Affinage

CMKLR1

Chemerin-like receptor 1 · UniProt Q99788

Length
373 aa
Mass
42.3 kDa
Annotated
2026-04-28
100 papers in source corpus 36 papers cited in narrative 36 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

CMKLR1 (ChemR23/Chemerin1) is a Gi/o-coupled seven-transmembrane receptor that transduces signals from its primary ligands chemerin and resolvin E1 to coordinate immune cell trafficking, inflammation resolution, metabolic homeostasis, and vascular protection. Chemerin binding activates Gαi/o-mediated inhibition of adenylyl cyclase, Ca²⁺ mobilization, and downstream PI3K/Akt, ERK/MAPK, RhoA/ROCK-SRF, and CAMKK2/AMPK cascades, with GRK6-mediated phosphorylation triggering β-arrestin 2 recruitment, receptor internalization, and signal desensitization (PMID:18391062, PMID:27716822, PMID:30576947, PMID:26363224). On plasmacytoid and myeloid dendritic cells, macrophages, and neutrophils, CMKLR1 directs chemotaxis toward chemerin-expressing tissues, promotes Syk-dependent macrophage efferocytosis and phagocytosis, suppresses neutrophil integrin activation to limit inflammatory tissue damage, and mediates RvE1-driven repolarization of M1 macrophages toward a resolution phenotype (PMID:15728234, PMID:20363975, PMID:23999103, PMID:25637017, PMID:29739755). In non-immune contexts, CMKLR1 signaling regulates adipogenesis and cold-induced thermogenesis through cAMP-PKA/IL-33 suppression in adipocytes, controls vascular smooth muscle cell phenotypic switching and calcification, and constrains tumor progression by stabilizing PTEN to suppress Akt and PD-L1 expression (PMID:19929432, PMID:34330814, PMID:30597013, PMID:29717200, PMID:32605911).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1996 Medium

    Establishing that CMKLR1 encodes an orphan GPCR with chemokine-receptor homology expressed in immune tissues provided the starting framework for identifying its ligands and immune functions.

    Evidence Molecular cloning, FISH mapping to 12q24.1, Northern blot in human tissues

    PMID:8976386

    Open questions at the time
    • No ligand identified
    • No signaling pathway characterized
    • Functional role entirely unknown
  2. 2003 High

    Identification of chemerin (TIG2) as the endogenous ligand of CMKLR1 via reverse pharmacology deorphanized the receptor and enabled all subsequent mechanistic dissection.

    Evidence Reverse pharmacology screening of human hemofiltrate peptide libraries with receptor binding assay

    PMID:14675762

    Open questions at the time
    • Active chemerin processing forms not yet defined
    • G protein coupling specificity unknown
    • Downstream signaling pathways uncharacterized
  3. 2005 High

    Demonstration that CMKLR1 mediates dendritic cell transendothelial migration toward chemerin established its primary physiological function as a chemoattractant receptor directing immune cell trafficking.

    Evidence Flow cytometry, transendothelial migration assay, immunohistochemical co-localization of ChemR23+ DCs with chemerin-expressing HEVs in lymphoid organs

    PMID:15728234

    Open questions at the time
    • In vivo DC trafficking not yet confirmed with KO mice
    • Signaling intermediates between receptor activation and migration not defined
  4. 2007 High

    Direct radioligand binding showed resolvin E1 as a second endogenous ligand for CMKLR1, linking this receptor to the resolution of inflammation and omega-3 fatty acid biology.

    Evidence [³H]RvE1 binding (Kd ~48 nM), adenylate cyclase and NF-κB reporter assays, BLT1 KO mouse peritonitis

    PMID:17339491

    Open questions at the time
    • Relative contributions of CMKLR1 vs. BLT1 to RvE1 effects not fully separated
    • RvE1-specific signaling downstream of CMKLR1 not distinguished from chemerin signaling
  5. 2008 High

    Using ChemR23-knockout mice, the processed C-terminal peptide chemerin15 was shown to suppress peritonitis entirely through CMKLR1, establishing that proteolytic activation of chemerin is essential for anti-inflammatory function.

    Evidence Zymosan peritonitis model, macrophage activation assays in ChemR23⁻/⁻ mice

    PMID:18391062

    Open questions at the time
    • Specific proteases responsible for generating bioactive chemerin forms in vivo not identified
    • Downstream anti-inflammatory signaling pathway not delineated
  6. 2009 High

    Parallel studies using KO mice and differentiation assays established two distinct CMKLR1 functions: Gαi/o-dependent calcium flux and chemotaxis in immune cells, and a required role in adipogenesis via PPARγ-chemerin autocrine signaling.

    Evidence ChemR23 KO mouse calcium mobilization and chemotaxis, LPS lung inflammation model; RNAi of CMKLR1 in bone marrow stromal cell adipogenesis, PPARγ rescue

    PMID:19841182 PMID:19929432

    Open questions at the time
    • Adipogenesis mechanism not linked to specific intracellular pathway
    • Relative importance of chemerin vs. RvE1 in metabolic contexts unknown
  7. 2010 High

    CMKLR1 was shown to enhance macrophage phagocytosis and efferocytosis through Syk kinase-dependent actin remodeling, providing a molecular mechanism for how this receptor promotes debris clearance during inflammation resolution.

    Evidence Phagocytosis and efferocytosis assays in ChemR23⁻/⁻ macrophages, Syk inhibitor, F-actin polymerization imaging

    PMID:20363975

    Open questions at the time
    • Adaptor linking CMKLR1 to Syk activation not identified
    • Whether RvE1 uses the same Syk pathway not tested
  8. 2011 High

    ChemR23 KO mice revealed dual in vivo roles: recruiting pDCs for type I IFN-dependent antiviral defense in pneumonia, and regulating whole-body adiposity and glucose homeostasis.

