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CXCR4 Gene

protein-coding   GIFtS: 76
GCID: GC02M136871

Chemokine (C-X-C Motif) Receptor 4

(Previous names: chemokine (C-X-C motif), receptor 4 (fusin))
  See CXCR4-related diseases
at  

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, 10fRNAdb, 12H-InvDB, 13NCBI, 14NONCODE, and/or 15RNAdb)
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Aliases
Chemokine (C-X-C Motif) Receptor 41 2     CD1842
Leukocyte-Derived Seven Transmembrane Domain Receptor2 3     HSY3RR2
Stromal Cell-Derived Factor 1 Receptor2 3     LAP32
FB222 3     NPYR2
HM892 3     NPYY3R2
LCR12 3     C-X-C Chemokine Receptor Type 42
LESTR2 3     fusin2
NPYRL2 3     Lipopolysaccharide-Associated Protein 32
CD184 Antigen2 3     Neuropeptide Y Receptor Y32
SDF-1 Receptor2 3     Seven Transmembrane Helix Receptor2
D2S201E2 5     Seven-Transmembrane-Segment Receptor, Spleen2
NPY3R2 5     CXC-R43
WHIM2 5     CXCR-43
Chemokine (C-X-C Motif), Receptor 4 (Fusin)1     Fusin3

External Ids:    HGNC: 25611   Entrez Gene: 78522   Ensembl: ENSG000001219667   OMIM: 1626435   UniProtKB: P610733   

Export aliases for CXCR4 gene to outside databases

Previous GC identifers: GC02M134526 GC02M135169 GC02M136894 GC02M137082 GC02M136705 GC02M136588 GC02M128864


(According to Entrez Gene, GeneCards, Tocris Bioscience, Wikipedia's Gene Wiki, PharmGKB,
UniProtKB/Swiss-Prot, and/or UniProtKB/TrEMBL)
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Entrez Gene summary for CXCR4 Gene:
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)

GeneCards Summary for CXCR4 Gene:
CXCR4 (chemokine (C-X-C motif) receptor 4) is a protein-coding gene. Diseases associated with CXCR4 include myelokathexis, isolated, and whim syndrome. GO annotations related to this gene include G-protein coupled receptor activity and ubiquitin protein ligase binding. An important paralog of this gene is CCR5.

UniProtKB/Swiss-Prot: CXCR4_HUMAN, P61073
Function: Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular
calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading
to enhanced intracellular calcium ions and reduced cellular cAMP levels. Involved in hematopoiesis and in cardiac
ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract,
probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in
cerebellar development. In the CNS, could mediate hippocampal-neuron survival. Acts as a coreceptor (CD4 being
the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes
Env-mediated fusion of the virus

summary for CXCR4 Gene:
Chemokines (chemotactic cytokines) belong to a family of chemoattractant molecules involved in the directed
migration of immune cells. Over fifty human chemokines have been identified that can be categorised into
four groups; CC, CXC, CX3C and C (XCL1 and XCL2); depending on the spacing of their first two cysteine
residues. Chemokines exert their effects by binding to G-protein-coupled chemokine receptors on the surface
of cells, predominantly leukocytes. Eighteen human chemokine receptors have been identified that are
classified according to the class of chemokines that they bind. The major function of chemokines is to
regulate leukocyte trafficking in hematopoiesis and in innate and adaptive immunity. Other functions include
angiogenic activity, apoptosis, T-cell differentiation and phagocyte activation. Inadvertent activation of
chemokine receptors leads to autoimmunity by inappropriately targeting self antigens for destruction by
cytotoxic T-cells and macrophages.

Gene Wiki entry for CXCR4 Gene


(According to GeneLoc and/or HGNC, and/or
Entrez Gene (NCBI build 37),
and/or miRBase,
Genomic Views according to UCSC (hg19) and Ensembl (release 75), Regulatory elements and Epigenetics data according to QIAGEN, and/or SwitchGear Genomics)
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RefSeq DNA sequence at NCBI GenBank:
NC_000002.11  NC_018913.2  NT_005403.18  
Regulatory elements:
   Regulatory transcription factor binding sites in the CXCR4 gene promoter:
         AP-2alpha isoform 3   AP-2alpha isoform 2   AP-2alpha   AP-2alphaA   
         Other transcription factors

SwitchGear Promoter luciferase reporter plasmids (see all 2): CXCR4 promoter sequence
   Search Chromatin IP Primers for CXCR4

