Receptor activity-modifying proteins (RAMPs) are transmembrane accessory proteins that influence the pharmacological profiles of the calcitonin receptor-like receptors (CRLR). RAMPs associate with CRLR in the endoplasmic reticulum and facilitate the glycosylation and transport of CRLR to the cell surface, where the mature protein then operates as a receptor for two structurally related vasodilatory peptides, calcitonin-gene-related peptide (CGRP) or adrenomedullin (ADM). RAMP-1 associating with CRLR confers a CGRP receptor, while RAMP-2 and RAMP-3 preferentially induce a responsiveness to ADM. RAMP proteins, including RAMP-1, RAMP-2 and RAMP-3, are structurally similar as they are type I receptors, which have a single extracellular N-terminus and a cytoplasmic C-terminus, and they share approximately 55% sequence similarity. RAMP-1 expression is highest in the uterus, brain and gastrointestinal tract, whereas RAMP-2 and RAMP-3 are highest in lung, breast and fetal tissues.
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