CXCR2 C-X-C motif chemokine receptor 2 [Homo sapiens (human)] - Gene

Summary

Official Symbol: CXCR2provided by HGNC
Official Full Name: C-X-C motif chemokine receptor 2provided by HGNC
Primary source: HGNC:HGNC:6027
See related: Ensembl:ENSG00000180871 MIM:146928
Gene type: protein coding
RefSeq status: REVIEWED
Organism: Homo sapiens
Lineage: Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
Also known as: CD182; IL8R2; IL8RA; IL8RB; CMKAR2; CDw128b
Summary: 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. This receptor also binds to chemokine (C-X-C motif) ligand 1 (CXCL1/MGSA), a protein with melanoma growth stimulating activity, and has been shown to be a major component required for serum-dependent melanoma cell growth. This receptor mediates neutrophil migration to sites of inflammation. The angiogenic effects of IL8 in intestinal microvascular endothelial cells are found to be mediated by this receptor. Knockout studies in mice suggested that this receptor controls the positioning of oligodendrocyte precursors in developing spinal cord by arresting their migration. This gene, IL8RA, a gene encoding another high affinity IL8 receptor, as well as IL8RBP, a pseudogene of IL8RB, form a gene cluster in a region mapped to chromosome 2q33-q36. Alternatively spliced variants, encoding the same protein, have been identified. [provided by RefSeq, Nov 2009]
Expression: Biased expression in appendix (RPKM 20.0), spleen (RPKM 13.2) and 7 other tissues See more
Orthologs: mouse all

Genomic context

Location:: 2q35

Exon count:: 6

Annotation release	Status	Assembly	Chr	Location
109	current	GRCh38.p12 (GCF_000001405.38)	2	NC_000002.12 (218125290..218137253)
105	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (218990013..219001976)

Chromosome 2 - NC_000002.12 Genomic Context describing neighboring genes

Genomic regions, transcripts, and products

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Go to reference sequence details

Genomic Sequence:

Go to nucleotide: Graphics FASTA GenBank

Expression

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See details

Project title: HPA RNA-seq normal tissues
Description: RNA-seq was performed of tissue samples from 95 human individuals representing 27 different tissues in order to determine tissue-specificity of all protein-coding genes
BioProject: PRJEB4337
Publication: PMID 24309898
Analysis date: Wed Apr 4 07:08:55 2018

Bibliography

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GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

These results suggest a direct involvement of IL-8-CXCR1/2 axes in GBM progression by promoting both cell proliferation and invasion and indirectly by promoting neovascularization in the form of vascular mimicry.
Title: IL-8/CXCR1/2 signalling promotes tumor cell proliferation, invasion and vascular mimicry in glioblastoma.
These data were in close agreement with the reduced cell migration and colony formation. Results from the present study suggested that reparixin and SCH527123 may be promising therapeutic agents for the treatment of pancreatic cancer by inhibiting the IL8/CXCR1/2 signaling cascade.
Title: Inhibition of interleukin 8/C‑X-C chemokine receptor 1,/2 signaling reduces malignant features in human pancreatic cancer cells.
The CXCR2 rs1126579 TT genotype had a significantly increased possibility of HCV spontaneous clearance.
Title: Association of CXCR2 genotype variations with HCV clearance in a Chinese population.
increased production of IL-8 associated with neutrophils infiltration into the liver and decreased CXCR1/2 expression on peripheral neutrophils. CXCR1 and CXCR2 expression levels could be served as early markers to predict the severity of acute-on-chronic liver failure.
Title: Low expression of CXCR1/2 on neutrophils predicts poor survival in patients with hepatitis B virus-related acute-on-chronic liver failure.
CXCR2 protein expression was up-regulated in both the epileptic foci of temporal lobe epilepsy patients and in the pilocarpine mouse model. The CXCR2 selective antagonist SB225002, which was i.p. administered during the spontaneous recurrent seizures (SRSs) latency window preceding SRS onset, suppressed SRSs activity during the chronic period of epilepsy.
Title: The effect of CXCR2 inhibition on seizure activity in the pilocarpine epilepsy mouse model.
inflammation triggered property of Microcystin-LR via IL-8/CXCR2 signaling
Title: The role of IL-8/CXCR2 signaling in microcystin-LR triggered endothelial cell activation and increased vascular permeability.
results indicated that the CXCR2 +1208 CT genotype is less frequent in advanced stages of prostate cancer, suggesting that this chemokine receptor plays a role in the pathogenesis of this disease
Title: CXCR2 +1208 CT genotype may predict earlier clinical stage at diagnosis in patients with prostate cancer.
CXCR2 expression is a promoter of CRC local as well as distant metastasis and unfavorably associated with CRC patients' prognosis. Moreover, CXCR2 can stratify high-risk patients especially in normally early stage low-risk CRC patients.
Title: Overexpression of CXCR2 predicts poor prognosis in patients with colorectal cancer.
PADI4 contributes to gastric tumorigenesis by upregulating CXCR2, KRT14 and TNF-alpha expression.
Title: PADI4 has genetic susceptibility to gastric carcinoma and upregulates CXCR2, KRT14 and TNF-α expression levels.
Association of polymorphic markers of chemokine genes, their receptors, and CD14 gene with coronary atherosclerosis
Title: [Association of polymorphic markers of chemokine genes, their receptors, and CD14 gene with coronary atherosclerosis].

