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

Gene ID: 7852, updated on 8-Oct-2024

Summary

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
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Genomic context

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_000002.12Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC124906078 Neighboring gene aspartyl-tRNA synthetase 1 Neighboring gene MPRA-validated peak3879 silencer Neighboring gene NANOG hESC enhancer GRCh37_chr2:136718531-136719032 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11984 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16580 Neighboring gene DARS1 antisense RNA 1 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16581 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16582 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16583 Neighboring gene ReSE screen-validated silencer GRCh37_chr2:136846458-136846659 Neighboring gene NANOG hESC enhancer GRCh37_chr2:136850708-136851567 Neighboring gene ATAC-STARR-seq lymphoblastoid silent region 11985 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16584 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16585 Neighboring gene heterogeneous nuclear ribonucleoprotein K pseudogene 2 Neighboring gene CDK7 strongly-dependent group 2 enhancer GRCh37_chr2:136993310-136994509 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16586 Neighboring gene Sharpr-MPRA regulatory region 14513 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:137001246-137001746 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:137001747-137002247 Neighboring gene H3K4me1 hESC enhancer GRCh37_chr2:137039837-137040338 Neighboring gene ATAC-STARR-seq lymphoblastoid active region 16587 Neighboring gene ubiquitin B pseudogene 1

Genomic regions, transcripts, and products

Expression

  • Project title: HPA RNA-seq normal tissues 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

GeneRIFs: Gene References Into Functions

What's a GeneRIF?

Phenotypes

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
Meta-analysis of genome scans and replication identify CD6, IRF8 and TNFRSF1A as new multiple sclerosis susceptibility loci.
EBI GWAS Catalog

HIV-1 interactions

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

Pathways from PubChem

Interactions

Products Interactant Other Gene Complex Source Pubs Description

General gene information

Markers

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 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

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)

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

  1. NG_011587.1 RefSeqGene

    Range
    5001..8807
    Download
    GenBank, FASTA, Sequence Viewer (Graphics), LRG_51

mRNA and Protein(s)

  1. NM_001008540.2NP_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:1042
    CXCR4_N; CXCR4 Chemokine receptor N terminal
    cd15179
    Location:43317
    7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors
  2. NM_001348056.2NP_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:77109
    CXCR4_N; CXCR4 Chemokine receptor N terminal
    cd15179
    Location:110384
    7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors
  3. NM_001348059.2NP_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:3971
    CXCR4_N; CXCR4 Chemokine receptor N terminal
    cd15179
    Location:72346
    7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors
  4. NM_001348060.2NP_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:223
    CXCR4_N; CXCR4 Chemokine receptor N terminal
    cd15179
    Location:24298
    7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors
  5. NM_003467.3NP_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:638
    CXCR4_N; CXCR4 Chemokine receptor N terminal
    cd15179
    Location:39313
    7tmA_CXCR4; CXC chemokine receptor type 4, member of the class A family of seven-transmembrane G protein-coupled receptors

RefSeqs of Annotated Genomes: GCF_000001405.40-RS_2024_08

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

Reference GRCh38.p14 Primary Assembly

Genomic

  1. NC_000002.12 Reference GRCh38.p14 Primary Assembly

    Range
    136114349..136118149 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_047445802.1XP_047301758.1  C-X-C chemokine receptor type 4 isoform X1

Alternate T2T-CHM13v2.0

Genomic

  1. NC_060926.1 Alternate T2T-CHM13v2.0

    Range
    136558831..136562630 complement
    Download
    GenBank, FASTA, Sequence Viewer (Graphics)

mRNA and Protein(s)

  1. XM_054343837.1XP_054199812.1  C-X-C chemokine receptor type 4 isoform X1