Affinage

MRAP2

Melanocortin-2 receptor accessory protein 2 · UniProt Q96G30

Length
205 aa
Mass
23.5 kDa
Annotated
2026-06-10
51 papers in source corpus 20 papers cited in narrative 20 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MRAP2 is a single-pass transmembrane accessory protein that broadly regulates G-protein-coupled receptor signaling in central and peripheral circuits controlling energy homeostasis (PMID:19329486, PMID:28959025). It assembles as a symmetric antiparallel homodimer at the plasma membrane, and proper domain orientation within this dimer is essential for its regulatory output (PMID:34759891), while a conserved arginine (R125) governs dimer formation and receptor binding (PMID:36077245). MRAP2 physically engages a diverse set of GPCRs — the melanocortin receptors MC1R–MC5R (PMID:19329486), the ghrelin receptor GHSR1a (PMID:28959025), prokineticin and orexin receptors (PMID:28939058), MCHR1 (PMID:35311242), and melatonin receptors (PMID:40510472) — preferentially forming 1:1 complexes that disrupt receptor homodimerization and contact receptor transmembrane helices 5 and 6 through the MRAP2 transmembrane domain, with the cytoplasmic C-terminus tuning constitutive activity (PMID:41401256, PMID:41722048). Mechanistically, MRAP2 biases signaling toward G-protein pathways while suppressing β-arrestin recruitment: at GHSR1a it blocks GRK2/PKC-mediated phosphorylation of Ser252 and Thr261 in the third intracellular loop, preventing β-arrestin recruitment and receptor internalization (PMID:35605660, PMID:31911434), and it exerts the same enhancement of G-protein signaling with reduced internalization at MC4R and MC3R (PMID:40998819, PMID:41401256). In vivo, MRAP2 is required in hypothalamic AgRP neurons for fasting- and ghrelin-driven hunger signaling (PMID:28959025), facilitates MC4R targeting to neuronal primary cilia for long-term energy balance (PMID:36692018), and acts in pancreatic δ cells where it is required for ghrelin's insulinostatic calcium response (PMID:32535024); its loss causes severe obesity with disrupted central melanocortin pathway gene expression (PMID:27106110). Loss-of-function MRAP2 variants in humans cause monogenic hyperphagic obesity, hyperglycemia, and hypertension, impairing MRAP2-regulated GPCR function (PMID:31700171).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 2009 High

    Established MRAP2 as a direct, bidirectional regulator of the melanocortin receptor family, defining its core role as a GPCR accessory protein rather than a single-receptor chaperone.

    Evidence Co-IP and cAMP signaling assays across MC1R–MC5R in heterologous cells

    PMID:19329486

    Open questions at the time
    • Did not resolve the structural basis of the interaction
    • In vivo physiological relevance not yet addressed
  2. 2013 High

    Showed MRAP2 control of MC4R is isoform- and development-specific in vivo, linking receptor modulation to organismal growth and feeding.

    Evidence Zebrafish genetic model with paralog-specific MRAP2a/MRAP2b binding and signaling assays

    PMID:23869017

    Open questions at the time
    • Mammalian equivalence of paralog-specific effects unclear
    • Molecular determinants of opposite paralog effects not mapped
  3. 2016 High

    Placed MRAP2 within the central melanocortin pathway by showing its deletion causes obesity and downregulates PVN neuropeptide gene expression.

    Evidence Two independent Mrap2-deficient mouse lines with body composition, PVN transcriptomics, and plasma lipid analysis

    PMID:27106110

    Open questions at the time
    • Did not identify which receptor(s) mediate the phenotype
    • Causal link between transcriptomic changes and obesity not established
  4. 2017 High

    Extended MRAP2 function to the ghrelin axis, demonstrating it is required in vivo for fasting and ghrelin to activate orexigenic AgRP neurons.

    Evidence Reciprocal Co-IP, in vitro signaling, and mouse KO with neuronal/behavioral readouts

    PMID:28959025

    Open questions at the time
    • Did not resolve the signaling-bias mechanism
    • Domain requirements not yet defined
  5. 2017 Medium

    Demonstrated that distinct MRAP2 domains regulate distinct GPCRs, showing the protein is not a uniform modulator across its receptor repertoire.

    Evidence Trafficking and signaling assays with MRAP2 deletion/truncation mutants on PKR1 and OX1R

    PMID:28939058

    Open questions at the time
    • Single lab
    • Precise domain-receptor contacts not structurally defined
  6. 2018 Medium

    Provided gain-of-function evidence that MRAP2 in PVN MC4R neurons potentiates melanocortin signaling and energy expenditure, complementing loss-of-function data.

    Evidence AAV-mediated MRAP2 overexpression in Mc4r-cre mice with energy homeostasis and c-Fos readouts

    PMID:30352741

    Open questions at the time
    • Single lab
    • Overexpression may not reflect physiological stoichiometry
  7. 2019 High

    Connected MRAP2 to human disease, establishing loss-of-function variants as causative for monogenic hyperphagic obesity with metabolic comorbidities.

    Evidence Sequencing of 9,418 individuals with functional assessment of each variant including pancreatic islet relevance

    PMID:31700171

    Open questions at the time
    • Tissue-specific contribution of each comorbidity not dissected
    • Variant effects on specific receptors not individually resolved
  8. 2020 High

    Defined the signaling-bias mechanism at GHSR1a, showing MRAP2 suppresses constitutive activity and β-arrestin recruitment while enhancing G-protein signaling via independent domains.

    Evidence cAMP, IP1, and β-arrestin recruitment assays with MRAP2 domain deletion constructs

    PMID:31911434

    Open questions at the time
    • Molecular block of β-arrestin recruitment not yet identified at residue level
  9. 2020 High

    Extended MRAP2's role to the endocrine pancreas, showing it is required in δ cells for ghrelin-evoked calcium responses and insulinostasis.

    Evidence Calcium imaging, global and δ-cell-conditional MRAP2 KO mice, and insulin secretion assays

    PMID:32535024

    Open questions at the time
    • Direct demonstration of δ-cell GHSR1a–MRAP2 complex in vivo not shown
  10. 2021 Medium

    Established that MRAP2 forms symmetric antiparallel homodimers and that domain orientation, not merely dimer assembly, dictates regulatory output on MC4R.

    Evidence Domain inversion mutagenesis with dimerization, surface expression, and cAMP assays

    PMID:34759891

    Open questions at the time
    • Single lab
    • No experimental structure of the dimer
  11. 2022 High

    Identified the molecular events by which MRAP2 blocks β-arrestin recruitment at GHSR1a, pinpointing kinase exclusion and specific phospho-sites.

    Evidence Phosphosite mutagenesis (Ser252/Thr261), GRK2/PKC interaction assays, and β-arrestin recruitment assays

    PMID:35605660

    Open questions at the time
    • Whether the same kinase-exclusion mechanism operates at other GPCRs not tested
  12. 2022 Medium

    Tied a conserved residue (R125) to MRAP2 conformation, dimerization, and receptor binding, providing a structural rationale for human R125 obesity variants.

    Evidence Site-directed mutagenesis with dimerization and PKR2 binding assays, cross-species comparison

    PMID:36077245

    Open questions at the time
    • Single lab
    • Structural mechanism of R125 action not resolved
  13. 2022 Medium

    Broadened the receptor repertoire to MCHR1, showing C-terminal-dependent inhibition of calcium signaling and trafficking.

    Evidence Co-IP, BiFC, Ca2+ signaling assays, and MRAP2 truncation mutants

    PMID:35311242

    Open questions at the time
    • Single lab
    • No in vivo validation of MCHR1 regulation
  14. 2023 High

    Revealed a trafficking-based mechanism by which MRAP2 controls MC4R, showing it is required for ciliary targeting of the receptor for long-term energy balance.

