XCR1 | Chemokine receptors | IUPHAR Guide to IMMUNOPHARMACOLOGY

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XCR1

  Target has curated data in GtoImmuPdb

Target id: 75

Nomenclature: XCR1

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

Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 333 3p21.3-p21.1 XCR1 X-C motif chemokine receptor 1 5,10
Mouse 7 322 9 F4 Xcr1 chemokine (C motif) receptor 1 11
Rat 7 322 8q32 Xcr1 X-C motif chemokine receptor 1
Previous and Unofficial Names
GPR5 [5,10] | CCXCR1 | chemokine XC receptor 1 | C motif-1/lymphotactin receptor
Database Links
Specialist databases
GPCRDB xcr1_human (Hs), xcr1_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
XCL1 {Sp: Human}
XCL2 {Sp: Human}
XCL1 {Sp: Mouse} , XCL1 {Sp: Rat}

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Agonists
Key to terms and symbols Click column headers to sort
Ligand Sp. Action Value Parameter Reference
[125I]XCL1 (human) Hs Full agonist 8.0 pKd 10
pKd 8.0 [10]
XCL1 {Sp: Human} Hs Agonist ~7.3 pEC50 4
pEC50 ~7.3 (EC50 ~5x10-8 M) [4]
Description: Measuring Ca2+ flux
XCL2 {Sp: Human} Hs Agonist ~7.3 pEC50 4
pEC50 ~7.3 (EC50 ~5x10-8 M) [4]
Description: Measuring Ca2+ flux
Immunopharmacology Comments
XCR1 is one of more than 20 distinct chemokine receptors expressed in human leukocytes. Chemokines primarily act to promote leukocyte chemotaxis to sites of inflammation. XCR1 is expressed by a subset of dendritic cells [7] and along with its ligand 3647 (lymphotactin), is important for dendritic-cell-mediated cytotoxic immune responses and for the induction of self-tolerance and generation of Treg cells in the thymus.
Cell Type Associations
Immuno Cell Type:  Dendritic cells
Cell Ontology Term:   CD141-positive myeloid dendritic cell (CL:0002394)
Comment:  Human XCR1 is expressed exclusively in CD141+ (BDCA3+) DCs, and in mouse expression is restricted to CD8+ DCs which are phenotypically similar to the human cells. XCR1 is NOT expressed in T cells, B cells, NK cells, granulocytes, monocytes, or other DC subsets.
References:  1,3,7
Immuno Process Associations
Immuno Process:  Inflammation
GO Annotations:  Associated to 1 GO processes
GO:0006954 inflammatory response TAS
Immuno Process:  Chemotaxis & migration
GO Annotations:  Associated to 2 GO processes
GO:0004950 chemokine receptor activity TAS
GO:0016493 C-C chemokine receptor activity IBA
Immuno Process:  Cytokine production & signalling
GO Annotations:  Associated to 2 GO processes
GO:0004950 chemokine receptor activity TAS
GO:0016493 C-C chemokine receptor activity IBA
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Calcium channel
References:  10
Tissue Distribution
Placenta > spleen, thymus > peripheral blood leukocytes.
Species:  Human
Technique:  Northern blotting.
References:  10
Placenta > thymus > spleen > fetal thymus > fetal spleen > peripheral blood leukocytes > lymph node > bone marrow.
Species:  Human
Technique:  Dot blot.
References:  8
CD8+ cells and NK1.1+ cells.
Species:  Mouse
Technique:  RT-PCR.
References:  11
Neutrophils and T lymphocytes.
Species:  Mouse
Technique:  RT-PCR.
References:  2,6
B lymphocytes.
Species:  Mouse
Technique:  RT-PCR.
References:  6
Spleen, lung.
Species:  Mouse
Technique:  Northern blotting.
References:  11
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
Measurement of Ca2+ levels in the murine pre-B cell line, L1.2, transfected with the human XCR1 receptor.
Species:  Human
Tissue:  L1.2 cells.
Response measured:  Ca2+ mobilisation.
References:  10
Measurement of chemotaxis of the murine pre-B cell line, L1.2, transfected with the human XCR1 receptor.
Species:  Human
Tissue:  L1.2 cells.
Response measured:  Chemotaxis.
References:  10
Measurement of Ca2+ levels in the murine pre-B cell line, B300-19, transfected with the mouse XCR1 receptor.
Species:  Mouse
Tissue:  B300-19 cells.
Response measured:  Ca2+ mobilisation.
References:  11
Measurement of chemotaxis of the murine pre-B cell line, B300-19, transfected with the mouse XCR1 receptor.
Species:  Mouse
Tissue:  B300-19 cells.
Response measured:  Chemotaxis.
References:  11
Measurement of chemotaxis of T and B lymphocytes and neutrophils endogenously expressing the XCR1 receptor.
Species:  Mouse
Tissue:  T and B lymphocytes, neutrophils.
Response measured:  Chemotaxis.
References:  6
Physiological Functions
Chemotaxis.
Species:  Mouse
Tissue:  T and B lymphocytes, neutrophils.
References:  6
Recruitment of mononuclear cells to the rheumatoid arthritic joint.
Species:  Human
Tissue:  Synovial fluid of the rheumatoid joint.
References:  9
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Xcr1tm1Dgen Xcr1tm1Dgen/Xcr1tm1Dgen
B6.129P2-Xcr1/J
MGI:1346338  MP:0002376 abnormal dendritic cell physiology PMID: 19913446 
Xcr1tm1Dgen Xcr1tm1Dgen/Xcr1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6
MGI:1346338  MP:0002169 no abnormal phenotype detected

