CXCR6 | Chemokine receptors | IUPHAR Guide to IMMUNOPHARMACOLOGY

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CXCR6

  Target has curated data in GtoImmuPdb

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

Contents:

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 CHEMBL5994 (Hs)
Ensembl Gene ENSG00000172215 (Hs), ENSMUSG00000048521 (Mm), ENSRNOG00000006319 (Rn)
Entrez Gene 10663 (Hs), 80901 (Mm), 100124593 (Rn)
Human Protein Atlas ENSG00000172215 (Hs)
KEGG Gene hsa:10663 (Hs), mmu:80901 (Mm), rno:100124593 (Rn)
OMIM 605163 (Hs)
RefSeq Nucleotide NM_006564 (Hs), NM_030712 (Mm), NM_001102587 (Rn)
RefSeq Protein NP_006555 (Hs), NP_109637 (Mm), NP_001096057 (Rn)
UniProtKB O00574 (Hs), Q9EQ16 (Mm)
Wikipedia CXCR6 (Hs)
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 Value Parameter 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].
Immunopharmacology Comments
CXCR6 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. CXCR6 is upregulated by IL-2 and IL-15 [14].
Immuno Process Associations
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes, IEA only
GO:0016493 C-C chemokine receptor activity IBA
click arrow to show/hide IEA associations
GO:0016494 C-X-C chemokine receptor activity IEA
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes, IEA only
click arrow to show/hide IEA associations
GO:0006954 inflammatory response IEA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes, IEA only
GO:0016493 C-C chemokine receptor activity IBA
click arrow to show/hide IEA associations
GO:0016494 C-X-C chemokine receptor activity IEA
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 19/08/2019. IUPHAR/BPS Guide to PHARMACOLOGY, http://www.guidetoimmunopharmacology.org/GRAC/ObjectDisplayForward?objectId=73.