Epigenetics:
DNA Methylation CpG Assay Predesigned for Pyrosequencing in human, mouse, rat CXCR4


Genomic Location:
Genomic View: UCSC Golden Path with GeneCards custom track

Entrez Gene cytogenetic band: 2q21   Ensembl cytogenetic band:  2q22.1   HGNC cytogenetic band: 2q21

CXCR4 Gene in genomic location: bands according to Ensembl, locations according to (and/or Entrez Gene and/or Ensembl if different)
CXCR4 gene location

GeneLoc information about chromosome 2         GeneLoc Exon Structure

GeneLoc location for GC02M136871:  view genomic region     (about GC identifiers)

Start:
136,871,919 bp from pter      End:
136,875,735 bp from pter
Size:
3,817 bases      Orientation:
minus strand

(According to 1UniProtKB, HORDE, 2neXtProt, Ensembl, and/or Reactome, Modification sites according to PhosphoSitePlus, Specific Peptides from DME, RefSeq according to NCBI, PDB rendering according to OCA and/or Proteopedia, Recombinant Proteins from EMD Millipore, R&D Systems, GenScript, Enzo Life Sciences, OriGene, Novus Biologicals, Sino Biological, ProSpec, Cloud-Clone Corp., eBioscience, and/or antibodies-online,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, Cloud-Clone Corp., eBioscience, and/or antibodies-online, Antibodies by EMD Millipore, R&D Systems, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, LSBio, Abcam, Cloud-Clone Corp, antibodies-online, and/or others.)
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UniProtKB/Swiss-Prot: CXCR4_HUMAN, P61073 (See protein sequence)
Recommended Name: C-X-C chemokine receptor type 4  
Size: 352 amino acids; 39746 Da
Subunit: Monomer. Can form dimers. Interacts with CD164. Interacts with HIV-1 surface protein gp120 and Tat.
Interacts with ARRB2; the interaction is dependent on the C-terminal phosphorylation of CXCR4 and allows
activation of MAPK1 and MAPK3. Interacts with ARRC; the interaction is dependent on the C-terminal
phosphorylation of CXCR4 and modulates calcium mobilization. Interacts (via the cytoplasmic C-terminal) with ITCH
(via the WW domains I and II); the interaction, enhanced by CXCL12, ubiquitinates CXCR4 and leads to its
degradation. Interacts with extracellular ubiquitin. Interacts with human cytomegalovirus/HHV-5 protein UL78.
Interacts with DBN1; this interaction is enhanced by antigenic stimulation
Miscellaneous: Plerixafor (AMD3100), an antagonist of CXCR4 activity, blocks HIV-1 entry, interaction with CXCL12
and subsequent CXCR4 signaling
Caution: Was originally (PubMed:8329116 and PubMed:8234909) thought to be a receptor for neuropeptide Y type 3
(NPY3R) (NPY3-R)
Sequence caution: Sequence=CAA12166.1; Type=Miscellaneous discrepancy; Note=Intron retention;
Selected PDB 3D structures from and Proteopedia for CXCR4 (see all 8):
2K03 (3D)        2K04 (3D)        2K05 (3D)        3ODU (3D)        3OE0 (3D)        3OE6 (3D)    
Secondary accessions: B2R5N0 O60835 P30991 P56438 Q53S69 Q9BXA0 Q9UKN2
Alternative splicing: 2 isoforms:  P61073-1, P30991-1   P61073-2, P30991-2   

Explore the universe of human proteins at neXtProt for CXCR4: NX_P61073

Explore proteomics data for CXCR4 at MOPED

Post-translational modifications: 

