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CXCR4 C-X-C motif chemokine receptor 4 [ Homo sapiens (human) ]

Gene ID: 7852, updated on 10-Dec-2024

Summary

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Official Symbol: CXCR4provided by HGNC
Official Full Name: C-X-C motif chemokine receptor 4provided by HGNC
Primary source: HGNC:HGNC:2561
See related: Ensembl:ENSG00000121966 MIM:162643; AllianceGenome:HGNC:2561
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: FB22; HM89; LAP3; LCR1; NPYR; WHIM; CD184; LAP-3; LESTR; NPY3R; NPYRL; WHIMS; HSY3RR; NPYY3R; WHIMS1; D2S201E
Summary: This gene encodes a CXC chemokine receptor specific for stromal cell-derived factor-1. The protein has 7 transmembrane regions and is located on the cell surface. It acts with the CD4 protein to support HIV entry into cells and is also highly expressed in breast cancer cells. Mutations in this gene have been associated with WHIM (warts, hypogammaglobulinemia, infections, and myelokathexis) syndrome. Alternate transcriptional splice variants, encoding different isoforms, have been characterized. [provided by RefSeq, Jul 2008]
Expression: Biased expression in bone marrow (RPKM 479.2), lymph node (RPKM 201.0) and 9 other tissues See more
Orthologs: mouse all
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Genomic context

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See CXCR4 in Genome Data Viewer

Location:: 2q22.1

Exon count:: 4

Annotation release	Status	Assembly	Chr	Location
RS_2024_08	current	GRCh38.p14 (GCF_000001405.40)	2	NC_000002.12 (136114349..136118149, complement)
RS_2024_08	current	T2T-CHM13v2.0 (GCF_009914755.1)	2	NC_060926.1 (136558831..136562630, complement)
RS_2024_09	previous assembly	GRCh37.p13 (GCF_000001405.25)	2	NC_000002.11 (136871919..136875719, complement)

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 Functions

What's a GeneRIF?

Potential protective association of the AA genotype and a allele of CXCR4 rs2228014 polymorphism with COVID-19 severity in adult egyptians.
Title: Potential protective association of the AA genotype and a allele of CXCR4 rs2228014 polymorphism with COVID-19 severity in adult egyptians.
CXCR4 Expression and Cancer-associated Fibroblasts May Play an Important Role in the Invasion of Low-grade Endometrioid Carcinoma.
Title: CXCR4 Expression and Cancer-associated Fibroblasts May Play an Important Role in the Invasion of Low-grade Endometrioid Carcinoma.
CXCR4 regulates macrophage M1 polarization by altering glycolysis to promote prostate fibrosis.
Title: CXCR4 regulates macrophage M1 polarization by altering glycolysis to promote prostate fibrosis.
RGS1 targeted by miR-191-3p inhibited the stemness properties of esophageal cancer cells by suppressing CXCR4/PI3K/AKT signaling.
Title: RGS1 targeted by miR-191-3p inhibited the stemness properties of esophageal cancer cells by suppressing CXCR4/PI3K/AKT signaling.
Recruitment of CXCR4+ type 1 innate lymphoid cells distinguishes sarcoidosis from other skin granulomatous diseases.
Title: Recruitment of CXCR4+ type 1 innate lymphoid cells distinguishes sarcoidosis from other skin granulomatous diseases.
CXCR4 promotes migration, invasion, and epithelial-mesenchymal transition of papillary thyroid carcinoma by activating STAT3 signaling pathway.
Title: CXCR4 promotes migration, invasion, and epithelial-mesenchymal transition of papillary thyroid carcinoma by activating STAT3 signaling pathway.
Comprehensive Analysis of CXCR4, JUNB, and PD-L1 Expression in Circulating Tumor Cells (CTCs) from Prostate Cancer Patients.
Title: Comprehensive Analysis of CXCR4, JUNB, and PD-L1 Expression in Circulating Tumor Cells (CTCs) from Prostate Cancer Patients.
ABCF1/CXCL12/CXCR4 Enhances Glioblastoma Cell Proliferation, Migration, and Invasion by Activating the PI3K/AKT Signal Pathway.
Title: ABCF1/CXCL12/CXCR4 Enhances Glioblastoma Cell Proliferation, Migration, and Invasion by Activating the PI3K/AKT Signal Pathway.
CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: A prospective, single-center, observational study.
Title: CXCR4 overexpression in chronic lymphocytic leukemia associates with poorer prognosis: A prospective, single-center, observational study.
CXCR4 WHIM syndrome is a cancer predisposition condition for virus-induced malignancies.
Title: CXCR4 WHIM syndrome is a cancer predisposition condition for virus-induced malignancies.

Submit: New GeneRIF Correction See all GeneRIFs (1618)

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

Associated conditions

Description	Tests
WHIM syndrome 1 MedGen: C5542296 OMIM: 193670 GeneReviews: Not available	Compare labs

EBI GWAS Catalog

Description
Genome-wide association identifies OBFC1 as a locus involved in human leukocyte telomere biology. EBI GWAS Catalog EBI GWAS CatalogPubMed
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci. EBI GWAS Catalog EBI GWAS 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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Replication interactions

Interaction	Pubs
HIV-1 LAI replication absolutely requires CCR5 and, to a lesser extent, CXCR4 as shown through CRISPR/Cas9 genome editing of each in primary CD4+ T cells	PubMed
HIV-1 requires cellular CXCR4 expression as genome editing by CRISPR/Cas9 of CXCR4 protects Ghost X4 cells from infection	PubMed
HIV-1 (NL4-3 derived NLENG1 (enhanced green fluorescent protein, (EGFP) gene linked with internal ribosome entry site between env and nef genes)) cell-to-cell transmission from lymphocytes to astrocytes requires CXCR4	PubMed
Knockdown of chemokine (C-X-C motif) receptor 4 (CXCR4) by siRNA inhibits HIV-1 replication in HeLa-derived TZM-bl cells	PubMed
Knockdown of chemokine (C-X-C motif) receptor 4 (CXCR4) by siRNA inhibits HIV-1 replication in HeLa P4/R5 cells	PubMed

