Gene Ontology annotation through association of InterPro records with GO terms
Manual transfer of experimentally-verified manual GO annotation data to orthologs by curator judgment of sequence similarity
Annotation inferences using phylogenetic trees
Gene Ontology annotation based on UniProtKB/Swiss-Prot Subcellular Location vocabulary mapping, accompanied by conservative changes to GO terms applied by UniProt
Gene Ontology annotation based on curation of immunofluorescence data
Automatic transfer of experimentally verified manual GO annotation data to orthologs using Ensembl Compara
Electronic Gene Ontology annotations created by ARBA machine learning models
Combined Automated Annotation using Multiple IEA Methods
Direct binding of the human homologue of the Drosophila disc large tumor suppressor gene to seven-pass transmembrane proteins, tumor endothelial marker 5 (TEM5), and a novel TEM5-like protein.
The human and mouse repertoire of the adhesion family of G-protein-coupled receptors.
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The reference is a genome-mining and phylogenetics survey of the adhesion-GPCR repertoire; its abstract reports no functional assay on ADGRA2 or any other receptor.
"Here, 2 new human adhesion-GPCRs, termed GPR133 and GPR144, have been found by searches done in the human genome databases."
Proteolytically processed soluble tumor endothelial marker (TEM) 5 mediates endothelial cell survival during angiogenesis by linking integrin alpha(v)beta3 to glycosaminoglycans.
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The MMP9-processed soluble ADGRA2 ectodomain binds integrin alpha-V/beta-3 directly; the full-length ectodomain does not.
"Matrix metalloprotease 9-processed, but not full-length, sTEM5 mediated endothelial cell adhesion by direct interaction with integrin alpha(v)beta3."
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The shed ADGRA2 ectodomain binds several glycosaminoglycans.
"We found that sTEM5 binds to several glycosaminoglycans."
Tumor endothelial marker 5 expression in endothelial cells during capillary morphogenesis is induced by the small GTPase Rac and mediates contact inhibition of cell proliferation.
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Blocking ADGRA2 with its soluble ectodomain or an inhibitory antibody abolishes contact inhibition of endothelial proliferation.
"An excess of the soluble TEM5 extracellular domain or an inhibitory monoclonal TEM5 antibody blocked contact inhibition of endothelial cell proliferation"
GPR124, an orphan G protein-coupled receptor, is required for CNS-specific vascularization and establishment of the blood-brain barrier.
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ADGRA2 is required for blood-vessel invasion of the neuroepithelium, for blood-brain barrier properties and for cortical expansion.
"Expression of GPR124 was found to be required for invasion and migration of blood vessels into neuroepithelium, establishment of BBB properties, and expansion of the cerebral cortex."
Thrombin-induced shedding of tumour endothelial marker 5 and exposure of its RGD motif are regulated by cell-surface protein disulfide-isomerase.
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Thrombin-induced shedding of the ADGRA2 N60 fragment requires the reducing activity of cell-surface protein disulfide-isomerase.
"Inhibition of the reducing function of cell-surface PDI (protein disulfide-isomerase) abrogated thrombin-induced N60 shedding."
Large-scale interaction profiling of PDZ domains through proteomic peptide-phage display using human and viral phage peptidomes.
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The interaction data come from proteomic peptide-phage display of human C-terminal peptides against PDZ domains.
"we generated phage libraries containing all human and viral C-terminal peptides using custom oligonucleotide microarrays"
Wnt proteins synergize to activate beta-catenin signaling.
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ADGRA2 and RECK are the WNT7B co-receptors required, with FZD5, FZD8 and LRP6, for synergistic beta-catenin signalling.
"WNT1- and WNT7B-mediated synergistic Wnt signaling requires FZD5, FZD8 and LRP6, as well as the WNT7B co-receptors GPR124 (also known as ADGRA2) and RECK."
Cell adhesion controlled by adhesion G protein-coupled receptor GPR124/ADGRA2 is mediated by a protein complex comprising intersectins and Elmo-Dock.
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Gbeta-gamma binds the ADGRA2 C-terminal tail and promotes GPR124-Elmo complex formation - G-protein subunits acting on the receptor, not the reverse.
"In addition, Gβγ interacts with the C-terminal tail of GPR124 and promotes the formation of a GPR124-Elmo complex."
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The authors state that ADGRA2's signalling properties remain poorly defined.
"However, the signaling properties of GPR124 remain poorly defined."
A molecular mechanism for Wnt ligand-specific signaling.
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ADGRA2 and RECK together confer Wnt7 selectivity on brain endothelial cells.
"Gpr124 and Reck enable brain endothelial cells to selectively respond to Wnt7."
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ADGRA2 and its RECK-bound Wnt7 are recruited into Wnt/Frizzled/LRP5/6 signalosomes, raising the local Wnt7 concentration available to Frizzled.
"Through polymerization, Dishevelled recruits Gpr124 and the associated Reck-bound Wnt7 into dynamic Wnt/Frizzled/Lrp5/6 signalosomes, resulting in increased local concentrations of Wnt7 available for Frizzled signaling."
An integrated model for Gpr124 function in Wnt7a/b signaling among vertebrates.
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Mammalian GPR124 engages Frizzled through an intracellular-domain-independent mechanism, unlike the zebrafish receptor.
"By contrast, mammalian Gpr124 receptors exhibit an ICD-independent interaction mechanism governed by species-specific attributes of their transmembrane and extracellular domains."
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Mouse GPR124 recruits Frizzled-4 without needing intracellular proteins bound to its intracellular domain.
"These data imply that an alternative interaction modality exists between Fz4 and mouse GPR124, which occurs independently of the recruitment of intracellular proteins to the GPR124 ICD."
Complex G-protein signaling of the adhesion GPCR, ADGRA3.
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ADGRA2 has never been shown to couple to heterotrimeric G proteins; its characterised role is signalosome assembly.
"Whereas ADGRA2 has never been shown to couple to heterotrimeric G proteins, it has been extensively studied for its role in the assembly of a complex signalosome"
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ADGRA3 activates Gi and Gs at low level, and its C-terminal fragment more strongly.
"We found low-level activation of Gi and Gs by ADGRA3 and slightly more by its CTF."
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Removing the first three residues of the ADGRA3 stachel tethered agonist abolishes G-protein-mediated signalling.
"This resulted in abrogated G protein-mediated signaling, as observed for other aGPCRs."
The atypical adhesion GPCR ADGRA1 controls hippocampal inhibitory circuit function.
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ADGRA1 activates several G proteins, notably G-alpha-13, on the full TRUPATH BRET2 panel.
"ADGRA1 activates several G proteins, notably Gα13, an important signaling pathway for inhibitory synaptic function"
Quantitative fragmentomics allow affinity mapping of interactomes.
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The interaction data come from quantitative affinity measurement of PDZ domains against PDZ-binding motifs at proteome scale.
"Here, we measure the affinities of 65,000 interactions involving PDZ domains and their target PDZ-binding motifs (PBM) within a human interactome region particularly relevant for viral infection and cancer."
Affinage mechanistic annotation for ADGRA2 (human)