    Evidence ChemR23 KO mice in pneumovirus infection (pDC adoptive transfer, chimeras) and metabolic phenotyping (glucose/insulin tolerance, body composition)

    PMID:22072972 PMID:22186410

    Open questions at the time
    • Non-leukocytic anti-inflammatory function observed in chimeras not molecularly defined
    • How CMKLR1 deficiency impairs insulin secretion mechanistically unclear
  9. 2013 High

    Chemerin15 was found to inhibit neutrophil integrin activation and adhesion through CMKLR1, providing a mechanism for limiting neutrophil-mediated tissue damage; intravital microscopy confirmed neutrophil detachment from inflamed endothelium reduced myocardial infarction injury.

    Evidence Integrin activation assay, intravital microscopy, murine MI model with ChemR23 KO

    PMID:23999103

    Open questions at the time
    • Signaling intermediate between CMKLR1 and integrin inactivation not identified
    • Whether chemerin15 or RvE1 is the physiological ligand in cardiac ischemia not determined
  10. 2016 High

    Comprehensive BRET-based profiling revealed CMKLR1 couples to all Gαi/o subtypes and recruits both β-arrestins; ERK1/2 activation requires Gαi/o plus β-arrestin 2 but not β-arrestin 1, establishing the receptor's full signaling repertoire.

    Evidence BRET G protein activation biosensors for Gαi1/2/3 and Gαoa/ob, β-arrestin recruitment assay, ERK phosphorylation

    PMID:27716822

    Open questions at the time
    • No structural basis for G protein selectivity
    • β-arrestin-scaffolded signaling complexes not characterized
  11. 2018 High

    GRK6 was identified as the kinase that phosphorylates CMKLR1 for β-arrestin 2 recruitment and internalization; GRK6 and β-arrestin 2 KO macrophages showed enhanced migration and altered Akt/ERK signaling, establishing the desensitization mechanism.

    Evidence GRK6 and β-arrestin 2 KO mouse macrophages, receptor internalization, co-expression experiments, Akt/ERK western blot

    PMID:30576947

    Open questions at the time
    • Specific phosphorylation sites on CMKLR1 C-tail not mapped
    • Other GRKs' contribution not excluded
  12. 2019 High

    Multiple studies established CMKLR1 as a vascular and neuroprotective receptor: RvE1/CMKLR1 inhibits VSMC calcification and phenotypic switching; chemerin/CMKLR1 suppresses hepatocellular carcinoma metastasis via physical interaction with PTEN stabilizing its expression and phosphatase activity; and CMKLR1 signals through CAMKK2/AMPK to reduce neuronal apoptosis.

    Evidence ChemR23 KO VSMCs and in vivo calcification; Co-IP of CMKLR1-PTEN, ubiquitination assay, xenograft; rat HIE model with pathway-specific inhibitors

    PMID:29717200 PMID:30597013 PMID:30718467

    Open questions at the time
    • CMKLR1-PTEN interaction domain not mapped
    • Whether PTEN stabilization occurs in non-cancer cells not tested
    • CAMKK2 activation mechanism downstream of Gαi not resolved
  13. 2020 High

    CMKLR1 was shown to suppress PD-L1 expression through PTEN-Akt-mTOR signaling, establishing a tumor-immune evasion mechanism; separately, ChemR23 was confirmed as required for omega-3 PUFA-mediated protection against aortic valve calcification via genetic epistasis.

    Evidence CMKLR1 siRNA plus PI3K/AKT/mTOR inhibitors in tumor cells and xenografts; ChemR23 KO × Fat-1tg × Apoe⁻/⁻ triple-cross mice with echocardiography

    PMID:32506925 PMID:32605911

    Open questions at the time
    • Whether CMKLR1-mediated PD-L1 suppression enhances anti-tumor immunity in immunocompetent models not shown
    • Specific RvE1-derived valve-protective signaling intermediates not identified
  14. 2021 High

    Adipocyte-specific CMKLR1 deletion revealed the receptor tonically suppresses beige adipocyte IL-33 production by dampening cAMP-PKA signaling, interrupting the feed-forward loop with type 2 innate immunity required for thermogenesis; an agonist anti-ChemR23 mAb separately confirmed that receptor activation directly promotes macrophage efferocytosis and resolves chronic colitis.

    Evidence Adipocyte-specific CMKLR1 KO mice under cold exposure and HFD, cAMP/PKA/IL-33 measurement; agonist mAb in peritonitis and colitis models with efferocytosis and neutrophil apoptosis readouts

    PMID:33811066 PMID:34330814

    Open questions at the time
    • Whether cAMP-PKA suppression is Gαi-mediated or involves arrestin-dependent mechanism not distinguished
    • Agonist mAb signaling bias relative to chemerin not characterized
  15. 2024 High

    CMKLR1 was found to regulate lipid metabolism in clear cell renal cell carcinoma by suppressing adipose triglyceride lipase and modulating SREBP1c/CD36-mediated lipid uptake; CMKLR1 loss induced apoptosis, ferroptosis, and autophagy, revealing a metabolic dependency in lipid-laden tumors.

