Affinage

ADGRF5

Adhesion G protein-coupled receptor F5 · UniProt Q8IZF2

Length
1346 aa
Mass
149.5 kDa
Annotated
2026-04-28
30 papers in source corpus 24 papers cited in narrative 24 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

ADGRF5 (GPR116) is an adhesion G protein-coupled receptor that functions as a molecular sensor across multiple epithelial, endothelial, and mesenchymal tissues, integrating extracellular cues—including surfactant protein D, soluble FNDC4, and hydrostatic pressure—to regulate secretory homeostasis, barrier integrity, and metabolic signaling. Autocatalytic cleavage of the ectodomain exposes a tethered agonist (Stachel) sequence that activates the receptor through interactions with extracellular loops 2/3 and TM7, coupling primarily to Gαq/11 to drive inositol phosphate turnover, calcium mobilization, and cortical F-actin stabilization; a non-cleavable knock-in phenocopies the knockout surfactant accumulation (PMID:36073784, PMID:28570277). In alveolar type II cells, ADGRF5–Gαq/11 signaling restrains surfactant secretion and promotes reuptake, and its loss causes massive phospholipid accumulation, macrophage activation, and emphysema-like pathology (PMID:23684610, PMID:25778400); in renal intercalated cells it controls apical V-ATPase trafficking and acid secretion (PMID:33004624), while in endothelium it maintains CNS vascular barrier integrity, glomerular basement membrane composition, and acts as a hydrostatic pressure mechanosensor (PMID:26394398, PMID:38844335, PMID:41237250). Beyond Gαq, ADGRF5 signals through β-arrestin1 nuclear translocation to interact with CREB and maintain muscle stem cell quiescence, and engages RhoA/Rac1 to regulate cell motility (PMID:36384129, PMID:24008316).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 Medium

    Establishing that GPR116 undergoes multi-step proteolytic processing—including furin cleavage of the proEGF2 region—provided the first biochemical framework for its ectodomain maturation, though the functional significance of individual fragments was unclear.

    Evidence Biochemical processing analysis and furin cleavage site identification in vitro

    PMID:16882675

    Open questions at the time
    • Functional consequence of each fragment not established
    • GAIN domain autocleavage not yet distinguished from furin processing
    • In vivo relevance of processing not tested
  2. 2012 Medium

    Adipose-specific deletion revealed that GPR116 is required for systemic glucose homeostasis and adipokine regulation, broadening the receptor's role beyond lung to metabolic tissues.

    Evidence Adipose-specific conditional KO mice with glucose/insulin tolerance tests and serum adipokine measurements

    PMID:22971422

    Open questions at the time
    • Downstream signaling pathway in adipocytes not defined
    • Direct versus indirect metabolic effects not resolved
    • Single lab
  3. 2013 High

    Multiple independent knockout studies converged on GPR116 as a critical sensor of alveolar surfactant pool size in type II pneumocytes, with loss causing massive surfactant accumulation, and SP-D was identified as an extracellular ligand engaging the ectodomain to couple surfactant sensing to secretion/reuptake control.

    Evidence Global and conditional Gpr116 KO mice from multiple labs; SP-D co-IP with GPR116 ectodomain; radioactive tracer surfactant metabolism; lipid quantification and mRNA microarray

    PMID:23590306 PMID:23684610 PMID:23922714

    Open questions at the time
    • SP-D as ligand confirmed by co-IP but direct binding affinity not measured with purified components
    • Downstream G-protein coupling in AT2 cells not yet identified
    • Mechanism by which GPR116 distinguishes surfactant pool size unknown
  4. 2013 High

    In parallel, GPR116 was placed in the Gαq–p63RhoGEF–RhoA/Rac1 signaling axis controlling cancer cell migration, providing the first pathway-level resolution of downstream effectors.

    Evidence shRNA knockdown and overexpression in breast cancer cell lines, in vitro migration/invasion assays, mouse metastasis model

    PMID:24008316

    Open questions at the time
    • Whether Gαq coupling in cancer cells reflects normal physiology unresolved
    • Direct Gαq interaction not shown biochemically at this stage
  5. 2015 High

    GPR116 loss was shown to trigger secondary inflammatory cascades—macrophage activation with NF-κB translocation, ROS, and MMP upregulation in lung, and endothelial barrier compromise in CNS vasculature—extending its role from surfactant homeostasis to tissue protection.