  • Phosphorylated on agonist stimulation. Rapidly phosphorylated on serine and threonine residues in the C-terminal.
    Phosphorylation at Ser-324 and Ser-325 leads to recruitment of ITCH, ubiquitination and protein degradation1
  • Ubiquitinated by ITCH at the cell membrane on agonist stimulation. The ubiquitin-dependent mechanism, endosomal
    sorting complex required for transport (ESCRT), then targets CXCR4 for lysosomal degradation. This process is
    dependent also on prior Ser-/Thr-phosphorylation in the C-terminal of CXCR4. Also binding of ARRB1 to STAM
    negatively regulates CXCR4 sorting to lysosomes though modulating ubiquitination of SFR5S1
  • Sulfation on Tyr-21 is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization. Tyr-7
    and Tyr-12 are sulfated in a sequential manner after Tyr-21 is almost fully sulfated, with the binding affinity
    for CXCL12/SDF-1alpha increasing with the number of sulfotyrosines present. Sulfotyrosines Tyr-7 and Tyr-12
    occupy clefts on opposing CXCL12 subunits, thus bridging the CXCL12 dimer interface and promoting CXCL12
    dimerization1
  • O- and N-glycosylated. Asn-11 is the principal site of N-glycosylation. There appears to be very little or no
    glycosylation on Asn-176. N-glycosylation masks coreceptor function in both X4 and R5 laboratory-adapted and
    primary HIV-1 strains through inhibiting interaction with their Env glycoproteins. The O-glycosylation
    chondroitin sulfate attachment does not affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity1
  • Ubiquitination2 at Lys310, Lys327
  • Glycosylation2 at Asn11, Ser18, Asn176
  • Modification sites at PhosphoSitePlus

  • See CXCR4 Protein Expression from SPIRE MOPED, PaxDB, and MaxQB

    REFSEQ proteins (2 alternative transcripts): 
    NP_001008540.1  NP_003458.1  

    ENSEMBL proteins: 
     ENSP00000386884   ENSP00000241393  
    Reactome Protein details: P61073

    CXCR4 Human Recombinant Protein Products:

    EMD Millipore Purified and/or Recombinant CXCR4 Protein
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    OriGene Protein Over-expression Lysate for CXCR4
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    Novus Biologicals CXCR4 Proteins
    Novus Biologicals CXCR4 Lysates
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    Browse Sino Biological Cell Lysates
    Browse ProSpec Recombinant Proteins
    Cloud-Clone Corp. Proteins for CXCR4

     
    Search eBioscience for Proteins for CXCR4 

     
    antibodies-online proteins for CXCR4 (7 products) 

     
    antibodies-online peptides for CXCR4

    CXCR4 Antibody Products:

    EMD Millipore Mono- and Polyclonal Antibodies for the study of CXCR4
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    Abcam antibodies for CXCR4
    Cloud-Clone Corp. Antibodies for CXCR4
    ThermoFisher Antibody for CXCR4
    LSBio Antibodies in human, mouse, rat for CXCR4
    antibodies-online antibodies for CXCR4 (254 products) 

    CXCR4 Assay Products:

    Browse Kits and Assays available from EMD Millipore
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    Browse Enzo Life Sciences for kits & assays
    Cloud-Clone Corp. ELISAs for CXCR4
    Cloud-Clone Corp. CLIAs for CXCR4
    Search eBioscience for ELISAs for CXCR4 
    antibodies-online kits for CXCR4 (23 products) 


    (According to HGNC, IUPHAR, InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
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    HGNC Gene Families:
    CD: CD molecules
    CXCR: GPCR / Class A : Chemokine receptors : C-X-C motif

    IUPHAR Guide to PHARMACOLOGY protein family classification: CXCR4
    Chemokine receptors

    5 InterPro protein domains:
     IPR022726 Chemokine_CXCR4_N_dom
     IPR017452 GPCR_Rhodpsn_7TM
     IPR001277 Chemokine_CXCR4
     IPR000355 Chemokine_rcpt
     IPR000276 GPCR_Rhodpsn

    Graphical View of Domain Structure for InterPro Entry P61073

    ProtoNet protein and cluster: P61073

    2 Blocks protein domains:
    IPB000355 Chemokine receptor signature
    IPB001277 LCR1 orphan receptor signature


    UniProtKB/Swiss-Prot: CXCR4_HUMAN, P61073
    Domain: The amino-terminus is critical for ligand binding. Residues in all four extracellular regions contribute
    to HIV-1 coreceptor activity
    Similarity: Belongs to the G-protein coupled receptor 1 family


    Find genes that share domains with CXCR4           About GenesLikeMe


    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013, inGenious Targeting Laboratory, genOway,
    transcription factor targeting from QIAGEN and/or HOMER, miRNA Gene Targets from miRTarBase, shRNA from OriGene, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, SwitchGear Genomics, Gene Editing from DNA2.0, Clones from OriGene, GenScript, Sino Biological, DNA2.0, Vector BioLabs and/or Addgene, Cell Lines from GenScript, ESI BIO, In Situ Hybridization Assays from Advanced Cell Diagnostics, Flow cytometry from eBioscience, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Molecular Function:

