CXCR6 | Chemokine receptors | IUPHAR Guide to IMMUNOPHARMACOLOGY

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CXCR6

Target id: 73

Nomenclature: CXCR6

Family: Chemokine receptors

Annotation status:  image of a green circle Annotated and expert reviewed. Please contact us if you can help with updates.  » Email us

   GtoImmuPdb view: ON :     CXCR6 has curated data in GtoImmuPdb

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 342 3p21 CXCR6 C-X-C motif chemokine receptor 6 3,7-8
Mouse 7 351 9 F Cxcr6 chemokine (C-X-C motif) receptor 6 9
Rat 7 351 8 Cxcr6 C-X-C motif chemokine receptor 6
Previous and Unofficial Names
BONZO [9] | TYMSTR [8] | CD186 | STRL33 [7] | chemokine (C-X-C motif) receptor 6
Database Links
Specialist databases
GPCRDB cxcr6_human (Hs), cxcr6_mouse (Mm)
Other databases
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands
CXCL16 {Sp: Human} , CXCL16 {Sp: Mouse} , CXCL16 {Sp: Rat}

Download all structure-activity data for this target as a CSV file

Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Affinity Units Reference
CXCL16 {Sp: Human} Hs Full agonist 9.0 pKd 15
pKd 9.0 (Kd 1x10-9 M) [15]
Agonist Comments
Mouse CXCL16 has also been cloned [11]. CXCL16 is identical to SR-PSOX, an acronym for its ability to function as a scavenger receptor that binds phosphatidylserine and oxidized lipoprotein [2].
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family
Comments:  CXCR6 functional assays also include Gi independent adhesion to CXCL16 expressing surfaces [12] and HIV-1 and SIV envelope glycoprotein-mediated cell-cell fusion or HIV-1 and SIV infectivity [3,7]
References:  1,9
Tissue Distribution
memory T cells
Th1 and Tc1, but not type-2, T cells
NK-T cells
plasma cells
Species:  Human
Technique:  immunocytochemistry.
References:  6,10,13-14
Bone marrow stromal cells (BMSCs).
Species:  Human
Technique:  Flow cytometry and RT-PCR.
References:  5
Memory T cells, coordinately regulated with CCR5
Species:  Mouse
Technique:  immunocytochemistry.
References:  14
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Chemotaxis
Species:  Human
Tissue:  Lymphocytes
Response measured:  Cell motility in response to ligand in vitro
References:  9,15
Calcium flux
Species:  Human
Tissue:  Lymphocytes
Response measured:  Increase in intracellular calcium ion concentration in response to agonist
References:  9,15
Physiological Functions
HIV and SIV entry
Species:  Human
Tissue:  T lymphocytes
References:  3,7
Leukocyte migration
Species:  Human
Tissue:  T lymphocytes
References:  9,15
Leukocyte adhesion
Species:  Human
Tissue:  T lymphocytes
References:  12
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cxcr6tm1Lex Cxcr6tm1Lex/Cxcr6tm1Lex
involves: 129S/SvEvBrd * C57BL/6J
MGI:1934582  MP:0006283 medulloblastoma PMID: 17413002 
Cxcr6+|Cxcr6tm1Lex Cxcr6tm1Lex/Cxcr6+
involves: 129S/SvEvBrd * C57BL/6J
MGI:1934582  MP:0006283 medulloblastoma PMID: 17413002 
Cxcr6tm1Litt Cxcr6tm1Litt/Cxcr6tm1Litt
involves: 129P2/OlaHsd * C57BL/6
MGI:1934582  MP:0002169 no abnormal phenotype detected PMID: 10975845 
Biologically Significant Variants
Type:  Single nucleotide polymorphism
Species:  Human
Description:  CXCR6-E3K: associated with accelerated mortality due to Pneumocystis carinii pneumonia in African-Americans
References:  4

References

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1. Chandrasekar B, Bysani S, Mummidi S. (2004) CXCL16 signals via Gi, phosphatidylinositol 3-kinase, Akt, I kappa B kinase, and nuclear factor-kappa B and induces cell-cell adhesion and aortic smooth muscle cell proliferation. J. Biol. Chem., 279 (5): 3188-96. [PMID:14625285]

