Receptor activity-modifying protein

Last updated
Receptor activity-modifying protein
Identifiers
SymbolRAMP
Pfam PF04901
InterPro IPR006985
Membranome 10
Available protein structures:
Pfam   structures / ECOD  
PDB RCSB PDB; PDBe; PDBj
PDBsum structure summary
Receptor activity-modifying protein 1
Identifiers
Symbol RAMP1
NCBI gene 10267
HGNC 9843
OMIM 605153
RefSeq NM_005855
UniProt O60894
Other data
Locus Chr. 2 q36-37.1
Search for
Structures Swiss-model
Domains InterPro
Receptor activity-modifying protein 2
Identifiers
Symbol RAMP2
NCBI gene 10266
HGNC 9844
OMIM 605154
RefSeq NM_005854
UniProt O60895
Other data
Locus Chr. 17 q12-21.1
Search for
Structures Swiss-model
Domains InterPro
Receptor activity-modifying protein 3
Identifiers
Symbol RAMP3
NCBI gene 10268
HGNC 9845
OMIM 605155
RefSeq NM_005856
UniProt O60896
Other data
Locus Chr. 7 q13-p12
Search for
Structures Swiss-model
Domains InterPro

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]

Contents

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]

GPCRRAMP isoformresultant 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
RAMP2amylin receptor AMY2
RAMP3amylin receptor AMY3

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Deborah Lucy Hay is a New Zealand academic. In 2022, she was elected a Fellow of the Royal Society Te Apārangi.

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 (1): 90–104. Bibcode:2006NYASA1070...90S. doi:10.1196/annals.1317.076. PMID   16888151. S2CID   83595488.
  2. Young A (2005). "Receptor Pharmacology". Amylin: Physiology and Pharmacology; Chapter 3: Receptor pharmacology. Advances in Pharmacology. Vol. 52. pp. 47–65. doi:10.1016/S1054-3589(05)52003-9. ISBN   978-0-12-032954-0. PMID   16492540.
  3. 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. Bibcode:1998Natur.393..333M. doi:10.1038/30666. PMID   9620797. S2CID   4364526.
  4. 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.
  5. 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. Bibcode:1999FEBSL.448..111K. doi: 10.1016/S0014-5793(99)00358-0 . PMID   10217420. S2CID   23729715.