CXC chemokine receptors

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 six known CXC chemokine receptors in mammals, named CXCR1 through CXCR6.[1][2]

CXCR1
Identifiers
SymbolIL8RA
NCBI gene3577
OMIM146929
RefSeqNM_000634
UniProtP25024
Other data
LocusChr. 2 q35
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DomainsInterPro
CXCR2
Identifiers
SymbolIL8RB
NCBI gene3579
OMIM146928
RefSeqNM_001557
UniProtP25025
Other data
LocusChr. 2 q35
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StructuresSwiss-model
DomainsInterPro
CXCR3
Identifiers
SymbolCXCR3
NCBI gene2833
OMIM300574
RefSeqNM_001504
UniProtP49682
Other data
LocusChr. X q13
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StructuresSwiss-model
DomainsInterPro
CXCR4
Identifiers
SymbolCXCR4
NCBI gene7852
OMIM162643
RefSeqNM_001008540
UniProtP61073
Other data
LocusChr. 2 q21
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DomainsInterPro
CXCR5
Identifiers
SymbolBLR1
NCBI gene643
OMIM601613
RefSeqNM_001716
UniProtP32302
Other data
LocusChr. 11 q23
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DomainsInterPro
CXCR6
Identifiers
SymbolCXCR6
NCBI gene10663
OMIM605163
RefSeqNM_006564
UniProtO00574
Other data
LocusChr. 3 p21
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DomainsInterPro

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.[3][4] 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.[5] It has three highly related ligands in mammals, CXCL9, CXCL10 and CXCL11.[6][7]

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).[8]

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.

History

ACKR3 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.[9] ACKR3 designation has been accepted by the IUIS/WHO Subcommittee on Chemokine Nomenclature.[1] This receptor has also been identified on memory B cells.

References
  1. Bachelerie, Françoise; Graham, Gerard J; Locati, Massimo; Mantovani, Alberto; Murphy, Philip M; Nibbs, Robert; Rot, Antal; Sozzani, Silvano; Thelen, Marcus (2015). "An atypical addition to the chemokine receptor nomenclature: IUPHAR Review 15". British Journal of Pharmacology. 172 (16): 3945–3949. doi:10.1111/bph.13182. ISSN 0007-1188. PMC 4543604. PMID 25958743.
  2. "Gene group: C-X-C motif chemokine receptors (CXCR)". HUGO Gene Nomenclature Committee.
  3. 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. doi:10.1016/s0092-8674(02)00838-3. PMID 12176324. S2CID 16880392.
  4. 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.
  5. 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.
  6. 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.
  7. 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. doi:10.1021/bi026020q. PMID 12173928.
  8. 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. doi:10.1084/jem.187.4.655. PMC 2212150. PMID 9463416.
  9. 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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