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

    Gene ID: 7852, updated on 19-May-2013
    Official Symbol
    CXCR4provided by HGNC
    Official Full Name
    chemokine (C-X-C motif) receptor 4provided by HGNC
    Primary source
    HGNC:2561
    See related
    Ensembl:ENSG00000121966; HPRD:01217; MIM:162643; Vega:OTTHUMG00000153583
    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; LESTR; NPY3R; NPYRL; HSY3RR; NPYY3R; 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]
    Location :
    2q21
    Sequence :
    Chromosome: 2; NC_000002.11 (136871919..136875725, complement)
    See CXCR4 in Epigenomics, MapViewer

    Chromosome 2 - NC_000002.11Genomic Context describing neighboring genes Neighboring gene mannosidase, endo-alpha-like pseudogene Neighboring gene aspartyl-tRNA synthetase Neighboring gene heterogeneous nuclear ribonucleoprotein K pseudogene 2 Neighboring gene ubiquitin B pseudogene 1

    Go to nucleotideGraphics FASTA GenBank

    Go to reference sequence details

    Related articles in PubMed

    1. CXCR4/CXCL12 mediate autocrine cell- cycle progression in NF1-associated malignant peripheral nerve sheath tumors. Mo W, et al. Cell, 2013 Feb 28. PMID 23434321.
    2. Epigenetic expansion of VHL-HIF signal output drives multiorgan metastasis in renal cancer. Vanharanta S, et al. Nat Med, 2013 Jan. PMID 23223005.
    3. Analysis by substituted cysteine scanning mutagenesis of the fourth transmembrane domain of the CXCR4 receptor in its inactive and active state. Boulais PE, et al. Biochem Pharmacol, 2013 Feb 15. PMID 23219524.
    4. Upregulating CXCR4 in human fetal mesenchymal stem cells enhances engraftment and bone mechanics in a mouse model of osteogenesis imperfecta. Jones GN, et al. Stem Cells Transl Med, 2012 Jan. PMID 23197643.
    5. CXCR4 stimulates macropinocytosis: implications for cellular uptake of arginine-rich cell-penetrating peptides and HIV. Tanaka G, et al. Chem Biol, 2012 Nov 21. PMID 23177198.

    See all (1034) citations in PubMed

    See citations in PubMed for homologs of this gene provided by HomoloGene

    GeneRIFs: Gene References Into Functions What's a GeneRIF?

    1. Levels of C-erbB-2, CXCR4 and ER-alpha in patients decreased after they received neo-adjuvant chemotherapy.
      Title: Decreased expression of C-erbB-2 and CXCR4 in breast cancer after primary chemotherapy.
    2. CXCR4 expression could be incorporated into the risk assessment of patients with acute myeloid leukemia.
      Title: The prognostic value of CXCR4 in acute myeloid leukemia.
    3. Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and impairs migration towards CXCL12
      Title: Dasatinib inhibits CXCR4 signaling in chronic lymphocytic leukaemia cells and impairs migration towards CXCL12.
    4. CXCR4 triggers macropinocytosis, which may have implications for the cellular uptake of oligoarginine cell-penetrating peptides and internalization of HIV.
      Title: CXCR4 stimulates macropinocytosis: implications for cellular uptake of arginine-rich cell-penetrating peptides and HIV.
    5. the role of the CXCL12-CXCR4 axis as a novel chemoattractant for LECs in promoting lymphangiogenesis, and support the potential application of combined targeting of both chemokines and lymphangiogenic factors in inhibiting lymphatic metastasis.
      Title: The CXCL12-CXCR4 chemokine pathway: a novel axis regulates lymphangiogenesis.
    6. In this review we describe the clinical significance of CXCR4 and its ligand, as well as the role of CXCR4 and its gene polymorphisms in disease susceptibility.
      Title: [Clinical relevance of chemokine receptor CXCR4].
    7. Study provides evidence that the CXCR4/CXCL12 axis is essential for Malignant peripheral nerve sheath tumors (MPNST) tumor progression. Specifically, the autocrine activation of CXCR4 by CXCL12 triggers intracellular PI3-kinase and beta-catenin signals to promote G1 to S phase transition in MPNST cells.
      Title: CXCR4/CXCL12 mediate autocrine cell- cycle progression in NF1-associated malignant peripheral nerve sheath tumors.
    8. hypoxia upregulates CXCR4 in gastric cancer cells in a HIF-1alpha-dependent manner, and upregulation of CXCR4 plays a role in cancer cell migration and invasion
      Title: Hypoxia induces CXCR4 expression and biological activity in gastric cancer cells through activation of hypoxia-inducible factor-1α.
    9. The positive correlation between HER2- and CXCR4-expression was validated in esophageal cancer patients.
      Title: Involvement of CXCR4 chemokine receptor in metastastic HER2-positive esophageal cancer.
    10. we provide additional evidence that the anti-apoptotic effect of stromal-derived factor-1 is mediated by interaction with CXCR4.
      Title: Role of the stromal-derived factor-1 (SDF-1)-CXCR4 axis in the interaction between hepatic stellate cells and cholangiocarcinoma.
    Submit: New GeneRIF Correction See all (686)

