JM4 is a four-transmembrane protein binding to the CCR5 receptor

The CC chemokine receptor 5 (CCR5) is a major coreceptor for human immunodeficiency virus (HIV) and CCR5 mutants lacking the carboxy (C)-terminus interfere with HIV infection. Therefore, we analysed the C-terminus of CCR5 and here describe Jena-Muenchen 4 (JM4), a novel CCR5-interacting protein. JM4 is membrane-associated, co-precipitates with CCR5, and is ubiquitously expressed. It shares about 62% sequence similarity with JWA and glutamate transporter-associated protein 3-18 (GTRAP3-18), a regulator of an amino acid transporter. JWA, like JM4, is a four-transmembrane protein, which binds to the CCR5 receptor. Furthermore, JM4, JWA, and GTRAP3-18 co-localise and heterodimerise indicating a functional relationship. JM4 co-localises with calnexin in the endoplasmic reticulum and with the mannose 6-phosphate receptor in the Golgi. JM4 and GTRAP3-18 harbor a Rab-acceptor motif, indicating a function in vesicle formation at the Golgi complex. In conclusion, we describe a CCR5-interacting protein, which is suggested to function in trafficking and membrane localisation of the receptor, possibly also other receptors or amino acid transporters. (c) 2005 Federation of European Biochemical Societies. Published by Elsevier B.V. All right reserved.