of both receptors and down-regulation of TGF-beta signaling Reactome:R-HSA-9839368 Soluble fragments of TGFBR3(1-783) genearted by MMPs maintain their TGFB1/TGFB2 binding ability |
| GO:0031100 animal organ regeneration | IEA GO_REF:0000107 | MARK AS OVER ANNOTATED | Summary: Animal organ regeneration (IEA from rat). Reason: Likely based on expression changes of rat betaglycan during regeneration; there is no evidence that TGFBR3 performs a step of organ regeneration in human. |
| GO:0032354 response to follicle-stimulating hormone | IDA PMID:14557487 Expression of betaglycan, an inhibin coreceptor, in normal h... | KEEP AS NON CORE | Summary: Response to follicle-stimulating hormone (IDA): betaglycan mRNA rises in FSH-treated human granulosa-luteal cells. Reason: This is an expression response; TGFBR3 is a regulated target of gonadotropin signaling in the ovary, relevant to its inhibin coreceptor role there, but not a function of the protein. Supporting Evidence: PMID:14557487 FSH and LH treatment increased dose-dependently the accumulation of betaglycan mRNA |
| GO:0034673 inhibin-betaglycan-ActRII complex | IDA PMID:10746731 Betaglycan binds inhibin and can mediate functional antagoni... | ACCEPT | Summary: Inhibin-betaglycan-ActRII complex (IDA, Lewis et al. 2000). Reason: Inhibin crosslinks into complexes with betaglycan and ActRII both in transfected and endogenous systems; this complex is the high-affinity inhibin receptor. Supporting Evidence: PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII PMID:10746731 betaglycan, can function as an inhibin co-receptor with ActRII |
| GO:0034695 response to prostaglandin E | IDA PMID:14557487 Expression of betaglycan, an inhibin coreceptor, in normal h... | KEEP AS NON CORE | Summary: Response to prostaglandin E (IDA): PGE2 increases betaglycan mRNA in granulosa-luteal cells. Reason: Expression response, retained as non-core. Supporting Evidence: PMID:14557487 Treatment with prostaglandin E(2) and with its receptor EP2 subtype agonist butaprost increased betaglycan mRNA accumulation |
| GO:0034699 response to luteinizing hormone | IDA PMID:14557487 Expression of betaglycan, an inhibin coreceptor, in normal h... | KEEP AS NON CORE | Summary: Response to luteinizing hormone (IDA): LH increases betaglycan mRNA in granulosa-luteal cells. Reason: Expression response, retained as non-core. Supporting Evidence: PMID:14557487 FSH and LH treatment increased dose-dependently the accumulation of betaglycan mRNA |
| GO:0035556 intracellular signal transduction | IMP PMID:14557487 Expression of betaglycan, an inhibin coreceptor, in normal h... | MARK AS OVER ANNOTATED | Summary: Intracellular signal transduction (IMP) from Liu et al. 2003. Reason: The abstract shows that betaglycan mRNA is induced by gonadotropins and PGE2 probably via protein kinase A; TGFBR3 is the transcriptional readout of the PKA pathway, not a participant in intracellular signal transduction. Without the full text this is treated as over-annotation rather than removed. Supporting Evidence: PMID:14557487 probably via the protein kinase A pathway |
| GO:0036122 BMP binding | IPI PMID:18184661 Bone morphogenetic proteins signal through the transforming ... | ACCEPT | Summary: BMP binding (IPI with BMP2/BMP4 or BMP7). Reason: Betaglycan directly and specifically binds BMP-2, BMP-4, BMP-7 and GDF-5 through the same ligand-binding domains used for TGF-beta. Supporting Evidence: PMID:18184661 TbetaRIII directly and specifically binds to multiple members of the BMP subfamily, including BMP-2, BMP-4, BMP-7, and GDF-5 |
| GO:0036122 BMP binding | IPI PMID:18184661 Bone morphogenetic proteins signal through the transforming ... | ACCEPT | Summary: BMP binding (IPI with BMP2/BMP4 or BMP7). Reason: Betaglycan directly and specifically binds BMP-2, BMP-4, BMP-7 and GDF-5 through the same ligand-binding domains used for TGF-beta. Supporting Evidence: PMID:18184661 TbetaRIII directly and specifically binds to multiple members of the BMP subfamily, including BMP-2, BMP-4, BMP-7, and GDF-5 |
