Receptor activity-modifying protein 2

Function

Accessory protein that interacts with and modulates the function of G protein-coupled receptors including calcitonin gene-related peptide type 1 receptor (CALCRL) and calcitonin receptor (CALCR). Required for the transport of CALCRL to the plasma membrane. Together with CALCRL, form a receptor complex for adrenomedullin/ADM. Together with CALCR, act as a receptor complex for calcitonin/CT/CALC. Together with CALCR, also act as a receptor complex for amylin/IAPP.

Classification

Family (Pfam)

PF04901 RAMP

InterPro

RAMP, RAMP_sf

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 10

• 2XVT X-ray 2.05A
• 3AQE X-ray 2.00A
• 3AQF X-ray 2.60A
• 4RWF X-ray 1.76A
• 6UUN EM 3.00A
• 6V2E X-ray 1.83A
• 7TYH EM 3.30A
• 7TYX EM 2.55A
• 7TYY EM 3.00A
• 9BQ3 EM 2.80A

A predicted model is available from AlphaFold.

Gene Ontology · 36

• GO:1903143 adrenomedullin receptor complex
• GO:0009986 cell surface
• GO:0005905 clathrin-coated pit
• GO:0005737 cytoplasm
• GO:0005764 lysosome
• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:1990409 adrenomedullin binding
• GO:0001605 adrenomedullin receptor activity
• GO:0015026 coreceptor activity
• GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0034333 adherens junction assembly
• GO:1990410 adrenomedullin receptor signaling pathway
• GO:0150060 amylin receptor 2 signaling pathway
• GO:0001525 angiogenesis
• GO:0070831 basement membrane assembly
• GO:0070830 bicellular tight junction assembly
• GO:0006816 calcium ion transport
• GO:0032870 cellular response to hormone stimulus
• GO:0035924 cellular response to vascular endothelial growth factor stimulus
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0007507 heart development
• GO:0006886 intracellular protein transport
• GO:2000352 negative regulation of endothelial cell apoptotic process
• GO:0043116 negative regulation of vascular permeability
• GO:0045766 positive regulation of angiogenesis
• GO:0010628 positive regulation of gene expression
• GO:2001214 positive regulation of vasculogenesis
• GO:0072659 protein localization to plasma membrane
• GO:0015031 protein transport
• GO:0031623 receptor internalization
• GO:0008217 regulation of blood pressure
• GO:0008277 regulation of G protein-coupled receptor signaling pathway
• GO:0002040 sprouting angiogenesis
• GO:0097084 vascular associated smooth muscle cell development
• GO:0001570 vasculogenesis

Drugs targeting this protein · 1

• PRAMLINTIDE ACETATE agonist

Related proteins · sequence + function similarity

• Receptor activity-modifying protein 2 0.95
• Receptor activity-modifying protein 2 0.94
• Receptor activity-modifying protein 2 0.92
• Receptor activity-modifying protein 1 0.84
• Receptor activity-modifying protein 3 0.84
• Receptor activity-modifying protein 3 0.83
• Receptor activity-modifying protein 3 0.83
• Receptor activity-modifying protein 1 0.83
• Receptor activity-modifying protein 3 0.83
• Receptor activity-modifying protein 1 0.83
• Receptor activity-modifying protein 3 0.82
• Receptor activity-modifying protein 1 0.82

Co-cited proteins · studied together in the literature

• Calcitonin gene-related peptide type 1 receptor 4 shared papers
• Receptor activity-modifying protein 3 3 shared papers
• Pro-adrenomedullin 2 shared papers
• Receptor activity-modifying protein 1 2 shared papers
• Protein ADM2 1 shared papers
• Calcitonin receptor 1 shared papers
• Islet amyloid polypeptide 1 shared papers
• Calcitonin gene-related peptide 2 1 shared papers
• Calcitonin 1 shared papers
• Calcitonin gene-related peptide 1 1 shared papers

Literature · 7 cited papers

• A structural basis for amylin receptor phenotype. Science · 2022
• Structure and Dynamics of Adrenomedullin Receptors AM1 and AM2 Reveal Key Mechanisms in the Control of Receptor Phenotype by Receptor Activity-Modifying Proteins. ACS Pharmacol. Transl. Sci. · 2020
• hCALCRL mutation causes autosomal recessive nonimmune hydrops fetalis with lymphatic dysplasia. J. Exp. Med. · 2018
• Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. · 2012
• DNA sequence of human chromosome 17 and analysis of rearrangement in the human lineage. Nature · 2006
• The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). Genome Res. · 2004
• RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature · 1998