    Review eQTL and phenotype association data in this region using PheGenI

    Protein Gene Interaction Pubs
    Env, gp160, envelope glycoprotein 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 surface glycoprotein gp120 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 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 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 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 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 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 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 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 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 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 entry of T cell-tropic HIV-1 isolates is blocked by SDF-1 or CXCR4 antagonists, which bind to CXCR4 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 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 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 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 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 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 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 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 transmembrane glycoprotein gp41 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
    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
    Gag, Pr55 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
    Nef, p27 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 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 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 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
    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
    Rev, p19 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, p14 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
    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

    Go to the HIV-1, Human Protein Interaction Database

    Products Interactant Other Gene Complex Source Pubs Description
    NP_003458.1 NP_954637.1 CXCL12    BIND  PubMed CXCR4 interacts with SDF-1-alpha. This interaction was modeled on a demonstrated interaction between human CXCR4 and SDF-1-alpha from an unspecified species. 
    NP_003458.1     BIND  PubMed CXCR4 interacts with the CD4/HIV-1 gp120 complex. 
    P61073 P35626 ADRBK2    HPRD  PubMed  
    P61073 P32121 ARRB2    HPRD  PubMed  
    P61073 P51681 CCR5    HPRD  PubMed  
    P61073 P01730 CD4    HPRD  PubMed  
    P61073 P08311 CTSG    HPRD  PubMed  
    P61073 P48061 CXCL12    HPRD  PubMed  
    P61073 P61073 CXCR4    HPRD  PubMed  
    P61073 P27487 DPP4    HPRD  PubMed  
    P61073 P08246 ELANE    HPRD  PubMed  
    P61073 Q14344 GNA13    HPRD  PubMed  
    P61073 P63096 GNAI1    HPRD  PubMed  
    P61073 P11142 HSPA8    HPRD  PubMed  
    P61073 P23458 JAK1    HPRD  PubMed  
    P61073 O60674 JAK2    HPRD  PubMed  
    P61073 P52333 JAK3    HPRD  PubMed  
    P61073 P35579 MYH9    HPRD  PubMed  
    P61073 Q05397 PTK2    HPRD  PubMed  
    P61073 Q06124 PTPN11    HPRD  PubMed  
    P61073 P29350 PTPN6    HPRD  PubMed  
    P61073 P08575 PTPRC    HPRD  PubMed  
    P61073 P31431 SDC4    HPRD  PubMed  
    P61073 O15524 SOCS1    HPRD  PubMed  
    P61073 O14543 SOCS3    HPRD  PubMed  
    P61073 P42224 STAT1    HPRD  PubMed  
    P61073 P52630 STAT2    HPRD  PubMed  
    P61073 P40763 STAT3    HPRD  PubMed  
    P61073 P51692 STAT5B    HPRD  PubMed  
    P61073 P15498 VAV1    HPRD  PubMed  
    BioGRID:113607 BioGRID:106666 ADRBK2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113607 BioGRID:116973 ATP13A2    BioGRID  PubMed Two-hybrid 
    BioGRID:113607 BioGRID:107305 CAV1    BioGRID  PubMed Co-fractionation 
    BioGRID:113607 BioGRID:107639 CCR5    BioGRID  PubMed Reconstituted Complex 
    BioGRID:113607 BioGRID:107358 CD4    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113607 BioGRID:112288 CXCL12    BioGRID  PubMed Co-crystal Structure 
    BioGRID:113607 BioGRID:109352 HLA-C    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
    BioGRID:113607 BioGRID:123747 ITCH    BioGRID  PubMed Affinity Capture-Western; Co-fractionation; FRET; Reconstituted Complex 