    Evidence Ciliary localization microscopy and MRAP2 KO mouse models with energy homeostasis readouts

    PMID:36692018

    Open questions at the time
    • Molecular machinery linking MRAP2 to ciliary transport not defined
  15. 2024 Low

    Added PKR2 to the set of receptors whose β-arrestin signaling MRAP2 inhibits.

    Evidence β-arrestin-2 recruitment assays with PKR2/MRAP2 co-expression

    PMID:38392222

    Open questions at the time
    • Single method described in abstract with limited mechanistic detail
    • No reciprocal interaction validation
    • No in vivo support
  16. 2025 High

    Unified MRAP2's mechanism across MC4R, MC3R, and GHSR, showing preferential 1:1 complexes, disruption of receptor homodimers, shared transmembrane contacts, and C-terminal modulation of constitutive activity.

    Evidence Single-molecule pull-down, stoichiometry by photobleaching, cAMP/β-arrestin assays, alanine and domain-deletion mutagenesis, and structural homology modeling across receptors

    PMID:39807633 PMID:40998819 PMID:41401256 PMID:41722048

    Open questions at the time
    • Structural models not experimentally validated by high-resolution structure
    • Some studies single-lab
  17. 2025 Medium

    Further extended the repertoire to melatonin receptors with receptor-divergent trafficking outcomes, reinforcing MRAP2 as a broad GPCR accessory protein.

    Evidence Co-IP, BiFC, GloSensor Gi signaling, and surface trafficking ELISA on MTNR1A/MTNR1B

    PMID:40510472

    Open questions at the time
    • Single lab
    • Physiological relevance of melatonin receptor regulation not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MRAP2 mechanistically distinguishes G-protein potentiation from β-arrestin/trafficking suppression across its diverse receptor partners, and whether a single structural mode generalizes, remains unresolved.
  • No experimentally determined high-resolution structure of any MRAP2–GPCR complex
  • Tissue-specific receptor selectivity in vivo only partially mapped
  • Mechanism of ciliary MC4R targeting unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0098772 molecular function regulator activity 5 GO:0060089 molecular transducer activity 4
Localization
GO:0005886 plasma membrane 2 GO:0005929 cilium 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1430728 Metabolism 3
Partners
GHSR1AMC2RMC3RMC4RMCHR1MTNR1AOX1RPKR2