    Evidence Gpr116 KO mice with bronchoalveolar lavage, NF-κB/ROS assays, MMP measurements; endothelial-specific conditional KO with vascular leakage assays and oxygen-induced retinopathy model

    PMID:25778400 PMID:26394398

    Open questions at the time
    • Whether inflammatory phenotype is cell-autonomous or secondary to surfactant excess not fully dissected
    • Endothelial ligand/activation mechanism unknown
  6. 2017 High

    The Gαq/11 pathway was definitively established as the effector coupling downstream of GPR116 in AT2 cells: synthetic Stachel peptides activated Gq-dependent IP turnover and calcium flux, and AT2-specific Gnaq/Gna11 double KO phenocopied the surfactant defect, resolving the core signaling mechanism.

    Evidence Synthetic tethered agonist peptide assays, IP conversion, calcium mobilization, F-actin imaging, AT2-specific Gnaq/Gna11 conditional KO epistasis

    PMID:28570277

    Open questions at the time
    • Whether Gαq/11 is the sole G-protein effector or whether Gα12/13 contributes not tested
    • Endogenous ligand-triggered versus constitutive activation balance unclear
  7. 2019 Medium

    Lung endothelial cells were identified as a source of CCL2-driven inflammation upon ADGRF5 loss, and retinal vascular patterning defects in KO mice established an endothelial-autonomous role in angiogenic regulation.

    Evidence Adgrf5 KO mice with primary lung EC gene expression, CCR2 inhibitor rescue; KO retinal angiogenesis analysis

    PMID:30654796 PMID:31256320

    Open questions at the time
    • Endothelial GPR116 ligand and downstream signaling pathway not identified
    • CCL2 upregulation mechanism in ECs not resolved
  8. 2020 High

    GPR116 was shown to regulate renal acid–base balance by controlling apical V-ATPase accumulation in intercalated cells, with synthetic Stachel peptide directly inhibiting proton flux, demonstrating a second epithelial tissue where GPR116 governs vesicular trafficking.

    Evidence Kidney-specific KO mice, immunogold EM, split-open collecting duct proton flux assay with synthetic agonist peptide

    PMID:33004624

    Open questions at the time
    • G-protein coupling in intercalated cells not confirmed
    • Endogenous trigger for GPR116 activation in kidney unknown
    • Whether V-ATPase trafficking is direct or secondary not established
  9. 2021 High

    Soluble FNDC4 was identified as a high-affinity ligand for GPR116 in adipocytes, coupling receptor engagement to enhanced insulin signaling and glucose uptake—providing the first ligand-receptor pair validated by direct binding and in vivo receptor-dependent rescue.

    Evidence Direct binding assay, GPR116 KO adipocytes, in vivo FcsFNDC4 rescue requiring GPR116, glucose tolerance tests in prediabetic mice

    PMID:34016966

    Open questions at the time
    • Whether FNDC4 and SP-D compete for the same binding site unknown
    • Signaling pathway downstream of FNDC4–GPR116 not fully resolved
    • Tissue-specific ligand hierarchy not determined
  10. 2022 High

    The requirement for autocatalytic ectodomain cleavage was proven in vivo: a non-cleavable GPR116 knock-in phenocopied the KO, and systematic mutagenesis mapped the Stachel sequence and ECL2/3 residues essential for activation, with TM7 residues governing species-specific signaling strength.

    Evidence Non-cleavable knock-in mice, site-directed mutagenesis, species-swapping, in vitro tethered agonist assays, in vivo pulmonary phenotyping

    PMID:36073784

    Open questions at the time
    • No crystal/cryo-EM structure of GPR116 available
    • Whether cleavage occurs constitutively or is regulated by ligand binding unknown
  11. 2022 High

    A β-arrestin1-dependent, G-protein-independent signaling arm was uncovered in muscle stem cells: GPR116 Stachel activation drives β-arrestin1 nuclear translocation and CREB interaction to maintain quiescence, revealing biased signaling capacity.

    Evidence Conditional KO in MuSCs, Stachel peptide stimulation, β-arrestin interaction assays, nuclear fractionation, co-IP with CREB, self-renewal assays

    PMID:36384129

    Open questions at the time
    • Whether β-arrestin and Gαq arms are simultaneously active or represent biased agonism in different tissues not tested
    • Transcriptional targets of β-arrestin1–CREB complex not catalogued
  12. 2023 Medium

    GPR116's Gαq coupling was extended to NK cells (regulating cytotoxicity via HIF1α/NF-κB) and to hepatocyte ferroptosis (via system Xc−/GSH/GPX4 suppression), revealing broad tissue-specific effector pathway engagement.