    BioGRID:113607 BioGRID:109920 JAK2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113607 BioGRID:109921 JAK3    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113607 BioGRID:110690 MYBL2    BioGRID  PubMed Two-hybrid 
    BioGRID:113607 BioGRID:111719 PTK2    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113607 BioGRID:111745 PTPN11    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113607 BioGRID:111742 PTPN6    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113607 BioGRID:114488 SOCS3    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113607 BioGRID:112644 ST13    BioGRID  PubMed Affinity Capture-Western 
    BioGRID:113607 BioGRID:113722 STAM    BioGRID  PubMed Co-fractionation; Co-localization 
    BioGRID:113607 BioGRID:132223 SUMO4    BioGRID  PubMed Affinity Capture-MS 
    BioGRID:113607 BioGRID:113164 UBC    BioGRID  PubMed Affinity Capture-MS; Affinity Capture-Western 
    BioGRID:113607 BioGRID:114551 USP14    BioGRID  PubMed Affinity Capture-Western; Reconstituted Complex 
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      Ephrin B reverse signaling, organism-specific biosystem
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    • G alpha (i) signalling events, organism-specific biosystem (from REACTOME)
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    • GPCR downstream signaling, organism-specific biosystem (from REACTOME)
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    • 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.cmbi.kun.nl/7tm/. The groupings are based on the GPCR phylogenetic tree available from the GPCRDB and the training sets used ...
    • HIF-1-alpha transcription factor network, organism-specific biosystem (from Pathway Interaction Database)
      HIF-1-alpha transcription factor network, organism-specific biosystem
      HIF-1-alpha transcription factor network
    • HIV Infection, organism-specific biosystem (from REACTOME)
      HIV Infection, organism-specific biosystemThe global pandemic of Human Immunodeficiency Virus (HIV) infection has resulted in tens of millions of people infected by the virus and millions more affected. UNAIDS estimates around 40 million ...
    • HIV Life Cycle, organism-specific biosystem (from REACTOME)
      HIV Life Cycle, organism-specific biosystemThe life cycle of HIV-1 is divided into early and late phases, shown schematically in the figure. In the early phase, an HIV-1 virion binds to receptors and co-receptors on the human host cell surfac...
    • IL-4 signaling Pathway, organism-specific biosystem (from WikiPathways)
      IL-4 signaling Pathway, organism-specific biosystemInterleukin-4 belongs to the IL-2 family of cytokines, which includes IL-2, IL-7, IL-9, IL-15 and IL-21. It signals through 2 different receptor complexes; Receptor complex 1 comprises of IL-4 recept...
    • Intestinal immune network for IgA production, organism-specific biosystem (from KEGG)
      Intestinal immune network for IgA production, organism-specific biosystemThe intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies tha...
    • Intestinal immune network for IgA production, conserved biosystem (from KEGG)
      Intestinal immune network for IgA production, conserved biosystemThe intestine is the largest lymphoid tissue in the body. One striking feature of intestinal immunity is its ability to generate great amounts of noninflammatory immunoglobulin A (IgA) antibodies tha...
    • Leukocyte transendothelial migration, organism-specific biosystem (from KEGG)
      Leukocyte transendothelial migration, organism-specific biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
    • Leukocyte transendothelial migration, conserved biosystem (from KEGG)
      Leukocyte transendothelial migration, conserved biosystemLeukocyte migaration from the blood into tissues is vital for immune surveillance and inflammation. During this diapedesis of leukocytes, the leukocytes bind to endothelial cell adhesion molecules (C...
    • 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.
    • S1P3 pathway, organism-specific biosystem (from Pathway Interaction Database)
      S1P3 pathway, organism-specific biosystem
      S1P3 pathway
    • 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...
    • Syndecan-4-mediated signaling events, organism-specific biosystem (from Pathway Interaction Database)
      Syndecan-4-mediated signaling events, organism-specific biosystem
      Syndecan-4-mediated signaling events