Submit: New GeneRIF Correction See all GeneRIFs (225)

Phenotypes

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Find tests for this gene in the NIH Genetic Testing Registry (GTR)

Review eQTL and phenotype association data in this region using PheGenI

NHGRI GWAS Catalog

Description
Genome-wide association studies of pit-and-fissure- and smooth-surface caries in permanent dentition. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease. NHGRI GWA Catalog NHGRI GWA CatalogPubMed
Meta-analysis identifies 29 additional ulcerative colitis risk loci, increasing the number of confirmed associations to 47. NHGRI GWA Catalog NHGRI GWA CatalogPubMed

Variation

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See variants in ClinVar

See studies and variants in dbVar

See Variation Viewer (GRCh37.p13)

See Variation Viewer (GRCh38)

HIV-1 interactions

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Protein interactions

Protein	Gene	Interaction	Pubs
Nef	nef	HIV-1 Nef induces variable levels of CXCR2 downregulation in different cell types in an ubiquitin-independent manner	PubMed
capsid	gag	CXCL8-induced upregulation of HIV-1 p24 levels and 2-LTR cycles is inhibited by CXCR1 or CXCR2 neutralization in HIV-1-infected monocytes-derived macrophages	PubMed
matrix	gag	HIV-1 MA interacts with CXCR2 in primary hepatocytes	PubMed
	gag	Epstein-Barr virus (EBV)-infected primary and fully transformed B-lymphocytes upregulate the expression of CXCR2 receptor, which binds HIV-1 MA and its natural variant S75X, and enhances their internalization in cells	PubMed
	gag	HIV-1 MA-induced upregulation of collagen-I and alpha-SMA expression is dependent on CXCR2 via the Rho/ROCK-1 pathway	PubMed
	gag	Treatment of human stellate cells with HIV-1 MA upregulates the expression of CXCR2, syndecan-2, collagen-I, alpha-SMA, vimentin, and endothelin-1	PubMed
	gag	HIV-1 MA and SIV MA induce migration of CXCR2-expressing B cells and Jurkat cells	PubMed
	gag	Surface plasmon resonance (SPR) binding assay demonstrates that SIV MA binds CXCR2 with higher affinity than HIV-1 MA binds CXCR2	PubMed
	gag	HIV-1 p17 induces capillary-like structures in human endothelial cells by binding to CXCR1 and CXCR2, which requires activation of the Akt-dependent ERK signaling pathway	PubMed

