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T V Novoselova, D Jackson, D C Campbell, A J L Clark and L F Chan

insufficiency, depression and sepsis. Figure 1 Schematic overview of the HPA axis and the sites of predominant MRAP/MRAP2 action. In short, CRH and AVP at the hypothalamus stimulate ACTH production in the anterior pituitary gland. ACTH released into the

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T V Novoselova, R Larder, D Rimmington, C Lelliott, E H Wynn, R J Gorrigan, P H Tate, L Guasti, The Sanger Mouse Genetics Project, S O’Rahilly, A J L Clark, D W Logan, A P Coll and L F Chan

Introduction Melanocortin receptor accessory protein (MRAP) and its paralogue MRAP2 are a recently identified class of small, single-pass transmembrane domain accessory proteins ( Chan et al . 2009 , Novoselova et al . 2013 ). Both MRAP and

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Jiannan Zhang, Xin Li, Yawei Zhou, Lin Cui, Jing Li, Chenlei Wu, Yiping Wan, Juan Li and Yajun Wang

findings also highlight the importance of the competitive interaction between α-MSH and AgRP at the MC4R(/MC3R) interface to control energy balance. Recently, two melanocortin-2 receptor accessory proteins, named MRAP (also called MRAP1) and MRAP2

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Francesca Spiga, Jamie J Walker, Rita Gupta, John R Terry and Stafford L Lightman

pregnenolone in the mitochondria) and MRAP (the gene encoding for the melanocortin receptor accessory protein (MRAP), which regulates the level and activity of MC2R at the cell surface, and thus the cell's responsiveness to ACTH; Metherell et al . 2005

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K S Wilson, C S Tucker, E A S Al-Dujaili, M C Holmes, P W F Hadoke, C J Kenyon and M A Denvir

associated with melanocortin receptor accessory proteins (also expressed in head kidney). The activity of Mcr4 in larval fish is inhibited by Mrap2a (a larval MRAP paralog which inhibits Mcr4 actions) ( Sebag et al . 2013 ). As GCs have been shown to

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Giulia Baldini and Kevin D Phelan

activity may contribute to receptor signal. MC4R activity can also be modulated by accessory factors. MRAP2 is a MC4R-interacting factor that is co-expressed with the receptor in the hypothalamus, localizes to the plasma membrane and endoplasmic reticulum

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R Prasad, J C Kowalczyk, E Meimaridou, H L Storr and L A Metherell

the adrenal, namely mutations in the ACTH receptor, melanocortin 2 receptor ( MC2R ), and its accessory protein MRAP (melanocortin receptor accessory protein) ( Clark et al . 1993 , Metherell et al . 2005 , Meimaridou et al . 2013 ). Novel

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E Meimaridou, M Goldsworthy, V Chortis, E Fragouli, P A Foster, W Arlt, R Cox and L A Metherell

. 2009 , Rubtsov et al . 2009 , Sahakitrungruang et al . 2010 , 2011 , Parajes et al . 2011 ). In FGD, the two most common gene defects are mutations in the melanocortin 2 receptor and its accessory protein ( MC2R and MRAP ), but recently, we