CXC chemokine receptors

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CXCR1
Identifiers
SymbolIL8RA
Entrez3577
OMIM146929
RefSeqNM_000634
UniProtP25024
Other data
LocusChr. 2 q35
CXCR2
Identifiers
SymbolIL8RB
Entrez3579
OMIM146928
RefSeqNM_001557
UniProtP25025
Other data
LocusChr. 2 q35
CXCR3
Identifiers
SymbolCXCR3
Entrez2833
OMIM300574
RefSeqNM_001504
UniProtP49682
Other data
LocusChr. X q13
CXCR4
Identifiers
SymbolCXCR4
Entrez7852
OMIM162643
RefSeqNM_001008540
UniProtP61073
Other data
LocusChr. 2 q21
CXCR5
Identifiers
SymbolBLR1
Entrez643
OMIM601613
RefSeqNM_001716
UniProtP32302
Other data
LocusChr. 11 q23
CXCR6
Identifiers
SymbolCXCR6
Entrez10663
OMIM605163
RefSeqNM_006564
UniProtO00574
Other data
LocusChr. 3 p21
CXCR7
Identifiers
SymbolCMKOR1
Alt. symbolsRDC1
Entrez57007
RefSeqNM_020311
UniProtP25106
Other data
LocusChr. 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 principle 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, H.-H., Frost, E., To, V., Robinson, S., ffrench-Constant, C., Geertman, R., Ransohoff, R.M., Miller, R.H. The chemokine receptor CXCR2 controls positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. Cell 110: 373-383, 2002.
  2. Pelus LM, Fukuda S. Peripheral blood stem cell mobilization: the CXCR2 ligand GRObeta rapidly mobilizes hematopoietic stem cells with enhanced engraftment properties. Exp Hematol. 2006 Aug;34(8):1010-20. 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. 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. J Exp Med. 2003 Jun 2;197(11):1537-49.
  4. Tensen et al. Human IP-9: a keratinocyte derived high affinity CXC-chemokine ligand for the IP-10/Mig receptor (CXCR3). J. Invest. Dermatol. 112:716-722, 1999.
  5. Booth et al. The CXCR3 binding chemokine IP-10/CXCL10: structure and receptor interactions. Biochemistry 41: 10418-10425, 2002.
  6. Legler D.F., Loetscher M., Stuber Roos R., Clark-Lewis I., Baggiolini M., Moser B.; B cell-attracting chemokine 1, a human CXC chemokine expressed in lymphoid tissues, selectively attracts B lymphocytes via BLR1/CXCR5. J. Exp. Med. 187:655-660, 1998. PubMed : 9463416
  7. Balabanian et al., The chemokine SDF-1/CXCL12 binds to and signals through the orphan receptor RDC1 in T lymphocytes, J Biol Chem, 2005, 280:35760-35766.

External links

  • "Chemokine Receptors". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology.