Affinage

ADGRL4

Adhesion G protein-coupled receptor L4 · UniProt Q9HBW9

Length
690 aa
Mass
77.8 kDa
Annotated
2026-06-09
61 papers in source corpus 21 papers cited in narrative 22 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADGRL4/ELTD1 is an orphan adhesion G-protein-coupled receptor expressed predominantly in endothelial cells that governs sprouting angiogenesis, endothelial plasticity, and vascular remodeling (PMID:23871637, PMID:33893326). It is a seven-transmembrane receptor with a large extracellular domain bearing EGF-like repeats; it forms stable dimers and undergoes GPS-mediated endoproteolytic cleavage of its ectodomain, an activity abolished by the T455A mutation, and localizes to the plasma membrane and cytoplasmic vesicles (PMID:11050079). Its 3.1 Å cryo-EM structure reveals coupling to heterotrimeric Gq through an unusually small receptor–G-protein interface, with no robust coupling to Gs, G12, Go, or β-arrestins, and an architecture consistent with tethered Stachel agonist activation (PMID:41469374). The receptor sheds a glycosylated extracellular domain into pro-angiogenic extracellular vesicles, and the ECD alone is sufficient to drive endothelial sprouting (PMID:38939053). In the vasculature, ADGRL4 expression is induced by VEGF/bFGF and repressed by DLL4/Notch signaling, and the receptor in turn balances Notch ligand expression (suppressing DLL4, promoting JAG1) to shape the endothelial tip-cell phenotype (PMID:23871637, PMID:33893326), while also driving endothelial-to-mesenchymal transition toward a myofibroblast-like state (PMID:34681953). In disease contexts it is transcriptionally activated by STAT5A to promote EndMT in diabetic nephropathy (PMID:35320597) and acts in tumors through Notch ligand rebalancing, JAK/STAT3/HIF-1α signaling, MMP2 transcription, and creation of an immunosuppressive vascular microenvironment (PMID:31554859, PMID:34421349, PMID:34347079). ADGRL4 also functions in non-angiogenic settings, restraining hemogenic endothelium progenitor differentiation via an HPIP–LEF1–Wnt axis (PMID:40456828) and a Gαs–cAMP–PKA cascade that suppresses YAP1 (PMID:41734371).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 2000 Medium

    Established the basic architecture of the receptor — a dimeric seven-transmembrane protein with an EGF-repeat ectodomain that is autoproteolytically cleaved — placing ADGRL4 within the adhesion GPCR paradigm of GPS cleavage.

    Evidence Myc-tagged rat ETL transfection in COS-7 cells with T455A site-directed mutagenesis and subcellular localization

    PMID:11050079

    Open questions at the time
    • No ligand or downstream signaling identified
    • Functional consequence of cleavage and dimerization not addressed
    • Done in heterologous overexpression only
  2. 2012 Medium

    First in vivo loss-of-function evidence that ELTD1 restrains MAPK signaling in a physiological stress context, linking the receptor to cardiac remodeling.

    Evidence ELTD1-knockout mice with aortic banding, phospho-ERK/JNK Western blot and histology

    PMID:22606234

    Open questions at the time
    • Mechanism connecting receptor to ERK/JNK not defined
    • Cell type responsible not resolved
    • No ligand identified
  3. 2013 High

    Positioned ELTD1 as a VEGF/Notch-regulated driver of tumor angiogenesis, defining its core endothelial function and therapeutic relevance.

    Evidence siRNA silencing, in vitro sprouting assays, and in vivo tumor models across cancer types

    PMID:23871637

    Open questions at the time
    • Signaling output downstream of the receptor not defined
    • No ligand identified
    • G-protein coupling unknown
  4. 2017 Medium

    Genetic epistasis revealed functional redundancy with GPR116/ADGRF5 in cardiovascular and renal development, and that the relevant cells are neither endothelial nor neural crest.

    Evidence Single and double ELTD1/GPR116 knockout plus cell-type-specific conditional knockouts with cardiovascular phenotyping

    PMID:28806758

    Open questions at the time
    • Identity of the relevant non-endothelial cell type unresolved
    • Molecular basis of redundancy unknown
    • No shared ligand/pathway defined
  5. 2019 Medium

    Connected ELTD1 to Notch ligand balance and endothelial metabolism, showing it suppresses DLL4 while supporting JAG1/HES2 and shapes citrate-related metabolic programs.

