Orphan chemokine receptor

Galligan C, Matsuyama W, Matsukawa A, et al. Up-regulated expression and activation of the orphan chemokine receptor, CCRL2, in rheumatoid arthritis. Arthritis Rheum 2004 50 1806-1814. 

The Constitutively Active Orphan Chemokine Receptor UL33... 

Rucker J, Edinger AL, Sharron M et al (1997) Utilization of chemokine receptors, orphan receptors, and herpesvirus-encoded receptors by diverse human and simian immunodefidency viruses. J Virol 71 8999-9007... 

A systematic nomenclature has been developed for the chemokine receptors (see Table 1). Thus, receptors for CC chemokines are referred to as CCR, receptors for CXC chemokines as CXCR, and the receptors for the XC and CX3C chemokines as XCR and CX3CR, respectively. To date, there are 10 CCRs (CCRs 1 to 10), 7 CXCRs, a single XCR, and a single CX3CR. The numbering is based on the date of deposition of the chemokine receptor sequence within the nucleic acid databases. For orphan receptors, this date refers to the point of identification of the orphan receptors as chemokine receptors and not to the date of initial deposition in the cDNA databases. 

Pairing Up with the Orphans—and Explosion in Confirmed Chemokine Receptors... 

The availability of large amounts of raw sequence data, due to public EST collections, and the ability of scientists to access this data, has led to a massive increase in the number of novel proteins identified in silico—that is purely on computational techniques. Nowhere has this been as fruitful as in the chemokine area where there has been an explosive increase in the number of chemokines identified. The challenge now is to piece together the roles that these new chemokines play in routine immunosurveillance and also in inflammatory diseases. This challenge has been taken up in the last year with the identification of ligands for four chemokine receptors previously classified as orphans. In terms of receptor function, we still have a long way to go, since there are still many chemokines for which receptors have not been identified, but at least we have a more complete list of the players as far as the ligands are concerned. 

The chemokine receptors are a subset of the G-protein-coupled receptor superfamily. They are seven-transmembrane receptors that bind G proteins at activation. For the chemokines, the receptors are highly related, and most exhibit a characteristic DRY box. For this reason, many so-called orphan receptors that showed significant homology with known chemokine receptors that contain a DRY box, were widely believed to be chemokine receptors. As shown in Table... 

The Chemokine Receptor-Related US27 and UL78 Orphan Receptors... 

Raport, C. J., Schweickart, V. L., Eddy, R. L., Jr., Shows, T. B., and Gray, P. W. (1995) The orphan G protein-coupled receptor-encod ing gene V28 is closely related to genes for chemokine receptors and is expressed in lymphoid and neural tisues. Gene 163, 295-299. 

At the time this chemokine gene deletion was reported, the SDF-1 was an orphan chemokine, subsequently shown to be a ligand for the receptor Humstr/Lestr/Fusin/ CXCR4. The dramatic findings with the SDF-1 knock-out bespoke a significant role in leukocyte development, and unexpectedly in cardiac development. 

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