Go to the HIV-1, Human Interaction Database

Pathways from BioSystems

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Chemokine receptors bind chemokines, organism-specific biosystem (from REACTOME)
Chemokine receptors bind chemokines, organism-specific biosystemChemokine receptors are cytokine receptors found on the surface of certain cells, which interact with a type of cytokine called a chemokine. Following interaction, these receptors trigger a flux of i...
Chemokine signaling pathway, organism-specific biosystem (from KEGG)
Chemokine signaling pathway, organism-specific biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
Chemokine signaling pathway, conserved biosystem (from KEGG)
Chemokine signaling pathway, conserved biosystemInflammatory immune response requires the recruitment of leukocytes to the site of inflammation upon foreign insult. Chemokines are small chemoattractant peptides that provide directional cues for th...
Class A/1 (Rhodopsin-like receptors), organism-specific biosystem (from REACTOME)
Class A/1 (Rhodopsin-like receptors), organism-specific biosystemRhodopsin-like receptors (class A/1) are the largest group of GPCRs and are the best studied group from a functional and structural point of view. They show great diversity at the sequence level and ...
Cytokine-cytokine receptor interaction, organism-specific biosystem (from KEGG)
Cytokine-cytokine receptor interaction, organism-specific biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
Cytokine-cytokine receptor interaction, conserved biosystem (from KEGG)
Cytokine-cytokine receptor interaction, conserved biosystemCytokines are soluble extracellular proteins or glycoproteins that are crucial intercellular regulators and mobilizers of cells engaged in innate as well as adaptive inflammatory host defenses, cell ...
Endocytosis, organism-specific biosystem (from KEGG)
Endocytosis, organism-specific biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
Endocytosis, conserved biosystem (from KEGG)
Endocytosis, conserved biosystemEndocytosis is a mechanism for cells to remove ligands, nutrients, and plasma membrane (PM) proteins, and lipids from the cell surface, bringing them into the cell interior. Transmembrane proteins en...
Epithelial cell signaling in Helicobacter pylori infection, organism-specific biosystem (from KEGG)
Epithelial cell signaling in Helicobacter pylori infection, organism-specific biosystemTwo major virulence factors of H. pylori are the vacuolating cytotoxin (VacA) and the cag type-IV secretion system (T4SS) and its translocated effector protein, cytotoxin-associated antigen A (CagA)....
Epithelial cell signaling in Helicobacter pylori infection, conserved biosystem (from KEGG)
Epithelial cell signaling in Helicobacter pylori infection, conserved biosystemTwo major virulence factors of H. pylori are the vacuolating cytotoxin (VacA) and the cag type-IV secretion system (T4SS) and its translocated effector protein, cytotoxin-associated antigen A (CagA)....
G alpha (i) signalling events, organism-specific biosystem (from REACTOME)
G alpha (i) signalling events, organism-specific biosystemThe classical signalling mechanism for G alpha (i) is inhibition of the cAMP dependent pathway through inhibition of adenylate cyclase. Decreased production of cAMP from ATP results in decreased act...
GPCR downstream signaling, organism-specific biosystem (from REACTOME)
GPCR downstream signaling, organism-specific biosystemG protein-coupled receptors (GPCRs) are classically defined as the receptor, G-protein and downstream effectors, the alpha subunit of the G-protein being the primary signaling molecule. However, it h...
GPCR ligand binding, organism-specific biosystem (from REACTOME)
GPCR ligand binding, organism-specific biosystemThere are more than 800 G-protein coupled receptor (GPCRs) in the human genome, making it the largest receptor superfamily. GPCRs are also the largest class of drug targets, involved in virtually all...
GPCRs, Class A Rhodopsin-like, organism-specific biosystem (from WikiPathways)
GPCRs, Class A Rhodopsin-like, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.gpcr.org/7tm/ (originally at http://www.cmbi.kun.nl/7tm/). The groupings are based on the GPCR phylogenetic tree available fr...
GPCRs, Other, organism-specific biosystem (from WikiPathways)
GPCRs, Other, organism-specific biosystemThis pathway was created using the GPCRDB (Horn et al., 1998), http://www.gpcr.org/7tm/ (originally at http://www.cmbi.kun.nl/7tm/). The groupings are based on the GPCR phylogenetic tree available fr...
Immune System, organism-specific biosystem (from REACTOME)
Immune System, organism-specific biosystemHumans are exposed to millions of potential pathogens daily, through contact, ingestion, and inhalation. Our ability to avoid infection depends on the adaptive immune system and during the first crit...
Innate Immune System, organism-specific biosystem (from REACTOME)
Innate Immune System, organism-specific biosystemInnate immunity encompases the nonspecific part of immunity tha are part of an individual's natural biologic makeup
Neutrophil degranulation, organism-specific biosystem (from REACTOME)
Neutrophil degranulation, organism-specific biosystemNeutrophils are the most abundant leukocytes (white blood cells), indispensable in defending the body against invading microorganisms. In response to infection, neutrophils leave the circulation and ...
Peptide GPCRs, organism-specific biosystem (from WikiPathways)
Peptide GPCRs, organism-specific biosystem
Peptide GPCRs
Peptide ligand-binding receptors, organism-specific biosystem (from REACTOME)
Peptide ligand-binding receptors, organism-specific biosystemThese receptors, a subset of the Class A/1 (Rhodopsin-like) family, all bind peptide ligands which include the chemokines, opioids and somatostatins.
Phospholipase D signaling pathway, organism-specific biosystem (from KEGG)
Phospholipase D signaling pathway, organism-specific biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
Phospholipase D signaling pathway, conserved biosystem (from KEGG)
Phospholipase D signaling pathway, conserved biosystemPhospholipase D (PLD) is an essential enzyme responsible for the production of the lipid second messenger phosphatidic acid (PA), which is involved in fundamental cellular processes, including membra...
Signal Transduction, organism-specific biosystem (from REACTOME)
Signal Transduction, organism-specific biosystemSignal transduction is a process in which extracellular signals elicit changes in cell state and activity. Transmembrane receptors sense changes in the cellular environment by binding ligands, such a...
Signaling by GPCR, organism-specific biosystem (from REACTOME)
Signaling by GPCR, organism-specific biosystemG protein-coupled receptors (GPCRs; 7TM receptors; seven transmembrane domain receptors; heptahelical receptors; G protein-linked receptors [GPLR]) are the largest family of transmembrane receptors i...