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 MRAP2 interacts with all five melanocortin receptors (MC1R–MC5R). This interaction enables MC2R surface expression and signaling, while reducing MC1R, MC3R, MC4R, and MC5R responsiveness to NDP-MSH, establishing MRAP2 as a bidirectional regulator of the MCR family. Co-immunoprecipitation, cell surface expression assays, cAMP signaling assays in heterologous cells Proceedings of the National Academy of Sciences of the United States of America High 19329486
2013 In zebrafish, MRAP2a binds MC4R and reduces its ability to bind α-MSH, blocking MC4R function and stimulating larval growth; a paralog MRAP2b also binds MC4R but increases ligand sensitivity, demonstrating developmental isoform-specific control of MC4R activity. Cell culture binding assays, signaling assays, zebrafish genetic model Science (New York, N.Y.) High 23869017
2017 MRAP2 interacts with the ghrelin receptor GHSR1a and potentiates ghrelin-stimulated G-protein signaling both in vitro and in vivo. In the absence of MRAP2, fasting fails to activate AgRP neurons and the orexigenic effect of ghrelin is lost in mice. Co-immunoprecipitation, in vitro signaling assays, mouse knockout model with neuronal activity readouts Nature communications High 28959025
2017 MRAP2 inhibits the trafficking and signaling of prokineticin receptor 1 (PKR1) and orexin receptor 1 (OX1R). Specific regions of MRAP2 are required for regulation of OX1R and PKR1, establishing that different MRAP2 domains mediate regulation of distinct GPCRs. Cell-based trafficking assays, signaling assays, MRAP2 deletion/truncation mutants Biochimica et biophysica acta. Molecular cell research Medium 28939058
2020 MRAP2 inhibits GHSR1a constitutive activity, enhances G-protein-dependent signaling in response to ghrelin, and blocks β-arrestin recruitment and signaling. The effects on Gαq and β-arrestin pathways are independent and involve distinct regions of MRAP2, establishing that MRAP2 biases GHSR1a signaling. In vitro signaling assays (cAMP, IP1, β-arrestin recruitment assays), MRAP2 domain deletion constructs Science signaling High 31911434
2019 Loss-of-function MRAP2 variants in humans are pathogenic for monogenic hyperphagic obesity, hyperglycemia, and hypertension, with functional assessment demonstrating these variants impair MRAP2-regulated GPCR function in relevant tissues including pancreatic islets. Large-scale sequencing of 9,418 individuals, functional assessment of each variant Nature medicine High 31700171
2023 MRAP2 is critical for the ciliary localization of MC4R in neurons. Loss of MRAP2 abolishes MC4R targeting to neuronal primary cilia, and disruption of ciliary MC4R localization impairs long-term energy homeostasis regulation. Fluorescence microscopy for ciliary localization, mouse genetic models (MRAP2 KO), functional energy homeostasis measurements JCI insight High 36692018
2022 MRAP2 inhibits β-arrestin recruitment to GHSR1a by blocking GRK2 and PKC interaction with the receptor, thereby preventing phosphorylation of Ser252 and Thr261 in the third intracellular loop of GHSR1a that are required for β-arrestin recruitment. Phosphorylation site mutagenesis, GRK2/PKC interaction assays, β-arrestin recruitment assays The Journal of biological chemistry High 35605660
2020 MRAP2 is expressed in pancreatic islet δ cells and is required for ghrelin to elicit a calcium response in those cells. Global and δ-cell-targeted deletion of MRAP2 abrogates the insulinostatic effect of ghrelin, establishing MRAP2 as a regulator of insulin secretion via δ cell GHSR1a signaling. Calcium imaging in δ cells, conditional and global MRAP2 knockout mice, insulin secretion assays iScience High 32535024
2018 Overexpression of MRAP2 specifically in PVN MC4R-expressing neurons reduces food intake, increases energy expenditure and core body temperature, and increases neuronal activation in response to melanocortin agonist MTII, demonstrating a site-specific role for MRAP2 in potentiating MC4R neuronal activation. Stereotaxic AAV-mediated MRAP2 overexpression in Mc4r-cre mice, energy homeostasis measurements, glucose/insulin profiling, c-Fos neuronal activation Molecular metabolism Medium 30352741
2025 MRAP2 co-expression with MC4R enhances G-protein-mediated signaling, impairs β-arrestin2 recruitment and internalization, and disrupts MC4R oligomers by increasing the fraction of MC4R monomers. A structural homology model suggests MRAP2 contacts MC4R at transmembrane helices 5 and 6. cAMP and β-arrestin signaling assays, single-molecule imaging for oligomerization state, structural homology modeling Nature communications Medium 40998819