    Evidence Two independent siRNAs in HUVECs with transcriptional profiling and LC-MS metabolomics

    PMID:31775252

    Open questions at the time
    • Direct vs indirect regulation of Notch ligands unclear
    • Receptor-proximal signaling not defined
    • Metabolic changes correlative
  6. 2019 Medium

    Defined a tumor-cell-intrinsic JAK/STAT3/HIF-1α axis activated by ELTD1 in glioma, extending its role beyond endothelium.

    Evidence qRT-PCR, Western blot, proliferation/invasion assays, orthotopic xenografts, and p-STAT3/HIF-1α co-IP

    PMID:31554859

    Open questions at the time
    • How the receptor engages JAK/STAT3 mechanistically unknown
    • No ligand identified
    • Conflicts with later reports of no STAT3 activation in endothelium
  7. 2021 High

    A rigorous panel of GPCR signaling assays found no canonical G-protein or β-arrestin coupling in endothelial/HEK systems, reframing ELTD1's angiogenic function as operating through Notch ligand rebalancing rather than classical GPCR signaling.

    Evidence Stable HUVEC overexpression, HEK293T transfection, HTRF/luciferase/Alphascreen signaling assays, and angiogenesis/transcriptional profiling

    PMID:33893326

    Open questions at the time
    • Cell-type or context dependence of coupling not resolved
    • Mechanism transducing Notch ligand changes unknown
    • Negative result later contrasted by Gq-coupling structure
  8. 2021 Medium

    Showed ELTD1 overexpression drives endothelial-to-mesenchymal transition to a pro-angiogenic, inflammatory myofibroblast-like phenotype, linking receptor activity to vascular cell-fate plasticity.

    Evidence Endothelial overexpression with cytoskeletal immunofluorescence, angiogenesis assays, and RNA-Seq

    PMID:34681953

    Open questions at the time
    • Trigger and signaling pathway for EndMT not defined
    • Overexpression-only system
    • Physiological relevance unclear
  9. 2021 Medium

    Placed ELTD1 upstream of MMP2 transcription in colorectal cancer invasion, with MMP2 rescue confirming the epistasis.

    Evidence siRNA/overexpression in CRC cells, invasion and metastasis assays, MMP2 promoter activity, and rescue experiments

    PMID:34421349

    Open questions at the time
    • Signaling between receptor and MMP2 promoter unknown
    • No ligand identified
    • Single tumor context
  10. 2021 Medium

    Identified a physical ELTD1–CSK interaction that activates MAPK/ERK to drive gastric cancer proliferation and EMT, giving a tumor-cell-intrinsic effector.

    Evidence siRNA/overexpression, MAPK/ERK Western blot, ELTD1-CSK co-IP, and in vitro/in vivo assays

    PMID:34475781

    Open questions at the time
    • Single Co-IP without reciprocal/structural validation
    • How CSK inhibition activates ERK not fully resolved
    • Contrasts with no-MAPK finding in endothelium
  11. 2021 Medium

    Demonstrated that endothelial ELTD1 remodels the tumor vasculature and immune microenvironment via tumor–endothelial crosstalk, increasing M2 macrophages and PD-L1.

    Evidence Syngeneic mouse breast cancer models with murine Eltd1, histology, and flow cytometry

    PMID:34348993

    Open questions at the time
    • Soluble factors mediating crosstalk not fully identified
    • Receptor signaling driving the secretome unknown
    • Single tumor model
  12. 2022 Medium

    Showed ELTD1 deletion normalizes tumor vasculature and enhances T-cell infiltration with checkpoint blockade, establishing it as a vascular determinant of immunotherapy response.

    Evidence ELTD1-/- mice with orthotopic glioma, tumor endothelial profiling, vascular function assays, and PD-1 treatment

    PMID:34347079

    Open questions at the time
    • Endothelial signaling underlying vascular dysfunction unknown
    • Generalizability beyond glioma untested
    • No ligand identified
  13. 2022 Medium

    Identified STAT5A as a direct transcriptional activator of ELTD1, linking hyperglycemia to ELTD1-driven EndMT in diabetic nephropathy.

    Evidence ChIP, luciferase reporter, STAT5A/ELTD1 siRNA and overexpression with rescue in glomerular endothelial cells and a DN rat model

    PMID:35320597

    Open questions at the time
    • Receptor-proximal signaling driving EndMT not defined
    • Single disease model
    • No ligand identified
  14. 2022 Medium

    Established that the shed, glycosylated ELTD1 ectodomain travels in extracellular vesicles and is itself pro-angiogenic, defining a paracrine, flow-regulated mode of action and a candidate disease biomarker.

