The amylin–calcitonin/RAMP receptor axis

Scope and exact ligand identity

This page maps human receptor pharmacology, not treatment. UniProt identifies mature human amylin as residues 34–70 of the 89-residue IAPP precursor. The mature product contains 37 residues, a disulfide bond between its second and seventh cysteines, and a C-terminal tyrosinamide. The sequence shown in the identity card preserves that mature form.

The map does not treat “amylin receptor” as one unnamed protein. It represents each defined receptor assembly and keeps endogenous amylin, approved pramlintide and investigational cagrilintide in separate evidence layers.

How CALCR and RAMPs construct the targets

The calcitonin receptor CTR is the protein encoded by CALCR. Association of that receptor with RAMP1, RAMP2 or RAMP3 defines the AMY1, AMY2 or AMY3 receptor complex, respectively. Each target card therefore lists every verified human protein component and its own UniProt identifier.

RAMPs are receptor activity-modifying proteins, not interchangeable labels. Changing the RAMP changes the pharmacological target. Co-expression, receptor splice variants, species and assay context complicate attribution in living systems, so a complex name must not be collapsed back to CALCR alone.

Endogenous amylin relations

GtoPdb records human amylin as an agonist at human AMY1, AMY2 and AMY3 receptors. The interaction records include cAMP readouts, while the receptor-family review defines the complexes as CALCR/RAMP1–3. The relation table therefore marks the three edges as canonical endogenous agonism with Gs → adenylyl cyclase → cAMP as the primary curated route.

“Primary” does not mean “exclusive”. The map does not infer equal potency, identical receptor reserve or the same signalling balance across the three complexes.

Separate engineered-agonist layer

Pramlintide is shown as an approved medicine because the current US label supports that status. Its receptor edges are supported separately by human AMY1, AMY2 and AMY3 interaction records and a comparative receptor-pharmacology study; the status label is not used as receptor evidence.

Cagrilintide remains investigational at the dated review point. A 2025 structural study resolved cagrilintide bound to active, Gs-coupled AMY1, AMY2, AMY3 and CTR. Those four directly observed complexes support the four edges; trial registration supplies development status only.

Evidence and naming boundaries

The terms AMY1, AMY2 and AMY3 describe receptor complexes, whereas IAPP is the human precursor gene and amylin is its processed peptide product. Pramlintide and cagrilintide are engineered analogues, not alternative names for endogenous amylin.

The receptor map does not rank agents by potency, efficacy or signalling bias. It also does not assume that a missing edge is biologically impossible. Every edge is limited to the ligand, human target and evidence source shown.

What this map cannot establish

A receptor relation cannot by itself establish appetite change, gastric emptying, glucose effects, body-weight change, safety, approval in every jurisdiction or benefit for an individual. Those require their own molecular, tissue, animal, clinical or regulatory evidence. The links to full monographs preserve that separation instead of allowing receptor activity to inherit clinical claims.