| GO:0043124 negative regulation of canonical NF-kappaB signal transduction | IDA PMID:29130787 miR-19a and miR-424 target TGFBR3 to promote epithelial-to-m... | KEEP AS NON CORE | Summary: Negative regulation of canonical NF-kappaB signal transduction (IDA, tongue carcinoma cells). Reason: Independently shown in breast epithelial cells: TGFBR3 via beta-arrestin2 reduces NF-kappaB transcriptional activation and IkappaBalpha degradation, and the T841A mutant that cannot bind beta-arrestin2 is inactive. Genuine but secondary. Supporting Evidence: PMID:29130787 overexpression of TGFBR3 decreased p-p65 expression and increased IΞΊBΞ± expression; these effects were subsequently abolished following knockdown of Ξ²-arrestin 2 PMID:19325136 TbetaRIII, through its interaction with beta-arrestin2, negatively regulates NFkappaB signaling in MCF10A breast epithelial and MDA-MB-231 breast cancer cells |
| GO:0043235 signaling receptor complex | IDA PMID:11157754 Type III TGF-beta receptor-independent signalling of TGF-bet... | ACCEPT | Summary: Signaling receptor complex. Reason: TGFBR3 forms ligand-dependent complexes with TGFBR2 (and transiently TGFBR1), with ActRII (inhibin), and with BMP type I receptors. The general term is appropriate since membership spans several receptor complexes. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII |
| GO:0043235 signaling receptor complex | IEA GO_REF:0000107 | ACCEPT | Summary: Signaling receptor complex. Reason: TGFBR3 forms ligand-dependent complexes with TGFBR2 (and transiently TGFBR1), with ActRII (inhibin), and with BMP type I receptors. The general term is appropriate since membership spans several receptor complexes. Supporting Evidence: PMID:11323414 thus promoting the preferential formation of a complex between the autophosphorylated type II receptor and the type I receptor and then dissociating from this active signaling complex PMID:10746731 Inhibin also forms crosslinked complexes with both recombinant and endogenously expressed betaglycan and ActRII |
| GO:0046328 regulation of JNK cascade | ISS NOT GO_REF:0000024 | UNDECIDED | Summary: NOT regulation of JNK cascade, ISS transfer of a negative mouse annotation. Reason: The source mouse experiment could not be identified among the cached papers, so the negative result cannot be evaluated. No human data either way. |
| GO:0046332 SMAD binding | IMP PMID:11157754 Type III TGF-beta receptor-independent signalling of TGF-bet... | UNDECIDED | Summary: SMAD binding (IMP) from Rotzer et al. 2001. Reason: An IMP is an unusual basis for a binding term, and the cached abstract concerns TbetaRII-B signaling independently of TbetaRIII. No direct SMAD binding by betaglycan, which has a short cytoplasmic tail without known SMAD-binding motifs, was found. Without the full text this cannot be adjudicated. Supporting Evidence: PMID:11157754 which mediates signalling via the Smad pathway in the absence of any TGF-beta type III receptor (TbetaRIII) |
| GO:0048185 activin binding | IEA GO_REF:0000107 | MODIFY | Summary: Activin binding (IEA from rat betaglycan). Reason: Betaglycan is a high-affinity inhibin (alpha-beta) receptor and mediates inhibin antagonism of activin; it is not an activin receptor. The rat-derived activin binding term most likely reflects inhibin binding. The specific supported term is inhibin complex binding. Proposed replacements: inhibin complex binding Supporting Evidence: PMID:10746731 Betaglycan binds inhibin with high affinity and enhances binding in cells co-expressing ActRII and betaglycan PMID:10746731 betaglycan confers inhibin sensitivity to cell lines that otherwise respond poorly to this hormone |
| GO:0048513 animal organ development | IEA GO_REF:0000117 | TOO GENERAL | Summary: Animal organ development (ARBA). Reason: True but uninformative; the supported developmental role is covered by heart morphogenesis (kept as non-core) and coronary vasculogenesis. |
| GO:0050431 transforming growth factor beta binding | IBA GO_REF:0000033 | ACCEPT | Summary: Transforming growth factor beta binding. Reason: Betaglycan binds all three TGF-beta isoforms with high affinity, through the endoglin-like N-terminal region and the ZP-C region; the soluble ectodomain retains this binding. Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:23826237 identify a novel major TGF-Ξ²-binding site in TGFR-3 PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor |
| GO:0050431 transforming growth factor beta binding | IDA PMID:11157754 Type III TGF-beta receptor-independent signalling of TGF-bet... | ACCEPT | Summary: Transforming growth factor beta binding. Reason: Betaglycan binds all three TGF-beta isoforms with high affinity, through the endoglin-like N-terminal region and the ZP-C region; the soluble ectodomain retains this binding. Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:23826237 identify a novel major TGF-Ξ²-binding site in TGFR-3 PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor |
| GO:0050431 transforming growth factor beta binding | IDA PMID:12958365 Beta-arrestin 2 mediates endocytosis of type III TGF-beta re... | ACCEPT | Summary: Transforming growth factor beta binding. Reason: Betaglycan binds all three TGF-beta isoforms with high affinity, through the endoglin-like N-terminal region and the ZP-C region; the soluble ectodomain retains this binding. Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:23826237 identify a novel major TGF-Ξ²-binding site in TGFR-3 PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor |
| GO:0050431 transforming growth factor beta binding | IEA GO_REF:0000120 | ACCEPT | Summary: Transforming growth factor beta binding. Reason: Betaglycan binds all three TGF-beta isoforms with high affinity, through the endoglin-like N-terminal region and the ZP-C region; the soluble ectodomain retains this binding. Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:23826237 identify a novel major TGF-Ξ²-binding site in TGFR-3 PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor |
| GO:0050431 transforming growth factor beta binding | IPI PMID:11157754 Type III TGF-beta receptor-independent signalling of TGF-bet... | ACCEPT | Summary: Transforming growth factor beta binding. Reason: Betaglycan binds all three TGF-beta isoforms with high affinity, through the endoglin-like N-terminal region and the ZP-C region; the soluble ectodomain retains this binding. Supporting Evidence: PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:23826237 identify a novel major TGF-Ξ²-binding site in TGFR-3 PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor |
| GO:0050680 negative regulation of epithelial cell proliferation | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Negative regulation of epithelial cell proliferation (ISS from mouse). Reason: TGFBR3 enhances TGF-beta-mediated growth inhibition in human cells and is needed for TGF-beta2 growth inhibition of fibroblasts. This is a consequence of its coreceptor role rather than a separate function. Supporting Evidence: PMID:11546783 Increased expression of the type III receptor mediated by GIPC enhanced cellular responsiveness to TGF-beta both in terms of inhibition of proliferation PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0055010 ventricular cardiac muscle tissue morphogenesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of ventricular cardiac muscle tissue morphogenesis, derived from Tgfbr3-null embryo cardiac phenotypes. Reason: Tgfbr3-null embryos have thin compact myocardium, reduced proliferation and septal/trabecular abnormalities, but these are secondary consequences of failed epicardial invasion and coronary vessel formation in a global knockout. TGFBR3 acts in epicardial and endocardial cells as a TGF-beta/BMP coreceptor; it is not shown to perform a step of myocardial or septal morphogenesis itself. Fine-grained organismal phenotypes are not transferred as process participation. Supporting Evidence: PMID:17704211 At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0060038 cardiac muscle cell proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of cardiac muscle cell proliferation, derived from Tgfbr3-null embryo cardiac phenotypes. Reason: Tgfbr3-null embryos have thin compact myocardium, reduced proliferation and septal/trabecular abnormalities, but these are secondary consequences of failed epicardial invasion and coronary vessel formation in a global knockout. TGFBR3 acts in epicardial and endocardial cells as a TGF-beta/BMP coreceptor; it is not shown to perform a step of myocardial or septal morphogenesis itself. Fine-grained organismal phenotypes are not transferred as process participation. Supporting Evidence: PMID:17704211 At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0060045 positive regulation of cardiac muscle cell proliferation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of positive regulation of cardiac muscle cell proliferation, derived from Tgfbr3-null embryo cardiac phenotypes. Reason: Tgfbr3-null embryos have thin compact myocardium, reduced proliferation and septal/trabecular abnormalities, but these are secondary consequences of failed epicardial invasion and coronary