    Evidence GPR116 KO mouse NK cell assays with pathway inhibitors; hepatocyte-specific KO/OE with ferroptosis marker assays

    PMID:36895027 PMID:37266730

    Open questions at the time
    • NK cell role based on single lab
    • Ferroptosis role based on single lab with no independent replication
    • Direct Gαq coupling in hepatocytes not biochemically confirmed
  13. 2024 Medium

    GPR116 was identified as a hydrostatic pressure mechanosensor in liver sinusoidal endothelial cells and was further shown to maintain glomerular endothelial integrity, regulate breast cancer immune evasion via RhoA–ERK–C/EBPβ–MMP8, and participate in pancreatic delta cell somatostatin release and beta cell mass maintenance.

    Evidence Hepatic hypertension-on-a-chip with GPR116 silencing and cirrhotic mouse validation; glomerular EC KO with EM and gene expression; breast cancer cell KD with ERK/RhoA assays and tumor models; pancreatic KO with secretion assays and islet morphometry; β-arrestin1–BiP co-IP in hepatocytes

    PMID:38228886 PMID:38844335 PMID:38937435 PMID:39001944 PMID:41237250

    Open questions at the time
    • Mechanosensor activation mechanism (conformational change under pressure) not elucidated
    • Whether glomerular and hepatic endothelial roles share common signaling axis unknown
    • Pancreatic delta cell signaling pathway not characterized

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of tethered agonist–receptor activation (no high-resolution structure exists), the hierarchy and tissue specificity of multiple reported ligands (SP-D, FNDC4, mechanical force), and whether G-protein versus β-arrestin biased signaling is determined by ligand identity, tissue context, or receptor processing state.
  • No cryo-EM or crystal structure of GPR116
  • Ligand competition or cooperativity between SP-D, FNDC4, and mechanical stimuli not tested
  • Biased agonism determinants unresolved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0140299 molecular sensor activity 3 GO:0098772 molecular function regulator activity 2
Localization
GO:0005886 plasma membrane 4 GO:0005576 extracellular region 2
Pathway
R-HSA-382551 Transport of small molecules 4 R-HSA-168256 Immune System 3 R-HSA-1430728 Metabolism 2 R-HSA-9609507 Protein localization 1
Partners
ARRB1CREB1FNDC4GNA11GNAQRAC1RHOASFTPD

