Affinage

Showing ADGRF5 — GPR116 is a alias.

ADGRF5

Adhesion G protein-coupled receptor F5 · UniProt Q8IZF2

Length
1346 aa
Mass
149.5 kDa
Annotated
2026-06-09
32 papers in source corpus 25 papers cited in narrative 25 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADGRF5 (GPR116/Ig-Hepta) is an adhesion G-protein-coupled receptor that acts as a cell-surface sensor coupling extracellular cues to Gαq/11 signaling across epithelial, endothelial, immune, and stem cell compartments (PMID:23684610, PMID:28570277, PMID:36073784). Like other adhesion GPCRs, it requires autocatalytic cleavage upstream of its tethered agonist (Stachel) sequence so that N-terminal fragment displacement exposes the agonist and activates the receptor; a non-cleavable knock-in mouse phenocopies the knockout pulmonary defect, establishing that this self-cleavage is obligatory for function in vivo, and the C-terminal helix 8 together with conserved Stachel and ECL2/3 residues are required for downstream signaling (PMID:36073784, PMID:42233720). Its best-defined role is in alveolar type II cells, where it senses surfactant levels — monitoring the ligand SP-D — and drives Gαq/11-dependent inositol phosphate turnover, calcium mobilization, and cortical F-actin stabilization to restrain surfactant secretion and promote recycling; loss of GPR116 or of AT2 Gnaq/Gna11 causes massive surfactant accumulation and respiratory disease (PMID:23684610, PMID:23922714, PMID:23590306, PMID:28570277). The receptor sustains epithelial transport homeostasis in the kidney, where it tonically inhibits V-ATPase trafficking and urinary acid secretion in intercalated cells (PMID:33004624), and functions as an endothelial mechanosensor, transducing shear stress through a Gαq/11-PKC-RAF1-MEK-ERK cascade that controls type IV collagen and KLF2 expression at the glomerular filtration barrier (PMID:38844335, PMID:42233720) and serving as a hydrostatic-pressure sensor in liver sinusoidal endothelium (PMID:41237250). Beyond Gαq, GPR116 engages β-arrestin1 signaling: Stachel stimulation drives nuclear β-arrestin1 that interacts with CREB to maintain the muscle stem cell pool (PMID:36384129), and β-arrestin1 mediates hepatoprotection against ER stress (PMID:39001944). The hepatokine FNDC4 binds GPR116 with high affinity to sensitize white adipocytes to insulin, linking the receptor to systemic glucose and energy homeostasis (PMID:22971422, PMID:34016966). In cancer, GPR116 promotes breast cancer migration and metastasis via Gαq-p63RhoGEF-RhoA/Rac1-driven actin remodeling and suppresses an antitumor neutrophil program through a RhoA-ERK-C/EBPβ-MMP8 axis (PMID:24008316, PMID:38937435).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 2006 Medium

    Established that GPR116 is a multiply processed adhesion-type receptor, defining the proteolytic architecture that would later prove essential for activation.

    Evidence biochemical fragment characterization and furin-inhibitor experiments

    PMID:16882675

    Open questions at the time
    • did not link cleavage to signaling or a physiological output
    • Stachel-mediated activation not yet recognized
  2. 2012 Medium

    First physiological role assigned to GPR116, showing adipose-specific deletion disrupts systemic glucose and energy homeostasis.

    Evidence adipose-specific conditional knockout mice with metabolic phenotyping

    PMID:22971422

    Open questions at the time
    • no ligand or signaling pathway identified
    • molecular mechanism in adipocytes unresolved
  3. 2013 High

    Defined the receptor's flagship role as an alveolar surfactant sensor and identified SP-D as a candidate ligand, answering what GPR116 detects and what it controls in the lung.

    Evidence global and conditional knockout mice, surfactant lipid/protein metabolic tracing, and co-IP of SP-D with the ectodomain

    PMID:23590306 PMID:23684610 PMID:23922714

    Open questions at the time
    • G protein coupling not yet demonstrated
    • whether SP-D is the activating agonist versus a co-factor unresolved
  4. 2013 Medium

    Placed GPR116 in a cancer-promoting signaling pathway, linking it to Gαq-p63RhoGEF-RhoA/Rac1-driven actin dynamics and metastasis.