    Evidence siRNA/shRNA and α-NETA pharmacological inhibition, lipidomics, transcriptomics, patient-derived xenografts

    PMID:38640229

    Open questions at the time
    • Direct signaling pathway from CMKLR1 to ATGL suppression not defined
    • Whether this lipid metabolic role applies beyond ccRCC not tested

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key open questions include the structural basis of CMKLR1's dual ligand recognition (chemerin vs. RvE1), the phosphosite-level code for biased signaling, whether CMKLR1's PTEN-stabilizing and metabolic functions are linked through a common signaling branch, and the therapeutic potential of biased agonists versus antagonists across its immune, metabolic, and oncologic roles.
  • No crystal or cryo-EM structure of CMKLR1
  • Biased agonism at CMKLR1 not systematically profiled
  • In vivo relevance of CMKLR1 as HIV/SIV coreceptor remains unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 4 GO:0098772 molecular function regulator activity 3
Localization
GO:0005886 plasma membrane 4 GO:0031410 cytoplasmic vesicle 2
Pathway
R-HSA-168256 Immune System 8 R-HSA-162582 Signal Transduction 6 R-HSA-1430728 Metabolism 4 R-HSA-5357801 Programmed Cell Death 3
Partners
ARRB2GRK6PTENRARRES2SYK

