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CXCR1

Family: Chemokine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Agonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Phenotypes, Alleles and Disease Models
Biologically Significant Variants
General Comments
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 350 2q35 CXCR1 chemokine (C-X-C motif) receptor 1 14,19
Mouse 7 351 1 C3 Cxcr1 chemokine (C-X-C motif) receptor 1 9
Rat 7 349 9q33 Cxcr1 chemokine (C-X-C motif) receptor 1 5
Previous and Unofficial Names
Names References
IL-8α
IL-8R1
IL8RA 19
CXCR1-like 5
IL8RA
IL-8 receptor type I
IL-8 receptor α
CMKAR1
CKR-1
CDw128a
CD181
interleukin 8 receptor, alpha
Cxcr1
C-X-C chemokine receptor type 1
CXC-R1
CXCR-1
IL-8R A
chemokine (C-X-C motif) receptor 1
high affinity interleukin-8 receptor A
Database Links
ChEMBL Target 11574 (Hs)
Ensembl ENSG00000163464 (Hs), ENSMUSG00000048480 (Mm)
Entrez Gene 3577 (Hs), 227288 (Mm), 54258 (Rn)
GeneCards CXCR1 (Hs)
GenitoUrinary Development Molecular Anatomy Project Cxcr1 (Mm)
HomoloGene 68074 (Hs)
Human Protein Reference Database 00908 (Hs)
InterPro P25024 (Hs), Q810W6 (Mm), P70612 (Rn)
KEGG Gene hsa:3577 (Hs), mmu:227288 (Mm), rno:54258 (Rn)
OMIM 146929 (Hs)
PharmGKB Gene PA29842 (Hs)
PhosphoSitePlus P25024 (Hs), Q810W6 (Mm), P70612 (Rn)
Protein Ontology (PRO) PRO:000001256 (Hs)
RefSeq Nucleotide NM_000634 (Hs), NM_178241 (Mm), NM_019310 (Rn)
RefSeq Protein NP_000625 (Hs), NP_839972 (Mm), NP_062183 (Rn)
TreeFam ENSG00000163464 (Hs), ENSMUSG00000048480 (Mm)
UniGene Hs. 194778 (Hs)
UniProt P25024 (Hs), Q810W6 (Mm), P70612 (Rn)
Wikipedia CXCR1
Chemokine receptors
Search for 3D structures on the PDB
Search by keyword: Chemokine receptors CXCR1 Search by accession number: P70612, P25024, Q810W6
Natural/Endogenous Ligand(s)
CXCL1 {Sp: Human} , CXCL1 {Sp: Mouse} , CXCL1 {Sp: Rat}
CXCL6 {Sp: Human}
CXCL8 {Sp: Human}
Comments: CXCL8 is the principal endogenous agonist
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]CXCL8 (human) Hs Full agonist 8.9 – 9.6 pKd 12,26
[125I]mini-TyrRS Hs Full agonist 7.7 pKd 29
CXCL8 {Sp: Human} Hs Full agonist 8.8 – 9.5 pKi 1,12,19,30,32
mini-TyrRS Hs Full agonist 8.1 pKi 29
CXCL6 {Sp: Human} Hs Full agonist 7.0 pKi 33
CXCL1 {Sp: Human} Hs Full agonist 6.4 pKi 19
Agonist Comments
Reference [25] measures agonist potency using a MAP kinase reporter gene.
Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Adenylate cyclase inhibition
Calcium channel
Comments:  The βγ subunit of the Gi G protein is necessary for chemotaxis [23] and calcium mobilisation [12].
References:  7,12,23
Secondary Transduction Mechanisms
Transducer Effector/Response
Gq/G11 family Calcium channel
References:  12
Tissue Distribution
Basophils.
Species:  Human
Technique:  Flow cytometry.
References:  16,24
Basophils.
Species:  Human
Technique:  RT-PCR.
References:  16
Keratinocytes.
Species:  Human
Technique:  Radioligand binding.
References:  22
Primary adult microglia and astrocytes.
Species:  Human
Technique:  Flow cytometry.
References:  8
Polymorphonuclear neutrophils.
Species:  Human
Technique:  Flow cytometry.
References:  4
Intestinal epithelial cells.
Species:  Human