    Evidence EV proteomics, in vitro/in vivo angiogenesis with purified ECD, laminar flow experiments, and FACS of preeclampsia patient plasma

    PMID:38939053

    Open questions at the time
    • Receptor/target on responding endothelium for the shed ECD unknown
    • Link between cleavage and vesicular packaging unresolved
    • Clinical biomarker value not validated in cohorts
  15. 2025 High

    The cryo-EM structure resolved the long-standing coupling question, showing ADGRL4 engages Gq weakly through an unusually small interface and activates via a tethered Stachel agonist, with no coupling to other transducers.

    Evidence 3.1 Å cryo-EM of ADGRL4–Gq, bioluminescent signaling assays, and Gq complex reconstitution

    PMID:41469374

    Open questions at the time
    • Endogenous agonist for the Stachel still undefined
    • Reconciliation with prior no-coupling functional reports incomplete
    • Downstream physiological relevance of weak Gq coupling unclear
  16. 2025 Medium

    Proposed Ku80 and beta spectrin as ELTD1 ligands and an autocrine activating factor, with Ku80 the more potent, offering candidate orphan-receptor agonists.

    Evidence Affinity-capture mass spectrometry, xCelligence functional assays, conditioned-medium transfer, and siRNA/INCA-X tube formation assays

    PMID:40245572

    Open questions at the time
    • Ligand identity from affinity capture not orthogonally confirmed
    • Canonical GPCR activation reported here contrasts with earlier negative results
    • Physiological context of extracellular Ku80 unclear
  17. 2025 Medium

    Revealed a developmental role: ELTD1 restrains hemogenic endothelium progenitor differentiation through a physical HPIP interaction feeding an LEF1–Wnt axis.

    Evidence hESC gain/loss-of-function, iCRISPR knockout, ELTD1-HPIP co-IP, and Wnt pathway/hematopoietic differentiation assays

    PMID:40456828

    Open questions at the time
    • Single Co-IP for ELTD1-HPIP interaction
    • How receptor activity controls HPIP not defined
    • Relevance to adult hematopoiesis untested
  18. 2026 Medium

    Defined a stress-induced signaling cascade in which JNK-driven ADGRL4 expression and ectodomain shedding activate a Gαs–cAMP–PKA axis that suppresses YAP1, giving the receptor dual tumor-suppressive and relapse-promoting functions.

    Evidence Loss/gain-of-function, JNK inhibition, cAMP/PKA and YAP1 assays, YAP1-β-catenin co-IP, and in vivo tumor models

    PMID:41734371

    Open questions at the time
    • Gαs coupling here contrasts with structural Gq-only result
    • Single study
    • Balance between tumor-suppressive and pro-angiogenic effects not quantified
  19. 2026 Medium

    Extended ADGRL4 function to metabolism, showing its activation drives beige adipocyte differentiation and UCP1 via a p-AKT/UCP1 cascade and reduces adiposity in vivo.

    Evidence In vitro beige differentiation, p-AKT/UCP1 Western blot, and high-fat-diet mouse metabolic phenotyping

    PMID:41740879

    Open questions at the time
    • Receptor-proximal coupling to AKT unknown
    • Activating ligand in adipose context undefined
    • Single study

Open questions

Synthesis pass · forward-looking unresolved questions
  • The endogenous physiological agonist(s) of ADGRL4 and how a single receptor reconciles weak Gq coupling, reported Gαs/cAMP and AKT cascades, and G-protein-independent Notch/EndMT outputs across endothelium, tumor, developmental, and metabolic contexts remain unresolved.
  • Bona fide endogenous ligand not established
  • Conflicting G-protein coupling results across cell systems unreconciled
  • Cell-type determinants of distinct downstream pathways unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 2 GO:0140096 catalytic activity, acting on a protein 1
Localization
GO:0005576 extracellular region 1 GO:0005886 plasma membrane 1 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-1266738 Developmental Biology 2 R-HSA-162582 Signal Transduction 2
Partners
CSKHPIPSPTBXRCC5