2025 MRAP2 directly interacts with MC3R with a preferential 1:1 stoichiometry, enhancing MC3R cAMP signaling, impairing β-arrestin recruitment, and reducing internalization. Five MRAP2 and two MC3R transmembrane residues identified by structural homology modeling are required for the interaction, and obesity-associated MRAP2 variants fail to enhance MC3R signaling. Single-molecule pull-down (SiMPull), fluorescence photobleaching stoichiometry, cAMP assays, β-arrestin recruitment assays, alanine mutagenesis Science signaling High 41401256
2025 MRAP2 regulates MC4R, MC3R, and GHSR via shared molecular mechanisms: all three GPCRs preferentially form 1:1 complexes with MRAP2, MRAP2 binding disrupts GPCR homodimerization, MRAP2 interacts with the same transmembrane regions across receptors, and deletion of the MRAP2 cytoplasmic region impairs GPCR signaling by modulating constitutive activity. Obesity-associated MRAP2 variants alter constitutive activity of all three GPCRs. Single-molecule pull-down, β-arrestin recruitment assays, constitutive activity measurements, MRAP2 domain deletion constructs, functional variant analysis Cell reports High 41722048
2025 Twelve obesity-associated MRAP2 variants impair MC4R function across multiple signaling pathways: seven impair cAMP signaling and nine impair IP3 signaling when expressed at equal concentrations; four C-terminal mutations affect MC4R internalization. Structural models predict MRAP2 interacts with MC4R transmembrane helices 5 and 6, and mutagenesis of two putative contact residues impaired MRAP2 facilitation of MC4R signaling. cAMP signaling assays, IP3 signaling assays, internalization assays, MRAP2 variant expression at equal concentrations, alanine mutagenesis of predicted contact sites Human molecular genetics Medium 39807633
2022 MRAP2 exists as a symmetric antiparallel homodimer on the plasma membrane. The arginine at position 125 (R125) is essential for MRAP2 function, affecting protein conformation, dimer formation, and PKR2 binding. Human obesity-associated mutations R125H and R125C impair these properties. MRAP2 mutant expression, dimerization assays, PKR2 binding assays, comparison with mouse MRAP2 (where position 125 is naturally histidine) International journal of molecular sciences Medium 36077245
2021 MRAP2 forms symmetric antiparallel homodimers on the plasma membrane; inversion of N-terminal, transmembrane, and C-terminal domains in six MRAP2 conformational variants showed that proper antiparallel homodimer assembly is maintained but regulatory profiles on MC4R surface expression and cAMP signaling are altered, revealing the functional importance of domain orientation. Domain inversion mutagenesis, dimerization assays, MC4R surface expression assays, cAMP signaling assays Frontiers in endocrinology Medium 34759891
2024 MRAP2 inhibits β-arrestin-2 recruitment to prokineticin receptor 2 (PKR2) and modulates PKR2-mediated β-arrestin signaling. β-arrestin-2 recruitment assays, PKR2/MRAP2 co-expression in cells Current issues in molecular biology Low 38392222
2022 MRAP2 interacts with melanin-concentrating hormone receptor 1 (MCHR1) and inhibits MCHR1 signaling in vitro. The C-terminal domain of MRAP2 is required for pharmacological modulation of intracellular Ca2+-coupled cascades and membrane transport of MCHR1. Co-immunoprecipitation, bimolecular fluorescence complementation (BiFC), Ca2+ signaling assays, MRAP2 truncation mutants Frontiers in endocrinology Medium 35311242
2016 Brain-specific and global deletion of Mrap2 in mice causes severe obesity with increased fat and lean mass. Transcriptomic analysis of Mrap2-deficient hypothalamic PVN revealed significantly decreased expression of Sim1, Trh, Oxt, and Crh, and circulating HDL and LDL were significantly elevated, indicating defective central melanocortin signaling downstream of MRAP2 loss. Two independently derived Mrap2-deficient mouse lines, body composition analysis, transcriptomic analysis of PVN, plasma lipid measurements The Journal of endocrinology High 27106110
2025 MRAP2 interacts with melatonin receptors MTNR1A and MTNR1B (shown by Co-IP and BiFC), inhibits their constitutive activity, enhances maximal agonist potency, suppresses membrane trafficking of MTNR1A, and promotes surface trafficking of MTNR1B. Co-immunoprecipitation, BiFC, GloSensor luminescence assay (Gi signaling), fixed-cell ELISA for surface trafficking Frontiers in endocrinology Medium 40510472

