Receptor activity-modifying protein 1

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 the receptor complex for the calcitonin gene-related peptides CGRP1/CALCA and CGRP2/CALCB. Together with CALCR, form the AMYR1 receptor complex for amylin/IAPP and CGRP1/CALCA.

Classification

Family (Pfam)

PF04901 RAMP

InterPro

RAMP, RAMP_sf

Functional cluster

Secreted Growth Factors & Cytokines

Experimental structures · PDB · 24

• 2YX8 X-ray 2.40A
• 3N7P X-ray 2.80A
• 3N7R X-ray 2.90A
• 3N7S X-ray 2.10A
• 4RWG X-ray 2.44A
• 5V6Y X-ray 2.80A
• 6D1U X-ray 2.05A
• 6E3Y EM 3.30A
• 6UMG X-ray 2.70A
• 6ZHO X-ray 1.60A
• 6ZIS X-ray 1.73A
• 7KNT EM 3.15A
• … and 12 more

A predicted model is available from AlphaFold.

Gene Ontology · 22

• GO:0009986 cell surface
• GO:1990406 CGRP receptor complex
• GO:0005886 plasma membrane
• GO:0043235 receptor complex
• GO:0097643 amylin receptor activity
• GO:1990407 calcitonin gene-related peptide binding
• GO:0001635 calcitonin gene-related peptide receptor activity
• GO:0015026 coreceptor activity
• GO:0007189 adenylate cyclase-activating G protein-coupled receptor signaling pathway
• GO:0150059 amylin receptor 1 signaling pathway
• GO:0097647 amylin receptor signaling pathway
• GO:0001525 angiogenesis
• GO:1990408 calcitonin gene-related peptide receptor signaling pathway
• GO:0006816 calcium ion transport
• GO:0032870 cellular response to hormone stimulus
• GO:0007186 G protein-coupled receptor signaling pathway
• GO:0006886 intracellular protein transport
• GO:0010560 positive regulation of glycoprotein biosynthetic process
• GO:0072659 protein localization to plasma membrane
• GO:0015031 protein transport
• GO:0031623 receptor internalization
• GO:0008277 regulation of G protein-coupled receptor signaling pathway

Drugs targeting this protein · 3

• DAVALINTIDE agonist
• ZAVEGEPANT antagonist
• PRAMLINTIDE ACETATE agonist

Related proteins · sequence + function similarity

• Receptor activity-modifying protein 1 0.97
• Receptor activity-modifying protein 1 0.96
• Receptor activity-modifying protein 1 0.94
• Receptor activity-modifying protein 1 0.94
• Receptor activity-modifying protein 2 0.84
• Receptor activity-modifying protein 2 0.82
• Receptor activity-modifying protein 3 0.79
• Receptor activity-modifying protein 2 0.77
• Receptor activity-modifying protein 3 0.76
• Receptor activity-modifying protein 2 0.75
• Receptor activity-modifying protein 3 0.73
• Receptor activity-modifying protein 3 0.72

Co-cited proteins · studied together in the literature

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

Literature · 7 cited papers

• Cryo-EM Structure of the Human Amylin 1 Receptor in Complex with CGRP and Gs Protein. Biochemistry · 2024
• A structural basis for amylin receptor phenotype. Science · 2022
• Structure and dynamics of the CGRP receptor in apo and peptide-bound forms. Science · 2021
• Crystal structure of the ectodomain complex of the CGRP receptor, a class-B GPCR, reveals the site of drug antagonism. Structure · 2010
• Crystal structure of the human receptor activity-modifying protein 1 extracellular domain. Protein Sci. · 2008
• 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