Receptor activity-modifying proteins (RAMPs) are a class of protein which interact with and modulate the activities of several Class B G Protein-Coupled Receptors including the receptors for secretin

Secretin receptor

Human secretin receptor is a G protein-coupled receptor which binds secretin and is the leading member of the class B GPCR subfamily.-Interactions:...

, calcitonin

Calcitonin receptor

The calcitonin receptor is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism ....

 (CT), glucagon

Glucagon receptor

The glucagon receptor is a 62 kDa protein that is activated by glucagon and is a member of the class B G-protein coupled family of receptors, coupled to G alpha i, Gs and to a lesser extent G alpha q. Stimulation of the receptor results in activation of adenylate cyclase and increased levels of...

, and vasoactive intestinal peptide

Vasoactive intestinal peptide receptor

There are two known receptors for the vasoactive intestinal peptide termed VPAC1 and VPAC2. These receptors bind both VIP and pituitary adenylate cyclase-activating polypeptide to some degree...

 (VIP). There are three distinct types of RAMPs, designated RAMP1, RAMP2, and RAMP3, each encoded by a separate gene.

Function

Currently the function of RAMPs is divided into classes activities. When associated with the Calcitonin receptor

Calcitonin receptor

The calcitonin receptor is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism ....

 (CTR) or Calcitonin receptor-like

CALCRL

Calcitonin receptor-like , also known as the calcitonin receptor-like receptor , is a human protein.- Function :The protein encoded by the CALCRL gene is a G protein-coupled receptor related to the calcitonin receptor...

 (CALCRL) (below) RAMPs can change the selectivity of the receptor for a specific hormone. In the cases of the other receptors mentioned however, there is no evidence that they can do this, but instead function to regulate trafficking of receptors from the ER

Endoplasmic reticulum

The endoplasmic reticulum is an organelle of cells in eukaryotic organisms that forms an interconnected network of tubules, vesicles, and cisternae...

 / golgi

Golgi apparatus

The Golgi apparatus is an organelle found in most eukaryotic cells. It was identified in 1898 by the Italian physician Camillo Golgi, after whom the Golgi apparatus is named....

 to the membrane. These functions appear to be ones where there is redundancy as neither RAMP1 nor RAMP3 knockout mice

Knockout mouse

A knockout mouse is a genetically engineered mouse in which researchers have inactivated, or "knocked out," an existing gene by replacing it or disrupting it with an artificial piece of DNA...

 (KO) have grossly abnormal phenotype

Phenotype

A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...

s. The likelihood is that the phenotype of RAMP2 KO mice is more connected with the abolition of most adrenomedullin

Adrenomedullin

Adrenomedullin is a peptide associated with pheochromocytoma- a tumour arising from adrenal medulla. It was discovered in 1993.Adrenomedullin is a ubiquitously expressed peptide initially isolated from phaechromyctoma in 1993...

 (AM) signalling than effects on trafficking of other receptors as those mice are almost identical to AM KO mice.

Types

Association of RAMPs with either the CT

Calcitonin receptor

The calcitonin receptor is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism ....

 or CALCRL

CALCRL

Calcitonin receptor-like , also known as the calcitonin receptor-like receptor , is a human protein.- Function :The protein encoded by the CALCRL gene is a G protein-coupled receptor related to the calcitonin receptor...

 proteins form 6 different receptors from the calcitonin receptor family:

GPCR	RAMP isoform	resultant receptor
Calcitonin receptor-like CALCRL Calcitonin receptor-like , also known as the calcitonin receptor-like receptor , is a human protein.- Function :The protein encoded by the CALCRL gene is a G protein-coupled receptor related to the calcitonin receptor...	RAMP1 RAMP1 Receptor activity modifying protein 1 is a protein that in humans is encode by the RAMP1 gene.The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor activity modifying proteins . RAMPs are type I transmembrane proteins with an...	CGRP
	RAMP2 RAMP2 Receptor activity modifying protein 2, also known as RAMP2, is a protein which in humans is encoded by the RAMP2 gene.- Function :...	adrenomedullin Adrenomedullin Adrenomedullin is a peptide associated with pheochromocytoma- a tumour arising from adrenal medulla. It was discovered in 1993.Adrenomedullin is a ubiquitously expressed peptide initially isolated from phaechromyctoma in 1993...  (AM) receptor, designated AM1
	RAMP3 RAMP3 Receptor activity modifying protein 3, also known as RAMP3, is a human gene.The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor activity modifying proteins . RAMPs are type I transmembrane proteins with an extracellular N...	dual CGRP/AM receptor, designated AM2
Calcitonin receptor Calcitonin receptor The calcitonin receptor is a G protein-coupled receptor that binds the peptide hormone calcitonin and is involved in maintenance of calcium homeostasis, particularly with respect to bone formation and metabolism ....	RAMP1	amylin Amylin Amylin, or Islet Amyloid Polypeptide , is a 37-residue peptide hormone secreted by pancreatic β-cells at the same time as insulin .-Clinical significance:... receptor AMY1
	RAMP2	amylin receptor AMY2
	RAMP3	amylin receptor AMY3