Nomenclature: CXCR1

Family: Chemokine receptors

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

Contents

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
Ensembl Gene
Entrez Gene
GPCRDB
GeneCards
GenitoUrinary Development Molecular Anatomy Project
HomoloGene
Human Protein Reference Database
InterPro
KEGG Gene
OMIM
PharmGKB Gene
PhosphoSitePlus
Protein Ontology (PRO)
RefSeq Nucleotide
RefSeq Protein
TreeFam
UniGene Hs.
UniProtKB
Wikipedia
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  Structure of human CXCR1 in phospholipid bilayers
PDB Id:  2LNL
Resolution:  0.0Å
Species:  Human
References:  25
Natural/Endogenous Ligands
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 12,27
pKd 8.9 – 9.6 (Kd 2.51x10-10 – 1.2x10-9 M) [12,27]
[125I]mini-TyrRS Hs Full agonist 7.7 pKd 30
pKd 7.7 [30]
CXCL8 {Sp: Human} Hs Full agonist 8.8 – 9.5 pKi 1,12,19,31,33
pKi 8.8 – 9.5 [1,12,19,31,33]
mini-TyrRS Hs Full agonist 8.1 pKi 30
pKi 8.1 [30]
CXCL6 {Sp: Human} Hs Full agonist 7.0 pKi 34
pKi 7.0 [34]
CXCL1 {Sp: Human} Hs Full agonist 6.4 pKi 19
pKi 6.4 [19]
Agonist Comments
Reference [26] 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:  29
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 chemotaxis of Jurkat cells transfected with the human CXCR1 receptor.
Species:  Human
Tissue:  Jurkat cells.
Response measured:  Chemotaxis.
References:  11,32
Measurement of chemotaxis in of HEK 293 cells transfected with the CXCR1 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Chemotaxis.
References:  7,23,34
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:  19,34-35
Measurement of Ca2+ levels in Jurkat cells transfected with the human CXCR1 receptor.
Species:  Human
Tissue:  Jurkat cells.
Response measured:  Ca2+ mobilisation.
References:  17-18,32
Measurement of elastase released by human neutrophils endogenously expressing the CXCR1 receptor.
Species:  Human
Tissue:  Neutrophils.
Response measured:  Release of elastase.
References:  17-18,32
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 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:  29
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
Type:  Naturally occurring SNPs.
Species:  Human
Description:  R335C polymorphism may be associated with an increased risk of developing chronic obstructive pulmonary disease and asthma. This polymorphism has a low frequency of expression (<10% in all tested populations).
Amino acids:  335
SNP accession: 
References:  28
Type:  Naturally occurring SNPs.
Species:  Human
Description:  M31R polymorphism may confer susceptibility to human immunodeficiency virus type 1 or slow progression to acquired immunodeficiency syndrome and may also be associated with an increased risk of developing chronic obstructive pulmonary disease and asthma. This polymorphism has a low frequency of expression (<10% in all tested populations).
Amino acids:  31
SNP accession: 
References:  28
Type:  SNP
Species:  Human
Change:  M268L
Global MAF (%):  1
Subpopulation MAF (%):  AFR: 2
Minor allele count:  G=0.006/13
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  HapMap, Frequency, Multiple observations
Type:  SNP
Species:  Human
Change:  S276T
Global MAF (%):  11
Subpopulation MAF (%):  AFR|AMR|ASN|EUR: 26|9|9|4
Minor allele count:  G=0.115/250
SNP accession: 
Validation:  1000 Genomes, HapMap, Cited, Frequency, Multiple observations
Type:  SNP
Species:  Human
Change:  S342L
Global MAF (%):  1
Subpopulation MAF (%):  AFR: 5
Minor allele count:  A=0.012/26
Comment on frequency:  Low frequency (<10% in all tested populations)
SNP accession: 
Validation:  1000 Genomes, HapMap
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.
Available Assays
DiscoveRx PathHunter® eXpress CXCR1 U2OS β-Arrestin GPCR Assay (Cat no. 93-0226E3CP0M)
PathHunter® U2OS CXCR1 β-Arrestin Cell Line (Cat no. 93-0226C3)
more info

REFERENCES

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10. Godaly G, Hang L, Frendéus B, Svanborg C. (2000) Transepithelial neutrophil migration is CXCR1 dependent in vitro and is defective in IL-8 receptor knockout mice. J Immunol165: 5287-5294. [PMID:11046063]

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13. Hang L, Frendéus B, Godaly G, Svanborg C. (2000) Interleukin-8 receptor knockout mice have subepithelial neutrophil entrapment and renal scarring following acute pyelonephritis. J Infect Dis182: 1738-1748. [PMID:11069247]

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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 31/03/2014. Accessed on 22/10/2014. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=68.

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