    Markers

    Genotypes

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    C-X-C chemokine binding IEA
    Inferred from Electronic Annotation
    more info
    		  
    C-X-C chemokine receptor activity NAS
    Non-traceable Author Statement
    more info
    		 PubMed 
    G-protein coupled receptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    actin binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    coreceptor activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    myosin light chain binding IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    protein binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    ubiquitin binding IDA
    Inferred from Direct Assay
    more info
    		  
    ubiquitin protein ligase binding IPI
    Inferred from Physical Interaction
    more info
    		 PubMed 
    Process Evidence Code Pubs
    G-protein coupled receptor signaling pathway IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    T cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    activation of MAPK activity TAS
    Traceable Author Statement
    more info
    		 PubMed 
    ameboidal cell migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    apoptotic process TAS
    Traceable Author Statement
    more info
    		 PubMed 
    brain development IEA
    Inferred from Electronic Annotation
    more info
    		  
    calcium-mediated signaling IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    dendritic cell chemotaxis TAS
    Traceable Author Statement
    more info
    		 PubMed 
    elevation of cytosolic calcium ion concentration IEA
    Inferred from Electronic Annotation
    more info
    		  
    entry into host cell TAS
    Traceable Author Statement
    more info
    		  
    germ cell development IEA
    Inferred from Electronic Annotation
    more info
    		  
    germ cell migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    inflammatory response TAS
    Traceable Author Statement
    more info
    		 PubMed 
    motor neuron axon guidance IEA
    Inferred from Electronic Annotation
    more info
    		  
    myelin maintenance ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    neural precursor cell proliferation IEA
    Inferred from Electronic Annotation
    more info
    		  
    neuron migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    neutrophil activation IEA
    Inferred from Electronic Annotation
    more info
    		  
    patterning of blood vessels IEA
    Inferred from Electronic Annotation
    more info
    		  
    positive regulation of oligodendrocyte differentiation ISS
    Inferred from Sequence or Structural Similarity
    more info
    		  
    regulation of cell migration IEA
    Inferred from Electronic Annotation
    more info
    		  
    regulation of chemotaxis IMP
    Inferred from Mutant Phenotype
    more info
    		 PubMed 
    response to hypoxia IEP
    Inferred from Expression Pattern
    more info
    		 PubMed 
    response to virus TAS
    Traceable Author Statement
    more info
    		 PubMed 
    viral reproduction TAS
    Traceable Author Statement
    more info
    		  
    viral reproductive process TAS
    Traceable Author Statement
    more info
    		  
    virus-host interaction IEA
    Inferred from Electronic Annotation
    more info
    		  
    Component Evidence Code Pubs
    cell leading edge IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cell surface IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytoplasm TAS
    Traceable Author Statement
    more info
    		 PubMed 
    cytoplasmic membrane-bounded vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    cytoplasmic vesicle IDA
    Inferred from Direct Assay
    more info
    		 PubMed 
    external side of plasma membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    growth cone IEA
    Inferred from Electronic Annotation
    more info
    		  
    integral to membrane IEA
    Inferred from Electronic Annotation
    more info
    		  
    plasma membrane TAS
    Traceable Author Statement
    more info
    		  
    Preferred Names
    C-X-C chemokine receptor type 4
    Names
    C-X-C chemokine receptor type 4
    fusin
    CXC-R4
    CXCR-4
    CD184 antigen
    SDF-1 receptor
    neuropeptide Y receptor Y3
    seven transmembrane helix receptor
    stromal cell-derived factor 1 receptor
    lipopolysaccharide-associated protein 3
    seven-transmembrane-segment receptor, spleen
    leukocyte-derived seven transmembrane domain receptor
    leukocyte-derived seven-transmembrane-domain receptor