    Evidence knockdown/ectopic expression in breast cancer lines plus in vivo metastasis models with pathway dissection

    PMID:24008316

    Open questions at the time
    • receptor activation mechanism in tumor cells not defined
    • endogenous activating ligand unknown
  5. 2015 Medium

    Extended GPR116 function to vascular barrier maintenance and immune regulation, showing endothelial deletion causes vascular leakage and loss provokes alveolar macrophage inflammation.

    Evidence endothelial-specific conditional knockout, oxygen-induced retinopathy model, and BAL/ROS/NF-κB/MMP analyses in knockout mice

    PMID:25778400 PMID:26394398

    Open questions at the time
    • mechanotransduction mechanism not yet delineated
    • macrophage effects could be secondary to surfactant pathology
  6. 2017 High

    Established the core signaling logic: tethered-agonist peptides activate Gαq/11 to inhibit surfactant secretion, and AT2 Gnaq/Gna11 deletion phenocopies the knockout, proving the effector pathway.

    Evidence synthetic Stachel peptides, IP/calcium/F-actin assays, and AT2-specific Gnaq/Gna11 double knockout mice

    PMID:28570277

    Open questions at the time
    • did not prove cleavage requirement in vivo
    • endogenous trigger for Stachel exposure unresolved
  7. 2017 Medium

    Revealed functional overlap with ELTD1 in non-endothelial cells controlling cardiovascular and renal development through genetic epistasis.

    Evidence single and double knockout plus cell-type-specific conditional double knockout mice

    PMID:28806758

    Open questions at the time
    • responsible cell type not identified
    • molecular basis of ADGRF5/ELTD1 redundancy unknown
  8. 2019 Medium

    Connected GPR116 loss to specific inflammatory and vascular-patterning programs, positioning CCL2/CCR2 signaling downstream and implicating the receptor in CNS endothelial and retinal vascular morphogenesis.

    Evidence knockout mice with CCR2-antagonist intervention; retinal vascular imaging compared with Rac1 knockout

    PMID:30654796 PMID:31256320

    Open questions at the time
    • whether inflammatory changes are cell-autonomous unresolved
    • link between receptor signaling and CCL2 induction not mechanistically traced
  9. 2020 High

    Defined a renal epithelial role, showing GPR116 tonically inhibits V-ATPase trafficking to restrain urinary acid secretion, with synthetic agonist functionally rescuing proton flux.

    Evidence kidney-specific knockout mice, immunogold EM of V-ATPase, split-open duct proton flux with agonist peptide, and blood gas analysis

    PMID:33004624

    Open questions at the time
    • physiological ligand in the collecting duct unknown
    • G protein/effector linking receptor to V-ATPase trafficking not identified
  10. 2021 High

    Identified FNDC4 as a direct high-affinity ligand mediating the receptor's white-adipocyte insulin-sensitizing function, providing a molecular ligand for the 2012 metabolic phenotype.

    Evidence direct binding assay, knockout mice, FcsFNDC4 supplementation in prediabetic mice, and glucose uptake assays

    PMID:34016966

    Open questions at the time
    • whether FNDC4 acts as a Stachel-exposing agonist or allosteric modulator unresolved
    • G protein/arrestin branch driving insulin sensitization not defined
  11. 2022 High

    Demonstrated obligatory autocatalytic cleavage for activation and a β-arrestin1 branch, showing a non-cleavable knock-in phenocopies the lung defect and that nuclear β-arrestin1-CREB signaling maintains muscle stem cells.

    Evidence non-cleavable knock-in mice, mutagenesis/species-swapping, Stachel stimulation, β-arrestin nuclear fractionation, and CREB co-IP

    PMID:36073784 PMID:36384129

    Open questions at the time
    • structural basis of Stachel:ECL engagement modeled but not solved
    • balance between Gαq and β-arrestin branches across tissues unclear
  12. 2023 Medium

    Expanded GPR116 into immune and hepatic injury contexts, showing it negatively regulates NK antitumor function via Gαq/HIF1α/NF-κB and promotes hepatocyte ferroptosis by suppressing the system Xc-/GSH/GPX4 axis.

