Receptor activity-modifying protein

Receptor activity-modifying proteins (RAMPs) are a class of protein that interact with and modulate the activities of several Class B G protein-coupled receptors including the receptors for secretin, calcitonin (CT), glucagon, and vasoactive intestinal peptide (VIP).[1] There are three distinct types of RAMPs in mammals (though more in fish), designated RAMP1, RAMP2, and RAMP3, each encoded by a separate gene.[2]

Receptor activity-modifying protein
Identifiers
SymbolRAMP
PfamPF04901
InterProIPR006985
Membranome10
Receptor activity-modifying protein 1
Identifiers
SymbolRAMP1
NCBI gene10267
HGNC9843
OMIM605153
RefSeqNM_005855
UniProtO60894
Other data
LocusChr. 2 q36-37.1
Receptor activity-modifying protein 2
Identifiers
SymbolRAMP2
NCBI gene10266
HGNC9844
OMIM605154
RefSeqNM_005854
UniProtO60895
Other data
LocusChr. 17 q12-21.1
Receptor activity-modifying protein 3
Identifiers
SymbolRAMP3
NCBI gene10268
HGNC9845
OMIM605155
RefSeqNM_005856
UniProtO60896
Other data
LocusChr. 7 q13-p12

Function

Currently, the function of RAMPs is divided into classes of activities. When associated with the Calcitonin receptor (CTR) or Calcitonin receptor-like (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 / golgi to the membrane. These functions appear to be ones where there is redundancy, as neither RAMP1 nor RAMP3 knockout mice (KO) have grossly abnormal phenotypes. The likelihood is that the phenotype of RAMP2 KO mice is more connected with the abolition of most adrenomedullin (AM) signalling than effects on trafficking of other receptors, as those mice are almost identical to AM KO mice and mice lacking the Calcitonin-like receptor which are unable to form either AM1 or AM-2 adrenomedullin receptors (CLR/RAMP2 and CLR/RAMP3 respectively).

Types

Association of RAMPs with either the CT or CALCRL proteins forms 6 different receptors from the calcitonin receptor family:[3][4][5]

GPCR RAMP isoform resultant receptor
Calcitonin receptor-like RAMP1 CGRP receptor
RAMP2 adrenomedullin (AM) receptor, designated AM1[6]
RAMP3 dual CGRP/AM receptor, designated AM2
Calcitonin receptor RAMP1 amylin receptor AMY1
RAMP2 amylin receptor AMY2
RAMP3 amylin receptor AMY3

References
  1. Sexton PM, Morfis M, Tilakaratne N, Hay DL, Udawela M, Christopoulos G, Christopoulos A (2006). "Complexing receptor pharmacology: modulation of family B G protein-coupled receptor function by RAMPs". Ann N Y Acad Sci. 1070: 90–104. doi:10.1196/annals.1317.076. PMID 16888151. S2CID 83595488.
  2. Young A (2005). Amylin: Physiology and Pharmacology; Chapter 3: Receptor pharmacology. Advances in Pharmacology. 52. pp. 47–65. doi:10.1016/S1054-3589(05)52003-9. ISBN 978-0-12-032954-0. PMID 16492540.
  4. McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM (May 1998). "RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor". Nature. 393 (6683): 333–9. doi:10.1038/30666. PMID 9620797. S2CID 4364526.
  5. Foord SM, Marshall FH (May 1999). "RAMPs: accessory proteins for seven transmembrane domain receptors". Trends Pharmacol. Sci. 20 (5): 184–7. doi:10.1016/S0165-6147(99)01347-4. PMID 10354609.
  6. Kamitani S, Asakawa M, Shimekake Y, Kuwasako K, Nakahara K, Sakata T (April 1999). "The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells". FEBS Lett. 448 (1): 111–4. doi:10.1016/S0014-5793(99)00358-0. PMID 10217420. S2CID 23729715.
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