Protein interactions

Protein	Gene	Interaction	Pubs
Envelope surface glycoprotein gp120	env	Analysis of the distribution of V3 loop's net charge and flexibility in HIV-1 gp120 shows its selection more positive toward CXCR4 than CCR5	PubMed
	env	CXCR4, a 45kDa cellular membrane protein, interacts with the cell surface HIV-1 gp120-CD4 complex and acts as a coreceptor to preferentially support T cell line-tropic HIV-1 Env-mediated cell fusion and HIV-1 infection	PubMed
	env	The specific amino acids 298-329 in the V3 loop of HIV-1 gp120 that determine cellular tropism also regulate chemokine coreceptor (CCR5 or CXCR4) preference for cell entry by the virus	PubMed
	env	HIV-1 Env (gp120) V3 loop binds to CXCR4 and CCR5 through in silico analysis	PubMed
	env	HIV-1 IIIB Env (gp120) engages CXCR4 and downregulates CHRFAM7A expression in neuronal cells and induces expression of CHRNA7	PubMed
	env	HIV-1 HXB2 Env (gp120) binds and fuses to CV-1 cells expressing CD4 and CXCR4	PubMed
	env	HIV-1 gp120 regulates CXCR4 utilization via cooperation between a threonine at gp120 position 123 and a N-glycan at gp120 position 262 without affecting CCR5 utilization	PubMed
	env	HIV-1 gp120 upregulates the level of CXCR4/CCR7 hetero-oligomerization in CD4+ T cells	PubMed
	env	HIV-1 gp120 interacts with CD4 and CXCR4 to enhance CCR7-dependent human CD4+ T cell migration	PubMed
	env	HIV-1 gp120 enhances CCL-21-induced CD4+ T cell chemotaxis in a CXCR4- and CD4-dependent manner	PubMed
	env	A CXCR4 mimetic peptide, which consists of the three extracellular loops of the receptor, binds to HIV-1 gp120 and neutralizes HIV-1 infection	PubMed
	env	The entry of T cell-tropic HIV-1 isolates is blocked by SDF-1 or CXCR4 antagonists, which bind to CXCR4	PubMed
	env	The coreceptor-binding site in HIV-1 gp120 is centered around an anti-parallel beta-sheet structure 'bridging sheet domain'; mutations in and adjacent to this domain have greater impact on CXCR4-mediated fusion than on CCR5-mediated fusion	PubMed
	env	CCR5 expression inhibits HIV-1 gp120 binding to CD4/CXCR4 complexes in 293T cells	PubMed
	env	CCR5 expression inhibits HIV-1 gp120-mediated early actin rearrangement and -induced LIMK1 activation and cofilin phosphorylation in CD4/CXCR4 expressing 293T cells	PubMed
	env	HIV-1 gp120-enhanced CD4/CXCR4 conformation changes are regulated by CCR5 expression in 293T cells	PubMed
	env	SMS2, but not SMS1, is involved in enhancement of HIV-1 gp120/gp41-mediated membrane fusion through CD4 receptor and CCR5/CXCR4 coreceptors	PubMed
	env	Positively charged Lys/Arg at position 322 in the V3 of gp120 and negatively charged Asp/Glu at position 440 in in the C4 of gp120 occur more frequently in CXCR4-using viruses	PubMed
	env	V1, V2, and V3 domains and N-linked glycosylation sites of HIV-1 gp120 confer coreceptor tropism; loss of an N-linked glycosylation site within V3 has a major influence on the virus switching from CCR5 to CXCR4 tropism in a V3 charge-dependent manner	PubMed
	env	HIV-1 gp120-CXCR4 signaling triggers cofilin activation and actin dynamics, which are important for a post entry process leading to viral nuclear localization	PubMed
	env	The interaction of CXCR4 with HIV-1 gp120 mediates gp120-induced CXCR3 and EMAP2 expression in human lung microvascular endothelial cells	PubMed
	env	HIV-1 gp120 upregulates the expression of chemokine (C-X-C motif) receptor 4 (CXCR4) in human B cells	PubMed
	env	HIV-1 gp120 induces mucus formation through CXCR4 on normal human bronchial epithelial cells	PubMed
	env	Antibodies to specific epitopes of the CCR5 or CXCR4 chemokine receptors inhibit the entry of M-tropic, T-tropic, or dual-tropic HIV-1 into target cells by blocking the interaction of the receptors with the HIV-1 gp120/CD4 complex	PubMed
	env	Gelsolin overexpression impairs HIV-1 gp120-induced cortical F-actin reorganization and capping and gp120-mediated CD4-CCR5 and CD4-CXCR4 redistribution in permissive lymphocytes	PubMed
	env	HIV-1 gp120-induced dephosphorylation of KV2.1 and re-localization of KV2.1 on the soma and proximal dendrites results in disruption of the clustered KV2.1 via activation of CCR5/CXCR4 co-receptors or SDF-1 alpha treatment	PubMed
	env	Stimulating CXCR4 with HIV-1 envelope glycoprotein 120 induces macropinocytosis, which may have implications for the internalization of HIV-1	PubMed
	env	Amino acid variants at positions 261 and 263 within the gp41-interactive region of gp120 and a variant at position 326 within the gp120 V3 loop are associated with efficient CXCR4-mediated monocyte-derived macrophages (MDM) entry	PubMed