Evidence

Reading pass · 22 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2000 ETL (ADGRL4) encodes a 738-aa seven-transmembrane receptor with a large extracellular domain containing EGF-like repeats. In COS-7 cells transfected with Myc-tagged rat ETL, the protein exists as a stable dimer and undergoes endoproteolytic cleavage of the extracellular domain. The proteolytic activity is abolished by the specific mutation T455A. In transfected mammalian cells, ETL is associated with cell membranes and is also observed in cytoplasmic vesicles. Myc-tagged receptor transfection in COS-7 cells, site-directed mutagenesis (T455A), immunofluorescence/subcellular fractionation The Journal of biological chemistry Medium 11050079
2013 ELTD1 expression in tumor-associated endothelial cells is induced by VEGF/bFGF signaling and repressed by DLL4/Notch signaling. ELTD1 silencing impairs endothelial sprouting and vessel formation in vitro and in vivo, drastically reducing tumor growth. siRNA silencing, in vitro sprouting assays, in vivo tumor models, transcriptional pathway analysis Cancer cell High 23871637
2012 ELTD1 deficiency in mice exacerbates pressure overload-induced cardiac hypertrophy and fibrosis, associated with enhanced ERK and JNK phosphorylation, indicating ELTD1 normally suppresses these MAPK pathways in the context of cardiac stress. ELTD1-knockout mice subjected to aortic banding (pressure overload), Western blot for phospho-ERK and phospho-JNK, histological analysis PloS one Medium 22606234
2017 Loss of both GPR116 (ADGRF5) and ELTD1 (ADGRL4) in mice causes aortic arch malformations, cardiac outflow tract defects, and postnatal renal thrombotic microangiopathy. Loss of either receptor alone had no obvious cardiovascular or kidney phenotype, indicating functional redundancy. Endothelial-specific or neural crest-specific deletion of both receptors did not recapitulate the phenotype, indicating the relevant expression is in non-endothelial, non-neural-crest cells. ELTD1 and GPR116 single and double knockout mice, conditional cell-type-specific knockouts, histological and cardiovascular phenotyping PloS one Medium 28806758
2019 ELTD1 silencing in endothelial cells induces expression of ACLY (cytoplasmic metabolic regulator) and SLC25A1 (mitochondria-to-cytoplasm citrate transporter), upregulates DLL4, and suppresses JAG1 and HES2, indicating ELTD1 regulates Notch ligand balance in endothelial cells. Metabolomics showed altered pyrimidine, amino acid, and sugar metabolism upon ELTD1 silencing. Two independent siRNAs for ELTD1 knockdown in HUVECs, transcriptional profiling, target gene validation (qPCR/Western blot), liquid chromatography–mass spectrometry metabolomics Metabolites Medium 31775252
2019 ELTD1 activates the JAK/STAT3/HIF-1α signaling axis in glioma cells; p-STAT3 binds with HIF-1α. ELTD1 high expression promotes proliferation, migration, invasion, and orthotopic xenograft tumor growth. qRT-PCR, Western blotting, cell proliferation assays, Matrigel migration/invasion assays, brain orthotopic xenografts, co-immunoprecipitation/interaction assays for p-STAT3 and HIF-1α Scientific reports Medium 31554859
2021 ELTD1 overexpression in endothelial cells promotes sprouting angiogenesis and decreases in vitro anastomoses without activating canonical GPCR signaling (Gq, Gs, G12, Go, β-arrestin) or MAPK/ERK, PI3K/AKT, JNK, JAK/HIF-1α, beta-catenin, or STAT3 pathways. Full-length and C-terminal fragment constructs, as well as Stachel peptides, failed to activate canonical GPCR signaling in HEK293T cells. Overexpression upregulated JAG1 and downregulated DLL4, modulating the endothelial tip-cell phenotype. Stable ADGRL4/ELTD1-overexpressing HUVEC line, HEK293T transfection, HTRF FRET/luciferase reporter/Alphascreen GPCR signalling assays, angiogenesis assays, transcriptional profiling Scientific reports High 33893326
2021 ELTD1 overexpression in endothelial cells results in endothelial-to-mesenchymal transition (EndMT) to a myofibroblast-like phenotype: loss of cell-cell contact, formation of stress fibers and mature focal adhesions, and increased smooth muscle actin expression. This transition is pro-angiogenic and associated with large increases in chemokines and cytokines regulating immune response. RNA-Seq identified pathways involved in myofibroblast biology (type II EMT). ELTD1 overexpression in endothelial cells, immunofluorescence for cytoskeletal markers, Matrigel network formation and sprouting assays, RNA-Seq with gene set enrichment analysis International journal of molecular sciences Medium 34681953