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

SHGC-35278 (e-PCR)
- UniSTS:8485

STS-L19593 (e-PCR)
- UniSTS:37178

IL8RB_163 (e-PCR)
- UniSTS:277382

RH69171 (e-PCR)
- UniSTS:15270

PMC135988P2 (e-PCR)
- UniSTS:270788

RH78907 (e-PCR)
- UniSTS:35029

IL8R-1 (e-PCR)
- UniSTS:251622

PMC155779P1 (e-PCR)
- UniSTS:271352

PMC155779P2 (e-PCR)
- UniSTS:271353

PMC155779P3 (e-PCR)
- UniSTS:271354

PMC310709P2 (e-PCR)
- UniSTS:272638

Homology

Homologs of the CXCR2 gene: The CXCR2 gene is conserved in chimpanzee, Rhesus monkey, dog, cow, mouse, rat, zebrafish, and frog.
Orthologs from Annotation Pipeline: 78 organisms have orthologs with human gene CXCR2
Orthologs

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
C-C chemokine binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
C-C chemokine receptor activity	IBA Inferred from Biological aspect of Ancestor more info	PubMed
C-X-C chemokine receptor activity	IDA Inferred from Direct Assay more info	PubMed
G protein-coupled receptor activity	IDA Inferred from Direct Assay more info	PubMed
chemokine binding	IBA Inferred from Biological aspect of Ancestor more info	PubMed
interleukin-8 binding	IPI Inferred from Physical Interaction more info	PubMed
interleukin-8 receptor activity	IDA Inferred from Direct Assay more info	PubMed
protein binding	IPI Inferred from Physical Interaction more info	PubMed

Process	Evidence Code	Pubs
G protein-coupled receptor signaling pathway	TAS Traceable Author Statement more info
acute inflammatory response to antigenic stimulus	IEA Inferred from Electronic Annotation more info
calcium-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell chemotaxis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
cell surface receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
cellular defense response	IDA Inferred from Direct Assay more info	PubMed
chemokine-mediated signaling pathway	IEA Inferred from Electronic Annotation more info
chemotaxis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
chemotaxis	IDA Inferred from Direct Assay more info	PubMed
dendritic cell chemotaxis	TAS Traceable Author Statement more info	PubMed
immune response	IBA Inferred from Biological aspect of Ancestor more info	PubMed
inflammatory response	TAS Traceable Author Statement more info	PubMed
interleukin-8-mediated signaling pathway	IDA Inferred from Direct Assay more info	PubMed
metanephric tubule morphogenesis	IEA Inferred from Electronic Annotation more info
midbrain development	IEA Inferred from Electronic Annotation more info
negative regulation of neutrophil apoptotic process	IEA Inferred from Electronic Annotation more info
neutrophil activation	IDA Inferred from Direct Assay more info	PubMed
neutrophil chemotaxis	IBA Inferred from Biological aspect of Ancestor more info	PubMed
neutrophil chemotaxis	IDA Inferred from Direct Assay more info	PubMed
neutrophil degranulation	TAS Traceable Author Statement more info
phospholipase C-activating G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
positive regulation of angiogenesis	IEA Inferred from Electronic Annotation more info
positive regulation of cardiac muscle cell apoptotic process	IEA Inferred from Electronic Annotation more info
positive regulation of cell proliferation	IDA Inferred from Direct Assay more info	PubMed
positive regulation of cytosolic calcium ion concentration	IBA Inferred from Biological aspect of Ancestor more info	PubMed
positive regulation of neutrophil chemotaxis	IEA Inferred from Electronic Annotation more info
positive regulation of vascular permeability	IEA Inferred from Electronic Annotation more info
receptor internalization	IDA Inferred from Direct Assay more info	PubMed
signal transduction	TAS Traceable Author Statement more info	PubMed