Source papers

Stage 0 corpus · 51 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 MRAP and MRAP2 are bidirectional regulators of the melanocortin receptor family. Proceedings of the National Academy of Sciences of the United States of America 197 19329486
2013 Developmental control of the melanocortin-4 receptor by MRAP2 proteins in zebrafish. Science (New York, N.Y.) 137 23869017
2019 Loss-of-function mutations in MRAP2 are pathogenic in hyperphagic obesity with hyperglycemia and hypertension. Nature medicine 82 31700171
2017 MRAP2 regulates ghrelin receptor signaling and hunger sensing. Nature communications 66 28959025
2017 Regions of MRAP2 required for the inhibition of orexin and prokineticin receptor signaling. Biochimica et biophysica acta. Molecular cell research 57 28939058
2020 The GPCR accessory protein MRAP2 regulates both biased signaling and constitutive activity of the ghrelin receptor GHSR1a. Science signaling 52 31911434
2017 The interaction of MC3R and MC4R with MRAP2, ACTH, α-MSH and AgRP in chickens. The Journal of endocrinology 48 28512117
2020 Emerging roles of melanocortin receptor accessory proteins (MRAP and MRAP2) in physiology and pathophysiology. Gene 39 32679290
2016 Loss of Mrap2 is associated with Sim1 deficiency and increased circulating cholesterol. The Journal of endocrinology 36 27106110
2023 MRAP2 regulates energy homeostasis by promoting primary cilia localization of MC4R. JCI insight 33 36692018
2016 Copy number variation (CNV) analysis and mutation analysis of the 6q14.1-6q16.3 genes SIM1 and MRAP2 in Prader Willi like patients. Molecular genetics and metabolism 29 26795956
2019 Orange-spotted grouper melanocortin-4 receptor: Modulation of signaling by MRAP2. General and comparative endocrinology 27 31398355
2021 MRAP2 Interaction with Melanocortin-4 Receptor in SnakeHead (Channa argus). Biomolecules 25 33807040
2020 The Insulinostatic Effect of Ghrelin Requires MRAP2 Expression in δ Cells. iScience 22 32535024
2012 Melanocortin 2 receptor-associated protein (MRAP) and MRAP2 in human adrenocortical tissues: regulation of expression and association with ACTH responsiveness. The Journal of clinical endocrinology and metabolism 22 22419722
2019 Pharmacological modulation of MRAP2 protein on melanocortin receptors in the sea lamprey. Endocrine connections 21 30856611
2018 Overexpression of melanocortin 2 receptor accessory protein 2 (MRAP2) in adult paraventricular MC4R neurons regulates energy intake and expenditure. Molecular metabolism 21 30352741
2018 Evaluating the interactions between red stingray (Dasyatis akajei) melanocortin receptors and elephant shark (Callorhinchus milii) MRAP1 and MRAP2 following stimulation with either stingray ACTH(1-24) or stingray Des-Acetyl-αMSH: A pharmacological study in Chinese Hamster Ovary cells. General and comparative endocrinology 20 29524525
2016 Hypothesis and Theory: Revisiting Views on the Co-evolution of the Melanocortin Receptors and the Accessory Proteins, MRAP1 and MRAP2. Frontiers in endocrinology 18 27445982
2013 Mrap2: an accessory protein linked to obesity. Cell metabolism 18 24011068
2020 Study of LEP, MRAP2 and POMC genes as potential causes of severe obesity in Brazilian patients. Eating and weight disorders : EWD 17 32578125
2019 Analyzing the signaling properties of gar (Lepisosteus oculatus) melanocortin receptors: Evaluating interactions with MRAP1 and MRAP2. General and comparative endocrinology 16 31276671
2017 Analyzing the effects of co-expression of chick (Gallus gallus) melanocortin receptors with either chick MRAP1 or MRAP2 in CHO cells on sensitivity to ACTH(1-24) or ACTH(1-13)NH2: Implications for the avian HPA axis and avian melanocortin circuits in the hypothalamus. General and comparative endocrinology 16 28888694
2019 Pharmacological modulation of two melanocortin-5 receptors by MRAP2 proteins in zebrafish. Journal of molecular endocrinology 14 30400043
2022 MRAP2 inhibits β-arrestin recruitment to the ghrelin receptor by preventing GHSR1a phosphorylation. The Journal of biological chemistry 13 35605660