Evidence

Reading pass · 24 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. shRNA knockdown, ectopic overexpression, in vitro migration/invasion assays, mouse metastasis models, pathway analysis Cancer research High 24008316
2013 GPR116 expression in alveolar type II (ATII) cells is required for maintaining normal pulmonary surfactant levels; global and conditional knockout mice develop progressive surfactant lipid and protein accumulation, labored breathing, and reduced lifespan. Global and conditional (cell-type-specific) Gpr116 knockout mice, bone marrow transplantation, histology, biochemical analysis of surfactant Cell reports High 23684610
2013 GPR116 functions as a molecular sensor of alveolar surfactant lipid pool size, regulating surfactant secretion; loss of GPR116 causes 12–30-fold accumulation of surfactant phospholipids and induces P2RY2 (purinergic receptor) expression in type II cells. Targeted Gpr116 knockout mice, lipid quantification, mRNA microarray, histology American journal of respiratory cell and molecular biology High 23590306
2013 Surfactant protein D (SP-D) was identified as a ligand of Ig-Hepta/GPR116 by co-expression and immunoprecipitation; GPR116 senses alveolar surfactant levels by monitoring SP-D and its signaling attenuates surfactant lipid/protein synthesis, secretion, and stimulates recycling/uptake. Co-expression and co-immunoprecipitation of SP-D with extracellular region of GPR116, radioactive tracer surfactant metabolism assays in KO vs WT mice PloS one High 23922714
2006 Ig-Hepta/GPR116 undergoes multiple proteolytic processing events: furin cleaves the proEGF2 region (residues 25–223) to generate EGF2 (residues 52–223), yielding four fragments (presequence, proEGF2/alpha, Ig-repeat beta-chain, TM7 gamma-chain); the alpha-fragment affects expression of certain mRNA species. Biochemical processing analysis, identification of furin cleavage site, mRNA expression assays Journal of biochemistry Medium 16882675
2015 Loss of Gpr116 in the lung results in macrophage activation, NF-κB nuclear translocation in alveolar macrophages, excessive ROS accumulation, and upregulation of MMP-2 and MMP-9 from alveolar macrophages, leading to emphysema-like pathology; increased monocyte chemotactic protein-1 (MCP-1) is observed in embryonic KO lungs prior to macrophage accumulation. Gpr116 knockout mouse model, bronchoalveolar lavage cytokine/lipid peroxide/MMP assays, NF-κB nuclear translocation assays, ROS detection, inhibitor experiments The Journal of biological chemistry High 25778400
2015 Endothelial-specific deletion of Gpr116 causes significant cerebral vascular leakage and attenuated pathological retinal vascular response in oxygen-induced retinopathy, demonstrating that Gpr116 modulates endothelial barrier properties in the CNS vasculature. Constitutive and endothelial-specific conditional Gpr116 knockout mice, vascular leakage assays, oxygen-induced retinopathy model PloS one High 26394398
2017 GPR116 controls surfactant secretion and reuptake in alveolar type II (AT2) cells through Gq/11 signaling; synthetic tethered 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/Gna11 phenocopied the Gpr116-/- surfactant accumulation phenotype. Synthetic agonist peptide assays, inositol phosphate conversion, calcium mobilization, F-actin assays, AT2 cell-specific Gnaq/Gna11 conditional KO, epistasis JCI insight High 28570277
2017 Loss of GPR116 and ELTD1 (ADGRL4) together in endothelial cells causes aortic arch malformations, cardiac outflow tract defects, and renal thrombotic microangiopathy; endothelial-specific or neural crest-specific deletion of both did not fully recapitulate the phenotype, indicating non-endothelial/non-neural crest expression accounts for cardiovascular defects. Double-KO mouse model, endothelial-specific and neural crest-specific conditional KO, cardiovascular and renal histopathology PloS one Medium 28806758
2019 Loss of ADGRF5 leads to airway inflammation including CCL2 upregulation specifically in lung endothelial cells; CCL2-mediated inflammation contributes to downstream inflammatory gene upregulation (S100a8, S100a9, Il5, Slc26a4), as shown by CCR2 inhibitor RS504393 treatment. Adgrf5 KO mouse model, qPCR/western blot in primary lung ECs, pharmacological inhibitor (RS504393) treatment, BALF analysis Respiratory research Medium 30654796
2019 Adgrf5 is highly expressed in CNS endothelium and regulates retinal vascular patterning; Adgrf5 mutant retinae exhibit increased perivenous vascular density, abnormal projections to the inner plexus, and transient vascular protrusions into the inner retinal space, indicating a role in subretinal vascularization prevention. Adgrf5 knockout mouse retinal angiogenesis analysis, vascular morphometry, live imaging Angiogenesis Medium 31256320
2020 Gpr116 is highly expressed in acid-secreting A-intercalated cells (A-ICs) of the kidney; kidney-specific Gpr116 KO causes urinary acidification (decreased urine pH) with metabolic alkalosis, and loss of Gpr116 results in greater accumulation of V-ATPase proton pumps at the apical surface of A-ICs; a synthetic agonist peptide for Gpr116 inhibits proton flux in collecting duct intercalated cells. Kidney-specific KO mice, immunogold electron microscopy, synthetic agonist peptide treatment, split-open collecting duct proton flux assay, in situ receptor activation Proceedings of the National Academy of Sciences of the United States of America High 33004624
2021 Soluble FNDC4 (sFNDC4) directly and with high affinity binds to GPR116 in white adipose tissue, acting as its ligand; sFNDC4-GPR116 engagement promotes insulin signaling and insulin-mediated glucose uptake in white adipocytes; the protective effects of FcsFNDC4 on glucose tolerance in prediabetic mice require GPR116. Direct binding assay, GPR116 KO adipocytes, in vivo GPR116-dependent rescue assay with FcsFNDC4, glucose tolerance tests Nature communications High 34016966