2021 ELTD1 promotes invasion and metastasis of colorectal cancer cells by accelerating the transcriptional activity of MMP2; MMP2 re-expression can rescue the impaired invasiveness caused by ELTD1 downregulation. siRNA knockdown and overexpression of ELTD1 in CRC cells, Matrigel invasion assays, in vivo metastasis models, MMP2 promoter activity assays, rescue experiments International journal of biological sciences Medium 34421349
2021 ELTD1 promotes gastric cancer proliferation, invasion, and EMT through MAPK/ERK signaling by interacting with and inhibiting C-terminal Src kinase (CSK). ELTD1 knockdown inhibits GC cell proliferation, migration, and invasion in vitro and in vivo, while overexpression has the opposite effect. siRNA knockdown, ELTD1 overexpression, Western blot for MAPK/ERK pathway, co-immunoprecipitation for ELTD1-CSK interaction, in vitro/in vivo functional assays International journal of general medicine Medium 34475781
2021 ELTD1 expression in murine breast cancer cells increases tumor growth and metastasis, enlarges vessel size and perfusion, and creates an immunosuppressive microenvironment with increased M2-like macrophages and PD-L1 expression via tumor-endothelial cell crosstalk releasing proangiogenic and immune-modulating factors. Syngeneic immunocompetent mouse breast cancer models with recombinant murine Eltd1 expression, histological analysis, flow cytometry, in vivo tumor growth/metastasis assays Molecular cancer research : MCR Medium 34348993
2022 ELTD1 deletion in mice improves tumor vascular function in orthotopic glioma, with transcriptional profiling of isolated tumor endothelial cells showing increased inflammatory response and decreased proliferation pathways. ELTD1 deletion also improves T-cell infiltration after PD-1 checkpoint blockade. ELTD1-/- mice with orthotopic glioma models, endothelial cell isolation and transcriptional profiling, tumor vascular function assays, PD-1 antibody treatment, immune infiltrate analysis Neuro-oncology Medium 34347079
2022 STAT5A directly regulates ELTD1 transcription (demonstrated by ChIP and luciferase assay). High glucose-induced STAT5A nuclear translocation leads to increased ELTD1 expression, which in turn promotes endothelial-to-mesenchymal transition (EndMT) in diabetic nephropathy. ELTD1 silencing reverses high glucose-mediated EndMT, and STAT5A overexpression-induced EndMT is inhibited by si-ELTD1. Chromatin immunoprecipitation (ChIP), luciferase reporter assay, siRNA silencing of ELTD1 and STAT5A, STAT5A overexpression in human glomerular endothelial cells, DN rat model Clinical and experimental pharmacology & physiology Medium 35320597
2022 A highly glycosylated form of the ELTD1 extracellular domain (ECD) is present in extracellular vesicles (EVs) derived from endothelial cells. ELTD1-enriched EVs are pro-angiogenic in vivo and in vitro, and the ECD alone is sufficient to induce endothelial sprouting. Under laminar flow (quiescent endothelium), ELTD1 levels in EVs are reduced. Elevated vesicular ELTD1 is detected in plasma of patients with preeclampsia. EV isolation and characterization, mass spectrometry-based proteomics, in vitro sprouting assay with purified ECD, in vivo angiogenesis assay, FACS for vesicular ELTD1 in patient plasma, laminar flow experiments Journal of extracellular biology Medium 38939053
2025 Cryo-EM structure of ADGRL4 coupled to heterotrimeric Gq determined at 3.1 Å resolution. ADGRL4 couples weakly to Gq (demonstrated by bioluminescent assay) but shows no robust coupling to Gs, G12, Go, or β-arrestin 1 or 2. The coupling to Gq involves fewer interactions between receptor and G protein compared to other aGPCRs. The structure is consistent with activation by a tethered agonist (Stachel mechanism). Cryo-EM structure determination (3.1 Å), bioluminescent GPCR signalling assay, heterotrimeric Gq complex reconstitution Nature communications High 41469374
