Interleukin 8 receptor, alpha

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)
End	218,166,962 bp
Gene location (Mouse)
Chr.	Chromosome 1 (mouse)
End	74,233,790 bp
RNA expression pattern
	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
	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
	3577
	227288
	ENSG00000163464
	ENSMUSG00000048480
	P25024
	Q810W6
	NM_000634
	NM_178241
	NP_000625
	NP_839972
	Wikidata
View/Edit Human	View/Edit Mouse

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 This name and the corresponding gene symbol IL8RA have been replaced by the HGNC approved name C-X-C motif chemokine receptor 1 and the approved symbol CXCR1.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.

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.^[5] Stimulation of CXCR1 in neutrophils by its primary ligand, Interleukin 8, leads to neutrophil chemotaxis and activation.^[6]

Clinical significance

Blocking CXCR1 (e.g., with repertaxin^[7]) inhibits some human breast cancer stem cells (in vitro and in mice).^[8]

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.^[9]

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.^[10]

Interactions

Interleukin 8 receptor, alpha has been shown to interact with GNAI2.^[11]^[12]

References

^ ^a ^b ^c GRCh38: Ensembl release 89: ENSG00000163464 – Ensembl, May 2017
^ ^a ^b ^c GRCm38: Ensembl release 89: ENSMUSG00000048480 – Ensembl, May 2017
^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
^ "Entrez Gene: IL8RA interleukin 8 receptor, alpha".
^ Bergin DA, Reeves EP, Meleady P, Henry M, McElvaney OJ, Carroll TP, et al. (December 2010). "α-1 Antitrypsin regulates human neutrophil chemotaxis induced by soluble immune complexes and IL-8". The Journal of Clinical Investigation. 120 (12): 4236–4250. doi:10.1172/JCI41196. PMC 2993580. PMID 21060150.
^ Casilli F, Bianchini A, Gloaguen I, Biordi L, Alesse E, Festuccia C, et al. (February 2005). "Inhibition of interleukin-8 (CXCL8/IL-8) responses by repertaxin, a new inhibitor of the chemokine receptors CXCR1 and CXCR2". Biochemical Pharmacology. 69 (3): 385–394. doi:10.1016/j.bcp.2004.10.007. PMID 15652230.
^
Ginestier C, Liu S, Diebel ME, Korkaya H, Luo M, Brown M, et al. (February 2010). "CXCR1 blockade selectively targets human breast cancer stem cells in vitro and in xenografts". The Journal of Clinical Investigation. 120 (2): 485–497. doi:10.1172/JCI39397. PMC 2810075. PMID 20051626.
- "Investigators Find Method to Suppress Breast Cancer Stem Cells". Genetic Engineering & Biotechnology News. January 5, 2010. Archived from the original on 2012-08-06.
^ Sharma B, Singh S, Varney ML, Singh RK (April 2010). "Targeting CXCR1/CXCR2 receptor antagonism in malignant melanoma". Expert Opinion on Therapeutic Targets. 14 (4): 435–442. doi:10.1517/14728221003652471. PMC 4229031. PMID 20230195.
^ Hartl D, Latzin P, Hordijk P, Marcos V, Rudolph C, Woischnik M, et al. (December 2007). "Cleavage of CXCR1 on neutrophils disables bacterial killing in cystic fibrosis lung disease". Nature Medicine. 13 (12): 1423–1430. doi:10.1038/nm1690. PMID 18059279. S2CID 9594986.
^ 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.
^ 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.

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.