    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_001008540.1 → NP_001008540.1  C-X-C chemokine receptor type 4 isoform a

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1), also known as CXCR4-Lo, represents the longer transcript and encodes the longer isoform (a).
      Source sequence(s)
      AF147204
      Consensus CDS
      CCDS33295.1
      UniProtKB/Swiss-Prot
      P61073
      Related
      ENSP00000386884, OTTHUMP00000204155, ENST00000409817, OTTHUMT00000331734
      Conserved Domains (2) summary
      pfam12109
      Location:10 – 42
      Blast Score: 183
      CXCR4_N; CXCR4 Chemokine receptor N terminal
      pfam00001
      Location:65 – 306
      Blast Score: 497
      7tm_1; 7 transmembrane receptor (rhodopsin family)

    2. NM_003467.2 → NP_003458.1  C-X-C chemokine receptor type 4 isoform b

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains a distinct 5' UTR and lacks an in-frame portion of the 5' coding region, compared to variant 1. The resulting isoform (b) has a shorter N-terminus when compared to isoform a.
      Source sequence(s)
      AC068492, AF147204, D10924
      Consensus CDS
      CCDS46420.1
      UniProtKB/Swiss-Prot
      P61073
      Related
      ENSP00000241393, OTTHUMP00000204154, ENST00000241393, OTTHUMT00000331732
      Conserved Domains (2) summary
      pfam12109
      Location:6 – 38
      Blast Score: 182
      CXCR4_N; CXCR4 Chemokine receptor N terminal
      pfam00001
      Location:61 – 302
      Blast Score: 500
      7tm_1; 7 transmembrane receptor (rhodopsin family)

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 104

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

    Reference GRCh37.p10 Primary Assembly

    Genomic

    1. NC_000002.11 Reference GRCh37.p10 Primary Assembly

      Range
      136871919..136875725, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate HuRef

    Genomic

    1. AC_000134.1 Alternate HuRef

      Range
      128864423..128868228, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.0

    Genomic

    1. NC_018913.1 Alternate CHM1_1.0

      Range
      136372174..136375979, complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)
    Nucleotide Protein
    Heading Accession and Version
    genomic AB065584.1 BAC05813.1
    genomic ABBA01028153.1 (44383..48188) None
    genomic AC068492.2 AAY24044.1
    genomic AF005058.1 AAB93982.1
    genomic AF052572.1 AAC34581.1
    genomic AJ224869.1 CAA12166.1
    genomic AMYH01011124.1 (363485..367290) None
    genomic AY728138.1 AAU05775.1
    genomic CH471058.2 EAX11616.1
    genomic HB976927.1 CBG22675.1
    genomic HC295432.1 CBJ06540.1
    genomic Y14739.1 CAA75034.1
    mRNA AF025375.1 AAB81970.1
    mRNA AF147204.1 AAF00130.1
    mRNA AF348491.1 AAK29630.1
    mRNA AK129916.1 None
    mRNA AK296674.1 BAG59271.1
    mRNA AK312244.1 BAG35177.1
    mRNA AY242129.1 AAO92296.1
    mRNA AY826773.1 AAV97584.1
    mRNA BC020968.2 AAH20968.1
    mRNA BT006660.1 AAP35306.1
    mRNA D10924.1 BAA01722.1
    mRNA L01639.1 AAA16594.1
    mRNA L06797.1 AAA03209.1
    mRNA M99293.1 AAA16617.1
    mRNA X71635.1 CAA50641.1
    other-genetic EU831811.1 ACE87329.1
    other-genetic EU831888.1 ACE86647.1
    other-genetic JF432649.1 ADZ15866.1
    Protein Accession Links
    GenPept Link UniProtKB Link
    P61073.1 GenPept UniProtKB/Swiss-Prot:P61073

    Additional Links

    • Epigenomics
    • MIM 162643
    • CXCR4base: Mutation registry for WHIM syndrome (warts, hypogammaglobulinemia, immunodeficiency, and myelokathexis) CXCR4base/
    • CXCR4 homepage - Mendelian genes CXCR4
    • Resource of Asian Primary Immunodeficiency Diseases (RAPID) AGID_49
    • UCSC UCSC
    • UniGene Hs.593413

    Gene LinkOut

    The following LinkOut resources are supplied by external providers. These providers are responsible for maintaining the links.