2025 Ku80 (a DNA repair factor) and erythrocyte beta spectrin (SPTB) were identified as ligands for ELTD1 by affinity capture and mass spectrometry. Ku80 demonstrated higher potency in activating ELTD1 than SPTB. When recombinantly expressed in U87 cells, ELTD1 activates canonical GPCR pathways, particularly the Gq pathway. Conditioned medium from U87 cells activates ELTD1 in HEK293 cells, supporting an autocrine ELTD1-activating factor. INCA-X (antibody targeting ku80/ku70 complex) and ELTD1 siRNA impaired endothelial tube formation similarly, suggesting a common pathway. Affinity capture and mass spectrometry for ligand identification, xCelligence label-free functional assay, conditioned medium transfer assay, siRNA knockdown, endothelial tube formation assay Biochemical and biophysical research communications Medium 40245572
2025 ELTD1 inhibits differentiation of hemogenic endothelium progenitors (HEPs) from hESCs through the HPIP-Wnt pathway. ELTD1 interacts physically with HPIP (protein-protein interaction), and HPIP modulates Wnt signaling through LEF1. Knockdown or deletion of ELTD1 facilitates HEP generation and promotes endothelial-to-hematopoietic transition; ELTD1 overexpression suppresses this. The ELTD1-HPIP-LEF1-Wnt regulatory axis governs HEP generation during early hematopoietic differentiation. ELTD1 gain- and loss-of-function experiments in hESCs, iCRISPR/Cas9 knockout, dynamic gene expression profiling, co-immunoprecipitation for ELTD1-HPIP interaction, luciferase/functional Wnt pathway assays, hematopoietic differentiation readouts Experimental & molecular medicine Medium 40456828
2026 Cellular stress induces ADGRL4 expression via the canonical JNK-ATF2/c-Jun pathway. Stress-induced shedding of the ADGRL4 N-terminal fragment activates the C-terminal fragment, which couples with Gαs to stimulate cAMP-PKA signaling and consequently suppress YAP1 activity. In the absence of ADGRL4, hyperactivated YAP1 forms a transcriptional complex with β-catenin to drive tumor growth. ADGRL4 simultaneously promotes angiogenesis extracellularly, creating dual tumor-suppressive and relapse-promoting effects. Loss-of-function and overexpression experiments, JNK pathway inhibition, cAMP/PKA signalling assays, YAP1 activity assays, co-immunoprecipitation for YAP1-β-catenin complex, in vivo tumor models Cancer research Medium 41734371
2026 ADGRL4 activation promotes beige adipocyte differentiation, upregulates UCP1 expression, and reduces lipid droplet accumulation in vitro. In vivo, ADGRL4 activation induces beige fat development and reduces fat deposition and body weight in mice on high-fat diet. Mechanistically, ADGRL4 enhances AKT phosphorylation without altering total AKT levels, activating a downstream p-AKT/UCP1 signaling cascade driving adipose browning. In vitro beige adipocyte differentiation assays, ADGRL4 activation in cell lines, Western blot for p-AKT and UCP1, in vivo mouse models (normal chow and high-fat diet), metabolic phenotyping Molecular and cellular endocrinology Medium 41740879
2025 ADGRL4 cryo-EM structure determination (same finding as PMID 41469374, preprint version). ADGRL4 couples weakly to Gq; no coupling to Gs, G12, Go, or β-arrestins. Cryo-EM structure at 3.1 Å shows distinct Gq coupling with fewer receptor-G protein interactions versus other aGPCRs. Consistent with tethered agonist (Stachel) activation. Cryo-EM structure determination (3.1 Å), bioluminescent signalling assay, heterotrimeric Gq complex reconstitution bioRxivpreprint High
2015 miR-139-5p suppresses glioma cell proliferation by directly targeting ELTD1; luciferase and Western blot assays confirmed ELTD1 as a direct target of miR-139-5p, and miR-139-5p overexpression reduces ELTD1 protein levels and regulates cell cycle in GBM cells. miR-139-5p mimic transfection in GBM cell lines, luciferase reporter assay, Western blot, MTT/colony formation assays Biochemical and biophysical research communications Low 26449464
2021 ELTD1 inhibition by siRNA decreases Y79 retinoblastoma cell migration in vitro and invasion in vivo in an orthotopic xenograft model. ELTD1 displays punctate clusters at cell-to-cell adhesion sites in Weri-Rb-1 cells (non-metastatic), while its subcellular localization at these sites is distinct from the polarized distribution of GPR125. siRNA knockdown of ELTD1 in Rb cell lines, migration assay (in vitro), orthotopic xenograft murine model for invasion (in vivo), immunofluorescence subcellular localization BMC cancer Low 33430814

Source papers

Stage 0 corpus · 61 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 A core human primary tumor angiogenesis signature identifies the endothelial orphan receptor ELTD1 as a key regulator of angiogenesis. Cancer cell 269 23871637
2000 ETL, a novel seven-transmembrane receptor that is developmentally regulated in the heart. ETL is a member of the secretin family and belongs to the epidermal growth factor-seven-transmembrane subfamily. The Journal of biological chemistry 90 11050079
2023 An extensive study on multiple ETL and HTL layers to design and simulation of high-performance lead-free CsSnCl3-based perovskite solar cells. Scientific reports 67 36781884
2013 ELTD1, a potential new biomarker for gliomas. Neurosurgery 66 23096411
2019 ELTD1 facilitates glioma proliferation, migration and invasion by activating JAK/STAT3/HIF-1α signaling axis. Scientific reports 44 31554859
1992 The mouse Enhancer trap locus 1 (Etl-1): a novel mammalian gene related to Drosophila and yeast transcriptional regulator genes. Mechanisms of development 41 1489724
2017 Developmental vascular remodeling defects and postnatal kidney failure in mice lacking Gpr116 (Adgrf5) and Eltd1 (Adgrl4). PloS one 37 28806758
2017 ELTD1, an effective anti-angiogenic target for gliomas: preclinical assessment in mouse GL261 and human G55 xenograft glioma models. Neuro-oncology 34 27416955
2015 MicroRNA-139-5p acts as a tumor suppressor by targeting ELTD1 and regulating cell cycle in glioblastoma multiforme. Biochemical and biophysical research communications 34 26449464
2012 Augmented cardiac hypertrophy in response to pressure overload in mice lacking ELTD1. PloS one 33 22606234
2021 ELTD1 promotes invasion and metastasis by activating MMP2 in colorectal cancer. International journal of biological sciences 32 34421349
2014 A review of ELTD1, a pro-angiogenic adhesion GPCR. Biochemical Society transactions 31 25399586
2021 Elevated expression of the adhesion GPCR ADGRL4/ELTD1 promotes endothelial sprouting angiogenesis without activating canonical GPCR signalling. Scientific reports 28 33893326
2019 ADGRL4/ELTD1 Silencing in Endothelial Cells Induces ACLY and SLC25A1 and Alters the Cellular Metabolic Profile. Metabolites 22 31775252
2019 Optimized monoclonal antibody treatment against ELTD1 for GBM in a G55 xenograft mouse model. Journal of cellular and molecular medicine 22 31863639
2016 Silencing of epidermal growth factor, latrophilin and seven transmembrane domain-containing protein 1 (ELTD1) via siRNA-induced cell death in glioblastoma. Journal of immunoassay & immunochemistry 22 27379831
2019 Targeting ELTD1, an angiogenesis marker for glioblastoma (GBM), also affects VEGFR2: molecular-targeted MRI assessment. American journal of nuclear medicine and molecular imaging 21 30911439
2022 ELTD1 deletion reduces vascular abnormality and improves T-cell recruitment after PD-1 blockade in glioma. Neuro-oncology 19 34347079
2018 ELTD1 Function in Hepatocellular Carcinoma is Carcinoma-Associated Fibroblast-Dependent. Journal of Cancer 19 30026838
2023 Tanshinone IIA normalized hepatocellular carcinoma vessels and enhanced PD-1 inhibitor efficacy by inhibiting ELTD1. Phytomedicine : international journal of phytotherapy and phytopharmacology 17 38000104
2019 ADGRL4/ELTD1 is a highly conserved angiogenesis-associated orphan adhesion GPCR that emerged with the first vertebrates and comprises 3 evolutionary variants. BMC evolutionary biology 17 31299890
2017 Antibacterial, antioxidant and cytotoxic activities of triterpenes and flavonoids from the aerial parts of Salvia barrelieri Etl. Natural product research 17 28925304
2010 DNA variation in the gene ELTD1 is associated with tick burden in cattle. Animal genetics 17 20880337
1993 The Etl-1 gene encodes a nuclear protein differentially expressed during early mouse development. Developmental dynamics : an official publication of the American Association of Anatomists 17 8219362
2006 Baculovirus ETL promoter acts as a shuttle promoter between insect cells and mammalian cells. Acta pharmacologica Sinica 16 16490168
2022 Facile NaF Treatment Achieves 20% Efficient ETL-Free Perovskite Solar Cells. ACS applied materials & interfaces 15 35979724
2021 ELTD1-An Emerging Silent Actor in Cancer Drama Play. International journal of molecular sciences 15 34068040
2020 Assessment of an scFv Antibody Fragment Against ELTD1 in a G55 Glioblastoma Xenograft Model. Translational oncology 15 32208341
2021 ELTD1 Activation Induces an Endothelial-EMT Transition to a Myofibroblast Phenotype. International journal of molecular sciences 14 34681953
2021 Adhesion G protein-coupled receptor, ELTD1, is a potential therapeutic target for retinoblastoma migration and invasion. BMC cancer 13 33430814
2020 Tumor endothelial ELTD1 as a predictive marker for treatment of renal cancer patients with sunitinib. BMC cancer 13 32321460
2021 ADGRL4/ELTD1 Expression in Breast Cancer Cells Induces Vascular Normalization and Immune Suppression. Molecular cancer research : MCR 12 34348993
2023 High efficiency Cu2MnSnS4 thin film solar cells with SnS BSF and CdS ETL layers: A numerical simulation. Heliyon 11 37159712
2021 A tale of two multi-focal therapies for glioblastoma: An antibody targeting ELTD1 and nitrone-based OKN-007. Journal of cellular and molecular medicine 11 34910361
2021 Labdane Diterpenoids from Salvia tingitana Etl. Synergize with Clindamycin against Methicillin-Resistant Staphylococcus aureus. Molecules (Basel, Switzerland) 10 34771089
2021 ELTD1 Promotes Gastric Cancer Cell Proliferation, Invasion and Epithelial-Mesenchymal Transition Through MAPK/ERK Signaling by Regulating CSK. International journal of general medicine 8 34475781
2022 STAT5A modulated EndMT via upregulation of ELTD1 expression in diabetic nephropathy. Clinical and experimental pharmacology & physiology 7 35320597
2025 ADGRL4 Promotes Cell Growth, Aggressiveness, EMT, and Angiogenesis in Neuroblastoma via Activation of ERK/STAT3 Pathway. Current molecular medicine 6 38178660
2022 ELTD1 is present in extracellular vesicles derived from endothelial cells as a cleaved extracellular domain which induces in vivo angiogenesis. Journal of extracellular biology 6 38939053
2021 Genome assembly and annotation of Photorhabdus heterorhabditis strain ETL reveals genetic features involved in pathogenicity with its associated entomopathogenic nematode and anti-host effectors with biocontrol potential applications. Gene 6 34147570
2013 Microsatellite scanning of the immunogenome associates MAPK14 and ELTD1 with graft-versus-host disease in hematopoietic stem cell transplantation. Immunogenetics 6 23474535
2012 Automated realtime data import for the i2b2 clinical data warehouse: introducing the HL7 ETL cell. Studies in health technology and informatics 6 22874194
2024 Enhancement of efficiency in CsSnI3 based perovskite solar cell by numerical modeling of graphene oxide as HTL and ZnMgO as ETL. Heliyon 5 38226290
2021 ELTD1 as a biomarker for multiple sclerosis: Pre-clinical molecular-targeted studies in a mouse experimental autoimmune encephalomyelitis model. Multiple sclerosis and related disorders 5 33517175
2024 Single-cell analysis reveals ADGRL4+ renal tubule cells as a highly aggressive cell type in clear cell renal cell carcinoma. Scientific reports 4 38287102
2025 Structure of the Gq-coupled adhesion receptor ADGRL4. Nature communications 3 41469374
2023 ELTD1 Review: New Regulator of Angiogenesis in Glioma. Current health sciences journal 3 38559823
2022 TiO2/AgO composites by one step photo reduction technique as electron transport layers (ETL) for dye-sensitized solar cells. Chemosphere 3 35598786
2025 The DNA repair factor ku80 binds and activates the adhesion receptor ELTD1/ADGRL4. Biochemical and biophysical research communications 2 40245572
2025 Computational modeling and photovoltaic performance evaluation of various ETL/HTL engineered CsCdI3-based perovskite solar cell architectures. RSC advances 2 40936958
2021 ELTD1 as a multi-focal target for malignant gliomas: preclinical studies. Neuro-oncology advances 2 34704036
2026 ADGRL4 induces adipose browning and weight loss via AKT activation. Molecular and cellular endocrinology 1 41740879
2026 Purification of the Active-State G Protein-Coupled Receptor ADGRL4 for Cryo-Electron Microscopy Using a Modular Tag System and a Tethered mini-Gq. Bio-protocol 1 41815845
2025 Advancing photovoltaics with Cs2NaInI6-based perovskites: a simulation study on ETL optimization. RSC advances 1 41090165
2021 Generation of an ELTD1 knockout human embryonic stem cell line by the iCRISPR/Cas9 system. Stem cell research 1 34087984
2026 Stress-Induced ADGRL4 Orchestrates Tumor Progression and Metastasis by Inhibiting YAP1 Signaling and Activating Angiogenesis. Cancer research 0 41734371
2026 Multifunctional 0D/2D SnO2-Mo2C litchi-pericarp-like ETL to achieve high-efficient perovskite solar cells. Journal of colloid and interface science 0 41849968
2026 Myocardial expression of ADGRL4 and AQP7 is related to regression of left ventricular hypertrophy after aortic valve replacement in a sex-dependent manner. American journal of physiology. Heart and circulatory physiology 0 42166614
2026 Proposed Schema Extensions and ETL Pathways for Integrating Wearable and Patient-Reported PGHD into OMOP-CDM for Secondary Use. Studies in health technology and informatics 0 42175235
2025 ELTD1 inhibits differentiation of hemogenic endothelium progenitors from human embryonic stem cells through the HPIP-Wnt pathway. Experimental & molecular medicine 0 40456828
2024 Performance analysis of un-doped and doped titania (TiO ) as an electron transport layer (ETL) for perovskite solar cells. Journal of molecular modeling 0 38691236

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