UniProt record for human ADGRV1 (Q8WXG9)
Molecular characterization of the ankle-link complex in cochlear hair cells and its role in the hair bundle functioning.
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
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
Sequence similarities between a novel putative G protein-coupled receptor and Na+/Ca2+ exchangers define a cation binding domain.
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Human VLGR1a surface localization and calcium binding by isolated two/four-repeat fragments are demonstrated.
"Bacterial fusion proteins containing two or four repeats specifically bind 45Ca in overlay experiments; binding is competed poorly by Mg2+ but competed well by neomycin, Al3+, and Gd3+."
Very large G protein-coupled receptor-1, the largest known cell surface protein, is highly expressed in the developing central nervous system.
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The historical paper defines VLGR1 isoforms and maps expression in developing mouse CNS and eye; its longest human sequence is reported as 6,307 residues.
"The longest gene product, VLGR1b, is 6307 amino acids (6298 amino acids in mice) due to a much larger ectodomain containing 35 calcium exchanger beta repeats and a pentraxin homology domain."
A nonsense mutation of the MASS1 gene in a family with febrile and afebrile seizures.
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A MASS1/ADGRV1 nonsense mutation (S2652X) segregates with febrile and afebrile seizures in one family, suggesting loss of function can confer seizure susceptibility.
"a nonsense mutation (S2652X) causing a deletion of the C-terminal 126 amino acid residues was identified in one family with febrile and afebrile seizures"
Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type II.
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Four isoform-specific truncating VLGR1 mutations establish VLGR1/ADGRV1 as the USH2C gene, implicating it in congenital hearing loss and progressive retinitis pigmentosa.
"These results establish VLGR1 as the USH2C gene and implicate the protein, which is the largest cell surface receptor known (McMillan et al. 2002 ), in the pathogenesis of USH2."
The human and mouse repertoire of the adhesion family of G-protein-coupled receptors.
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VLGR1 belongs to the 33-member human adhesion GPCR family of membrane-bound 7TM receptors with long multi-domain N-termini.
"The adhesion G-protein-coupled receptors (GPCRs) (also termed LN-7TM or EGF-7TM receptors) are membrane-bound proteins with long N-termini containing multiple domains."
Disease expression in Usher syndrome caused by VLGR1 gene mutation (USH2C) and comparison with USH2A phenotype.
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USH2C patients show pan-retinal photoreceptor dysfunction (rod greater than cone) and outer nuclear layer thinning, i.e. progressive photoreceptor degeneration.
"USH2C and USH2A manifest photoreceptor disease with rod- and cone-mediated visual losses and thinning of the outer nuclear layer."
The DFNB31 gene product whirlin connects to the Usher protein network in the cochlea and retina by direct association with USH2A and VLGR1.
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Whirlin directly associates with VLGR1b and USH2A and co-localizes with them at photoreceptor connecting cilium, outer limiting membrane, and synaptic regions.
"we provide evidence that whirlin directly associates with USH2A isoform b and VLGR1b, two proteins that we previously reported to be part of the Usher protein interactome"
Large-scale proteomics and phosphoproteomics of urinary exosomes.
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Human urinary exosomes were profiled by LC-MS/MS; the ADGRV1-specific identification is not visible in the cached abstract.
"Here, we used LC-MS/MS to profile the proteome of human urinary exosomes."
PDZD7 is a modifier of retinal disease and a contributor to digenic Usher syndrome.
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PDZD7 PDZ2 binds the GPR98/ADGRV1 C-terminal PDZ-binding motif (Y2H and co-IP), and Pdzd7 knockdown reduces Gpr98 localization at the photoreceptor connecting cilium in zebrafish.
"We confirmed this interaction by coimmunoprecipitation studies and showed that it is mediated by the PDZ2 domain of PDZD7 and the PDZ-binding motif of GPR98."
Structural basis for endosomal trafficking of diverse transmembrane cargos by PX-FERM proteins.
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The study analyzes PX-FERM cargo recognition; the ADGRV1-specific experiment underlying the signaling-complex annotation was not recovered.
"We further show that the PX-FERM proteins share a promiscuous ability to bind a wide array of putative cargo molecules, including receptor tyrosine kinases, and propose a model for their coordinated molecular interactions with membrane, cargo, and regulatory proteins."
Whirlin and PDZ domain-containing 7 (PDZD7) proteins are both required to form the quaternary protein complex associated with Usher syndrome type 2.
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Mouse-derived cytoplasmic and PDZ fragments reconstitute a USH2A–GPR98–WHRN–PDZD7 complex; WHRN and PDZD7 have different binding preferences.
"Importantly, both WHRN and PDZD7 are required for the complex formation with USH2A and GPR98. In this USH2 quaternary complex, WHRN prefers to bind to USH2A, whereas PDZD7 prefers to bind to GPR98."
Constitutive Gαi coupling activity of very large G protein-coupled receptor 1 (VLGR1) and its regulation by PDZD7 protein.
Affinity Proteomics Identifies Interaction Partners and Defines Novel Insights into the Function of the Adhesion GPCR VLGR1/ADGRV1.
The Adhesion GPCR VLGR1/ADGRV1 Regulates the Ca(2+) Homeostasis at Mitochondria-Associated ER Membranes.
Very large G protein-coupled receptor 1 regulates myelin-associated glycoprotein via Gαs/Gαq-mediated protein kinases A/C.
GPR98/Gpr98 gene is involved in the regulation of human and mouse bone mineral density.
Existing Falcon deep research report for ADGRV1
The very large G protein coupled receptor (Vlgr1) in hair cells.
Adhesion G protein-coupled receptor VLGR1/ADGRV1 regulates cell spreading and migration by mechanosensing at focal adhesions.
Genetics, pathogenesis and therapeutic developments for Usher syndrome type 2.
The genetic and phenotypic landscapes of Usher syndrome: from disease mechanisms to a new classification.
The adhesion G protein-coupled receptor VLGR1/ADGRV1 controls autophagy.
Adenylyl cyclase 6 plays a minor role in the mouse inner ear and retina.
Generation and Characterization of a Zebrafish Model for ADGRV1-Associated Retinal Dysfunction Using CRISPR/Cas9 Genome Editing Technology.
Detailed Clinical, Ophthalmic, and Genetic Characterization of ADGRV1-Associated Usher Syndrome.
Combined Presence in Heterozygosis of Two Variant Usher Syndrome Genes in Two Siblings Affected by Isolated Profound Age-Related Hearing Loss.
Deciphering the largest disease-associated transcript isoforms in the human neural retina with advanced long-read sequencing approaches.
The adhesion GPCR ADGRV1 controls glutamate homeostasis in hippocampal astrocytes supporting neurons.