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 CMKLR1 encodes a seven-transmembrane G protein-linked receptor with sequence homology to chemokine receptors, expressed in hematopoietic and immune tissues; chromosomal localization to 12q24.1 established by FISH. Molecular cloning, FISH chromosomal mapping, Northern blot expression profiling Cytogenetics and cell genetics Medium 8976386
1998 ChemR23 (CMKLR1) is expressed in monocyte-derived dendritic cells and macrophages and functions as a coreceptor for SIV and some primary HIV-1 strains in cell fusion assays. RT-PCR expression profiling, cell fusion coreceptor assay European journal of immunology Medium 9603476
2003 TIG2/chemerin (residues 21–154 of the prepropeptide) was identified as the natural ligand of ChemR23 (CMKLR1) via reverse pharmacology screening of peptide libraries from human hemofiltrate. Reverse pharmacology peptide library screening, receptor binding assay FEBS letters High 14675762
2005 ChemR23 (CMKLR1) is expressed and functional in plasmacytoid and myeloid dendritic cells; recombinant chemerin induces transmigration of these DCs across endothelial monolayers, and ChemR23+ DCs localize near chemerin-expressing high endothelial venules in lymphoid organs. Flow cytometry, transendothelial migration assay, immunohistochemistry, co-localization The Journal of experimental medicine High 15728234
2007 RvE1 binds specifically to ChemR23 (CMKLR1) on human PMNs (Kd ~48 nM); RvE1 also binds recombinant BLT1 (Kd 45 nM) and acts as a partial agonist at BLT1, inhibiting adenylate cyclase and NF-κB activation, while its anti-inflammatory actions at higher doses involve ChemR23-mediated counterregulatory mechanisms. [3H]RvE1 radioligand binding assay, adenylate cyclase assay, NF-κB reporter assay, BLT1 knockout mouse peritonitis model Journal of immunology High 17339491
2008 Chemerin requires proteolytic processing of its C-terminus for anti-inflammatory activity; the C-terminal peptide chemerin15 (A140–A154) suppresses macrophage activation and peritonitis at picomolar concentrations in a ChemR23-dependent manner, as shown by complete loss of activity in ChemR23−/− mice. In vitro macrophage activation assay, zymosan peritonitis model, ChemR23 knockout mice The Journal of experimental medicine High 18391062
2009 Mouse ChemR23 mediates chemerin-induced calcium mobilization and chemotaxis in dendritic cells and macrophages; these responses are abrogated in ChemR23 knockout mice. Chemerin reduces neutrophil infiltration and inflammatory cytokine release in LPS-induced lung inflammation in a ChemR23-dependent manner. Calcium mobilization assay, chemotaxis assay, ChemR23 KO mice, LPS-induced lung inflammation model Journal of immunology High 19841182
2009 Chemerin/CMKLR1 signaling is required for adipocyte differentiation of bone marrow stromal cells; RNAi knockdown of chemerin or CMKLR1 abrogates adipogenesis and clonal expansion, while increasing osteoblast marker expression and mineralization; PPARγ-induced chemerin expression partially rescues adipogenesis. RNAi knockdown, differentiation assays, PPARγ overexpression rescue experiment Journal of bone and mineral research High 19929432
2009 Chemerin activates ChemR23 in human endothelial cells, inducing angiogenesis through activation of PI3K/Akt and MAPK signaling pathways, and dose-dependently increases MMP-2 and MMP-9 gelatinolytic activity. In vitro angiogenesis assays (tube formation, migration), phosphorylation western blot, zymography Biochemical and biophysical research communications Medium 20044979
2010 Chemerin15 enhances macrophage phagocytosis of microbial particles and efferocytosis of apoptotic cells via ChemR23, associated with increased actin polymerization and F-actin localization to the phagocytic cup; these effects require Syk kinase activity and are absent in ChemR23−/− macrophages. Phagocytosis assays, ChemR23 KO macrophages, Syk inhibitor, actin polymerization assay, in vivo peritonitis Journal of immunology High 20363975
2010 Chemerin binding to ChemR23 in human articular chondrocytes induces phosphorylation of ERK1/2 and Akt, and promotes secretion of pro-inflammatory cytokines (IL-6, IL-8, TNF-α, IL-1β) and matrix metalloproteases (MMP-1, -2, -3, -8, -13). Phosphorylation western blot, ELISA cytokine quantification, cell stimulation assay Arthritis research & therapy Medium 21192818
2011 ChemR23 knockout mice show increased neutrophilic infiltration, delayed viral clearance, and higher mortality in pneumonia virus of mice infection; ChemR23 recruits plasmacytoid DCs to promote type I interferon production and adaptive immune responses, while ChemR23 on non-leukocytic cells provides a separate anti-inflammatory function. ChemR23 KO mice, depletion/adoptive transfer of pDCs, chimeric mice, lung function measurement, interferon quantification PLoS pathogens High 22072972
2011 CMKLR1-deficient mice show reduced adiposity, lower food consumption, decreased adipose/hepatic inflammation, and glucose intolerance with impaired glucose-stimulated insulin secretion and reduced skeletal muscle/adipose tissue glucose uptake, demonstrating CMKLR1's role in adipose development, inflammation, and glucose homeostasis. CMKLR1 KO mouse model, body composition analysis, glucose/insulin tolerance tests, immune cell profiling, glucose uptake assay Endocrinology High 22186410
2013 ChemR23 is expressed in neutrophil granules and is upregulated upon neutrophil activation; chemerin15 inhibits integrin activation and clustering via ChemR23, reducing neutrophil adhesion and chemotaxis in vitro and inducing detachment of adherent neutrophils from inflamed endothelium, reducing heart damage in a murine myocardial infarction model. Flow cytometry, integrin activation assay, intravital microscopy, murine MI model, ChemR23 KO EMBO reports High 23999103
2014 The small molecule α-NETA inhibits chemerin-stimulated β-arrestin2 association with CMKLR1 and blocks chemerin-triggered CMKLR1+ cell migration, acting as a CMKLR1 antagonist; α-NETA delays EAE onset and reduces CNS mononuclear cell infiltrates. β-arrestin2 recruitment assay, chemotaxis assay, EAE mouse model (active immunization and adoptive transfer) PloS one High 25437209
2015 Chemerin signals through CMKLR1 via the RhoA/ROCK pathway to activate the transcriptional regulator SRF; RhoA, ROCK, p38, and Gαi/o signaling are all required for chemerin-mediated chemotaxis; GPR1 is confirmed as a functional chemerin receptor with similar but distinct signaling properties. Luciferase reporter assays, pathway-specific inhibitors, chemotaxis assay, CMKLR1/GPR1 transfection Molecular and cellular endocrinology Medium 26363224
2015 Aβ42 binds specifically to CMKLR1 in stably transfected RBL cells; Aβ42 induces CMKLR1-dependent cell migration through ERK1/2, PKA, and Akt pathways (but not Ca2+ mobilization), and CMKLR1 mediates internalization of the Aβ42-CMKLR1 complex in primary glial cells. Radioligand-like specific binding in transfected cells, migration assays, signaling pathway inhibitors, internalization assay Journal of Alzheimer's disease Medium 25079809
2015 ChemR23 expression is regulated at the transcriptional level; M1 macrophages (stimulated by LPS or IFN-γ) upregulate ChemR23 from promoter P3, are chemotactic to chemerin, and are repolarized toward a resolution phenotype by RvE1 through ChemR23, increasing IL-10 and phagocytosis; M2 macrophages do not express surface ChemR23. 5' RACE, promoter analysis, FACS, chemotaxis assay, RvE1 stimulation, phagocytosis assay Journal of immunology High 25637017
2016 Chemerin binding to CMKLR1 activates all three Gαi subtypes (Gαi1, Gαi2, Gαi3) and both Gαo isoforms (Gαoa, Gαob), recruits β-arrestin1 and β-arrestin2, and induces receptor internalization and ERK1/2 phosphorylation; ERK1/2 phosphorylation requires both Gαi/o and β-arrestin2 activation but not β-arrestin1. BRET-based G protein activation biosensors, β-arrestin recruitment assay, receptor internalization assay, ERK phosphorylation western blot PloS one High 27716822
