International Union of Pharmacology. XXX. Update on Chemokine Receptor Nomenclature PHILIP M. MURPHY 1 Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland This paper is available online at http://pharmrev.aspetjournals.org Abstract ............................................................................... 227 I. Introduction ............................................................................ 227 A. CXCR6 ............................................................................. 227 B. CCR11 ............................................................................. 228 References ............................................................................. 229 Abstract——An update of the International Union of Pharmacology nomenclature for chemokines is out- lined, defining one new receptor type, CXCR6, and disqualifying the putative receptor, CCR11. I. Introduction In the year 2000, the International Union of Pharma- cology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR 2 ) approved a nomenclature system for chemokine receptors, the major seven trans- membrane (7TM) receptors of the immune system, as recommended by the NC-IUPHAR Chemokine Receptor Subcommittee (Murphy et al., 2000). At that time, the chemokine receptor family consisted of 18 7TM proteins in humans, which were divided into four subfamilies based on chemokine subclass specificity. Two additional molecules, named Duffy and D6, which both have 7TM structure and bind chemokines but lack a known signal- ing function, were excluded from the nomenclature sys- tem, as were a group of functional 7TM chemokine re- ceptors encoded by herpesviruses (Rosenkilde et al., 2001). The nomenclature system is logical, noncontro- versial, and universally accepted and used (Table 1). Moreover, it has served as a template for the creation of a chemokine ligand nomenclature system (Zlotnik and Yoshie, 2000). Both systems have facilitated communi- cation among immunologists and pharmacologists as these molecules have become important drug targets in immunologically mediated disease and HIV/acquired immunodeficiency syndrome. Since publication of the NC-IUPHAR document reporting the nomenclature sys- tem in the year 2000, one new receptor subtype, CXCR6, has been identified (Matloubian et al., 2000; Wilbanks et al., 2001), and one other subtype, CCR11, has been dis- qualified (Schweickart et al., 2000, 2001). Duffy and D6 remain as binding sites. The aim of the present article is to provide a brief update on these receptors. A. CXCR6 CXCR6 was originally cloned as an orphan receptor in 1997 by three independent groups who assigned three different names to it: STRL33 (seven transmembrane receptor-like from clone 33), BONZO, and TYMSTR (T lymphocyte-expressed seven-transmembrane domain receptor) (Alkhatib et al., 1997; Deng et al., 1997; Liao et al., 1997; Loetscher et al., 1997). It was considered most likely to be a chemokine receptor because 1) the gene was located on human chromosome 3p21 within the major chemokine receptor cluster, 2) the sequence was most highly related to chemokine receptors, 3) the RNA was expressed in activated T lymphocytes, and 4) like many other chemokine receptors, it could function as a cell entry factor for HIV. A particularly interesting fea- ture is its ability to support cell entry by simian immu- nodeficiency virus and both X4 and R5 strains of HIV. Although many chemokine receptors have multiple shared ligands, CXCR6 binds a distinct ligand, desig- nated CXCL16 (Matloubian et al., 2000; Wilbanks et al., 2001). CXCL16 has a unique hybrid structure, with fea- tures heretofore found separately in two other chemo- kine subclasses. In particular, it has the CXC motif, Address correspondence to: Dr. Philip M. Murphy, Laboratory of Host Defenses, Bldg. 10, Room 11N113, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD 20892. E-mail: pmm@nih.gov 1 Chairman of the Subcommittee on Chemokine Receptors, Inter- national Union of Pharmacology Committee on Receptor Nomencla- ture and Drug Classification. 2 Abbreviations: NC-IUPHAR, International Union of Pharmacol- ogy Committee on Receptor Nomenclature and Drug Classification; 7TM, seven transmembrane; HIV, human immunodeficiency virus. 0031-6997/02/5402-227–229$7.00 PHARMACOLOGICAL REVIEWS Vol. 54, No. 2 U.S. Government work not protected by U.S. copyright 20203/989284 Pharmacol Rev 54:227–229, 2002 Printed in U.S.A 227 by guest on December 12, 2016 Downloaded from