Technique:  RT-PCR and flow cytometry.
References:  28
Bronchial epithelial cells.
Species:  Human
Technique:  RT-PCR and flow cytometry.
References:  6
Urinary tract epithelial cells.
Species:  Human
Technique:  Immunohistochemistry.
References:  10
Chondrocytes.
Species:  Human
Technique:  Flow cytometry.
References:  21
Glomerular podocytes.
Species:  Human
Technique:  RT-PCR.
References:  15
Umbilical vein endothelial cells (HUVECs).
Species:  Human
Technique:  immunocytochemistry.
References:  20
Peripheral blood leukocytes, isolated neutrophils > thymus, peritoneal monocytes/macrophages.
Species:  Mouse
Technique:  RT-PCR.
References:  9
Lung, spleen.
Species:  Mouse
Technique:  Northern blotting.
References:  9
Lung and native macrophages.
Species:  Rat
Technique:  Northern blotting.
References:  5
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 intracellular Ca2+ levels in HEK 293 cells transfected with the human CXCR1 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Increase in intracellular Ca2+.
References:  19,33-34
Measurement of chemotaxis in of HEK 293 cells transfected with the CXCR1 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Chemotaxis.
References:  7,23,33
Measurement of Ca2+ levels in Jurkat cells transfected with the human CXCR1 receptor.
Species:  Human
Tissue:  Jurkat cells.
Response measured:  Ca2+ mobilisation.
References:  17-18,31
Measurement of elastase released by human neutrophils endogenously expressing the CXCR1 receptor.
Species:  Human
Tissue:  Neutrophils.
Response measured:  Release of elastase.
References:  17-18,31
Measurement of superoxide production (indicating respiratory burst) in human neutrophils endogenously expressing the CXCR1 receptor.
Species:  Human
Tissue:  Neutrophils.
Response measured:  Superoxide production.
References:  17-18
Measurement of phospholipase D (PLD) activity in human neutrophils endogenously expressing the CXCR1 receptor.
Species:  Human
Tissue:  Neutrophils.
Response measured:  Activation of PLD.
References:  18
Measurement of focal adhesion kinase (FAK) activity and chemotaxis of HEK 293 and RBL cells transfected with the CXCR1 receptor.
Species:  Human
Tissue:  HEK 293 and RBL cells.
Response measured:  FAK phosphorylation.
References:  7
Measurement of chemotaxis of Jurkat cells transfected with the human CXCR1 receptor.
Species:  Human
Tissue:  Jurkat cells.
Response measured:  Chemotaxis.
References:  11,31
Measurement of cAMP levels in CHO cells transfected with the human CXCR1 receptor.
Species:  Human
Tissue:  CHO cells.
Response measured:  Inhibition of cAMP accumulation.
References:  12
Physiological Functions
Chemotaxis.
Species:  Human
Tissue:  Keratinocytes.
References:  22
Chemotaxis.
Species:  Human
Tissue:  Intestinal epithelial cells.
References:  28
Chemotaxis across the epithelial barrier of the urinary tract.
Species:  Human
Tissue:  Neutrophils.
References:  10
Cell proliferation and inhibition of apoptosis.
Species:  Human
Tissue:  Umbilical vein endothelial cells (HUVECs).
References:  20
Negative regulation of myeloid progenitor cells.
Species:  Mouse
Tissue:  In vivo.
References:  2
Phenotypes, Alleles and Disease Models Mouse data from MGI