	env	The interaction of HIV-1 gp120 with CXCR4 is inhibited by neutralizing monoclonal antibodies that prevent the interaction of gp120 with CD4 and by antibodies specific for the gp120 V2 and V3 loops	PubMed
	env	HIV-1 gp120-induced synapse loss requires sequential activation of CXCR4, IL-1beta receptor, and NMDA receptor	PubMed
	env	HIV-1 gp120-mediated CXCR4 activation induces upregulation of neuronal nicotinic receptor, alpha-7	PubMed
	env	HIV-1 gp120 binding to CXCR4 results in cellular proliferation in osteoblast-like cells	PubMed
	env	HIV-1 X4-tropic gp120 upregulates alpha-SMA (ACTA2) and collagen I alpha 1 expression via the ERK1/2 pathway in a CXCR4-dependent manner in activated human hepatic stellate cells	PubMed
	env	Deaminases APOBEC3F- and APOBEC3G-mediated G-to-A mutations in the V3 region of HIV-1 gp120 lead to the co-receptor switch from R5 to X4 strains	PubMed
	env	Adsorption of multivalent gp120-containing HIV-1 virion particles into CD4+ T lymphocytes results in segregation of CD4 and CXCR4 into distinct lipid micro domains	PubMed
	env	Binding of HIV-1 gp120 to CXCR4 induces cell apoptosis through decreased binding of 14-3-3tau to the pro-apoptotic molecule, Bad	PubMed
	env	HIV-1 gp120-induced PI3-kinase activity and calcium mobilization are inhibited by pertussis toxin and blocking antibodies directed against CCR5 and CXCR4, suggesting that this signaling is mediated through these chemokine receptors	PubMed
	env	HIV-1 gp120 and gp41-mediated virus-cell fusion is more dependent on viral core maturation for viruses bearing CXCR4-tropic gp120 than for those bearing CCR5-tropic gp120	PubMed
	env	HIV-1 gp120 promotes filamin binding to both CD4 and CXCR4	PubMed
	env	HIV-1 gp120-induced Ca(2+) fluxing is CD4 dependent and coreceptor specific, and is mediated by the CCR5 and CXCR4 coreceptors	PubMed
	env	HIV-1 and gp120 can induce breast cancer cell apoptosis through gp120-CXCR4 interaction without a CD4-induced conformational change of gp120	PubMed
	env	CCL2 upregulates CXCR4 on resting CD4(+) T cells in a CCR2-dependent mechanism, increases the ability of these cells to be chemoattracted to CXCR4 using gp120 and renders them more permissive to X4-tropic HIV-1 infection	PubMed
	env	Association and clustering of CD4-CXCR4 induced by HIV-1 gp120 requires moesin-mediated anchoring of actin in the plasma membrane	PubMed
	env	The presence of HIV-1 envelope glycoprotein (gp120) in the rat preoptic anterior hypothalamus provokes fever via interaction CXCR4 pathway	PubMed
	env	IgE-FcepsilonRI coaggregation mediated by HIV-1 gp120 accelerates maximal CXCR4 expression and susceptibility to X4 virus by progenitor mast cells (prMCs)	PubMed
	env	HIV-1 gp120 from a T-cell-tropic virus causes CD4-dependent antagonism of CXCR4 response to SDF-1alpha, whereas gp120 from macrophage-tropic viruses causes CD4-dependent antagonism of CCR5 response to MIP-1alpha	PubMed
	env	HIV-1 gp120-induced neuronal cell death involves p38 mitogen-activated protein kinase; both HIV-1 coreceptors, CCR5 and CXCR4, can mediate HIV-1 gp120-induced neurotoxicity	PubMed
	env	Induction of apoptosis in cell cultures through binding of HIV-1 gp120 or gp160 to CXCR4 involves protein kinase C, basic fibroblast growth factor, caspase-3, and the pro-apoptotic molecule Bax	PubMed
	env	CCR5 and CXCR4 coreceptor engagement by HIV-1 gp120 in primary macrophages activates 2 members of the mitogen-activated protein kinase (MAPK) superfamily, c-Jun amino-terminal kinase and p38 MAPK	PubMed
	env	N-glycosylation at N11 of CXCR4 inhibits the binding of CXCR4 to CXCR4- and CCR5-tropic HIV-1 gp120	PubMed
	env	HIV-1 gp120 binding to CXCR4 induces NADPH oxidase-mediated production of superoxide radicals in neurons, which is involved in the activation of neutral sphingomyelinase	PubMed
	env	Stimulation of neurons with HIV-1 gp120 or the endogenous CXCR4 agonist, SDF-1 alpha, results in inducing p53 activity and expression of the p53 pro-apoptotic target Apaf-1	PubMed
	env	In T cell lines and peripheral blood mononuclear cells, HIV-1 gp120-induced apoptosis is regulated by CD45 through the induction of CD45 association with the HIV-1 coreceptor CXCR4	PubMed
	env	Raji-DC-SIGN cells preferentially enhance CXCR4 usage of dual-tropic HIV-1 with higher V3 charges in gp120	PubMed
	env	Transcription factor E2F1 is necessary for neuronal cell death induced by HIV-1 gp120 via neuronal CXCR4	PubMed
	env	An HIV-1 gp120 mutant with a deletion of amino acids E61 to S85 in its C1 region exhibits a strong interaction with CXCR4, although CD4 binding is undetectable	PubMed
	env	HIV-1 gp120 inhibits monocyte response to chemokines and activation by chemoattractants by interacting with CD4 and downregulating the cell surface receptor CXCR4	PubMed