         UniProtKB/Swiss-Prot Summary: CXCR4_HUMAN, P61073
    Function: Receptor for the C-X-C chemokine CXCL12/SDF-1 that transduces a signal by increasing intracellular
    calcium ion levels and enhancing MAPK1/MAPK3 activation. Acts as a receptor for extracellular ubiquitin; leading
    to enhanced intracellular calcium ions and reduced cellular cAMP levels. Involved in hematopoiesis and in cardiac
    ventricular septum formation. Also plays an essential role in vascularization of the gastrointestinal tract,
    probably by regulating vascular branching and/or remodeling processes in endothelial cells. Involved in
    cerebellar development. In the CNS, could mediate hippocampal-neuron survival. Acts as a coreceptor (CD4 being
    the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes
    Env-mediated fusion of the virus

         Genatlas biochemistry entry for CXCR4:
    fusin,chemokine (CXC) motif,receptor 4,preferentially expressed on the more immature CD34+ hematopoietic stem
    cells,G protein coupled receptor superfamily,required for entry of T cell line-tropic strains HIV-1 into CD4
    cells,bovine locus coeruleus homolog

         Gene Ontology (GO): Selected molecular function terms (see all 10):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0001618virus receptor activity IEA--
    GO:0003779actin binding IDA12421915
    GO:0004930G-protein coupled receptor activity TAS8276799
    GO:0005515protein binding IPI10644702
    GO:0015026coreceptor activity TAS10754293
         
    Find genes that share ontologies with CXCR4           About GenesLikeMe


    Phenotypes:
         3 GenomeRNAi human phenotypes for CXCR4:
     Decreased p24 protein expressi  Increased gamma-H2AX phosphory  Synthetic lethal with imatinib 

         Selected MGI mutant phenotypes (inferred from 8 alleles(MGI details for Cxcr4) (see all 16):
     cardiovascular system  cellular  craniofacial  digestive/alimentary  embryogenesis 
     growth/size/body  hematopoietic system  homeostasis/metabolism  immune system  mortality/aging 
     muscle  nervous system  renal/urinary system  reproductive system  respiratory system 

    Find genes that share phenotypes with CXCR4           About GenesLikeMe

    Animal Models:
         MGI mouse knock-outs for CXCR4: Cxcr4tm1Qma Cxcr4tm1Yzo Cxcr4tm3.1Yzo Cxcr4tm1Tng

       inGenious Targeting Laboratory: Let us create your new Knockout/Knockin mouse model for CXCR4
       inGenious Targeting Laboratory: Contact us about creating complex and humanized mouse models for CXCR4

       genOway customized KO model: permanent, tissue-specific or time-controlled inactivation for CXCR4
       genOway customized Knockin model: humanization, point mutation, expression monitoring, etc. for CXCR4

    miRNA
    Products:
        
    miRTarBase miRNAs that target CXCR4:
    hsa-mir-146a-5p (MIRT000006), hsa-mir-150-5p (MIRT006668), hsa-mir-224-5p (MIRT000635), hsa-mir-26b-5p (MIRT030235)

    Block miRNA regulation of human, mouse, rat CXCR4 using miScript Target Protectors
    4 qRT-PCR Assays for microRNAs that regulate CXCR4:
    hsa-miR-9 hsa-miR-588 hsa-miR-3135 hsa-miR-622
    SwitchGear 3'UTR luciferase reporter plasmidCXCR4 3' UTR sequence
    Inhib. RNA
    Products:
        
    OriGene RNAi products in human, mouse, rat for CXCR4
    Predesigned siRNA for gene silencing in human, mouse, rat CXCR4

    Gene Editing
    Products:
    DNA2.0 Custom Protein Engineering Service for CXCR4

    Clone
    Products:
         
    OriGene clones in human, mouse for CXCR4 (see all 11)
    OriGene ORF clones in mouse, rat for CXCR4
    OriGene custom cloning services - gene synthesis, subcloning, mutagenesis, variant library, vector shuttling
    GenScript: all cDNA clones in your preferred vector (see all 2): CXCR4 (NM_001008540)
    Sino Biological Human cDNA Clone for CXCR4
    DNA2.0 Custom Codon Optimized Gene Synthesis Service for CXCR4
    Vector BioLabs ready-to-use adenovirus/AAV for human, mouse, rat CXCR4
    Addgene plasmids for CXCR4 