2017 The IUPHAR nomenclature review confirmed that chemerin activates CMKLR1 (Chemerin1) via Gi/o coupling causing inhibition of adenylyl cyclase and increased Ca2+ flux; human chemerin21-157 is the most active form; CCX832 selectively blocks CMKLR1; resolvin E1 also activates CMKLR1. Pharmacological review integrating radioligand binding, cAMP, Ca2+ assays from multiple labs Pharmacological reviews High 29279348
2018 Targeted deletion of ERV1/ChemR23 in hyperlipidemic mice increases oxidized LDL uptake, reduces phagocytosis, and enlarges atherosclerotic plaques; resolvin E1-mediated effects on oxLDL uptake and phagocytosis in macrophages are dependent on ERV1/ChemR23 signaling. Erv1/ChemR23 KO × Apoe−/− mice, atherosclerosis histology, macrophage phagocytosis/oxLDL uptake assays, lipidomics Circulation High 29739755
2018 Chemerin activates CMKLR1 in oesophageal squamous cancer cells, increasing MMP-1, MMP-2, and MMP-3 abundance and activity through protein kinase C and p44/42 MAPK pathways, promoting cancer cell invasion; the ChemR23 antagonist CCX832 inhibits this invasion. Boyden chamber invasion assays, organotypic assays, siRNA, immunoneutralisation, CCX832 antagonist, western blot/enzyme assay for MMPs British journal of cancer Medium 27092781
2018 Chemerin-activated CMKLR1 signaling in inflammatory macrophages is regulated by GRK6 phosphorylation and β-arrestin 2 recruitment; GRK6- and β-arrestin 2-deficient macrophages show decreased CMKLR1 internalization following chemerin stimulation, increased migration toward chemerin, and altered AKT and ERK signaling. GRK6 and β-arrestin 2 KO mouse macrophages, receptor internalization assay, co-expression of GRK6 with CMKLR1, chemotaxis assay, AKT/ERK western blot Molecular immunology High 30576947
2019 Chemerin suppresses hepatocellular carcinoma metastasis through CMKLR1 by upregulating PTEN expression and phosphatase activity via interference with PTEN-CMKLR1 interaction, reducing PTEN ubiquitination and decreasing p-Akt (Ser473); CMKLR1 knockdown abolishes chemerin-induced PTEN/Akt modulation. Co-immunoprecipitation, RNAi knockdown, phosphatase activity assay, ubiquitination assay, in vivo xenograft British journal of cancer High 29717200
2019 ChemR23 deletion in smooth muscle cells prevents phenotypic switching to a synthetic/osteoblastic state; ChemR23-deficient VSMCs are resistant to phosphate-induced calcification; resolvin E1 inhibits VSMC calcification through ChemR23; ChemR23-deficient mice are protected against vitamin D3-induced vascular calcification. ChemR23 KO mouse VSMCs, in vitro calcification assay, in vivo calcification model, Fat-1 transgene epistasis Cardiovascular research High 30597013
2019 ChemR23-deficient pDCs exhibit reduced migratory capacity and decreased CCR7 expression; adoptive transfer of WT vs. ChemR23 KO pDCs into Apoe−/− mice shows reduced accumulation of ChemR23-deficient pDCs in atherosclerotic lesions; hematopoietic ChemR23 deficiency increases M2 macrophage proportion and cholesterol efflux in atherosclerotic plaques. ChemR23 KO knockin eGFP mice, adoptive pDC transfer, bone marrow chimeras, atherosclerosis histology, cholesterol efflux assay Arteriosclerosis, thrombosis, and vascular biology High 30786742
2019 Chemerin reduces neuronal apoptosis after neonatal hypoxic-ischemic encephalopathy via ChemR23/CAMKK2/AMPK signaling; specific inhibition of ChemR23, CAMKK2, or AMPK abolishes the anti-apoptotic effects of recombinant chemerin. Rat HIE model, intranasal chemerin administration, specific inhibitors, western blot for phospho-CAMKK2/AMPK, TUNEL/Fluoro-Jade staining Cell death & disease Medium 30718467
2020 Chemerin/CMKLR1 axis promotes inflammation and pyroptosis in diabetic cardiomyopathy through NLRP3 inflammasome activation; CMKLR1 siRNA knockdown in vivo attenuates NLRP3, activated caspase-1, and IL-1β; in vitro, silencing either CMKLR1 or NLRP3 suppresses pyroptosis. siRNA knockdown in vivo and in vitro, NLRP3 KD double knockdown, LDH release, caspase-1 western blot, EthD-III staining Frontiers in physiology Medium 32390873
2020 Exogenous chemerin exposure upregulates PTEN expression/activity and suppresses PD-L1 expression in human prostate and sarcoma tumor lines through CMKLR1; CMKLR1 knockdown abolishes these effects; signaling proceeds through PI3K/AKT/mTOR pathway; forced chemerin expression in DU145 xenografts suppresses tumor growth with increased PTEN and decreased PD-L1 in vivo. siRNA knockdown, specific PI3K/AKT/mTOR inhibitors, western blot, in vivo xenograft, T-cell cytotoxicity assay Clinical cancer research High 32605911
2020 Abrogation of ChemR23 in Apoe−/− Fat-1tg mice abolishes the protective effects of endogenous omega-3 fatty acids on aortic valve calcification; resolvin E1 acts as a calcification inhibitor and its receptor ChemR23 is required for n-3 PUFA-mediated valve protection. ChemR23 KO × Fat-1tg × Apoe−/− mouse model, valvular lipidomics, echocardiography, histology Circulation High 32506925
2021 The chemerin-CMKLR1 axis in adipocytes suppresses beige adipocyte-derived IL-33 by dampening cAMP-PKA signaling, thereby interrupting the feed-forward circuit between beige adipocytes and type 2 innate immunity required for cold-induced thermogenesis; adipocyte-specific CMKLR1 deletion enhances thermogenesis and protects against diet-induced obesity. Adipocyte-specific CMKLR1 KO mice, cold exposure, cAMP/PKA signaling assays, IL-33 quantification, innate immune cell profiling, diet-induced obesity model Science immunology High 34330814
2021 An agonist anti-ChemR23 monoclonal antibody that induces receptor signaling promotes macrophage efferocytosis and reduces neutrophil apoptosis at the site of inflammation; it accelerates resolution of acute inflammation and triggers resolution in chronic colitis models. Agonist mAb characterization, macrophage efferocytosis assay, neutrophil apoptosis assay, acute peritonitis model, chronic colitis mouse model Science advances High 33811066
2022 Chemerin enhances mesenchymal features of glioblastoma via CMKLR1 by suppressing ubiquitin-proteasomal degradation of CMKLR1, thereby enhancing NF-κB pathway activation; chemerin promotes TAM recruitment and M2 polarization via CMKLR1/NF-κB axis, which further drives GBM mesenchymal phenotype. CMKLR1 ubiquitination/degradation assay, NF-κB reporter assay, TAM co-culture, GBM xenograft, α-NETA pharmacological blockade Oncogene Medium 35459783
2022 ChemR23 agonists RvE1 and chemerin-9 ameliorate diabetes-associated cognitive impairment by inhibiting NLRP3 inflammasome activation through the Nrf2/TXNIP pathway; genetic deletion of ChemR23 in diabetic mice exacerbates cognitive impairment and oxidative stress, abolishing beneficial effects of agonists. ChemR23 KO mice, RvE1/chemerin-9 treatment, Nrf2/TXNIP western blot, NLRP3 inflammasome assays, cognitive behavioral tests Redox biology Medium 36446229
2023 RvE1/ChemR23 ameliorates angiotensin II-induced hypertension and vascular remodeling by activating AMPKα/Nrf2 signaling in VSMCs, inhibiting the canonical NF-κB/Ccl5 pathway to reduce macrophage and T-cell infiltration and suppressing VSMC phenotypic transformation and proliferation; knockdown of ChemR23 reverses these protective effects. AAV9-shRNA ChemR23 knockdown in mice, Ang II hypertension model, blood pressure measurement, aortic histology, AMPKα/Nrf2/NF-κB pathway western blot, immune cell quantification Hypertension Medium 37800344
2024 CMKLR1 controls lipid metabolism in clear cell renal cell carcinoma by enforcing suppression of adipose triglyceride lipase, regulating sterol regulatory element-binding protein 1c and CD36 scavenger receptor-mediated lipid uptake; genetic or pharmacological suppression of CMKLR1 induces apoptosis, ferroptosis, and autophagy, reducing ccRCC tumor growth in patient-derived xenografts. siRNA/shRNA knockdown, α-NETA pharmacological inhibition, lipidomic profiling, transcriptomic profiling, patient-derived xenograft models Cancer research High 38640229