	env	Conversion of Asp-187 to the neutral amino acid Val in the second extracellular loop of CXCR4, which is a coreceptor for dual-tropic and T-tropic strains of HIV-1, unmasked activity with M-tropic gp120 in fusion and infection experiments	PubMed
	env	The death rate of CD8+ T cells by apoptosis, which is induced by HIV-1 gp120 from CXCR4-tropic HIV strains or by the ligand of the chemokine receptor CXCR4 (SDF-1), is increased markedly during HIV infection of peripheral blood mononuclear cells	PubMed
	env	A gp120 protein derived from the HIV-1 IIIB strain utilizes CXCR4 as a primary receptor in the absence of CD4 on T- and B- lymphoid cell lines	PubMed
	env	A synthetic peptide corresponding to amino acid residues 414-434 of HIV-1 gp120 downregulates the expression and function of chemokine receptors CCR5 and CXCR4 in monocytes by activating the 7-transmembrane G-protein-coupled receptor FPRL1/LXA4R	PubMed
	env	HIV-1 gp120, but not SDF-1alpha, induces rapid tyrosine phosphorylation of src-like kinase p56lck in CD4+ T cells, whereas both gp120 and SDF-1alpha cause phosphorylation of CXCR4	PubMed
	env	Cathepsin D may induce conformational modification of HIV-1 gp120, allowing direct interaction with the CXCR4 coreceptor and enhancing HIV-1 infectivity and entry into cells	PubMed
	env	HIV-1 gp120 from both CCR5- and CXCR4-tropic HIV-1 strains opens calcium-activated potassium (K(Ca)), chloride, and calcium-permeant nonselective cation channels in macrophages; these signals are mediated by CCR5 and CXCR4	PubMed
	env	T-tropic HIV-1 gp120s are capable of priming phorbol ester (PMA) induced co-down-modulation of gp120 complexes with tailless CD4 by interacting with CXCR4, whereas M-tropic gp120 are not, even in the presence of CCR5	PubMed
	env	The cis expression of DC-SIGN on multiple lymphoid cell lines enables more efficient entry and replication of CXCR4-tropic and CCR5/CXCR4 dual-tropic HIV-1 through its binding to the HIV-1 gp120-CD4-CXCR4 complex	PubMed
	env	SDF-1alpha and HIV-1 gp120 induce the appearance of pseudopodia in which CD26 and CXCR4 colocalize	PubMed
	env	Production of the C-X-C chemokine growth-regulated oncogene alpha (GRO-alpha) is markedly stimulated by CXCR4-tropic HIV-1; HIV-1 gp120 engagement of CXCR4 initiates the stimulation of GRO-alpha production, which is blocked by antibodies to CXCR4	PubMed
	env	Syncytial apoptosis mediated by the fusion of cells expressing HIV-1 gp120 with cells expressing the CD4/CXCR4 receptor/coreceptor complex causes phosphorylation of p53 on serine 15 and Bax upregulation	PubMed
	env	A CD4-independent, CXCR4-tropic HIV-1 isolate directly interacts with CXCR4 through its mutated gp120, and downregulates CXCR4 membrane expression in CD4-positive or -negative cells chronically infected with the strain	PubMed
	env	The proteasome inhibitors, lactacystin and epoxomicin, inhibit SDF-1alpha and gp120 protein-induced down-modulation of CXCR4 in Jurkat cells	PubMed
	env	Kappa-opioid receptor (KOR) agonist treatment of CD4(+) lymphocytes inhibits HIV-1 envelope gp120/41-mediated membrane fusion via downregulation of CXCR4	PubMed
	env	HIV-1 gp120 interactions with CXCR4 and CCR5 lead to the cross-desensitization of CCR6 and CCR7; this gp120-induced inhibition is strictly dependent on CXCR4 or CCR5 and lipid rafts but not on CD4 or V(H)3-expressing BCR	PubMed
	env	Brain-derived neurotrophic factor (BDNF) prevents HIV-1 gp120-mediated neuronal cell death by reducing the levels of CXC chemokine receptor-4 (CXCR4), a receptor that mediates HIV-1 gp120-induced apoptosis	PubMed
	env	Binding of HIV-1 gp120 to SupT1 lymphoblastoid cells triggers association between CXCR4 and ganglioside GM3	PubMed
	env	Engagement of the CCR5 and CXCR4 receptors by HIV-1 gp120 induces tyrosine phosphorylation of the protein tyrosine kinase Pyk2	PubMed
	env	The first (residues 1-39) and third (residues 176-202) extracellular domains of human CXCR4 are required for the functional interaction with HIV-1 gp120; HIV-1 strains have different requirements for their interaction with CXCR4	PubMed
Envelope surface glycoprotein gp160, precursor	env	HIV-1 envelope protein gp140 oligomers enter cells by binding to the chemokine receptor CXCR4	PubMed
	env	HIV-1 Env co-localizes with CXCR4 and downregulates the coreceptor in HIV-1 infected human cells	PubMed
Envelope transmembrane glycoprotein gp41	env	SMS2, but not SMS1, is involved in enhancement of HIV-1 gp120/gp41-mediated membrane fusion through CD4 receptor and CCR5/CXCR4 coreceptors	PubMed
	env	HIV-1 gp120 and gp41 form a transitional complex with the CD4 receptor and CCR5/CXCR4 coreceptors during virus-cell and cell-cell membrane fusion	PubMed