vessel formation in a global knockout. TGFBR3 acts in epicardial and endocardial cells as a TGF-beta/BMP coreceptor; it is not shown to perform a step of myocardial or septal morphogenesis itself. Fine-grained organismal phenotypes are not transferred as process participation. Supporting Evidence: PMID:17704211 At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0060216 definitive hemopoiesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of definitive hemopoiesis, from mouse genetic phenotypes. Reason: This is a downstream developmental phenotype of mouse Tgfbr3 loss. No evidence in human or mouse that betaglycan executes a step of this process beyond acting as a broadly expressed TGF-beta superfamily coreceptor; no human data. Retained only as an over-annotation. Supporting Evidence: PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0060317 cardiac epithelial to mesenchymal transition | IDA PMID:18184661 Bone morphogenetic proteins signal through the transforming ... | KEEP AS NON CORE | Summary: Cardiac epithelial to mesenchymal transition (IDA). Reason: BMP-2 stimulates TbetaRIII-mediated endocardial EMT in the cardiac cushion model; consistent with TGFBR3-dependent epicardial EMT/invasion in mouse. Retained as non-core, consistent with the EMT rows. Supporting Evidence: PMID:18184661 BMP-2 specifically stimulates TbetaRIII-mediated epithelial to mesenchymal cell transformation PMID:22033038 the Par6/Smurf1/RhoA pathway is activated downstream of TGFΞ²R3 in epicardial cells |
| GO:0060318 definitive erythrocyte differentiation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of definitive erythrocyte differentiation, from mouse genetic phenotypes. Reason: This is a downstream developmental phenotype of mouse Tgfbr3 loss. No evidence in human or mouse that betaglycan executes a step of this process beyond acting as a broadly expressed TGF-beta superfamily coreceptor; no human data. Retained only as an over-annotation. Supporting Evidence: PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0060347 heart trabecula formation | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of heart trabecula formation, derived from Tgfbr3-null embryo cardiac phenotypes. Reason: Tgfbr3-null embryos have thin compact myocardium, reduced proliferation and septal/trabecular abnormalities, but these are secondary consequences of failed epicardial invasion and coronary vessel formation in a global knockout. TGFBR3 acts in epicardial and endocardial cells as a TGF-beta/BMP coreceptor; it is not shown to perform a step of myocardial or septal morphogenesis itself. Fine-grained organismal phenotypes are not transferred as process participation. Supporting Evidence: PMID:17704211 At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0060391 positive regulation of SMAD protein signal transduction | IDA PMID:18184661 Bone morphogenetic proteins signal through the transforming ... | ACCEPT | Summary: Positive regulation of SMAD protein signal transduction (IDA). Reason: TGFBR3 silencing attenuates BMP-induced Smad1 phosphorylation and TGFBR3 knockdown reduces Smad1 phosphorylation in atrial fibroblasts; loss also reduces TGF-beta2-induced Smad2 nuclear localization. Supporting Evidence: PMID:18184661 short hairpin RNA-mediated silencing of endogenous TbetaRIII attenuates BMP-mediated Smad1 phosphorylation PMID:30729664 Consistently, phosphorylated Smad1 (pβSmad1) was decreased, but pβSmad3 was increased in HAFs after transfection with miRβ23bβ3p, miRβ27bβ3p and TGFBR3 siRNA respectively PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0060391 positive regulation of SMAD protein signal transduction | IMP PMID:11157754 Type III TGF-beta receptor-independent signalling of TGF-bet... | ACCEPT | Summary: Positive regulation of SMAD protein signal transduction (IMP). Reason: TGFBR3 silencing attenuates BMP-induced Smad1 phosphorylation and TGFBR3 knockdown reduces Smad1 phosphorylation in atrial fibroblasts; loss also reduces TGF-beta2-induced Smad2 nuclear localization. Supporting Evidence: PMID:18184661 short hairpin RNA-mediated silencing of endogenous TbetaRIII attenuates BMP-mediated Smad1 phosphorylation PMID:30729664 Consistently, phosphorylated Smad1 (pβSmad1) was decreased, but pβSmad3 was increased in HAFs after transfection with miRβ23bβ3p, miRβ27bβ3p and TGFBR3 siRNA respectively PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0060391 