CXC chemokine receptors

CXCR1
Identifiers
Symbol IL8RA
Entrez 3577
OMIM 146929
RefSeq NM_000634
UniProt P25024
Other data
Locus Chr. 2 q35
CXCR2
Identifiers
Symbol IL8RB
Entrez 3579
OMIM 146928
RefSeq NM_001557
UniProt P25025
Other data
Locus Chr. 2 q35
CXCR3
Identifiers
Symbol CXCR3
Entrez 2833
OMIM 300574
RefSeq NM_001504
UniProt P49682
Other data
Locus Chr. X q13
CXCR4
Identifiers
Symbol CXCR4
Entrez 7852
OMIM 162643
RefSeq NM_001008540
UniProt P61073
Other data
Locus Chr. 2 q21
CXCR5
Identifiers
Symbol BLR1
Entrez 643
OMIM 601613
RefSeq NM_001716
UniProt P32302
Other data
Locus Chr. 11 q23
CXCR6
Identifiers
Symbol CXCR6
Entrez 10663
OMIM 605163
RefSeq NM_006564
UniProt O00574
Other data
Locus Chr. 3 p21
CXCR7
Identifiers
Symbol CMKOR1
Alt. symbols RDC1
Entrez 57007
RefSeq NM_020311
UniProt P25106
Other data
Locus Chr. 2 q37

CXC chemokine receptors are integral membrane proteins that specifically bind and respond to cytokines of the CXC chemokine family. They represent one subfamily of chemokine receptors, a large family of G protein-linked receptors that are known as seven transmembrane (7-TM) proteins, since they span the cell membrane seven times. There are currently seven known CXC chemokine receptors in mammals, named CXCR1 through CXCR7.

CXCR1 and CXCR2

CXCR1 and CXCR2 are closely related receptors that recognize CXC chemokines that possess an E-L-R amino acid motif immediately adjacent to their CXC motif. CXCL8 (otherwise known as interleukin-8) and CXCL6 can both bind CXCR1 in humans, while all other ELR-positive chemokines, such as CXCL1 to CXCL7 bind only CXCR2.[1][2] They are both expressed on the surface of neutrophils in mammals.

CXCR3

CXCR3 is expressed predominantly on T cells (T lymphocytes), and also on other lymphocytes [some B cells (B lymphocytes) and NK cells] and is highly induced following cell activation. There are two isoforms, CXCR3-A and CXCR3-B.[3] It has three highly related ligands in mammals, CXCL9, CXCL10 and CXCL11.[4][5]

CXCR4

CXCR4 (also known as fusin) is the receptor for a chemokine known as CXCL12 (or SDF-1) and, as with CCR5, is utilized by HIV-1 to gain entry into target cells. This receptor has a wide cellular distribution, with expression on most immature and mature hematopoietic cell types (e.g. neutrophils, monocytes, T and B cells, dendritic cells, Langerhans cells and macrophages). In addition, CXCR4 can also be found on vascular endothelial cells and neuronal/nerve cells.

CXCR5

The chemokine receptor CXCR5 is expressed on B cells and CD4+ Tfh cells and is involved in lymphocyte homing and the development of normal lymphoid tissue. Its principal ligand is CXCL13 (or BLC).[6]

CXCR6

CXCR6 was formerly called three different names (STRL33, BONZO, and TYMSTR) before being assigned CXCR6 based on its chromosomal location (within the chemokine receptor cluster on human chromosome 3p21) and its similarity to other chemokine receptors in its gene sequence. CXCR6 binds the ligand CXCL16. However, CXCR6 is more closely related in structure to CC chemokine receptors than to other CXC chemokine receptors.

CXCR7

CXCR7 was originally called RDC-1 (an orphan receptor) but has since been shown to cause chemotaxis in T lymphocytes in response to CXCL12 (the ligand for CXCR4) prompting the renaming of this molecule as CXCR7.[7] CXCR7 was recently renamed ACKR3. There is no information publicly available to confirm whether this designation has been accepted by the IUIS/WHO Subcommittee on Chemokine Nomenclature at this time. This receptor has also been identified on memory B cells.

References

  1. ↑ Tsai HH, Frost E, To V, Robinson S, Ffrench-Constant C, Geertman R, Ransohoff RM, Miller RH (August 2002). "The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration". Cell. 110 (3): 373–83. PMID 12176324.
  2. ↑ Pelus LM, Fukuda S (August 2006). "Peripheral blood stem cell mobilization: the CXCR2 ligand GRObeta rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties". Experimental Hematology. 34 (8): 1010–20. doi:10.1016/j.exphem.2006.04.004. PMID 16863907.
  3. ↑ Lasagni L, Francalanci M, Annunziato F, Lazzeri E, Giannini S, Cosmi L, Sagrinati C, Mazzinghi B, Orlando C, Maggi E, Marra F, Romagnani S, Serio M, Romagnani P (June 2003). "An alternatively spliced variant of CXCR3 mediates the inhibition of endothelial cell growth induced by IP-10, Mig, and I-TAC, and acts as functional receptor for platelet factor 4". The Journal of Experimental Medicine. 197 (11): 1537–49. doi:10.1084/jem.20021897. PMC 2193908. PMID 12782716.
  4. ↑ Tensen CP, Flier J, Van Der Raaij-Helmer EM, Sampat-Sardjoepersad S, Van Der Schors RC, Leurs R, Scheper RJ, Boorsma DM, Willemze R (May 1999). "Human IP-9: A keratinocyte-derived high affinity CXC-chemokine ligand for the IP-10/Mig receptor (CXCR3)". The Journal of Investigative Dermatology. 112 (5): 716–22. doi:10.1046/j.1523-1747.1999.00581.x. PMID 10233762.
  5. ↑ Booth V, Keizer DW, Kamphuis MB, Clark-Lewis I, Sykes BD (August 2002). "The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions". Biochemistry. 41 (33): 10418–25. PMID 12173928.
  6. ↑ Legler DF, Loetscher M, Roos RS, Clark-Lewis I, Baggiolini M, Moser B (February 1998). "B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5". The Journal of Experimental Medicine. 187 (4): 655–60. PMC 2212150. PMID 9463416.
  7. ↑ Balabanian K, Lagane B, Infantino S, Chow KY, Harriague J, Moepps B, Arenzana-Seisdedos F, Thelen M, Bachelerie F (October 2005). "The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes". The Journal of Biological Chemistry. 280 (42): 35760–6. doi:10.1074/jbc.M508234200. PMID 16107333.
  • "Chemokine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.
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