    Chemical Information
    Medical
    Molecular Biology Databases
    Research Materials
    Tools
    Miscellaneous

      Supplemental Content

      Table of contents

      Related information

      • Order cDNA clone
        Order cDNA clone
      • 3D structures
        3D structure of a gene
      • BioAssay
        Related PubChem BioAssays
      • BioAssay, by Protein Target
        BioAssay, by Protein Target
      • BioProjects
        BioProjects related to a gene
      • BioSystems
        BioSystems
      • Books
        Links between Entrez Gene and 'Books' are established if a GeneID is explicitly referenced in a book.
      • CCDS
        Links from Gene to CCDS are established if a gene encodes a protein sequence that is a member of a Consensus CDS (CCDS).
      • ClinVar
        Related medical variations
      • Conserved Domains
        Conserved Domain Database Links between Entrez Gene and Conserved Domain Database (CDD) are calculated from the domains annotated by the CDD group on Reference Sequence proteins.
      • dbVar
        Link from Gene to dbVar
      • Full text in PMC
        PMC links
      • Full text in PMC_nucleotide
        Full text in PubMedCentral identified from shared sequence links
      • Genome
        Genome records having the gene annotated on corresponding genomic reference sequence.
      • GEO Profiles
        Related GEO
      • HomoloGene
        Links between HomoloGene and Gene are provided by the HomoloGene group when a gene is included in a HomoloGene record.
      • Map Viewer
        These links are maintained by the Map Viewer group and are provided when a GeneID is annotated on a map for the same species.
      • MedGen
        Related information in MedGen
      • Nucleotide
        Link to related Nucleotide entry
      • OMIM
        Links between OMIM and Gene are calculated by Gene based on MIM numbers included in the summary and phenotype sections of the Gene record.
      • Probe
        Related Probe entry
      • Protein
        Link to related protein entry
      • PubChem Compound
        PubChem Compounds
      • PubChem Substance
        PubChem Substances
      • PubMed
        Links between Gene and PubMed are the result of the following: 1. Manual curation within NCBI. Part of the process of generating a REVIEWED RefSeq is an analysis of the current literature. Papers that are seminal in defining the gene, its sequence, and its function are added to the record at that time. Alert users point out gaps or errors in papers associated with a Gene record. These messages are reviewed and implemented as required. 2. Integration of information from other public databases. Gene integrates gene-citation from resources external to NCBI such as model organism-specific databases, Gene Ontology (GO), groups curating interactions, and sequence databases. The assumption in using these source is that they report citations specific to a gene in a known species. Gene does not process citations from OMIM automatically, because many of citations in OMIM refer to studies of genes in species other than human.
      • PubMed (GeneRIF)
        GeneRIF -- Gene Reference Into Function Staff of the Index Section in the National Library of Medicine review the current literature. When they find articles focused on the structure and function of a gene, they write a brief summary of the impact of the paper and make the connection between the citation (PubMed) and Gene. An interface exists for interested users to submit such data as well. http://www.ncbi.nlm.nih.gov/projects/GeneRIF/GeneRIFhelp.html
      • PubMed (OMIM)
        Links are provided when Gene has a link to a record in OMIM, and OMIM explicitly cites these publications in PubMed.
      • PubMed(nucleotide/PMC)
        Citations in PubMed identified from shared sequence and PMC links.
      • RefSeq Proteins
        Link to Protein RefSeqs
      • RefSeq RNAs
        Link to Nucleotide RefSeq RNAs
      • RefSeqGene
        Link to Nucleotide RefSeqGenes
      • SNP
        Related SNP records
      • SNP: GeneView
        SNPs linked from GeneView
      • SNP: Genotype
        Gene Genotype Report
      • SNP: VarView
        Related Clinical SNP
      • Taxonomy
        Link to related taxonomy entry
      • UniGene
        Links are provided between Gene and UniGene when both databases calculate links to the same mRNA record (gi).
      • UniSTS
        Related UniSTS records

      Links to other resources

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