positive regulation of SMAD protein signal transduction | IMP PMID:30729664 Novel role of the clustered miR-23b-3p and miR-27b-3p in enh... | ACCEPT | Summary: Positive regulation of SMAD protein signal transduction (IMP). Reason: TGFBR3 silencing attenuates BMP-induced Smad1 phosphorylation and TGFBR3 knockdown reduces Smad1 phosphorylation in atrial fibroblasts; loss also reduces TGF-beta2-induced Smad2 nuclear localization. Supporting Evidence: PMID:18184661 short hairpin RNA-mediated silencing of endogenous TbetaRIII attenuates BMP-mediated Smad1 phosphorylation PMID:30729664 Consistently, phosphorylated Smad1 (pβSmad1) was decreased, but pβSmad3 was increased in HAFs after transfection with miRβ23bβ3p, miRβ27bβ3p and TGFBR3 siRNA respectively PMID:12773577 TbetaRIII-null cells exhibited significantly reduced sensitivity to TGFbeta2 in terms of growth inhibition, reporter gene activation, and Smad2 nuclear localization |
| GO:0060392 negative regulation of SMAD protein signal transduction | IMP PMID:30729664 Novel role of the clustered miR-23b-3p and miR-27b-3p in enh... | KEEP AS NON CORE | Summary: Negative regulation of SMAD protein signal transduction (IMP, atrial fibroblasts). Reason: TGFBR3 knockdown increased Smad3 phosphorylation and nuclear accumulation in human atrial fibroblasts, consistent with the known attenuation of TGF-beta1/Smad3 signaling by TGFBR3 in some contexts. Coexists with positive regulation of Smad1 signaling in the same cells; context-dependent and secondary. Supporting Evidence: PMID:30729664 Consistently, phosphorylated Smad1 (pβSmad1) was decreased, but pβSmad3 was increased in HAFs after transfection with miRβ23bβ3p, miRβ27bβ3p and TGFBR3 siRNA respectively |
| GO:0060412 ventricular septum morphogenesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of ventricular septum morphogenesis, derived from Tgfbr3-null embryo cardiac phenotypes. Reason: Tgfbr3-null embryos have thin compact myocardium, reduced proliferation and septal/trabecular abnormalities, but these are secondary consequences of failed epicardial invasion and coronary vessel formation in a global knockout. TGFBR3 acts in epicardial and endocardial cells as a TGF-beta/BMP coreceptor; it is not shown to perform a step of myocardial or septal morphogenesis itself. Fine-grained organismal phenotypes are not transferred as process participation. Supporting Evidence: PMID:17704211 At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0060939 epicardium-derived cardiac fibroblast cell development | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of epicardium-derived cardiac fibroblast cell development, from mouse genetic phenotypes. Reason: This is a downstream developmental phenotype of mouse Tgfbr3 loss. No evidence in human or mouse that betaglycan executes a step of this process beyond acting as a broadly expressed TGF-beta superfamily coreceptor; no human data. Retained only as an over-annotation. Supporting Evidence: PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0060979 vasculogenesis involved in coronary vascular morphogenesis | ISS GO_REF:0000024 | KEEP AS NON CORE | Summary: Vasculogenesis involved in coronary vascular morphogenesis (ISS from mouse). Reason: The best-characterized developmental requirement of Tgfbr3: null mice fail to form coronary vessels. Mechanistically TGFBR3 acts in epicardial cells, mediating TGF-beta/BMP2-induced EMT and invasion that supply coronary vessel precursors, i.e. it does part of the work in epicardial cells. Kept as non-core and inferred from mouse, not shown in human. Supporting Evidence: PMID:17704211 Targeted deletion of Tgfbr3 revealed a requirement for Tgfbr3 during development of the coronary vessels PMID:21871877 lower rate of epicardial cell proliferation and decreased epicardially derived cell invasion in Tgfbr3(-/-) hearts PMID:22237159 Tgfbr3(-/-) cells show decreased invasion in response to BMP2 and overexpression of TGFΞ²R3 in Tgfbr3(-/-) cells rescued invasion |