    Evidence knockout mice and NK cytotoxicity/tumor models; hepatocyte-specific knockout and overexpression with ferroptosis pathway readouts

    PMID:36895027 PMID:37266730

    Open questions at the time
    • activating ligands in NK cells and hepatocytes unidentified
    • direct receptor-to-pathway coupling steps incompletely defined
  13. 2024 Medium

    Resolved the receptor as an endothelial mechanosensor and refined its β-arrestin1 and RhoA-ERK signaling roles in kidney filtration, hepatoprotection, breast cancer neutrophil polarization, and pancreatic islet biology.

    Evidence glomerular endothelial knockout/human-cell knockdown, β-arrestin1/BiP co-IP with APAP/FNDC4 models, RhoA-ERK-C/EBPβ-MMP8 dissection, and islet-specific knockout secretion assays

    PMID:38228886 PMID:38844335 PMID:38937435 PMID:39001944

    Open questions at the time
    • how a single receptor selects Gαq versus β-arrestin outputs by tissue unresolved
    • force-to-Stachel coupling mechanism not directly shown
  14. 2025 Medium

    Confirmed GPR116 as a pressure/shear mechanosensor in vascular endothelium and delineated its shear cascade, establishing the full Gαq/11-PKC-RAF1-MEK-ERK pathway with Stachel and helix 8 requirements.

    Evidence hepatic hypertension-on-a-chip with LSEC silencing and cirrhotic models; flow assays with inhibitor/knockdown/mutagenesis and human primary glomerular endothelial validation

    PMID:41237250 PMID:42233720

    Open questions at the time
    • physical mechanism converting force into NTF displacement not directly demonstrated
    • in vivo relevance of helix 8 requirement untested

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how GPR116 physically converts diverse stimuli (SP-D, FNDC4, shear, hydrostatic pressure) into tethered-agonist exposure, and what governs the tissue-specific choice between Gαq/11 and β-arrestin1 signaling outputs.
  • no atomic structure of the activated receptor
  • no unified model linking ligand binding, force, and cleavage-dependent activation
  • determinants of Gαq-versus-arrestin bias unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140299 molecular sensor activity 4 GO:0060089 molecular transducer activity 3 GO:0048018 receptor ligand activity 2 GO:0140096 catalytic activity, acting on a protein 2
Localization
GO:0005886 plasma membrane 4
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1430728 Metabolism 2 R-HSA-168256 Immune System 2 R-HSA-382551 Transport of small molecules 2
Partners
ARRB1BIP (HSPA5)CREBELTD1FNDC4GNA11GNAQSP-D (SFTPD)