    Cell Line
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CXCR4

    Flow Cytometry
    Products:
       

     
    eBioscience FlowRNA Probe Sets ( VA1-10263) for CXCR4 


    (According to UniProtKB, COMPARTMENTS Subcellular localization database, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene.)
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    Subcellular locations from UniProtKB/Swiss-Prot
    CXCR4_HUMAN, P61073: Cell membrane; Multi-pass membrane protein. Cell junction. Early endosome. Late endosome.
    Lysosome. Note=In unstimulated cells, diffuse pattern on plasma membrane. On agonist stimulation, colocalizes
    with ITCH at the plasma membrane where it becomes ubiquitinated. In the presence of antigen, distributes to the
    immunological synapse forming at the T cell-APC contact area, where it localizes at the peripheral and distal
    supramolecular activation cluster (SMAC)
    Subcellular locations from COMPARTMENTS: 

    CompartmentConfidence
    plasma membrane5
    cytoskeleton2
    endosome2
    extracellular2
    nucleus2

    Gene Ontology (GO): Selected cellular component terms (see all 14):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm TAS10415069
    GO:0005764lysosome IDA--
    GO:0005769early endosome IDA--
    GO:0005770late endosome IDA--
    GO:0005886plasma membrane TAS--

    Find genes that share ontologies with CXCR4           About GenesLikeMe


    (SuperPaths according to PathCards, Pathways according to R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Sino Biological, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to QIAGEN, and/or STRING, Interactions according to 1UniProtKB, 2MINT, 3I2D, and/or 4STRING, with links to IntAct and Ensembl, Ontologies according to Gene Ontology Consortium 01 Apr 2014 via Entrez Gene).
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    SuperPaths for CXCR4 About   (see all 31)  
    See pathways by source

    SuperPathContained pathways About
    1Peptide ligand-binding receptors
    Class A/1 (Rhodopsin-like receptors)0.71
    G alpha (i) signalling events0.44
    GPCR ligand binding0.71
    GPCRs, Class A Rhodopsin-like0.43
    Peptide ligand-binding receptors0.60
    2EphB-EphrinB Signaling
    EphB-EphrinB Signaling0.58
    Cytoskeleton remodeling Reverse signaling by ephrin B0.34
    Ephrin-Eph Signaling0.58
    3Chemokine Superfamily: Human/Mouse Ligand-Receptor Interactions
    Chemokine Superfamily: Human/Mouse Ligand-Receptor Interactions0.81
    Chemokine receptors bind chemokines0.81
    4Neuropeptides signaling through G protein alpha i and G protein alpha q
    Peptide GPCRs0.46
    Neuropeptides signaling through G protein alpha i and G protein alpha q0.46
    5PEDF Induced Signaling
    STAT3 Pathway0.47
    Cytokine-cytokine receptor interaction0.43


    Find genes that share SuperPaths with CXCR4           About GenesLikeMe

    Pathways by source                                                                                                                                                                 See SuperPaths
    Show all pathways

    1 R&D Systems Pathway for CXCR4
        Chemokine Superfamily: Human/Mouse Ligand-Receptor Interactions

    Selected Downloadable PowerPoint Slides of GeneGlobe Pathway Central Maps for CXCR4 (see all 15)
        Chemokine Signaling
    STAT3 Pathway
    CXCR4 Pathway
    Molecular Mechanisms of Cancer
    Antioxidant Action of Vitamin-C

    3 GeneGo (Thomson Reuters) Pathways for CXCR4
        Cell adhesion Integrin inside-out signaling
    Cytoskeleton remodeling Reverse signaling by ephrin B
    Chemotaxis CXCR4 signaling pathway

    Selected BioSystems Pathways for CXCR4 (see all 9)
        Cardiac Progenitor Differentiation
    IL-4 signaling Pathway
    GPCRs, Class A Rhodopsin-like
    S1P3 pathway
    Syndecan-4-mediated signaling events


    3 Reactome Pathways for CXCR4
        Binding and entry of HIV virion
    Chemokine receptors bind chemokines
    G alpha (i) signalling events


    Selected Kegg Pathways  (Kegg details for CXCR4) (see all 6):
        Cytokine-cytokine receptor interaction
    Chemokine signaling pathway
    Endocytosis
    Axon guidance
    Leukocyte transendothelial migration

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CXCR4 (see all 15): 
              HIV Host Response in human mouse rat
              Fibrosis in human mouse rat
              Terminal Differentiation Markers in human mouse rat
              Lymphoma in human mouse rat
              Autophagy in human mouse rat

