Interleukin 8 receptor, alpha

Interleukin 8 receptor, alpha is a chemokine receptor. This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1. It has also been designated as CD181 (cluster of differentiation 181). The IUPHAR Committee on Receptor Nomenclature and Drug Classification use the HGNC recommended name, CXCR1.

CXCR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 1ILP, 1ILQ, 2LNL
Identifiers
Aliases	CXCR1, C-C, C-C-CKR-1, CD128, CD181, CDw128a, CKR-1, CMKAR1, IL8R1, IL8RA, IL8RBA, Interleukin 8 receptor, C-X-C motif chemokine receptor 1
External IDs	OMIM: 146929; MGI: 2448715; HomoloGene: 68074; GeneCards: CXCR1; OMA:CXCR1 - orthologs
Gene location (Human) Chr. Chromosome 2 (human) Band 2q35 Start 218,162,841 bp End 218,166,962 bp
Gene location (Mouse) Chr. Chromosome 1 (mouse) Band 1 C3|1 38.44 cM Start 74,230,944 bp End 74,233,790 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in blood granulocyte periodontal fiber spleen bone marrow bone marrow cells appendix right lung upper lobe of left lung nasal epithelium Top expressed in granulocyte blastocyst placenta lung zone of skin More reference expression data BioGPS More reference expression data
Gene ontology Molecular function C-X-C chemokine receptor activity interleukin-8 binding G protein-coupled receptor activity chemokine receptor activity interleukin-8 receptor activity signal transducer activity C-C chemokine receptor activity chemokine binding C-C chemokine binding Cellular component integral component of membrane plasma membrane secretory granule membrane membrane external side of plasma membrane Biological process G protein-coupled receptor signaling pathway cell surface receptor signaling pathway receptor internalization dendritic cell chemotaxis signal transduction chemokine-mediated signaling pathway interleukin-8-mediated signaling pathway neutrophil degranulation chemotaxis immune response positive regulation of cytosolic calcium ion concentration calcium-mediated signaling neutrophil chemotaxis cell chemotaxis Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 3577 227288 Ensembl ENSG00000163464 ENSMUSG00000048480 UniProt P25024 Q810W6 RefSeq (mRNA) NM_000634 NM_178241 RefSeq (protein) NP_000625 NP_839972 Location (UCSC) Chr 2: 218.16 – 218.17 Mb Chr 1: 74.23 – 74.23 Mb PubMed search
Wikidata
View/Edit Human View/Edit Mouse

Function

The protein encoded by this gene is a member of the G-protein-coupled receptor family. This protein is a receptor for interleukin 8 (IL8). It binds to IL8 with high affinity, and transduces the signal through a G-protein-activated second messenger system. Knockout studies in mice suggested that this protein inhibits embryonic oligodendrocyte precursor migration in developing spinal cord. IL8RA, IL8RB, which encodes another high affinity IL8 receptor, and IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. Stimulation of CXCR1 in neutrophils by its primary ligand, Interleukin 8, leads to neutrophil chemotaxis and activation.

Clinical significance

Blocking CXCR1 (e.g., with repertaxin) inhibits some human breast cancer stem cells (in vitro and in mice).

In malignant melanoma expression of CXCR1 at the cell surface is present, independent of the cancers stage. It is thought to have a role in the cell growth and angiogenesis required for tumour survival. In this way it has been identified as a potential therapeutic target.

CXCR1 can be cleaved and inactivated by Neutrophil Derived Serine Proteases (NSPs), leading to neutrophil dysfunction and impaired bacterial killing in cystic fibrosis lung disease.

Interactions

Interleukin 8 receptor, alpha has been shown to interact with GNAI2.

See also

• Interleukin
• Interleukin 8
• Interleukin 8 receptor, beta
• Interleukin receptor
• Interleukin-8 receptor