Evidence

Reading pass · 25 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2013 GPR116 promotes breast cancer cell migration and invasion through the Gαq-p63RhoGEF-RhoA/Rac1 pathway, modulating lamellipodia formation and actin stress fibers in a RhoA- and Rac1-dependent manner. Knockdown in MDA-MB-231 cells, ectopic expression in MCF-7/Hs578T cells, in vivo mammary tumor metastasis mouse models, pathway dissection via Gαq-p63RhoGEF-RhoA/Rac1 signaling analysis Cancer research Medium 24008316
2013 GPR116 expression in alveolar type II (ATII) cells is required for maintaining normal pulmonary surfactant homeostasis; global and conditional knockout mice show progressive surfactant lipid and protein accumulation, labored breathing, and reduced lifespan. Global Gpr116 gene disruption in mice, bone marrow transplantation studies, conditional knockout mice with cell-type-specific deletion, surfactant structure/function analysis Cell reports High 23684610
2013 Surfactant protein D (SP-D) was identified as a ligand of Ig-Hepta/GPR116; GPR116 on alveolar type II cells senses surfactant levels by monitoring SP-D concentration, and its signaling attenuates surfactant lipid/protein synthesis and secretion while stimulating surfactant recycling/uptake. Co-expression of SP-D and extracellular region of Ig-Hepta/GPR116 followed by immunoprecipitation; radioactive tracer studies of surfactant metabolism in wildtype vs knockout mice PloS one Medium 23922714
2013 GPR116 functions as a molecular sensor of alveolar surfactant lipid pool sizes by regulating surfactant secretion; knockout mice show 12–30-fold accumulation of alveolar surfactant phospholipids with increased saturated phosphatidylcholine synthesis; P2RY2 purinergic receptor is induced in knockout type II cells. Targeted mutation of Gpr116 locus (Gpr116Δexon17) in mice, mRNA microarray analyses, lipid quantification American journal of respiratory cell and molecular biology High 23590306
2006 Ig-Hepta/GPR116 undergoes multiple proteolytic processing events yielding four fragments (presequence, proEGF2/alpha, Ig repeats/beta-chain, TM7/gamma-chain); the proEGF2 region is cleaved by furin to generate EGF2 and the alpha-fragment influences expression of some mRNA species. Biochemical characterization of processing fragments, furin inhibitor experiments, mRNA expression analysis Journal of biochemistry Medium 16882675
2017 GPR116/ADGRF5 controls surfactant secretion and reuptake in alveolar type II cells via Gq/11 signaling; synthetic agonist peptides derived from the GPR116 ectodomain activated Gq/11-dependent inositol phosphate conversion, calcium mobilization, and cortical F-actin stabilization to inhibit surfactant secretion; AT2 cell-specific deletion of Gnaq and Gna11 phenocopied GPR116 knockout surfactant accumulation. Synthetic tethered agonist peptides, inositol phosphate conversion assay, calcium mobilization assay, F-actin imaging, AT2 cell-specific Gnaq/Gna11 double knockout mice JCI insight High 28570277
2015 Loss of Gpr116 in mice causes cerebral vascular leakage beginning at ~1.5 months; endothelial-specific deletion of Gpr116 results in significant increase of brain vascular leakage, and Gpr116 knockout mice show attenuated pathological retinal vascular response in oxygen-induced retinopathy, indicating Gpr116 modulates endothelial barrier properties. Constitutive Gpr116 knockout mouse model (exon 4–21 deletion), endothelial-specific conditional knockout, oxygen-induced retinopathy model, vascular permeability assays PloS one Medium 26394398
2015 Ig-Hepta/GPR116 deficiency leads to activation of alveolar macrophages producing reactive oxygen species, NF-κB activation and nuclear translocation in alveolar macrophages, and release of MMP-2 and MMP-9; monocyte chemotactic protein-1 (MCP-1) is elevated in embryonic lungs of knockout mice, suggesting GPR116 regulates macrophage immune responses. Analysis of bronchoalveolar lavage fluid from knockout mice, ROS detection, NF-κB immunofluorescence, MMP inhibitor experiments, MCP-1 ELISA The Journal of biological chemistry Medium 25778400
2017 Loss of both GPR116 and ELTD1 (but not either alone) in mice causes aortic arch artery and cardiac outflow tract malformations, renal thrombotic microangiopathy, hemolysis, and splenomegaly; these phenotypes are not recapitulated by endothelial- or neural crest-specific double deletions, indicating expression in non-endothelial, non-neural crest cells accounts for these defects. Double knockout mouse model, endothelial-specific and neural crest-specific conditional double knockouts, histological and cardiovascular analyses PloS one Medium 28806758
