RAMP2 explained

Receptor activity modifying protein 2, also known as RAMP2, is a protein which in humans is encoded by the RAMP2 gene.^{[1] [2]}

Function

The protein encoded by this gene is a member of the RAMP family of single-transmembrane-domain proteins, called receptor (calcitonin) activity modifying proteins (RAMPs). RAMPs are type I transmembrane proteins with an extracellular N-terminus and a cytoplasmic C-terminus. RAMPs are required to transport calcitonin-receptor-like receptor (CRLR) to the plasma membrane. CRLR, a receptor with seven transmembrane domains, can function as either a calcitonin gene-related peptide (CGRP) receptor or an adrenomedullin receptor, depending on which members of the RAMP family are expressed. In the presence of this (RAMP2) protein, CRLR functions as an adrenomedullin receptor. The RAMP2 protein is involved in core glycosylation and transportation of adrenomedullin receptor to the cell surface.^[1]

Further reading

• Ichikawa-Shindo Y, Sakurai T, Kamiyoshi A, Kawate H, Iinuma N, Yoshizawa T, Koyama T, Fukuchi J, Iimuro S, Moriyama N, Kawakami H, Murata T, Kangawa K, Nagai R, Shindo T . The GPCR modulator protein RAMP2 is essential for angiogenesis and vascular integrity . The Journal of Clinical Investigation . 118 . 1 . 29–39 . January 2008 . 18097473 . 2147670 . 10.1172/JCI33022 .
• Fritz-Six KL, Dunworth WP, Li M, Caron KM . Adrenomedullin signaling is necessary for murine lymphatic vascular development . The Journal of Clinical Investigation . 118 . 1 . 40–50 . January 2008 . 18097475 . 2147672 . 10.1172/JCI33302 .
• Kuwasako K, Kitamura K, Nagata S, Kato J . Functions of the extracellular histidine residues of receptor activity-modifying proteins vary within adrenomedullin receptors. . Biochem. Biophys. Res. Commun. . 377 . 1 . 109–13 . 2008 . 18835256 . 10.1016/j.bbrc.2008.09.105 .
• Oliver KR, Wainwright A, Edvinsson L, etal . Immunohistochemical localization of calcitonin receptor-like receptor and receptor activity-modifying proteins in the human cerebral vasculature. . J. Cereb. Blood Flow Metab. . 22 . 5 . 620–9 . 2002 . 11973435 . 10.1097/00004647-200205000-00014 . free .
• Christopoulos A, Christopoulos G, Morfis M, etal . Novel receptor partners and function of receptor activity-modifying proteins. . J. Biol. Chem. . 278 . 5 . 3293–7 . 2003 . 12446722 . 10.1074/jbc.C200629200 . free .
• Dumont CE, Muff R, Flühmann B, etal . Paracrine/autocrine function of adrenomedullin in peripheral nerves of rats. . Brain Res. . 955 . 1–2 . 64–71 . 2002 . 12419522 . 10.1016/S0006-8993(02)03365-6 . 33819362 .
• Kuwasako K, Cao YN, Nagoshi Y, etal . Characterization of the human calcitonin gene-related peptide receptor subtypes associated with receptor activity-modifying proteins. . Mol. Pharmacol. . 65 . 1 . 207–13 . 2004 . 14722252 . 10.1124/mol.65.1.207 .
• Nagoshi Y, Kuwasako K, Cao YN, etal . Tumor necrosis factor-alpha downregulates adrenomedullin receptors in human coronary artery smooth muscle cells. . Peptides . 25 . 7 . 1115–21 . 2004 . 15245870 . 10.1016/j.peptides.2004.04.010 . 54255777 .
• Kuwasako K, Kitamura K, Nagoshi Y, Eto T . Novel calcitonin-(8-32)-sensitive adrenomedullin receptors derived from co-expression of calcitonin receptor with receptor activity-modifying proteins. . Biochem. Biophys. Res. Commun. . 301 . 2 . 460–4 . 2003 . 12565884 . 10.1016/S0006-291X(02)03072-3 .