2022 GPR116 activation requires autocatalytic cleavage upstream of its tethered agonist (Stachel) sequence; a knock-in mouse expressing non-cleavable GPR116 phenocopies the pulmonary surfactant accumulation of GPR116 KO mice; key conserved amino acids in the tethered agonist sequence and extracellular loops 2/3 (ECL2/3) are essential for receptor activation; residues in TM7 mediate differential signaling strength between mouse and human GPR116. Knock-in non-cleavable mutant mice, site-directed mutagenesis, species-swapping approaches, in vitro tethered agonist assays, in vivo pulmonary phenotyping eLife High 36073784
2022 GPR116 is essential for long-term maintenance of the skeletal muscle stem cell (MuSC) pool; Stachel peptide stimulation of GPR116 leads to strong interaction with β-arrestins; activated GPR116 increases nuclear localization of β-arrestin1, which interacts with CREB (cAMP response element binding protein) to regulate gene expression, thereby delaying MuSC activation and differentiation. Gpr116 conditional KO in MuSCs, Stachel peptide stimulation, β-arrestin interaction assays, nuclear fractionation, co-IP with CREB, MuSC self-renewal assays Cell reports High 36384129
2023 GPR116 regulates NK cell antitumor function via the Gαq/HIF1α/NF-κB signaling pathway; GPR116 deficiency in NK cells enhances cytotoxicity with increased GzmB and IFNγ production. GPR116 KO mouse NK cell functional assays, in vitro and in vivo cytotoxicity assays, pathway inhibition experiments Cell & bioscience Medium 36895027
2023 GPR116 promotes ferroptosis in sepsis-induced liver injury by inhibiting the system Xc-/GSH/GPX4 pathway; hepatocyte-specific GPR116 deletion prevents hepatic ferroptosis and alleviates liver dysfunction; GPR116 aggravates mitochondrial damage and lipid peroxidation in hepatocytes. Hepatocyte-specific GPR116 KO mice, GPR116 overexpression, ferroptosis markers (GSH, GPX4, lipid peroxidation assays), mitochondrial damage assays Cell biology and toxicology Medium 37266730
2024 GPR116 inhibits endoplasmic reticulum stress during acetaminophen-induced liver injury through interaction with β-arrestin1, which in turn inhibits BiP (binding immunoglobulin protein), a critical ER regulator; GPR116 activation by its ligand FNDC4 protects against early hepatotoxicity. Hepatocyte-specific GPR116 KO mice, GPR116 overexpression, co-immunoprecipitation of GPR116 with β-arrestin1 and BiP, RNA-seq, FNDC4 ligand treatment Cellular and molecular life sciences Medium 39001944
2024 GPR116 promotes breast cancer metastasis by inhibiting ERK1/2 via RhoA activation, reducing C/EBPβ phosphorylation at Thr235 and its nuclear translocation, thereby suppressing MMP8 transcription; loss of ADGRF5 increases MMP8 expression and CXCL8 secretion, polarizing tumor-associated neutrophils to the antitumor N1 phenotype. ADGRF5 knockdown in breast cancer cells, ERK1/2 phosphorylation assays, RhoA activation assays, C/EBPβ nuclear translocation assays, MMP8 promoter analysis, in vivo tumor models Cell death & disease Medium 38937435
2024 GPR116 is involved in somatostatin release from pancreatic delta cells; whole-body GPR116 deficiency causes decreased beta-cell mass, lower number of small islets, and reduced pancreatic insulin content, with glucose homeostasis maintained by compensatory modulation of insulin degradation. Whole-body and cell-specific GPR116 KO mouse models, somatostatin secretion assays, islet morphometry, insulin content measurement Communications biology Medium 38228886
2024 ADGRF5 is specifically expressed in glomerular capillary endothelial cells; its deletion causes albuminuria, glomerular basement membrane defects, and altered expression of type IV collagens and KLF2 in glomerular endothelial cells. Adgrf5 KO mice, immunohistochemistry, electron microscopy, gene expression analysis in primary human glomerular ECs with ADGRF5 knockdown Journal of the American Society of Nephrology Medium 38844335
2025 GPR116 acts as a hydrostatic pressure (HP) mechanosensor in liver sinusoidal endothelial cells (LSECs); using a hepatic hypertension-on-a-chip system, GPR116 was identified as the key HP sensor whose downstream mechanotransduction pathway drives endothelial injury; genetic silencing of GPR116 protected LSECs from HP-induced damage in vitro and in cirrhotic mice. Hepatic hypertension-on-a-chip (2D and 3D), genetic silencing of GPR116, in vivo cirrhotic mouse model, decoupled mechanical parameter regulation Science advances Medium 41237250
2026 Endothelial ADGRF5/GPR116 is required for sustained thermogenic remodeling of brown adipose tissue (BAT) during prolonged cold exposure; endothelial deletion impairs thermogenic capacity, induces endothelial transcriptional reprogramming with EndMT-like features, and disrupts endothelial-adipocyte paracrine signaling that supports full thermogenic adipocyte adaptation. Inducible endothelial-specific ADGRF5 KO mice, snRNA-seq, vascular functional assays, CellChat/NicheNet cell-cell communication modeling, cold exposure challenges Molecular metabolism Medium 41796902
2012 Adipose tissue-specific deletion of Gpr116 causes glucose intolerance and insulin resistance, hepatosteatosis, reduced circulating adiponectin, and increased serum resistin, establishing a role for GPR116 in adipocyte biology and systemic energy homeostasis. Adipose tissue-specific conditional Gpr116 KO mice, glucose and insulin tolerance tests, serum adipokine measurements, liver histology FEBS letters Medium 22971422

