Receptor activity-modifying protein explained

Symbol:RAMP
Receptor activity-modifying protein
Pfam:PF04901
Interpro:IPR006985
Membranome Superfamily:10
Receptor activity-modifying protein 1
Width:500px
Hgncid:9843
Symbol:RAMP1
Entrezgene:10267
Omim:605153
Refseq:NM_005855
Uniprot:O60894
Chromosome:2
Arm:q
Band:36
Locussupplementarydata:-37.1
Receptor activity-modifying protein 2
Hgncid:9844
Symbol:RAMP2
Entrezgene:10266
Omim:605154
Refseq:NM_005854
Uniprot:O60895
Chromosome:17
Arm:q
Band:12
Locussupplementarydata:-21.1
Receptor activity-modifying protein 3
Hgncid:9845
Symbol:RAMP3
Entrezgene:10268
Omim:605155
Refseq:NM_005856
Uniprot:O60896
Chromosome:7
Arm:q
Band:13
Locussupplementarydata:-p12

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]

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-likeRAMP1CGRP receptor
RAMP2adrenomedullin (AM) receptor, designated AM1[6]
RAMP3dual CGRP/AM receptor, designated AM2
Calcitonin receptorRAMP1amylin receptor AMY1
RAMP2amylin receptor AMY2
RAMP3amylin receptor AMY3

External links

Notes and References

  1. Sexton PM, Morfis M, Tilakaratne N, Hay DL, Udawela M, Christopoulos G, Christopoulos A . Complexing receptor pharmacology: modulation of family B G protein-coupled receptor function by RAMPs. Ann N Y Acad Sci . 1070 . 90–104 . 2006 . 1 . 16888151 . 10.1196/annals.1317.076 . 2006NYASA1070...90S . 83595488.
  2. Book: Young A . Receptor Pharmacology . Amylin: Physiology and Pharmacology; Chapter 3: Receptor pharmacology. 52 . 47–65 . 2005 . 16492540 . 10.1016/S1054-3589(05)52003-9 . Advances in Pharmacology . 978-0-12-032954-0 .
    • Web site: Calcitonin Receptors: Introduction . IUPHAR Database of Receptors and Ion Channels . International Union of Basic and Clinical Pharmacology . 2008-12-12 . 2016-03-03 . https://web.archive.org/web/20160303193818/http://www.iuphar-db.org/GPCR/IntroductionDisplayForward?chapterID=1358 . dead .
  3. McLatchie LM, Fraser NJ, Main MJ, Wise A, Brown J, Thompson N, Solari R, Lee MG, Foord SM . RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor . Nature . 393 . 6683 . 333–9 . May 1998 . 9620797 . 10.1038/30666 . 1998Natur.393..333M . 4364526 .
  4. Foord SM, Marshall FH . RAMPs: accessory proteins for seven transmembrane domain receptors . Trends Pharmacol. Sci.. 20 . 5 . 184–7 . May 1999 . 10354609 . 10.1016/S0165-6147(99)01347-4 .
  5. Kamitani S, Asakawa M, Shimekake Y, Kuwasako K, Nakahara K, Sakata T . The RAMP2/CRLR complex is a functional adrenomedullin receptor in human endothelial and vascular smooth muscle cells . FEBS Lett. . 448 . 1 . 111–4 . April 1999 . 10217420 . 10.1016/S0014-5793(99)00358-0 . 23729715 . free . 1999FEBSL.448..111K .