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CXCR6

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Immunopharmacology Ligand  Target has curated data in GtoImmuPdb

Target id: 73

Nomenclature: CXCR6

Family: Chemokine receptors

Gene and Protein Information Click here for help
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 342 3p21.31 CXCR6 C-X-C motif chemokine receptor 6 3,7-8
Mouse 7 351 9 74.57 cM Cxcr6 C-X-C motif chemokine receptor 6 9
Rat 7 351 8 Cxcr6 C-X-C motif chemokine receptor 6
Previous and Unofficial Names Click here for help
BONZO [9] | TYMSTR [8] | CD186 | STRL33 [7] | chemokine (C-X-C motif) receptor 6
Database Links Click here for help
Specialist databases
GPCRdb cxcr6_human (Hs), cxcr6_mouse (Mm)
Other databases
Alphafold
ChEMBL Target
Ensembl Gene
Entrez Gene
Human Protein Atlas
KEGG Gene
OMIM
Pharos
RefSeq Nucleotide
RefSeq Protein
UniProtKB
Wikipedia
Natural/Endogenous Ligands Click here for help
CXCL16 {Sp: Human} , CXCL16 {Sp: Mouse} , CXCL16 {Sp: Rat}

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Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
CXCL16 {Sp: Human} Peptide Ligand is endogenous in the given species Immunopharmacology Ligand 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
Immuno Process:  Inflammation
Immuno Process:  Cytokine production & signalling
Primary Transduction Mechanisms Click here for help
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 Click here for help
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 Click here for help

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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 Click here for help
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 Click here for help
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 Click here for help 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 Click here for help
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 (5447): 2098-102. [PMID:10617422]

3. Deng HK, Unutmaz D, KewalRamani VN, Littman DR. (1997) Expression cloning of new receptors used by simian and human immunodeficiency viruses. Nature, 388 (6639): 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 (4): 245-50. [PMID:12761559]

5. Honczarenko M, Le Y, Swierkowski M, Ghiran I, Glodek AM, Silberstein LE. (2006) Human bone marrow stromal cells express a distinct set of biologically functional chemokine receptors. Stem Cells, 24 (4): 1030-41. [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 (5): 595-601. [PMID:11238560]

7. Liao F, Alkhatib G, Peden KW, 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 (11): 2015-23. [PMID:9166430]

8. Loetscher M, Amara A, Oberlin E, Brass N, Legler D, Loetscher P, D'Apuzzo M, Meese E, Rousset D, Virelizier JL et al.. (1997) TYMSTR, a putative chemokine receptor selectively expressed in activated T cells, exhibits HIV-1 coreceptor function. Curr Biol, 7 (9): 652-60. [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. Nat Immunol, 1 (4): 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 (3): 1136-40. [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 et al.. (2004) Cell surface-anchored SR-PSOX/CXC chemokine ligand 16 mediates firm adhesion of CXC chemokine receptor 6-expressing cells. J Leukoc Biol, 75 (2): 267-74. [PMID:14634054]

13. Thomas SY, Hou R, Boyson JE, Means TK, Hess C, Olson DP, Strominger JL, Brenner MB, Gumperz JE, Wilson SB et al.. (2003) CD1d-restricted NKT cells express a chemokine receptor profile indicative of Th1-type inflammatory homing cells. J Immunol, 171 (5): 2571-80. [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 (6): 3284-92. [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/TYMSTRligand reveals elements of CC, CXC, and CX3C chemokines. J Immunol, 166 (8): 5145-54. [PMID:11290797]

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