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Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cxcr1tm1Dgen Cxcr1tm1Dgen/Cxcr1tm1Dgen
involves: 129P2/OlaHsd * C57BL/6		 MGI:2448715  MP:0002169 no abnormal phenotype detected
Biologically Significant Variants
Met31 -> Arg and Arg335 -> Cys polymorphisms may be associated with an increased risk of developing chronic obstructive pulmonary disease and asthma.
Type:  Single nucleotide polymorphisms.
Species:  Human
References:  27
General Comments
It has been shown that CXCR1 receptor expression on epithelial cells is enhanced by bacterial infection (E.coli [10,13] and H. pylori[3]). This induces transepithelial neutrophil migration and clearing of the infection.

REFERENCES

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1. Bertini, R., Allegretti, M., Bizzarri, C., Moriconi, A., Locati, M., Zampella, G., Cervellera, M. N., Di Cioccio, V., Cesta, M. C., Galliera, E., Martinez, F. O., Di Bitondo, R., Troiani, G., Sabbatini, V., D'Anniballe, G., Anacardio, R., Cutrin, J. C., Cavalieri, B., Mainiero, F., Strippoli, R., Villa, P., Di Girolamo, M., Martin, F., Gentile, M., Santoni, A., Corda, D., Poli, G., Mantovani, A., Ghezzi, P. and Colotta, F. (2004) Noncompetitive allosteric inhibitors of the inflammatory chemokine receptors CXCR1 and CXCR2: prevention of reperfusion injury. Proc Natl Acad Sci U S A, 101: 11791-11796. [PMID:15282370]

2. Broxmeyer, H. E., Cooper, S., Cacalano, G., Hague, N. L., Bailish, E. and Moore, M. W. (1996) Involvement of Interleukin (IL) 8 receptor in negative regulation of myeloid progenitor cells in vivo: evidence from mice lacking the murine IL-8 receptor homologue. J Exp Med, 184: 1825-1832. [PMID:8920870]

3. Bäckhed, F., Torstensson, E., Seguin, D., Richter-Dahlfors, A. and Rokbi, B. (2003) Helicobacter pylori infection induces interleukin-8 receptor expression in the human gastric epithelium. Infect Immun, 71: 3357-3360. [PMID:12761119]

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10. Godaly, G., Hang, L., Frendéus, B. and Svanborg, C. (2000) Transepithelial neutrophil migration is CXCR1 dependent in vitro and is defective in IL-8 receptor knockout mice. J Immunol, 165: 5287-5294. [PMID:11046063]

11. Gouwy, M., Struyf, S., Catusse, J., Proost, P. and Van Damme, J. (2004) Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration. J Leukoc Biol, 76: 185-194. [PMID:15075362]

12. Hall, D. A., Beresford, I. J., Browning, C. and Giles, H. (1999) Signalling by CXC-chemokine receptors 1 and 2 expressed in CHO cells: a comparison of calcium mobilization, inhibition of adenylyl cyclase and stimulation of GTPgammaS binding induced by IL-8 and GROalpha. Br J Pharmacol, 126: 810-818. [PMID:10188995]

13. Hang, L., Frendéus, B., Godaly, G. and Svanborg, C. (2000) Interleukin-8 receptor knockout mice have subepithelial neutrophil entrapment and renal scarring following acute pyelonephritis. J Infect Dis, 182: 1738-1748. [PMID:11069247]

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15. Huber, T. B., Reinhardt, H. C., Exner, M., Burger, J. A., Kerjaschki, D., Saleem, M. A. and Pavenstädt, H. (2002) Expression of functional CCR and CXCR chemokine receptors in podocytes. J Immunol, 168: 6244-6252. [PMID:12055238]

16. Iikura, M., Miyamasu, M., Yamaguchi, M., Kawasaki, H., Matsushima, K., Kitaura, M., Morita, Y., Yoshie, O., Yamamoto, K. and Hirai, K. (2001) Chemokine receptors in human basophils: inducible expression of functional CXCR4. J Leukoc Biol, 70: 113-120. [PMID:11435493]

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To cite this database page, please use the following:

Israel F. Charo, Rebecca Hills, Richard Horuk, Kouji Matsushima, Philip M. Murphy, Joost J. Oppenheim.
Chemokine receptors: CXCR1. Last modified on 31/01/2013. Accessed on 21/05/2013. IUPHAR database (IUPHAR-DB), http://iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=68.


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