	env	The engagement of gp120 by CXCR4 in the HIV-1 Env-mediated fusion process results in a quick HIV-1 gp41 six-helix bundle formation	PubMed
	env	Sequences in the gp41 transmembrane (TM) can modulate coreceptor specificity and that Env sequences other than that of V3 may facilitate efficient CXCR4-mediated entry	PubMed
	env	The interactions between HIV-1 gp120/41, CD4 receptor, and CXCR4 result in cell-virus and cell-cell membrane fusion	PubMed
	env	Peptide P5 (residues 628-683), comprising the entire membrane proximal region of HIV-1 gp41 and its calcium-binding site, inhibits HIV-1 envelope mediated cell-cell fusion and infection of PBMCs by both X4- and R5-tropic HIV-1 strains	PubMed
Nef	nef	HIV-1 NL4-3 Nef downregulates CXCR4; downregulation is dependent on Nef amino acids 66-77, termed the 'secretion modification region' (SMR; 66-70aa)	PubMed
	nef	HIV-1 Nef downregulates the second major HIV-1 coreceptor, CXCR4, from the surface of HIV-infected primary CD4 T lymphocytes with efficiencies comparable to the natural CXCR4 ligand, stromal cell-derived factor-1 alpha	PubMed
	nef	HIV-1 Nef expression from unintegrated HIV-1 DNA downregulates the surface levels of CD4, CCR5, and CXCR4 on T-lymphocytes and monocytes	PubMed
	nef	HIV-1 Nef co-localizes with CXCR4, AIP4, NEDD4, CD63/LAMP-1-positive vesicles, and HRS/VPS27-positive ESCRT-0 structures	PubMed
	nef	The Lys residues (K327/331/333) in the C-terminal tail of CXCR4 and the catalytic Cys830 in the HECT domain of AIP4 are critically required for HIV-1 Nef-mediated downregulation of CXCR4	PubMed
	nef	HIV-1 Nef dramatically enhances the binding of AIP4 with CXCR4 and alanine substitutions at positions Q297 and N329 of AIP4 eliminate this binding	PubMed
	nef	HIV-1 Nef-mediated CXCR4 downregulation is dependent on ubiquitinylation, which is mediated by the E3 ubiquitin ligase AIP4	PubMed
	nef	Specific sequences spanning amino-acids 50 to 60 and 170 to 180 in the HIV-1 Nef protein appear to be necessary for Nef-induced apoptosis as well as for physical interaction with CXCR4 receptors	PubMed
	nef	The inhibition of T-cell migration of HIV-1 Nef expressing cells by CD3 stimulation results from the inhibition of surface expression of CXCR4	PubMed
	nef	HIV-1 Nef significantly upregulates the expression of CXCR4 on the Caco-2 cell surface	PubMed
	nef	The HIV-1 Nef highly conserved valine-glycine-phenylalanine amino acid triplet (VGF) motif, which links the acidic cluster and the proline-rich motif, is important for downregulation of CXCR4 and MHC-I	PubMed
	nef	Disruption of the proline-rich region of HIV-1 Nef inhibits T-cell migration to SDF-1 alpha, suggesting Nef occupies a position in the CXCR4-mediated signaling pathway that is upstream of an SH3-dependent pathway	PubMed
	nef	An intracellular signaling pathway mediated by the binding of SDF-1alpha and CXCR4 is inhibited by Nef in both Jurkat T cells and primary peripheral CD4+ T lymphocytes	PubMed
	nef	HIV-1 Nef-induced increase in monocyte migration may be caused through CXCR4 function	PubMed
	nef	The interaction of HIV-1 Nef with the cell surface receptor CXCR4 induces apoptosis in CD4+ T cells, an effect that can be inhibited with CXCR4 antibodies, as well as the endogenous CXCR4 ligand SDF-1alpha	PubMed
Pr55(Gag)	gag	HIV-1 Gag co-localizes with CXCR4 in HIV-1 infected CD4 + T cells	PubMed
	gag	Expression of HIV-1 Gag attenuates SDF-1-mediated downregulation of CXCR4. The effect of Gag is dependent on a TSG101 interacting motif within the C-terminal p6 region of Gag	PubMed
Rev	rev	Rev(34-50) peptide with AAAAC at the C-terminus inhibits HIV-1 replication by antagonism of Rev and the CXCR4 co-receptor	PubMed
Tat	tat	HIV-1 Tat upregulates CXCR4 expression on lymphocytes, monocytes/macrophages and erythroid cells, indicating a role for Tat in HIV-1 pathogenesis and in promoting the infectivity of HIV-1	PubMed
	tat	HIV-1 Tat-mediated inhibition of autophagy in bystander macrophages/monocytic cells requires CXCR4, VEGFR1, and beta-integrins	PubMed
	tat	HIV-1 Tat increases CXCL12-induced internalization of CXCR4, and the Tat-mediated CXCR4 internalization requires activity of protein kinase C (zeta)	PubMed
	tat	HIV-1 Tat binds to CXCR4, competes with the natural ligand of CXCR4, SDF-1alpha, and selectively inhibits the entry and replication of X4-tropic HIV-1 in peripheral blood mononuclear cells (PBMCs), indicating a role for Tat in selecting against X4 virus	PubMed
	tat	HIV-1 Tat can inhibit CXCR4-mediated functions by interfering with the chemotactic activity of SDF-1/CXCL12, an effect mediated by Tat amino acids 25-31	PubMed
Vpu	vpu	HIV-1 Vpu downregulates the cell surface expression of chemokine (C-X-C motif) receptor 4 (CXCR4, CD184)	PubMed