2012 Adipose tissue-specific deletion of Gpr116 in mice causes glucose intolerance and insulin resistance, hepatosteatosis, reduced circulating adiponectin, and increased serum resistin, indicating GPR116 controls adipocyte biology and systemic energy homeostasis. Adipose tissue-specific conditional Gpr116 knockout mice on standard chow and high-fat diet, glucose tolerance tests, insulin tolerance tests, serum adipokine measurements FEBS letters Medium 22971422
2021 FNDC4 (a hepatokine) directly binds GPR116 in white adipose tissue with high affinity; sFNDC4 binding to GPR116 promotes insulin signaling and insulin-mediated glucose uptake in white adipocytes; GPR116 mediates the insulin-sensitizing effects of FNDC4 in a white-adipocyte-selective manner. Direct binding assay (high-affinity binding of sFNDC4 to GPR116), GPR116 knockout mice, FcsFNDC4 supplementation in prediabetic mice, glucose uptake assays Nature communications High 34016966
2020 Kidney-specific knockout of Gpr116 causes urinary acidification (reduced urine pH), increased blood pH, decreased pCO2, and greater accumulation of V-ATPase at the apical surface of acid-secreting A-intercalated cells; pretreatment with synthetic Gpr116 agonist peptide inhibits proton flux in intercalated cells; Gpr116 tonically inhibits V-ATPase trafficking and urinary acid secretion in the collecting duct. Kidney-specific Gpr116 knockout mice, immunogold electron microscopy of V-ATPase localization, split-open collecting duct proton flux assay with synthetic agonist peptide, blood gas analysis Proceedings of the National Academy of Sciences of the United States of America High 33004624
2019 Loss of ADGRF5 in mice results in upregulation of CCL2, S100a8, and S100a9 in embryonic and neonatal lungs and in lung endothelial cells; RS504393 (CCR2 antagonist) treatment suppressed downstream inflammatory gene upregulation, placing ADGRF5-mediated CCL2 signaling upstream of airway inflammation including type 2 immune responses. Adgrf5 knockout mice, qPCR and western blotting of primary lung endothelial cells, pharmacological intervention with RS504393, histology, BAL cell counting, ELISA Respiratory research Medium 30654796
2022 GPR116 maintains the muscle stem cell (MuSC) pool via nuclear functions of β-arrestin1; Stachel (tethered agonist) peptide stimulation of GPR116 leads to strong β-arrestin interaction and increased nuclear localization of β-arrestin1, where it interacts with CREB to regulate gene expression; GPR116-deficient MuSCs show progressive depletion and defective self-renewal. Gpr116 knockout mice, Stachel peptide stimulation, β-arrestin interaction assays, nuclear fractionation/localization studies, CREB co-immunoprecipitation, MuSC isolation and self-renewal assays Cell reports Medium 36384129
2022 Autocatalytic cleavage upstream of the GPR116 tethered agonist (Stachel) sequence is required for N-terminal fragment (NTF) displacement and receptor activation; a non-cleavable GPR116 knock-in mouse phenocopies the pulmonary phenotype of GPR116 knockout mice; key conserved amino acids in the Stachel sequence and ECL2/3 are required for receptor activation, and residues in TM7 mediate stronger signaling in mouse vs. human GPR116. Non-cleavable knock-in mouse model, site-directed mutagenesis, species-swapping approaches, in vitro signaling assays, molecular modeling of tethered agonist:ECL2 interactions eLife High 36073784
2019 ADGRF5/Gpr116 is highly expressed in CNS endothelium and regulates blood-brain barrier formation; Adgrf5 mutant retinae show increased perivenous vascular density and abnormal projections toward the inner plexus, with transient vascular protrusions into the inner retinal space, implicating ADGRF5 in vein-derived endothelial patterning of the deep retinal layer. Adgrf5 knockout mouse model, retinal vascular imaging, endothelial-specific analyses, comparison with Rac1 knockout retinae Angiogenesis Medium 31256320
2023 GPR116 promotes ferroptosis in sepsis-induced liver injury by inhibiting the system Xc-/GSH/GPX4 pathway, aggravating mitochondrial damage and lipid peroxidation; hepatocyte-specific GPR116 deletion prevents hepatic ferroptosis and alleviates sepsis-induced liver dysfunction. Hepatocyte-specific GPR116 knockout mice (in vivo sepsis model), GPR116 overexpression experiments, measurement of system Xc-/GSH/GPX4 pathway components, mitochondrial and lipid peroxidation assays Cell biology and toxicology Medium 37266730