Component	Evidence Code	Pubs
cell surface	IDA Inferred from Direct Assay more info	PubMed
external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info	PubMed
integral component of plasma membrane	TAS Traceable Author Statement more info	PubMed
mast cell granule	IDA Inferred from Direct Assay more info	PubMed
membrane	IDA Inferred from Direct Assay more info	PubMed
plasma membrane	TAS Traceable Author Statement more info
secretory granule membrane	TAS Traceable Author Statement more info

General protein information

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Preferred Names: C-X-C chemokine receptor type 2

Names: CXC-R2; CXCR-2; CXCR2 gene for IL8 receptor type B; GRO/MGSA receptor; IL-8 receptor type 2; IL-8R B; chemokine (CXC) receptor 2; high affinity interleukin-8 receptor B; interleukin 8 receptor type 2; interleukin 8 receptor, beta; interleukin-8 receptor type B

NCBI Reference Sequences (RefSeq)

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RefSeqs maintained independently of Annotated Genomes

These reference sequences exist independently of genome builds. Explain

These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

Genomic

NG_052975.1 RefSeqGene

Range

5001..16964

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

NM_001168298.1 → NP_001161770.1 C-X-C chemokine receptor type 2

See identical proteins and their annotated locations for NP_001161770.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) differs in the 5' UTR compared to variant 1. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AC124768, AJ710879, DA674925

Consensus CDS

CCDS2408.1

UniProtKB/Swiss-Prot

P25025

UniProtKB/TrEMBL

Q53PC4

Conserved Domains (1) summary

cd15178
Location:49 → 325

7tmA_CXCR1_2; CXC chemokine receptor types 1 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001557.4 → NP_001548.1 C-X-C chemokine receptor type 2

See identical proteins and their annotated locations for NP_001548.1

Status: REVIEWED

Description

Transcript Variant: This variant (1) represents the longer transcript. Both variants 1 and 2 encode the same protein.

Source sequence(s)

AC124768, L19593

Consensus CDS

CCDS2408.1

UniProtKB/Swiss-Prot

P25025

UniProtKB/TrEMBL

Q53PC4

Related

ENSP00000319635.2, ENST00000318507.6

Conserved Domains (1) summary

cd15178
Location:49 → 325

7tmA_CXCR1_2; CXC chemokine receptor types 1 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 109

The following sections contain reference sequences that belong to a specific genome build. Explain

Reference GRCh38.p12 Primary Assembly

Genomic

NC_000002.12 Reference GRCh38.p12 Primary Assembly

Range

218125290..218137253

Download

GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

XM_017003990.1 → XP_016859479.1 C-X-C chemokine receptor type 2 isoform X1

UniProtKB/Swiss-Prot

P25025

UniProtKB/TrEMBL

Q53PC4

Conserved Domains (1) summary

cd15178
Location:49 → 325

7tmA_CXCR1_2; CXC chemokine receptor types 1 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors
XM_005246530.3 → XP_005246587.1 C-X-C chemokine receptor type 2 isoform X1

See identical proteins and their annotated locations for XP_005246587.1

UniProtKB/Swiss-Prot

P25025

UniProtKB/TrEMBL

Q53PC4

Conserved Domains (1) summary

cd15178
Location:49 → 325

7tmA_CXCR1_2; CXC chemokine receptor types 1 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors
XM_017003992.1 → XP_016859481.1 C-X-C chemokine receptor type 2 isoform X1

UniProtKB/Swiss-Prot

P25025

UniProtKB/TrEMBL

Q53PC4

Conserved Domains (1) summary

cd15178
Location:49 → 325

7tmA_CXCR1_2; CXC chemokine receptor types 1 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors
XM_017003991.1 → XP_016859480.1 C-X-C chemokine receptor type 2 isoform X1

UniProtKB/Swiss-Prot

P25025

UniProtKB/TrEMBL

Q53PC4

Conserved Domains (1) summary

cd15178
Location:49 → 325

7tmA_CXCR1_2; CXC chemokine receptor types 1 and 2, member of the class A family of seven-transmembrane G protein-coupled receptors