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 Resolvin E1 selectively interacts with leukotriene B4 receptor BLT1 and ChemR23 to regulate inflammation. Journal of immunology (Baltimore, Md. : 1950) 489 17339491
2008 Synthetic chemerin-derived peptides suppress inflammation through ChemR23. The Journal of experimental medicine 309 18391062
2009 Identification of chemerin receptor (ChemR23) in human endothelial cells: chemerin-induced endothelial angiogenesis. Biochemical and biophysical research communications 280 20044979
2005 Role of ChemR23 in directing the migration of myeloid and plasmacytoid dendritic cells to lymphoid organs and inflamed skin. The Journal of experimental medicine 235 15728234
2009 Mouse ChemR23 is expressed in dendritic cell subsets and macrophages, and mediates an anti-inflammatory activity of chemerin in a lung disease model. Journal of immunology (Baltimore, Md. : 1950) 207 19841182
2005 Erv1 mediates the Mia40-dependent protein import pathway and provides a functional link to the respiratory chain by shuttling electrons to cytochrome c. Journal of molecular biology 198 16185707
1998 ChemR23, a putative chemoattractant receptor, is expressed in monocyte-derived dendritic cells and macrophages and is a coreceptor for SIV and some primary HIV-1 strains. European journal of immunology 198 9603476
2003 Characterization of human circulating TIG2 as a ligand for the orphan receptor ChemR23. FEBS letters 167 14675762
2010 Mitochondrial disulfide bond formation is driven by intersubunit electron transfer in Erv1 and proofread by glutathione. Molecular cell 158 20188670
2017 International Union of Basic and Clinical Pharmacology CIII: Chemerin Receptors CMKLR1 (Chemerin1) and GPR1 (Chemerin2) Nomenclature, Pharmacology, and Function. Pharmacological reviews 148 29279348
2016 Signaling Properties of Chemerin Receptors CMKLR1, GPR1 and CCRL2. PloS one 143 27716822
2010 Chemokine-like receptor 1 (CMKLR1) and chemokine (C-C motif) receptor-like 2 (CCRL2); two multifunctional receptors with unusual properties. Experimental cell research 138 21056554
2015 ChemR23, the receptor for chemerin and resolvin E1, is expressed and functional on M1 but not on M2 macrophages. Journal of immunology (Baltimore, Md. : 1950) 137 25637017
2011 Disruption of the chemokine-like receptor-1 (CMKLR1) gene is associated with reduced adiposity and glucose intolerance. Endocrinology 132 22186410
2010 Role of chemerin/CMKLR1 signaling in adipogenesis and osteoblastogenesis of bone marrow stem cells. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 132 19929432
2014 Chemerin/chemR23 axis in inflammation onset and resolution. Inflammation research : official journal of the European Histamine Research Society ... [et al.] 131 25548799
2005 The essential mitochondrial protein Erv1 cooperates with Mia40 in biogenesis of intermembrane space proteins. Journal of molecular biology 130 16181637
2022 Correction: Chen et al. The Chemerin/CMKLR1 Axis Is Involved in the Recruitment of Microglia to Aβ Deposition through p38 MAPK Pathway. Int. J. Mol. Sci. 2022, 23, 9041. International journal of molecular sciences 129 36614339
2000 An African swine fever virus ERV1-ALR homologue, 9GL, affects virion maturation and viral growth in macrophages and viral virulence in swine. Journal of virology 126 10627538
2000 A viral member of the ERV1/ALR protein family participates in a cytoplasmic pathway of disulfide bond formation. Proceedings of the National Academy of Sciences of the United States of America 125 11035794
2018 ERV1/ChemR23 Signaling Protects Against Atherosclerosis by Modifying Oxidized Low-Density Lipoprotein Uptake and Phagocytosis in Macrophages. Circulation 118 29739755
2010 Human articular chondrocytes express ChemR23 and chemerin; ChemR23 promotes inflammatory signalling upon binding the ligand chemerin(21-157). Arthritis research & therapy 113 21192818
2007 The Erv1-Mia40 disulfide relay system in the intermembrane space of mitochondria. Biochimica et biophysica acta 95 18179776
2010 Growth factor erv1-like modulates Drp1 to preserve mitochondrial dynamics and function in mouse embryonic stem cells. Molecular biology of the cell 93 20147447
2011 ChemR23 dampens lung inflammation and enhances anti-viral immunity in a mouse model of acute viral pneumonia. PLoS pathogens 84 22072972
2017 Repurposing Approach Identifies Auranofin with Broad Spectrum Antifungal Activity That Targets Mia40-Erv1 Pathway. Frontiers in cellular and infection microbiology 75 28149831
2020 Chemerin/CMKLR1 Axis Promotes Inflammation and Pyroptosis by Activating NLRP3 Inflammasome in Diabetic Cardiomyopathy Rat. Frontiers in physiology 74 32390873
2011 The possible role of ChemR23/Chemerin axis in the recruitment of dendritic cells in lupus nephritis. Kidney international 73 21346723
2015 CMKLR1 and GPR1 mediate chemerin signaling through the RhoA/ROCK pathway. Molecular and cellular endocrinology 70 26363224
2017 Resolvin E1/E2 ameliorate lipopolysaccharide-induced depression-like behaviors via ChemR23. Psychopharmacology 68 29090333
1994 ERV1 is involved in the cell-division cycle and the maintenance of mitochondrial genomes in Saccharomyces cerevisiae. Current genetics 66 7954891
2009 Reconstitution of the mia40-erv1 oxidative folding pathway for the small tim proteins. Molecular biology of the cell 63 19477928
2021 Agonist anti-ChemR23 mAb reduces tissue neutrophil accumulation and triggers chronic inflammation resolution. Science advances 62 33811066