2014 Melanocortin receptor accessory protein 2 (MRAP2) interplays with the zebrafish melanocortin 1 receptor (MC1R) but has no effect on its pharmacological profile. General and comparative endocrinology 13 24709359
2020 Pharmacological properties of whale shark (Rhincodon typus) melanocortin-2 receptor and melancortin-5 receptor: Interaction with MRAP1 and MRAP2. General and comparative endocrinology 11 32213301
2025 Obesity-associated MRAP2 variants impair multiple MC4R-mediated signaling pathways. Human molecular genetics 10 39807633
2024 MRAP2 Inhibits β-Arrestin-2 Recruitment to the Prokineticin Receptor 2. Current issues in molecular biology 9 38392222
2022 Determination of the Interaction and Pharmacological Modulation of MCHR1 Signaling by the C-Terminus of MRAP2 Protein. Frontiers in endocrinology 9 35311242
2022 Arginine 125 Is an Essential Residue for the Function of MRAP2. International journal of molecular sciences 9 36077245
2021 MC2R/MRAP2 activation could affect bovine ovarian steroidogenesis potential after ACTH treatment. Theriogenology 9 34425302
2023 A novel pathogenic variant in MRAP2 in an obese patient with successful outcome of bariatric surgery. European journal of endocrinology 8 37888144
2021 Regulation of melanocortin-5 receptor pharmacology by two isoforms of MRAP2 in ricefield eel (Monopterus albus). General and comparative endocrinology 7 34653433
2025 MRAP2 modifies the signaling and oligomerization state of the melanocortin-4 receptor. Nature communications 6 40998819
2021 Functional Characterization of the Internal Symmetry of MRAP2 Antiparallel Homodimer. Frontiers in endocrinology 6 34759891
2022 Analyzing the Hypothalamus/Pituitary/Interrenal axis of the neopterygian fish, Lepisosteus oculatus: Co-localization of MC2R, MC5R, MRAP1, and MRAP2 in interrenal cells. General and comparative endocrinology 5 35447133
2022 Reversion of MRAP2 Protein Sequence Generates a Functional Novel Pharmacological Modulator for MC4R Signaling. Biology 5 35741395
2021 Elucidation of the dimeric interplay of dual MRAP2 proteins in the zebrafish. Journal of cellular physiology 5 33559170
2021 Pharmacological properties of whale shark (Rhincodon typus) melanocortin-2 receptor and melancortin-5 receptor: Interaction with MRAP1 and MRAP2. General and comparative endocrinology 5 34607718
2019 MRAP2 regulates endometrial receptivity and function. Gene 5 30951854
2010 siRNA-mediated knockdown of the melanocortin 2 receptor accessory protein 2 (MRAP2) gene confers resistance to methylmercury on HEK293 cells. The Journal of toxicological sciences 5 21139347
2024 The MRAP2 accessory protein directly interacts with melanocortin-3 receptor to enhance signaling. bioRxiv : the preprint server for biology 4 39574659
2025 The accessory protein MRAP2 directly interacts with melanocortin-3 receptor to enhance signaling. Science signaling 3 41401256
2023 Molecular and pharmacological analysis of the melanocortin-2 receptor and its accessory proteins Mrap1 and Mrap2 in a Squalomorph shark, the Pacific spiny dogfish. General and comparative endocrinology 3 37454980
2026 MRAP2 potentiates GPCR signaling by conserved mechanisms that are disrupted by obesity-associated genetic variants. Cell reports 1 41722048
2025 MRAP2 potentiates GPCR signaling by conserved mechanisms that are disrupted by obesity-associated genetic variants. bioRxiv : the preprint server for biology 1 41040264
2026 Association of Mutations in the Melanocortin-2 Receptor Accessory Protein 2 Gene (MRAP2) and Obesity: A Systematic Review and Meta-Analysis. International journal of molecular sciences 0 41596694
2026 Functional characterisation of obesity-associated MRAP2 variants on MC4R and GHSR signalling. Human molecular genetics 0 41758604
2025 Pharmacological modulation of MRAP2 protein on murine melatonin receptor signaling. Frontiers in endocrinology 0 40510472
2022 Pharmacology of orange-spotted grouper (Epinephelus coioides) melanocortin-5 receptor and its modulation by Mrap2. General and comparative endocrinology 0 36455644

Missed literature

Know a paper Affinage missed for MRAP2? Flag it for the maintainers and the community.

No submissions yet.