Go to the HIV-1, Human Interaction Database

Interactions

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Products	Interactant	Other Gene	Complex	Source	Pubs	Description

General gene information

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Markers

CXCR4 (e-PCR)
- UniSTS:480008

RH17365 (e-PCR)
- UniSTS:9776

PMC109434P1 (e-PCR)
- UniSTS:270163

PMC109444P3 (e-PCR)
- UniSTS:270168

PMC109895P1 (e-PCR)
- UniSTS:270179

PMC110622P1 (e-PCR)
- UniSTS:270191

SHGC-31461 (e-PCR)
- UniSTS:80512

RH78321 (e-PCR)
- UniSTS:35222

CXCR4_564 (e-PCR)
- UniSTS:277147

PMC112647P1 (e-PCR)
- UniSTS:270237

Cxcr4 (e-PCR), detects polymorphism
- UniSTS:528302

PMC149544P1 (e-PCR)
- UniSTS:271047

Gene Ontology Provided by GOA

Function	Evidence Code	Pubs
enables C-C chemokine binding	IBA Inferred from Biological aspect of Ancestor more info
enables C-C chemokine binding	IPI Inferred from Physical Interaction more info	PubMed
enables C-C chemokine receptor activity	IBA Inferred from Biological aspect of Ancestor more info
enables C-X-C chemokine receptor activity	NAS Non-traceable Author Statement more info	PubMed
enables C-X-C motif chemokine 12 receptor activity	IDA Inferred from Direct Assay more info	PubMed
enables G protein-coupled receptor activity	TAS Traceable Author Statement more info	PubMed
enables actin binding	IDA Inferred from Direct Assay more info	PubMed
enables coreceptor activity	TAS Traceable Author Statement more info	PubMed
enables myosin light chain binding	IDA Inferred from Direct Assay more info	PubMed
enables protein binding	IPI Inferred from Physical Interaction more info	PubMed
enables small molecule binding	IEA Inferred from Electronic Annotation more info
enables ubiquitin binding	IDA Inferred from Direct Assay more info	PubMed
enables ubiquitin protein ligase binding	IPI Inferred from Physical Interaction more info	PubMed
enables virus receptor activity	IEA Inferred from Electronic Annotation more info

Process	Evidence Code	Pubs
involved_in CXCL12-activated CXCR4 signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in CXCL12-activated CXCR4 signaling pathway	IGI Inferred from Genetic Interaction more info	PubMed
involved_in CXCL12-activated CXCR4 signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in G protein-coupled receptor signaling pathway	IDA Inferred from Direct Assay more info	PubMed
involved_in apoptotic process	TAS Traceable Author Statement more info	PubMed
involved_in brain development	IBA Inferred from Biological aspect of Ancestor more info
involved_in calcium-mediated signaling	IBA Inferred from Biological aspect of Ancestor more info
acts_upstream_of_or_within calcium-mediated signaling	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in cardiac muscle contraction	IEA Inferred from Electronic Annotation more info
involved_in cell chemotaxis	IBA Inferred from Biological aspect of Ancestor more info
involved_in cellular response to cytokine stimulus	IDA Inferred from Direct Assay more info	PubMed
involved_in cellular response to xenobiotic stimulus	IEA Inferred from Electronic Annotation more info
involved_in dendritic cell chemotaxis	TAS Traceable Author Statement more info	PubMed
involved_in detection of mechanical stimulus involved in sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in detection of temperature stimulus involved in sensory perception of pain	IEA Inferred from Electronic Annotation more info
involved_in endothelial cell differentiation	IEA Inferred from Electronic Annotation more info
involved_in endothelial tube morphogenesis	IEA Inferred from Electronic Annotation more info
involved_in epithelial cell development	IEA Inferred from Electronic Annotation more info
involved_in immune response	IBA Inferred from Biological aspect of Ancestor more info
involved_in inflammatory response	TAS Traceable Author Statement more info	PubMed
involved_in myelin maintenance	ISS Inferred from Sequence or Structural Similarity more info
involved_in neurogenesis	IBA Inferred from Biological aspect of Ancestor more info
involved_in neuron migration	IEA Inferred from Electronic Annotation more info
involved_in neuron recognition	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cell migration	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of chemotaxis	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of cold-induced thermogenesis	ISS Inferred from Sequence or Structural Similarity more info	PubMed
involved_in positive regulation of cytosolic calcium ion concentration	IBA Inferred from Biological aspect of Ancestor more info
involved_in positive regulation of dendrite extension	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of macrophage migration inhibitory factor signaling pathway	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in positive regulation of mesenchymal stem cell migration	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of oligodendrocyte differentiation	ISS Inferred from Sequence or Structural Similarity more info
involved_in positive regulation of vascular wound healing	IEA Inferred from Electronic Annotation more info
involved_in positive regulation of vasculature development	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of calcium ion transport	IEA Inferred from Electronic Annotation more info
involved_in regulation of cell adhesion	IDA Inferred from Direct Assay more info	PubMed
involved_in regulation of chemotaxis	IMP Inferred from Mutant Phenotype more info	PubMed
involved_in regulation of programmed cell death	IEA Inferred from Electronic Annotation more info
involved_in regulation of viral process	IEA Inferred from Electronic Annotation more info
involved_in response to activity	IEA Inferred from Electronic Annotation more info
involved_in response to hypoxia	IEP Inferred from Expression Pattern more info	PubMed
involved_in response to tacrolimus	IEA Inferred from Electronic Annotation more info
involved_in response to ultrasound	IEA Inferred from Electronic Annotation more info
involved_in response to virus	TAS Traceable Author Statement more info	PubMed
involved_in symbiont entry into host cell	IEA Inferred from Electronic Annotation more info
involved_in telencephalon cell migration	IEA Inferred from Electronic Annotation more info