• Wang YF, Zhang J, Li J, etal . [Increased atria expression of receptor activity-modifying proteins in heart failure patients] . Zhonghua Yi Xue Yi Chuan Xue Za Zhi . 21 . 4 . 351–4 . 2004 . 15300632 .
• Foord SM, Marshall FH . RAMPs: accessory proteins for seven transmembrane domain receptors. . Trends Pharmacol. Sci. . 20 . 5 . 184–7 . 1999 . 10354609 . 10.1016/S0165-6147(99)01347-4 .
• Prado MA, Evans-Bain B, Oliver KR, Dickerson IM . The role of the CGRP-receptor component protein (RCP) in adrenomedullin receptor signal transduction. . Peptides . 22 . 11 . 1773–81 . 2001 . 11754963 . 10.1016/S0196-9781(01)00517-4 . 37139980 .
• Bomberger JM, Parameswaran N, Hall CS, etal . Novel function for receptor activity-modifying proteins (RAMPs) in post-endocytic receptor trafficking. . J. Biol. Chem. . 280 . 10 . 9297–307 . 2005 . 15613468 . 10.1074/jbc.M413786200 . free .
• Udawela M, Christopoulos G, Tilakaratne N, etal . Distinct receptor activity-modifying protein domains differentially modulate interaction with calcitonin receptors. . Mol. Pharmacol. . 69 . 6 . 1984–9 . 2006 . 16531504 . 10.1124/mol.105.021915 . 1957141 .
• Aiyar N, Disa J, Ao Z, etal . Molecular cloning and pharmacological characterization of bovine calcitonin receptor-like receptor from bovine aortic endothelial cells. . Biochem. Pharmacol. . 63 . 11 . 1949–59 . 2002 . 12093471 . 10.1016/S0006-2952(02)00990-5 .
• Kuwasako K, Cao YN, Chu CP, etal . Functions of the cytoplasmic tails of the human receptor activity-modifying protein components of calcitonin gene-related peptide and adrenomedullin receptors. . J. Biol. Chem. . 281 . 11 . 7205–13 . 2006 . 16410241 . 10.1074/jbc.M511147200 . free .
• Gerhard DS, Wagner L, Feingold EA, etal . The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC). . Genome Res. . 14 . 10B . 2121–7 . 2004 . 15489334 . 10.1101/gr.2596504 . 528928 .
• Strausberg RL, Feingold EA, Grouse LH, etal . Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. . Proc. Natl. Acad. Sci. U.S.A. . 99 . 26 . 16899–903 . 2002 . 12477932 . 10.1073/pnas.242603899 . 139241 . 2002PNAS...9916899M . free .
• Yue W, Dacic S, Sun Q, etal . Frequent inactivation of RAMP2, EFEMP1 and Dutt1 in lung cancer by promoter hypermethylation. . Clin. Cancer Res. . 13 . 15 Pt 1 . 4336–44 . 2007 . 17671114 . 10.1158/1078-0432.CCR-07-0015 . free .
• Udawela M, Christopoulos G, Morfis M, etal . A critical role for the short intracellular C terminus in receptor activity-modifying protein function. . Mol. Pharmacol. . 70 . 5 . 1750–60 . 2006 . 16912219 . 10.1124/mol.106.024257 . 7249716 .
• Michou L, Garnier S, Barbet S, etal . Lack of linkage and association of adrenomedullin and its receptor genes in French Caucasian rheumatoid arthritis trio families. . Clin. Exp. Rheumatol. . 26 . 6 . 1083–6 . 2008. 19210874 .
• Qi T, Christopoulos G, Bailey RJ, etal . Identification of N-terminal receptor activity-modifying protein residues important for calcitonin gene-related peptide, adrenomedullin, and amylin receptor function. . Mol. Pharmacol. . 74 . 4 . 1059–71 . 2008 . 18593822 . 10.1124/mol.108.047142 . 33491956 .

Notes and References

1. Web site: Entrez Gene: RAMP2 .
2. 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 .