2014 Chemerin and CMKLR1 expression in human arteries and periadventitial fat: a possible role for local chemerin in atherosclerosis? BMC cardiovascular disorders 62 24779513
2018 Chemerin suppresses hepatocellular carcinoma metastasis through CMKLR1-PTEN-Akt axis. British journal of cancer 60 29717200
2014 A novel CMKLR1 small molecule antagonist suppresses CNS autoimmune inflammatory disease. PloS one 60 25437209
1999 Identification and characterization of receptor for mammalian hepatopoietin that is homologous to yeast ERV1. The Journal of biological chemistry 60 10206950
2020 Omega-3 Polyunsaturated Fatty Acids Decrease Aortic Valve Disease Through the Resolvin E1 and ChemR23 Axis. Circulation 59 32506925
2010 Chemerin peptides promote phagocytosis in a ChemR23- and Syk-dependent manner. Journal of immunology (Baltimore, Md. : 1950) 59 20363975
1995 A new human gene located in the PKD1 region of chromosome 16 is a functional homologue to ERV1 of yeast. Genomics 59 8575761
2020 Chemerin Reactivates PTEN and Suppresses PD-L1 in Tumor Cells via Modulation of a Novel CMKLR1-mediated Signaling Cascade. Clinical cancer research : an official journal of the American Association for Cancer Research 56 32605911
2011 The role of ChemR23 in the induction and resolution of cigarette smoke-induced inflammation. Journal of immunology (Baltimore, Md. : 1950) 56 21430224
2007 The sulfhydryl oxidase Erv1 is a substrate of the Mia40-dependent protein translocation pathway. FEBS letters 55 17336303
2019 Chemerin reverses neurological impairments and ameliorates neuronal apoptosis through ChemR23/CAMKK2/AMPK pathway in neonatal hypoxic-ischemic encephalopathy. Cell death & disease 54 30718467
2016 Development by Genetic Immunization of Monovalent Antibodies (Nanobodies) Behaving as Antagonists of the Human ChemR23 Receptor. Journal of immunology (Baltimore, Md. : 1950) 54 26864035
1996 Molecular cloning of a novel receptor (CMKLR1) with homology to the chemotactic factor receptors. Cytogenetics and cell genetics 53 8976386
2022 ChemR23 signaling ameliorates cognitive impairments in diabetic mice via dampening oxidative stress and NLRP3 inflammasome activation. Redox biology 47 36446229
2015 The chemerin receptor CMKLR1 is a functional receptor for amyloid-β peptide. Journal of Alzheimer's disease : JAD 47 25079809
2021 The chemerin-CMKLR1 axis limits thermogenesis by controlling a beige adipocyte/IL-33/type 2 innate immunity circuit. Science immunology 45 34330814
2019 Chemerin/ChemR23 axis promotes inflammation of glomerular endothelial cells in diabetic nephropathy. Journal of cellular and molecular medicine 45 30784180
2016 The role of chemerin and ChemR23 in stimulating the invasion of squamous oesophageal cancer cells. British journal of cancer 45 27092781
2011 Adiponectin upregulates hepatocyte CMKLR1 which is reduced in human fatty liver. Molecular and cellular endocrinology 45 22118966
2013 Chemerin15 inhibits neutrophil-mediated vascular inflammation and myocardial ischemia-reperfusion injury through ChemR23. EMBO reports 44 23999103
2012 In vivo evidence for cooperation of Mia40 and Erv1 in the oxidation of mitochondrial proteins. Molecular biology of the cell 44 22918950
2012 Divergence of Erv1-associated mitochondrial import and export pathways in trypanosomes and anaerobic protists. Eukaryotic cell 42 23264646
2017 Inhibition of chemerin/CMKLR1 axis in neuroblastoma cells reduces clonogenicity and cell viability in vitro and impairs tumor growth in vivo. Oncotarget 41 29221117
2017 ERV1 Overexpression in Myeloid Cells Protects against High Fat Diet Induced Obesity and Glucose Intolerance. Scientific reports 37 28993702
2019 The G-protein coupled receptor ChemR23 determines smooth muscle cell phenotypic switching to enhance high phosphate-induced vascular calcification. Cardiovascular research 36 30597013
2019 Hematopoietic ChemR23 (Chemerin Receptor 23) Fuels Atherosclerosis by Sustaining an M1 Macrophage-Phenotype and Guidance of Plasmacytoid Dendritic Cells to Murine Lesions-Brief Report. Arteriosclerosis, thrombosis, and vascular biology 35 30786742
2019 Chemerin acts via CMKLR1 and GPR1 to stimulate migration and invasion of gastric cancer cells: putative role of decreased TIMP-1 and TIMP-2. Oncotarget 34 30719206
2018 Chemerin/ChemR23 axis triggers an inflammatory response in keratinocytes through ROS-sirt1-NF-κB signaling. Journal of cellular biochemistry 34 30426542
2023 Resolvin E1/ChemR23 Protects Against Hypertension and Vascular Remodeling in Angiotensin II-Induced Hypertensive Mice. Hypertension (Dallas, Tex. : 1979) 33 37800344
2023 ChemR23 activation attenuates cognitive impairment in chronic cerebral hypoperfusion by inhibiting NLRP3 inflammasome-induced neuronal pyroptosis. Cell death & disease 33 37932279
2017 Chemokine Like Receptor-1 (CMKLR-1) Receptor: A Potential Therapeutic Target in Management of Chemerin Induced Type 2 Diabetes Mellitus and Cancer. Current pharmaceutical design 32 28625137
2017 Association of a variant in the gene encoding for ERV1/ChemR23 with reduced inflammation in visceral adipose tissue from morbidly obese individuals. Scientific reports 32 29146976
2012 The chemerin/ChemR23 system does not affect the pro-inflammatory response of mouse and human macrophages ex vivo. PloS one 32 22768214