2. Cyster JG. (1999) Chemokines and cell migration in secondary lymphoid organs. Science, 286: 2098-2102. [PMID:10617422]

3. Deng H, Unutmaz D, KewalRamani VN, Littman DR. (1997) Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature, 388: 296-300. [PMID:9230441]

4. Duggal P, An P, Beaty TH, Strathdee SA, Farzadegan H, Markham RB, Johnson L, O'Brien SJ, Vlahov D, Winkler CA. (2003) Genetic influence of CXCR6 chemokine receptor alleles on PCP-mediated AIDS progression among African Americans. Genes Immun., 4: 245-250. [PMID:12761559]

5. Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek A, Silberstein LE. (2005) HUMAN BONE MARROW STROMAL CELLS EXPRESS A DISTINCT SET OF BIOLOGICALLY FUNCTIONAL CHEMOKINE RECEPTORS. Stem Cells,: -. [PMID:16253981]

6. Kim CH, Kunkel EJ, Boisvert J, Johnston B, Campbell JJ, Genovese MC, Greenberg HB, Butcher EC. (2001) Bonzo/CXCR6 expression defines type 1-polarized T-cell subsets with extralymphoid tissue homing potential. J. Clin. Invest., 107: 595-601. [PMID:11238560]

7. Liao F, Alkhatib G, Peden KWC, Sharma G, Berger EA, Farber JM. (1997) STRL33, a novel chemokine receptor-like protein, functions as a fusion cofactor for both macrophage-tropic and T cell line-tropic HIV-1. J. Exp. Med., 185: 2015-2023. [PMID:9166430]

8. Loetscher M, Amara A, Oberlin E, Brass N, Legler D, Loetscher P, D'Apuzzo M, Meese E, Rousset D, Virelizier JL, Baggiolini M, Arenzana-Seisdedos F, Moser B. (1997) TYMSTR, a putative chemokine receptor selectively expressed in activated T cells, exhibits HIV-1 coreceptor function. Curr. Biol., 7: 652-660. [PMID:9285716]

9. Matloubian M, David A, Engel S, Ryan JE, Cyster JG. (2000) A transmembrane CXC chemokine is a ligand for HIV-coreceptor Bonzo. Nature Immun., 1: 298-304. [PMID:11017100]

10. Nakayama T, Hieshima K, Izawa D, Tatsumi Y, Kanamaru A, Yoshie O. (2003) Cutting edge: profile of chemokine receptor expression on human plasma cells accounts for their efficient recruitment to target tissues. J. Immunol., 170: 1136-1140. [PMID:12538668]

11. Schweickart VL, Epp A, Raport CJ, Gray PW. (2000) CCR11 is a functional receptor for the monocyte chemoattractant protein family of chemokines. J. Biol. Chem., 75: 9550-9556. [PMID:10734104]

12. Shimaoka T, Nakayama T, Fukumoto N, Kume N, Takahashi S, Yamaguchi J, Minami M, Hayashida K, Kita T, Ohsumi J, Yoshie O, Yonehara S. (2004) Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells. J. Leukoc. Biol., 75: 267-274. [PMID:14634054]

13. Thomas SY, Hou R, Boyson JE, Means TK, Hess C, Olson DP, Strominger JL, Brenner MB, Gumperz JE, Wilson SB, Luster AD. (2003) CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells. J. Immunol., 171: 2571-2580. [PMID:12928408]

14. Unutmaz D, Xiang W, Sunshine MJ, Campbell J, Butcher E, Littman DR. (2000) The primate lentiviral receptor Bonzo/STRL33 is coordinately regulated with CCR5 and its expression pattern is conserved between human and mouse. J. Immunol., 165: 3284-3292. [PMID:10975845]

15. Wilbanks A, Zondlo SC, Murphy K, Mak S, Soler D, Langdon P, Andrew DP, Wu L, Briskin M. (2001) Expression cloning of the STRL33/BONZO/TYMSTR ligand reveals elements of CC, CXC, and CX3C chemokines. J. Immunol., 166: 5145-5154. [PMID:11290797]

Contributors

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How to cite this page

Israel F. Charo, Rebecca Hills, Richard Horuk, Kouji Matsushima, Philip M. Murphy, Joost J. Oppenheim.
Chemokine receptors: CXCR6. Last modified on 19/02/2018. Accessed on 20/01/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=73.