| GO:0061384 heart trabecula morphogenesis | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of heart trabecula morphogenesis, derived from Tgfbr3-null embryo cardiac phenotypes. Reason: Tgfbr3-null embryos have thin compact myocardium, reduced proliferation and septal/trabecular abnormalities, but these are secondary consequences of failed epicardial invasion and coronary vessel formation in a global knockout. TGFBR3 acts in epicardial and endocardial cells as a TGF-beta/BMP coreceptor; it is not shown to perform a step of myocardial or septal morphogenesis itself. Fine-grained organismal phenotypes are not transferred as process participation. Supporting Evidence: PMID:17704211 At embryonic day 13.5, these defects include an irregular and hypercellular epicardium with abundant subepicardial mesenchyme and a thin compact zone myocardium PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0062009 secondary palate development | ISS GO_REF:0000024 | MARK AS OVER ANNOTATED | Summary: ISS transfer from mouse Tgfbr3 (O88393) of secondary palate development, from mouse genetic phenotypes. Reason: This is a downstream developmental phenotype of mouse Tgfbr3 loss. No evidence in human or mouse that betaglycan executes a step of this process beyond acting as a broadly expressed TGF-beta superfamily coreceptor; no human data. Retained only as an over-annotation. Supporting Evidence: PMID:12773577 mice with mutations in TbetaRIII developed lethal proliferative defects in heart and apoptosis in liver |
| GO:0065003 protein-containing complex assembly | IEA GO_REF:0000107 | TOO GENERAL | Summary: Protein-containing complex assembly (IEA). Reason: True but uninformative; the specific accepted term is transforming growth factor beta receptor complex assembly. |
| GO:0070062 extracellular exosome | HDA PMID:19056867 Large-scale proteomics and phosphoproteomics of urinary exos... | KEEP AS NON CORE | Summary: Extracellular exosome (HDA, PMID:19056867). Reason: Detection in urinary/parotid exosome proteomes is plausible for a membrane proteoglycan but has no known functional significance. |
| GO:0070062 extracellular exosome | HDA PMID:19199708 Proteomic analysis of human parotid gland exosomes by multid... | KEEP AS NON CORE | Summary: Extracellular exosome (HDA, PMID:19199708). Reason: Detection in urinary/parotid exosome proteomes is plausible for a membrane proteoglycan but has no known functional significance. |
| GO:0070123 transforming growth factor beta receptor activity, type III | IDA PMID:10746731 Betaglycan binds inhibin and can mediate functional antagoni... | ACCEPT | Summary: Type III TGF-beta receptor activity (IDA). Reason: This is the defining molecular function of betaglycan: it binds TGF-beta (and inhibin, BMPs) with high affinity and facilitates ligand binding to the type II and type I signaling receptors, without kinase activity of its own. Supporting Evidence: PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:10746731 Betaglycan binds inhibin with high affinity and enhances binding in cells co-expressing ActRII and betaglycan |
| GO:0070123 transforming growth factor beta receptor activity, type III | IDA PMID:11157754 Type III TGF-beta receptor-independent signalling of TGF-bet... | ACCEPT | Summary: Type III TGF-beta receptor activity (IDA). Reason: This is the defining molecular function of betaglycan: it binds TGF-beta (and inhibin, BMPs) with high affinity and facilitates ligand binding to the type II and type I signaling receptors, without kinase activity of its own. Supporting Evidence: PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:10746731 Betaglycan binds inhibin with high affinity and enhances binding in cells co-expressing ActRII and betaglycan |
| GO:0070123 transforming growth factor beta receptor activity, type III | IEA GO_REF:0000107 | ACCEPT | Summary: Type III TGF-beta receptor activity (IEA). Reason: This is the defining molecular function of betaglycan: it binds TGF-beta (and inhibin, BMPs) with high affinity and facilitates ligand binding to the type II and type I signaling receptors, without kinase activity of its own. Supporting Evidence: PMID:11323414 The type III receptor with the cytoplasmic domain deleted is able to bind TGF-beta, to bind the type II receptor, and to enhance TGF-beta binding to the type II receptor PMID:17704211 binds all 3 TGFbeta ligands and inhibin with high affinity but lacks the serine/threonine kinase domain found in the type I and type II receptors PMID:10746731 Betaglycan binds inhibin with high affinity and enhances binding in cells co-expressing ActRII and betaglycan |
| GO:0070372 regulation of ERK1 and ERK2 cascade | ISS NOT GO_REF:0000024 | UNDECIDED | Summary: NOT regulation of ERK1 and ERK2 cascade, ISS transfer of a negative mouse annotation. Reason: The source mouse experiment could not be identified among the cached papers, so the negative result cannot be evaluated. |