Source papers

Stage 0 corpus · 30 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 94 24008316
2013 Essential regulation of lung surfactant homeostasis by the orphan G protein-coupled receptor GPR116. Cell reports 64 23684610
2013 Orphan G protein-coupled receptor GPR116 regulates pulmonary surfactant pool size. American journal of respiratory cell and molecular biology 60 23590306
2013 Lung surfactant levels are regulated by Ig-Hepta/GPR116 by monitoring surfactant protein D. PloS one 60 23922714
2017 Epithelial Gpr116 regulates pulmonary alveolar homeostasis via Gq/11 signaling. JCI insight 52 28570277
2015 Gpr116 Receptor Regulates Distinctive Functions in Pneumocytes and Vascular Endothelium. PloS one 49 26394398
2021 Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue. Nature communications 48 34016966
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 34 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 33 30654796
2020 Adhesion-GPCR Gpr116 (ADGRF5) expression inhibits renal acid secretion. Proceedings of the National Academy of Sciences of the United States of America 32 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 23 25778400
2023 GPR116 promotes ferroptosis in sepsis-induced liver injury by suppressing system Xc-/GSH/GPX4. Cell biology and toxicology 21 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 21 16882675
2022 The adhesion G-protein-coupled receptor Gpr116 is essential to maintain the skeletal muscle stem cell pool. Cell reports 18 36384129
2020 In silico molecular docking and physicochemical property studies on effective phytochemicals targeting GPR116 for breast cancer treatment. Molecular and cellular biochemistry 16 33106912
2019 Adgrf5 contributes to patterning of the endothelial deep layer in retina. Angiogenesis 15 31256320
2022 Regulation of pulmonary surfactant by the adhesion GPCR GPR116/ADGRF5 requires a tethered agonist-mediated activation mechanism. eLife 13 36073784
2024 The adhesion-GPCR ADGRF5 fuels breast cancer progression by suppressing the MMP8-mediated antitumorigenic effects. Cell death & disease 11 38937435
2023 The transcription factor Foxi1 promotes expression of V-ATPase and Gpr116 in M-1 cells. American journal of physiology. Renal physiology 8 36603001
2024 The adhesion GPCR GPR116/ADGRF5 has a dual function in pancreatic islets regulating somatostatin release and islet development. Communications biology 7 38228886
2023 GPR116 receptor regulates the antitumor function of NK cells via Gαq/HIF1α/NF-κB signaling pathway as a potential immune checkpoint. Cell & bioscience 7 36895027
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 5 38844335
2018 Organic barn dust inhibits surfactant protein D production through protein kinase-c alpha dependent increase of GPR116. PloS one 5 30543664
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 3 41073785
2024 GPR116 alleviates acetaminophen-induced liver injury in mice by inhibiting endoplasmic reticulum stress. Cellular and molecular life sciences : CMLS 3 39001944
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
2025 Hepatic hypertension on-a-chip identifies GPR116 as a hydrostatic pressure mechanosensor to regulate vascular injury in cirrhosis. Science advances 1 41237250
2026 Endothelial ADGRF5(GPR116) governs vascular adaptation required for sustained thermogenic remodeling of brown adipose tissue. Molecular metabolism 0 41796902