References

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1. Bachem A, Güttler S, Hartung E, Ebstein F, Schaefer M, Tannert A, Salama A, Movassaghi K, Opitz C, Mages HW et al.. (2010) Superior antigen cross-presentation and XCR1 expression define human CD11c+CD141+ cells as homologues of mouse CD8+ dendritic cells. J. Exp. Med., 207 (6): 1273-81. [PMID:20479115]

2. Cairns CM, Gordon JR, Li F, Baca-Estrada ME, Moyana T, Xiang J. (2001) Lymphotactin expression by engineered myeloma cells drives tumor regression: mediation by CD4+ and CD8+ T cells and neutrophils expressing XCR1 receptor. J. Immunol., 167 (1): 57-65. [PMID:11418632]

3. Crozat K, Guiton R, Contreras V, Feuillet V, Dutertre CA, Ventre E, Vu Manh TP, Baranek T, Storset AK, Marvel J et al.. (2010) The XC chemokine receptor 1 is a conserved selective marker of mammalian cells homologous to mouse CD8alpha+ dendritic cells. J. Exp. Med., 207 (6): 1283-92. [PMID:20479118]

4. Fox JC, Nakayama T, Tyler RC, Sander TL, Yoshie O, Volkman BF. (2015) Structural and agonist properties of XCL2, the other member of the C-chemokine subfamily. Cytokine, 71 (2): 302-11. [PMID:25497737]

5. Heiber M, Docherty JM, Shah G, Nguyen T, Cheng R, Heng HH, Marchese A, Tsui LC, Shi X, George SR et al.. (1995) Isolation of three novel human genes encoding G protein-coupled receptors. DNA Cell Biol., 14 (1): 25-35. [PMID:7832990]

6. Huang H, Li F, Cairns CM, Gordon JR, Xiang J. (2001) Neutrophils and B cells express XCR1 receptor and chemotactically respond to lymphotactin. Biochem. Biophys. Res. Commun., 281 (2): 378-82. [PMID:11181058]

7. Lei Y, Takahama Y. (2012) XCL1 and XCR1 in the immune system. Microbes Infect., 14 (3): 262-7. [PMID:22100876]

8. Shan L, Qiao X, Oldham E, Catron D, Kaminski H, Lundell D, Zlotnik A, Gustafson E, Hedrick JA. (2000) Identification of viral macrophage inflammatory protein (vMIP)-II as a ligand for GPR5/XCR1. Biochem Biophys Res Commun, 268: 938-941. [PMID:10679309]

9. Stemmler S, Arinir U, Klein W, Rohde G, Hoffjan S, Wirkus N, Reinitz-Rademacher K, Bufe A, Schultze-Werninghaus G, Epplen JT. (2005) Association of interleukin-8 receptor alpha polymorphisms with chronic obstructive pulmonary disease and asthma. Genes Immun, 6: 225-230. [PMID:15772681]

10. Yoshida T, Imai T, Kakizaki M, Nishimura M, Takagi S, Yoshie O. (1998) Identification of single C motif-1/lymphotactin receptor XCR1. J. Biol. Chem., 273 (26): 16551-4. [PMID:9632725]

11. Yoshida T, Izawa D, Nakayama T, Nakahara K, Kakizaki M, Imai T, Suzuki R, Miyasaka M, Yoshie O. (1999) Molecular cloning of mXCR1, the murine SCM-1/lymphotactin receptor. FEBS Lett., 458 (1): 37-40. [PMID:10518929]

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