2024 In breast cancer cells, ADGRF5 inhibits ERK1/2 activity by enhancing RhoA activation, leading to decreased phosphorylation of C/EBPβ at Thr235, hindering its nuclear translocation and subsequent MMP8 transcriptional activation; ADGRF5 silencing increases MMP8 expression, CXCL8 secretion, and shifts tumor-associated neutrophils toward antitumor N1 phenotype. ADGRF5 knockdown in breast cancer cells, RhoA activation assays, ERK1/2 phosphorylation, C/EBPβ Thr235 phosphorylation and nuclear translocation, MMP8 promoter analysis, in vivo tumor models Cell death & disease Medium 38937435
2024 GPR116 is expressed in pancreatic delta cells and regulates somatostatin release; whole-body GPR116 deficiency also causes decreased beta-cell mass, lower number of small islets, and reduced pancreatic insulin content; glucose homeostasis in global knockout mice is maintained by counter-acting mechanisms modulating insulin degradation. Whole-body and cell-specific Gpr116 knockout mouse models, islet hormone secretion assays, histomorphometry of pancreatic islets, insulin content measurement Communications biology Medium 38228886
2024 GPR116 protects against acetaminophen-induced liver injury by interacting with β-arrestin1, which in turn inhibits BiP (a critical ER stress regulator), thereby mitigating ER stress; activation of GPR116 by its ligand FNDC4 confers protection against early hepatotoxicity. Hepatocyte-specific GPR116 knockout mice, GPR116 overexpression, co-immunoprecipitation of GPR116 with β-arrestin1 and BiP, RNA-sequencing, APAP challenge model, FNDC4 treatment Cellular and molecular life sciences Medium 39001944
2024 ADGRF5 loss in glomerular endothelial cells alters expression of type IV collagens (COL4A3, COL4A4) and the mechanosensitive transcription factor KLF2, leading to glomerular filtration barrier dysfunction, albuminuria, and impaired kidney function; ADGRF5 knockdown in human primary glomerular endothelial cells reproduces these gene expression changes. Adgrf5 knockout mice (histology, kidney function tests), ADGRF5 siRNA knockdown in human primary glomerular endothelial cells, gene/protein expression analysis Journal of the American Society of Nephrology Medium 38844335
2023 GPR116 negatively regulates NK cell antitumor function via the Gαq/HIF1α/NF-κB signaling pathway; GPR116-deficient NK cells show higher cytotoxicity and produce more GzmB and IFNγ; downregulation of GPR116 in NKG2D-CAR-NK92 cells enhances their antitumor activity. GPR116 knockout mice, in vitro NK cell cytotoxicity assays, in vivo tumor models with GPR116-/- NK cells, pathway analysis (Gαq/HIF1α/NF-κB) Cell & bioscience Medium 36895027
2025 GPR116 was identified as the key hydrostatic pressure mechanosensor in liver sinusoidal endothelial cells (LSECs); genetic silencing of GPR116 protected endothelial cells from hydrostatic pressure-induced damage in vitro and in cirrhotic murine models, and its downstream mechanotransduction pathway was delineated. Hepatic hypertension-on-a-chip system (2D static and 3D dynamic), genetic silencing of GPR116 in LSECs, cirrhotic murine models, cell- and gene-based therapies Science advances Medium 41237250
2026 ADGRF5 mediates shear stress mechanotransduction in glomerular endothelial cells via the Gαq/11-PKC-RAF1-MEK1/2-ERK1/2 cascade; activation requires the tethered agonist (Stachel) sequence and C-terminal helix 8; ADGRF5 knockdown attenuates shear flow-induced immediate early response genes and COL4A3/COL4A4 expression in human primary renal glomerular endothelial cells. ADGRF5 overexpression in PEAKrapid cells under laminar flow, inhibitor and knockdown experiments, mutagenesis of Stachel sequence and helix 8, endogenous validation in human primary renal glomerular endothelial cells Journal of biochemistry High 42233720
2018 Organic barn dust increases GPR116 mRNA expression via protein kinase C alpha (PKCα) signaling, which in turn inhibits SP-D (surfactant protein D) production in alveolar epithelial cells; PKCα inhibition reverses both GPR116 upregulation and SP-D suppression. PKCα inhibitor experiments in human alveolar epithelial cell line and in vivo mouse model, mRNA and protein expression analysis of SP-D and GPR116 PloS one Low 30543664