| GO:0090050 positive regulation of cell migration involved in sprouting angiogenesis | IMP PMID:30467960 MicroRNA let-7a regulates angiogenesis by targeting TGFBR3 m... | MARK AS OVER ANNOTATED | Summary: Positive regulation of cell migration involved in sprouting angiogenesis (IMP, HUVEC knockdown). Reason: The evidence is reduced wound-closure migration and tube formation of HUVECs after about 40% knockdown of TGFBR3 in a microRNA study. This supports an effect on endothelial migration in vitro, but the sprouting-angiogenesis-specific process is not directly tested and TGFBR3's role is as a coreceptor upstream of these responses. Supporting Evidence: PMID:30467960 As expected, knockdown of TGFBR3 decreased HUVEC migration |
| GO:0090100 positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway | IEA GO_REF:0000117 | TOO GENERAL | Summary: Positive regulation of transmembrane receptor protein serine/threonine kinase signaling pathway (ARBA). Reason: True but uninformative; covered by the accepted positive regulation of TGF-beta receptor signaling and SMAD signaling. |
| GO:1901202 negative regulation of extracellular matrix assembly | IMP PMID:30729664 Novel role of the clustered miR-23b-3p and miR-27b-3p in enh... | MARK AS OVER ANNOTATED | Summary: Negative regulation of extracellular matrix assembly (IMP, atrial fibroblasts). Reason: The readout was increased COL1A1/COL3A1/ACTA2 expression after TGFBR3 knockdown, i.e. increased fibrotic gene expression downstream of Smad3. Matrix assembly itself was not measured, so the term over-interprets the result. Supporting Evidence: PMID:30729664 In parallel with miRβ23bβ3p and miRβ27bβ3p, TGFBR3 knockdown enhanced the expressions of COL1A1, COL3A1 and ACTA2 in HAFs |
| GO:0032926 negative regulation of activin receptor signaling pathway | IDA PMID:10746731 Betaglycan binds inhibin and can mediate functional antagoni... | NEW | Summary: Betaglycan is the inhibin coreceptor that enables inhibin to antagonize activin signaling. Reason: Participation test: TGFBR3 itself does the work, binding inhibin and forming the inhibin-betaglycan-ActRII complex that sequesters type II activin receptors; it is not merely a target or substrate. Betaglycan confers inhibin sensitivity to otherwise poorly responsive cells, and gonadotrope-specific Tgfbr3 knockout in mouse abolishes inhibin A suppression of FSH. This complements the accepted inhibin-betaglycan-ActRII complex and coreceptor activity annotations. Supporting Evidence: PMID:10746731 betaglycan, can function as an inhibin co-receptor with ActRII PMID:10746731 betaglycan confers inhibin sensitivity to cell lines that otherwise respond poorly to this hormone PMID:30364975 TGFBR3 (betaglycan) functions as an inhibin A, but not an inhibin B, coreceptor in gonadotrope cells in vivo |
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Download this section (compressed HTML)Q: Does the human TGFBR3 core protein bind glycosaminoglycans or heparin non-covalently, or do the existing glycosaminoglycan/heparin binding annotations (including the PAINT IBD at PTN002678643) reflect its covalent GAG substitution? If the latter, should the IBD be revisited?
Q: What experiments underlie the mouse NOT annotations to regulation of JNK and ERK1/2 cascades that were transferred by ISS to human TGFBR3, and are they valid in human cells?
Q: Is betaglycan required for inhibin action in human gonadotropes, given that in mouse it is needed for inhibin A but not inhibin B, with TGFBR3L acting as the inhibin B coreceptor?
Experiment: CRISPR knockout of TGFBR3 (and TGFBR3L) in human gonadotrope-like cells or pituitary organoids, measuring inhibin A and inhibin B suppression of activin-induced FSHB transcription.
Hypothesis: TGFBR3 is required for inhibin A-mediated suppression of FSH in human pituitary gonadotropes.
Type: genetic and cell-based assay
Experiment: Rescue of TGFBR3-null human epithelial cells with wild-type, T841A, PDZ-motif-deleted and ectodomain-only constructs, measuring Cdc42 activation, random migration and NF-kappaB activity.
Hypothesis: The ligand-independent anti-migratory function of TGFBR3 depends solely on beta-arrestin 2 binding via phospho-Thr841.
Type: structure-function cell biology
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