2010 The N-terminal shuttle domain of Erv1 determines the affinity for Mia40 and mediates electron transfer to the catalytic Erv1 core in yeast mitochondria. Antioxidants & redox signaling 32 20367271
2021 Chemerin promotes the pathogenesis of preeclampsia by activating CMKLR1/p-Akt/CEBPɑ axis and inducing M1 macrophage polarization. Cell biology and toxicology 31 34398343
2019 Chemerin-9, a potent agonist of chemerin receptor (ChemR23), prevents atherogenesis. Clinical science (London, England : 1979) 31 31399499
2020 Chemerin facilitates intervertebral disc degeneration via TLR4 and CMKLR1 and activation of NF-kB signaling pathway. Aging 30 32526705
2019 Parental Dietary Protein Source and the Role of CMKLR1 in Determining the Severity of Dahl Salt-Sensitive Hypertension. Hypertension (Dallas, Tex. : 1979) 30 30595125
2019 Chemerin inhibits vascular calcification through ChemR23 and is associated with lower coronary calcium in chronic kidney disease. Journal of internal medicine 30 31197872
2017 Effects of chemerin/CMKLR1 in obesity-induced hypertension and potential mechanism. American journal of translational research 30 28670396
2017 Osm1 facilitates the transfer of electrons from Erv1 to fumarate in the redox-regulated import pathway in the mitochondrial intermembrane space. Molecular biology of the cell 29 28814504
2016 Pro- and Anti-Inflammatory Role of ChemR23 Signaling in Pollutant-Induced Inflammatory Lung Responses. Journal of immunology (Baltimore, Md. : 1950) 29 26773141
2012 Rosiglitazone ameliorates diabetic nephropathy by reducing the expression of Chemerin and ChemR23 in the kidney of streptozotocin-induced diabetic rats. Inflammation 29 22350950
2020 Chemerin Impairs In Vitro Testosterone Production, Sperm Motility, and Fertility in Chicken: Possible Involvement of Its Receptor CMKLR1. Cells 28 32630345
2020 Chemerin/CMKLR1 ameliorates nonalcoholic steatohepatitis by promoting autophagy and alleviating oxidative stress through the JAK2-STAT3 pathway. Peptides 28 33144092
2018 Opposing Effects on Vascular Smooth Muscle Cell Proliferation and Macrophage-induced Inflammation Reveal a Protective Role for the Proresolving Lipid Mediator Receptor ChemR23 in Intimal Hyperplasia. Frontiers in pharmacology 28 30515096
2016 CMKLR1 deficiency maintains ovarian steroid production in mice treated chronically with dihydrotestosterone. Scientific reports 28 26893072
2012 Targeting and maturation of Erv1/ALR in the mitochondrial intermembrane space. ACS chemical biology 28 22296668
2010 Cloning of porcine chemerin, ChemR23 and GPR1 and their involvement in regulation of lipogenesis. BMB reports 28 20663411
2022 Chemerin enhances mesenchymal features of glioblastoma by establishing autocrine and paracrine networks in a CMKLR1-dependent manner. Oncogene 27 35459783
2011 Chemerin/ChemR23 pathway: a system beyond chemokines. Arthritis research & therapy 27 21542878
2021 HOXA9-induced chemerin signals through CMKLR1/AMPK/TXNIP/NLRP3 pathway to induce pyroptosis of trophoblasts and aggravate preeclampsia. Experimental cell research 26 34461109
2017 Gax suppresses chemerin/CMKLR1-induced preadipocyte biofunctions through the inhibition of Akt/mTOR and ERK signaling pathways. Journal of cellular physiology 26 28326537
2012 Chronic mild restraint stress rats decreased CMKLR1 expression in distinct brain region. Neuroscience letters 26 22796467
2022 Role of Chemerin/ChemR23 axis as an emerging therapeutic perspective on obesity-related vascular dysfunction. Journal of translational medicine 25 35317838
2018 Chemerin-activated functions of CMKLR1 are regulated by G protein-coupled receptor kinase 6 (GRK6) and β-arrestin 2 in inflammatory macrophages. Molecular immunology 24 30576947
2017 Erv1 of Arabidopsis thaliana can directly oxidize mitochondrial intermembrane space proteins in the absence of redox-active Mia40. BMC biology 24 29117860
2016 CMKLR1 deficiency influences glucose tolerance and thermogenesis in mice on high fat diet. Biochemical and biophysical research communications 24 26972253
2015 Evidence from studies in rodents and in isolated adipocytes that agonists of the chemerin receptor CMKLR1 may be beneficial in the treatment of type 2 diabetes. PeerJ 24 25699203
2015 Local chemerin levels are positively associated with DSS-induced colitis but constitutive loss of CMKLR1 does not protect against development of colitis. Physiological reports 24 26265756
2012 Structure of yeast sulfhydryl oxidase erv1 reveals electron transfer of the disulfide relay system in the mitochondrial intermembrane space. The Journal of biological chemistry 24 22910915
2024 GPR1 and CMKLR1 Control Lipid Metabolism to Support the Development of Clear Cell Renal Cell Carcinoma. Cancer research 23 38640229
2019 Aerobic exercise decreases chemerin/CMKLR1 in the serum and peripheral metabolic organs of obesity and diabetes rats by increasing PPARγ. Nutrition & metabolism 23 30873215
2019 CMKLR1-targeting peptide tracers for PET/MR imaging of breast cancer. Theranostics 23 31588246
2012 The Regulation of Chemerin and CMKLR1 Genes Expression by TNF-α, Adiponectin, and Chemerin Analog in Bovine Differentiated Adipocytes. Asian-Australasian journal of animal sciences 23 25049696
2023 Icosapent ethyl in cardiovascular prevention: Resolution of inflammation through the eicosapentaenoic acid - resolvin E1 - ChemR23 axis. Pharmacology & therapeutics 22 37201735
2022 The Chemerin-CMKLR1 Axis is Functionally important for Central Regulation of Energy Homeostasis. Frontiers in physiology 22 35711300