Source papers

Stage 0 corpus · 32 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2013 GPR116, an adhesion G-protein-coupled receptor, promotes breast cancer metastasis via the Gαq-p63RhoGEF-Rho GTPase pathway. Cancer research 95 24008316
2013 Essential regulation of lung surfactant homeostasis by the orphan G protein-coupled receptor GPR116. Cell reports 67 23684610
2013 Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D. PloS one 62 23922714
2013 Orphan G protein-coupled receptor GPR116 regulates pulmonary surfactant pool size. American journal of respiratory cell and molecular biology 61 23590306
2017 Epithelial Gpr116 regulates pulmonary alveolar homeostasis via Gq/11 signaling. JCI insight 56 28570277
2021 Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue. Nature communications 51 34016966
2015 Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium. PloS one 51 26394398
2012 Adipose tissue deletion of Gpr116 impairs insulin sensitivity through modulation of adipose function. FEBS letters 47 22971422
2017 Developmental vascular remodeling defects and postnatal kidney failure in mice lacking Gpr116 (Adgrf5) and Eltd1 (Adgrl4). PloS one 37 28806758
2019 Loss of the adhesion G-protein coupled receptor ADGRF5 in mice induces airway inflammation and the expression of CCL2 in lung endothelial cells. Respiratory research 36 30654796
2020 Adhesion-GPCR Gpr116 (ADGRF5) expression inhibits renal acid secretion. Proceedings of the National Academy of Sciences of the United States of America 33 33004624
2020 Recurrent novel THBS1-ADGRF5 gene fusion in a new tumor subtype "Acral FibroChondroMyxoid Tumors". Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc 24 32047233
2015 Targeted Disruption of Ig-Hepta/Gpr116 Causes Emphysema-like Symptoms That Are Associated with Alveolar Macrophage Activation. The Journal of biological chemistry 24 25778400
2023 GPR116 promotes ferroptosis in sepsis-induced liver injury by suppressing system Xc-/GSH/GPX4. Cell biology and toxicology 22 37266730
2006 Multiple processing of Ig-Hepta/GPR116, a G protein-coupled receptor with immunoglobulin (Ig)-like repeats, and generation of EGF2-like fragment. Journal of biochemistry 22 16882675
2022 The adhesion G-protein-coupled receptor Gpr116 is essential to maintain the skeletal muscle stem cell pool. Cell reports 21 36384129
2019 Adgrf5 contributes to patterning of the endothelial deep layer in retina. Angiogenesis 17 31256320
2020 In silico molecular docking and physicochemical property studies on effective phytochemicals targeting GPR116 for breast cancer treatment. Molecular and cellular biochemistry 16 33106912
2022 Regulation of pulmonary surfactant by the adhesion GPCR GPR116/ADGRF5 requires a tethered agonist-mediated activation mechanism. eLife 15 36073784
2024 The adhesion-GPCR ADGRF5 fuels breast cancer progression by suppressing the MMP8-mediated antitumorigenic effects. Cell death & disease 13 38937435
2023 The transcription factor Foxi1 promotes expression of V-ATPase and Gpr116 in M-1 cells. American journal of physiology. Renal physiology 9 36603001
2023 GPR116 receptor regulates the antitumor function of NK cells via Gαq/HIF1α/NF-κB signaling pathway as a potential immune checkpoint. Cell & bioscience 9 36895027
2025 Single-cell multi-omic and spatial profiling of esophageal squamous cell carcinoma reveals the immunosuppressive role of GPR116+ pericytes in cancer metastasis. Nature genetics 7 41073785
2024 The adhesion GPCR GPR116/ADGRF5 has a dual function in pancreatic islets regulating somatostatin release and islet development. Communications biology 7 38228886
2024 Glomerular Endothelial Cell Receptor Adhesion G-Protein-Coupled Receptor F5 (ADGRF5) and the Integrity of the Glomerular Filtration Barrier. Journal of the American Society of Nephrology : JASN 7 38844335
2018 Organic barn dust inhibits surfactant protein D production through protein kinase-c alpha dependent increase of GPR116. PloS one 5 30543664
2024 GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress. Cellular and molecular life sciences : CMLS 4 39001944
2025 Hepatic hypertension on-a-chip identifies GPR116 as a hydrostatic pressure mechanosensor to regulate vascular injury in cirrhosis. Science advances 3 41237250
2025 Transcriptome analysis and CRISPR-Cas9-mediated mutagenesis identify gpr116 as a candidate gene for growth promotion in grass carp (Ctenopharyngodon idella). Comparative biochemistry and physiology. Part A, Molecular & integrative physiology 2 40158793
2026 Endothelial ADGRF5(GPR116) governs vascular adaptation required for sustained thermogenic remodeling of brown adipose tissue. Molecular metabolism 0 41796902
2026 Serum Exosomal ADGRF5: A Potential Diagnostic Biomarker for Metastasis in Triple-Negative Breast Cancer. Journal of proteome research 0 42081321
2026 Adhesion G protein-coupled receptor F5 (ADGRF5) mediates shear stress mechanotransduction in glomerular endothelial cells. Journal of biochemistry 0 42233720

Missed literature

Know a paper Affinage missed for ADGRF5? Flag it for the maintainers and the community.

No submissions yet.