Minireview: the melanocortin 2 receptor accessory proteins

Webb, Tom R.; Clark, Adrian J. L.

doi:10.1210/me.2009-0283

Cited by 125Receptor Mechanisms and SignalingNeuropeptides and Animal PhysiologyAdrenal Hormones and Disorders

Minireview: the melanocortin 2 receptor accessory proteins

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Webb, Tom R., Clark, Adrian J. L.·2010·Molecular Endocrinology

DOI 10.1210/me.2009-0283PMC PMC5419097

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Abstract

The melanocortin 2 receptor (MC2R) accessory protein, MRAP, is one of a growing number of G protein-coupled receptor accessory proteins that have been identified in recent years that add control and complexity to G protein-coupled receptor functional expression and signal transduction. MRAP interacts directly with MC2R and is essential for its trafficking from the endoplasmic reticulum to the cell surface, where it acts as the receptor for the pituitary hormone ACTH. In addition, MRAP2, a newly described homolog of MRAP, is also able to support the cell surface expression of MC2R. Although it is clear that MRAP is required for MC2R function, the mechanism of MRAP action is only beginning to be understood. Recent work has started to reveal some of these mechanisms and the MRAP domains involved in MC2R functional expression, and new data have shown a potential role for both MRAP and MRAP2 in the regulation of the other melanocortin receptors.

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MC2R is absolutely dependent on MRAP for cell surface expression and function.
“The ACTH receptor, also known as the melanocortin 2 receptor (MC2R), is unusual in that it is absolutely dependent on a small accessory protein, melanocortin receptor accessory protein (MRAP) for cell surface expression and function.”
From ACTH Antagonists (2016) · cites this paper as [35]
In “MRAP Is Required for Functional MC2R Expression” (page unavailable), the review says MRAP enables MC2R to reach the cell surface and form a functional ACTH-responsive receptor. But its MRAP2 discussion (page unavailable) reports that MRAP2 can also support MC2R surface expression and function in heterologous cells, so absolute dependence on MRAP specifically is too strong. (LLM, conf=0.86)
Experimental — accuracy not yet measured
FGD2, clinically indistinguishable from FGD1, is caused by mutations in the gene for melanocortin 2 receptor accessory protein (MRAP).
“FGD2, which is clinically indistinguishable from FGD1, is caused by mutations in the gene for melanocortin 2 receptor accessory protein (MRAP) (119, 625, 626).”
From The Molecular Biology, Biochemistry, and Physiology of Human Steroidogenesis and Its Disorders (2011) · cites this paper as [626]

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“The discovery that deficiency of a small, single transmembrane domain protein caused a clinical syndrome essentially identical to that caused by MC2R deficiency led to the identification of the melanocortin 2 receptor accessory protein (MRAP) as the MC2R co-receptor (34, 35).”
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Authors: Webb, T. R., & Clark, A. J. L.
Affiliations: William Harvey Research Institute (GB)
Corresponding author: Clark, Adrian J. L.
ORCID: Webb, Tom R.
Clark, Adrian J. L.
Venue: Molecular Endocrinology
Publisher: The Endocrine Society
Published: 2010-03-01
Volume: 24
Issue: 3
Pages: 475-484
ISSN: 0888-8809 (ISSN-L)
1944-9917
DOI: 10.1210/me.2009-0283
PMC: PMC5419097
OpenAlex: W2023114108
Cited by: 125
References: 34
Citations by year: 2026: 3 · 2025: 3 · 2024: 1 · 2023: 6 · 2022: 10 · 2021: 8 · 2020: 3 · 2019: 5 · 2018: 5 · 2017: 7 · 2016: 11 · 2015: 4 · 2014: 15 · 2013: 14 · 2012: 12
FWCI: 0.79
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: Molecular Endocrinology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Leicester Research Archive (University of Leicester) (submittedVersion)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords: melanocortin 2 receptor, MRAP, MRAP2, receptor trafficking, ACTH signaling, melanocortin receptors, signal transduction
MeSH terms: Humans, Membrane Proteins, Models, Biological, Protein Structure, Tertiary, Receptor, Melanocortin, Type 2

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Minireview: the melanocortin 2 receptor accessory proteins

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