Several receptors for neuropeptide Y (NPY; 162640) have been demonstrated and shown to differ in pharmacologic characteristics, tissue distribution, and structure of the encoding genes; see the NPY Y1 receptor (NPY1R; 162641) and the NPY Y2 receptor (NPY2R; 162642). Herzog et al. (1993) cloned, sequenced, and mapped the human homolog of a proposed bovine NPY Y3 receptor reported by Rimland et al. (1991). The human cDNA clone was derived from a human lung cDNA library. The 1,670-bp sequence predicts a single open reading frame (ORF) of 352 amino acids, with 92% amino acid identity to the reported bovine sequence. The amino acid sequence shares features common to many other G protein-coupled receptors, including the 7-transmembrane regions and putative glycosylation and phosphorylation sites. The receptor shows 36% identity to the interleukin-8 receptor (IL8RA; 146929), which is located on chromosome 2, and to the angiotensin II receptor (AGTR1; 106165), but only 21% identity to the NPY Y1 receptor. The recruitment of leukocytes to inflamed tissues involves interleukin-8 (IL8; 146930) and several related chemotactic cytokines that attract and activate leukocytes. Loetscher et al. (1994) noted that these proteins are similar in size, have marked sequence similarities, and are characterized by 4 conserved cysteines that form 2 essential disulfide bonds. Two subfamilies are distinguished according to the arrangement of the first 2 cysteines, which are either adjacent (CC subfamily) or separated by one amino acid (CXC subfamily). The CXC cytokines activate primarily neutrophil leukocytes, while CC cytokines act on monocytes, basophils, and eosinophils. These chemotactic agonists act via 7-transmembrane domain, G protein-coupled receptors, e.g., the 2 interleukin-8 receptors, IL8RA and IL8RB (146928). Chemotactic cytokines of the CC subfamily do not bind to IL8 receptors. Loetscher et al. (1994) isolated from a human blood monocyte cDNA library a cDNA clone encoding a protein of 352 amino acids, corresponding to a receptor of the 7-transmembrane domain, G protein-coupled type. They referred to the gene and the deduced protein as LESTR for 'leukocyte-derived seven-transmembrane domain receptor.' It shows 92.6% identity with a bovine neuropeptide Y receptor. In the monocyte library, LESTR cDNA fragments were about 20 times as frequent as cDNA coding for IL8RA and IL8RB, and much higher levels of mRNA specific for LESTR than for IL8R were found in human blood neutrophils and lymphocytes. Although the ligand for LESTR could not be identified among a large number of chemotactic cytokines, the high expression in white blood cells and the marked sequence relation to IL8RA and IL8RB suggested to Loetscher et al. (1994) that LESTR may function in the activation of inflammatory cells. The human CD4 molecule (186940) acts as the primary receptor for the human immunodeficiency virus type 1 (HIV-1), but CD4 supports viral entry into cells only when it is expressed on specific human cell types (Clapham et al., 1991). Weiner et al. (1991) and Dragic and Alizon (1993) presented evidence that the restriction of HIV-1 infection to certain human cell types is the result of a specific cofactor, encoded in the human genome, which is required for cell virus membrane fusion. Feng et al. (1996) undertook the isolation and characterization of the putative human HIV-1 fusion cofactor using an approach that made no assumptions about the mode of action of the cofactor other than that the cofactor would allow a CD4-expressing nonhuman cell to undergo viral fusion. They transfected CD4-expressing NIH 3T3 cells with a HeLa cell cDNA library and then incubated the transfected cells with an NIH 3T3 cell line expressing the HIV-1 Env gene (which is required by HIV-1 for fusion); transfected CD4+ cells that fused with Env-expressing cells could be distinguished by utilizing a lacZ biochemical marker specific to such fusion products. Feng et al. (1996) isolated a 1.7-kb human cDNA clone that allowed the CD4-expressing NIH 3T3 cells to undergo fusion. The cDNA contained a 352-codon ORF whose predicted amino acid sequence has 7 predicted transmembrane segments and resembles that of the G protein-coupled receptor superfamily. The predicted molecular weight of the protein is 39,745 Da and its primary sequence includes 2 potential N-linked glycosylation sites. The cDNA had in fact been cloned previously by Federsppiel et al. (1993) from a human fetal spleen cDNA library and was designated D2S201E. The predicted protein has 37% amino acid identity with the interleukin-8 receptor and is 93% identical to that of a cDNA isolated from bovine locus ceruleus, which apparently encodes a neuropeptide Y receptor.