Further reading

• Ahuja SK, Ozçelik T, Milatovitch A, Francke U, Murphy PM (September 1992). "Molecular evolution of the human interleukin-8 receptor gene cluster". Nature Genetics. 2 (1): 31–36. doi:10.1038/ng0992-31. PMID 1303245. S2CID 19732372.
• Lee J, Horuk R, Rice GC, Bennett GL, Camerato T, Wood WI (August 1992). "Characterization of two high affinity human interleukin-8 receptors". The Journal of Biological Chemistry. 267 (23): 16283–16287. doi:10.1016/S0021-9258(18)41997-7. PMID 1379593.
• Morris SW, Nelson N, Valentine MB, Shapiro DN, Look AT, Kozlosky CJ, et al. (November 1992). "Assignment of the genes encoding human interleukin-8 receptor types 1 and 2 and an interleukin-8 receptor pseudogene to chromosome 2q35". Genomics. 14 (3): 685–691. doi:10.1016/S0888-7543(05)80169-7. PMID 1427896.
• Holmes WE, Lee J, Kuang WJ, Rice GC, Wood WI (September 1991). "Structure and functional expression of a human interleukin-8 receptor". Science. 253 (5025): 1278–1280. Bibcode:1991Sci...253.1278H. doi:10.1126/science.1840701. PMID 1840701.
• Chuntharapai A, Lee J, Hébert CA, Kim KJ (December 1994). "Monoclonal antibodies detect different distribution patterns of IL-8 receptor A and IL-8 receptor B on human peripheral blood leukocytes". Journal of Immunology. 153 (12): 5682–5688. doi:10.4049/jimmunol.153.12.5682. PMID 7527448. S2CID 8872590.
• Chuntharapai A, Kim KJ (September 1995). "Regulation of the expression of IL-8 receptor A/B by IL-8: possible functions of each receptor". Journal of Immunology. 155 (5): 2587–2594. doi:10.4049/jimmunol.155.5.2587. PMID 7650389. S2CID 24746695.
• Morohashi H, Miyawaki T, Nomura H, Kuno K, Murakami S, Matsushima K, et al. (January 1995). "Expression of both types of human interleukin-8 receptors on mature neutrophils, monocytes, and natural killer cells". Journal of Leukocyte Biology. 57 (1): 180–187. doi:10.1002/jlb.57.1.180. PMID 7829970. S2CID 7819367.
• Schönbeck U, Brandt E, Petersen F, Flad HD, Loppnow H (March 1995). "IL-8 specifically binds to endothelial but not to smooth muscle cells". Journal of Immunology. 154 (5): 2375–2383. doi:10.4049/jimmunol.154.5.2375. PMID 7868904. S2CID 31884586.
• Ahuja SK, Shetty A, Tiffany HL, Murphy PM (October 1994). "Comparison of the genomic organization and promoter function for human interleukin-8 receptors A and B". The Journal of Biological Chemistry. 269 (42): 26381–26389. doi:10.1016/S0021-9258(18)47205-5. PMID 7929358.
• Sprenger H, Lloyd AR, Meyer RG, Johnston JA, Kelvin DJ (September 1994). "Genomic structure, characterization, and identification of the promoter of the human IL-8 receptor A gene". Journal of Immunology. 153 (6): 2524–2532. doi:10.4049/jimmunol.153.6.2524. PMID 8077663. S2CID 12014231.
• Schnitzel W, Monschein U, Besemer J (June 1994). "Monomer-dimer equilibria of interleukin-8 and neutrophil-activating peptide 2. Evidence for IL-8 binding as a dimer and oligomer to IL-8 receptor B". Journal of Leukocyte Biology. 55 (6): 763–770. doi:10.1002/jlb.55.6.763. PMID 8195702. S2CID 5948202.
• Wu D, LaRosa GJ, Simon MI (July 1993). "G protein-coupled signal transduction pathways for interleukin-8". Science. 261 (5117): 101–103. Bibcode:1993Sci...261..101W. doi:10.1126/science.8316840. PMID 8316840.
• Sebok K, Woodside D, al-Aoukaty A, Ho AD, Gluck S, Maghazachi AA (February 1993). "IL-8 induces the locomotion of human IL-2-activated natural killer cells. Involvement of a guanine nucleotide binding (Go) protein". Journal of Immunology. 150 (4): 1524–1534. doi:10.4049/jimmunol.150.4.1524. PMID 8381837. S2CID 29083621.
• Cerretti DP, Kozlosky CJ, Vanden Bos T, Nelson N, Gearing DP, Beckmann MP (March 1993). "Molecular characterization of receptors for human interleukin-8, GRO/melanoma growth-stimulatory activity and neutrophil activating peptide-2". Molecular Immunology. 30 (4): 359–367. doi:10.1016/0161-5890(93)90065-J. PMID 8384312.
• Mollereau C, Muscatelli F, Mattei MG, Vassart G, Parmentier M (April 1993). "The high-affinity interleukin 8 receptor gene (IL8RA) maps to the 2q33-q36 region of the human genome: cloning of a pseudogene (IL8RBP) for the low-affinity receptor". Genomics. 16 (1): 248–251. doi:10.1006/geno.1993.1167. PMID 8486366.
• Lloyd A, Modi W, Sprenger H, Cevario S, Oppenheim J, Kelvin D (1993). "Assignment of genes for interleukin-8 receptors (IL8R) A and B to human chromosome band 2q35". Cytogenetics and Cell Genetics. 63 (4): 238–240. doi:10.1159/000133541. PMID 8500355.
• Damaj BB, McColl SR, Mahana W, Crouch MF, Naccache PH (May 1996). "Physical association of Gi2alpha with interleukin-8 receptors". The Journal of Biological Chemistry. 271 (22): 12783–12789. doi:10.1074/jbc.271.22.12783. PMID 8662698.
• Ahuja SK, Murphy PM (August 1996). "The CXC chemokines growth-regulated oncogene (GRO) alpha, GRObeta, GROgamma, neutrophil-activating peptide-2, and epithelial cell-derived neutrophil-activating peptide-78 are potent agonists for the type B, but not the type A, human interleukin-8 receptor". The Journal of Biological Chemistry. 271 (34): 20545–20550. doi:10.1074/jbc.271.34.20545. PMID 8702798.
• Damaj BB, McColl SR, Neote K, Songqing N, Ogborn KT, Hébert CA, et al. (October 1996). "Identification of G-protein binding sites of the human interleukin-8 receptors by functional mapping of the intracellular loops". FASEB Journal. 10 (12): 1426–1434. doi:10.1096/fasebj.10.12.8903513. PMID 8903513. S2CID 9744575.
• Jerva LF, Sullivan G, Lolis E (August 1997). "Functional and receptor binding characterization of recombinant murine macrophage inflammatory protein 2: sequence analysis and mutagenesis identify receptor binding epitopes". Protein Science. 6 (8): 1643–1652. doi:10.1002/pro.5560060805. PMC 2143775. PMID 9260277.

External links

• "Chemokine Receptors: CXCR1". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2016-03-03. Retrieved 2008-12-03.

This article incorporates text from the United States National Library of Medicine, which is in the public domain.