Component	Evidence Code	Pubs
located_in anchoring junction	IEA Inferred from Electronic Annotation more info
located_in cell leading edge	IDA Inferred from Direct Assay more info	PubMed
located_in cell surface	IDA Inferred from Direct Assay more info	PubMed
located_in cytoplasm	TAS Traceable Author Statement more info	PubMed
located_in cytoplasmic vesicle	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with early endosome	IDA Inferred from Direct Assay more info	PubMed
located_in early endosome	IDA Inferred from Direct Assay more info	PubMed
is_active_in external side of plasma membrane	IBA Inferred from Biological aspect of Ancestor more info
located_in extracellular exosome	HDA more info	PubMed
located_in late endosome	IDA Inferred from Direct Assay more info	PubMed
colocalizes_with lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in lysosome	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	IDA Inferred from Direct Assay more info	PubMed
located_in plasma membrane	TAS Traceable Author Statement more info
part_of protein-containing complex	IDA Inferred from Direct Assay more info	PubMed
part_of protein-containing complex	IMP Inferred from Mutant Phenotype more info	PubMed

General protein information

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Preferred Names: C-X-C chemokine receptor type 4

Names: CD184 antigen; LPS-associated protein 3; SDF-1 receptor; chemokine (C-X-C motif) receptor 4; fusin; leukocyte-derived seven transmembrane domain receptor; lipopolysaccharide-associated protein 3; neuropeptide Y receptor Y3; neuropeptide Y3 receptor; seven transmembrane helix receptor; seven-transmembrane-segment receptor, spleen; stromal cell-derived factor 1 receptor

NCBI Reference Sequences (RefSeq)

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NEW Try the new Transcript table

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_011587.1 RefSeqGene

Range

5001..8807

Download

GenBank, FASTA, Sequence Viewer (Graphics), LRG_51

mRNA and Protein(s)

NM_001008540.2 → NP_001008540.1 C-X-C chemokine receptor type 4 isoform a

See identical proteins and their annotated locations for NP_001008540.1

Status: REVIEWED

Description

Transcript Variant: This variant (1), also known as CXCR4-Lo, differs in the 5' UTR and coding sequence compared to variant 3. The resulting isoform (a) has a shorter and distinct N-terminus compared to isoform c.

Source sequence(s)

AF147204

Consensus CDS

CCDS33295.1

UniProtKB/Swiss-Prot

P61073

Related

ENSP00000386884.1, ENST00000409817.1

Conserved Domains (2) summary

pfam12109
Location:10 → 42

CXCR4_N; CXCR4 Chemokine receptor N terminal

cd15179
Location:43 → 317

7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001348056.2 → NP_001334985.1 C-X-C chemokine receptor type 4 isoform c

Status: REVIEWED

Description

Transcript Variant: This variant (3) encodes the longest isoform (c).

Source sequence(s)

AF147204, DA940702, KU245646

UniProtKB/TrEMBL

A0A0U3GXA9

Conserved Domains (2) summary

pfam12109
Location:77 → 109

CXCR4_N; CXCR4 Chemokine receptor N terminal

cd15179
Location:110 → 384

7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001348059.2 → NP_001334988.1 C-X-C chemokine receptor type 4 isoform d

Status: REVIEWED

Description

Transcript Variant: This variant (4) lacks an alternate in-frame exon compared to variant 3. The resulting isoform (d) has the same N- and C-termini but is shorter compared to isoform c.

Source sequence(s)

AF147204, DA940702, KU245647

UniProtKB/TrEMBL

A0A0U3FJG0

Conserved Domains (2) summary

pfam12109
Location:39 → 71

CXCR4_N; CXCR4 Chemokine receptor N terminal

cd15179
Location:72 → 346

7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_001348060.2 → NP_001334989.1 C-X-C chemokine receptor type 4 isoform e

Status: REVIEWED

Description

Transcript Variant: This variant (5) differs in the 5' UTR and coding sequence compared to variant 3. The resulting isoform (e) is shorter at the N-terminus compared to isoform c.

Source sequence(s)

AC068492, AF147204, AK309885

Consensus CDS

CCDS92871.1

UniProtKB/TrEMBL

A0A8Q3WLL1

Related

ENSP00000512430.1, ENST00000466288.1

Conserved Domains (2) summary

pfam12109
Location:2 → 23

CXCR4_N; CXCR4 Chemokine receptor N terminal

cd15179
Location:24 → 298

7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors
NM_003467.3 → NP_003458.1 C-X-C chemokine receptor type 4 isoform b

See identical proteins and their annotated locations for NP_003458.1

Status: REVIEWED

Description

Transcript Variant: This variant (2) lacks an alternate in-frame exon compared to variant 3. The resulting isoform (b) has the same N- and C-termini but is shorter compared to isoform c.

Source sequence(s)

AF147204, DA940702

Consensus CDS

CCDS46420.1

UniProtKB/Swiss-Prot

B2R5N0, O60835, P30991, P56438, P61073, Q53S69, Q9BXA0, Q9UKN2

Related

ENSP00000241393.3, ENST00000241393.4

Conserved Domains (2) summary

pfam12109
Location:6 → 38

CXCR4_N; CXCR4 Chemokine receptor N terminal

cd15179
Location:39 → 313

7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors