ArticleBMC evolutionary biology2019
ADGRL4/ELTD1 is a highly conserved angiogenesis-associated orphan adhesion GPCR that emerged with the first vertebrates and comprises 3 evolutionary variants.
Article in BMC evolutionary biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 17 citations in OpenAlex.
- Dynamic cellular programs of human cardiac allograft rejection revealed by spatial transcriptomics.Nature cardiovascular research · 2026Article
- Identification of the adhesion GPCR ADGRL4/ELTD1 as a novel potential prognostic biomarker for cerebral cavernous malformation disease.Molecular medicine (Cambridge, Mass.) · 2026Article
- Transcriptomic Profiling Reveals Isoform-Specific Regulatory Roles of miR-196A and miR-196B in Colorectal Cancer Cells.International journal of molecular sciences · 2026Article
- aGPCR-HEK: A Stable High-Expression Inducible Mammalian Cell Expression System for Adhesion GPCR Structural Biology Applications.Bio-protocol · 2026Article
- Purification of the Active-State G Protein-Coupled Receptor ADGRL4 for Cryo-Electron Microscopy Using a Modular Tag System and a Tethered mini-GBio-protocol · 2026Article
- Structure of the GNature communications · 2025Article
- Differential implications of tumor endothelial cell and lymphocyte densities in advanced hepatocellular carcinoma patients treated with immunotherapy.NPJ precision oncology · 2025Article
- Adhesion G-Protein Coupled Receptors in Neurological and Psychiatric Disorders.Journal of psychiatry and brain science · 2025Article
- Apoptotic effect of melatonin on ER-positive breast cancer cell lines: ADGRL4 gene expression and promoter methylation.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Bioinformatic characterization of ENPEP, the gene encoding a potential cofactor for SARS-CoV-2 infection.PloS one · 2024Article
- Dissection of key factors correlating with H5N1 avian influenza virus driven inflammatory lung injury of chicken identified by single-cell analysis.PLoS pathogens · 2023Article
- Prioritization and functional validation of target genes from single-cell transcriptomics studies.Communications biology · 2023Article
- Article
- ADGRL4/ELTD1 Expression in Breast Cancer Cells Induces Vascular Normalization and Immune Suppression.Molecular cancer research : MCR · 2021Article
- ELTD1-An Emerging Silent Actor in Cancer Drama Play.International journal of molecular sciences · 2021Review
- Elevated expression of the adhesion GPCR ADGRL4/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling.Scientific reports · 2021Article
- ADGRL4/ELTD1 Silencing in Endothelial Cells Induces ACLY and SLC25A1 and Alters the Cellular Metabolic Profile.Metabolites · 2019Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
backgroundOur laboratory identified ADGRL4/ELTD1, an orphan GPCR belonging to the adhesion GPCR (aGPCR) family, as a novel regulator of angiogenesis and a potential anti-cancer therapeutic target. Little is known about how ADGRL4/ELTD1 (and aGPCRs in general) function, a problem compounded by a lack of known ligands or means of activation. With this in mind, we turned to computational evolutionary biology with the aim of better understanding ADGRL4/ELTD1.
resultsWe identified ADGRL4/ELTD1 as a highly conserved early angiogenic gene which emerged in the first true vertebrates (bony fish) approximately 435 million years ago (mya), evolving alongside key angiogenic genes VEGFR2 and DLL4. We identified 3 evolutionary ADGRL4/ELTD1 variants based on EGF domain deletions with variant 2 first emerging 101 mya (95% CI 96-105) in Afrotheria and 82 mya (95% CI 76-89) in Primates. Additionally, conservation mapping across all orthologues reveals highest level conservation in EGF Ca binding domain 1, suggesting that this motif plays an essential role, as well as specific regions of the GAIN domain, GPS motif and 7TM domain, suggesting possible activation mechanisms and ligand binding positions. Additionally, we found that ADGRL4/ELTD1 (a member aGPCR family 1) is possibly ancestral to members of aGPCR family 2.
conclusionThis work establishes ADGRL4/ELTD1's evolution, sheds light on its possible activation and ligand binding zones, and establishes the first temporal references for the emergence of ADGRL4/ELTD1 variants during vertebrate evolution. Our approach is applicable to the greater aGPCR family and opens up new avenues for future experimental work.
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