    Interactions:

        GeneGlobe Interaction Network for CXCR4

    STRING Interaction Network Preview (showing 5 interactants - click image to see 25)

    Selected Interacting proteins for CXCR4 (P610731, 2, 3 ENSP000003868844) via UniProtKB, MINT, STRING, and/or I2D (see all 144)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    ENSG00000212866P081073I2D: score=1 
    ENSG00000215328P081073I2D: score=1 
    ENSG00000224501P081073I2D: score=1 
    ENSG00000231555P081073I2D: score=1 
    ENSG00000232804P081073I2D: score=1 
    About this table

    Gene Ontology (GO): Selected biological process terms (see all 29):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0000187activation of MAPK activity TAS10570282
    GO:0001569patterning of blood vessels IEA--
    GO:0001666response to hypoxia IEP15174142
    GO:0001667ameboidal cell migration IEA--
    GO:0001764neuron migration IEA--

    Find genes that share ontologies with CXCR4           About GenesLikeMe



    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience, ApexBio, HMDB, BitterDB, and/or Novoseek, Ligands according to IUPHAR, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB)
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      Browse compounds at ApexBio 

    Compounds for CXCR4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    RS 504393Highly selective CCR2 chemokine receptor antagonist[300816-15-3]
    MaravirocSelective CCR5 antagonist[376348-65-1]
    SB 225002Potent and selective CXCR2 antagonist[182498-32-4]
    SB 265610Potent CXCR2 antagonist[211096-49-0]
    TC 14012CXCR4 antagonist; CXCR7 agonist[368874-34-4]

    1 HMDB Compound for CXCR4    About this table
    CompoundSynonyms CAS #PubMed Ids
    CalciumCa (see all 2)7440-70-2--

    2 DrugBank Compounds for CXCR4    About this table
    CompoundSynonyms CAS #TypeActionsPubMed Ids
    FramycetinFramycetinum [INN-Latin] (see all 3)119-04-0targetantagonist11747436 14638394
    PlerixaforAMD3100 (see all 2)110078-46-1targetantagonist23204107 18847313

    Selected IUPHAR Ligands for CXCR4 (CXCR4) (see all 18)    About this table
    LigandTypeActionAffinityPubmed IDs
    T140
    AntagonistInverse agonist7.8 - 8.69918823 11923301
    [125I]SDF-1alpha (human)
    AgonistFull agonist8.1 - 8.49551924 11104827
    T134
    AntagonistAntagonist8.49918823
    SDF-1alpha
    AgonistFull agonist7.7 - 8.29551924 9712844
    vMIP-II
    AntagonistAntagonist8.29287217
    isothiourea-1t
    AgonistAgonist8.119053768
    isothiourea-1a
    AgonistAgonist7.9619053768
    [125I]SDF-1beta (human)
    AgonistFull agonist7.99551924
    SDF-1beta
    AgonistFull agonist7.869551924
    T22
    AntagonistAntagonist7.39918823

    Selected Novoseek inferred chemical compound relationships for CXCR4 gene (see all 86)    About this table
    Compound   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    bicyclam 87 16 9882699 (2), 9646721 (1), 9733901 (1), 16005254 (1) (see all 13)
    sdf 1 85.2 79 18698020 (8), 10656438 (6), 17108064 (6), 15781337 (3) (see all 28)
    rantes 82.9 68 14717979 (2), 20065862 (2), 19127964 (2), 10679062 (2) (see all 53)
    c-d4i 66.7 1 12208966 (1)
    enfuvirtide 64.7 1 16250877 (1)
    cgp64222 62.6 1 10617686 (1)
    jm2763 61.1 1 10400726 (1)
    ccl3 56.1 9 15818740 (1), 19001077 (1), 15542651 (1), 11145678 (1) (see all 8)
    matrigel 54.2 13 17521613 (2), 12791666 (1), 15059909 (1), 19885584 (1) (see all 10)
    mdms 53.9 5 11049991 (2), 15804293 (2), 12699419 (1)



    Find genes that share compounds with CXCR4           About GenesLikeMe



    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 236 Homo sapiens; Apr 25 2013) or GenBank,
    RefSeq according to Entrez Gene,
    DOTS (version 10), and/or AceView, transcript ids from Ensembl with links to UCSC,
    exon structure from GeneLoc, alternative splicing isoforms according to ASD and/or ECgene,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN, SwitchGear Genomics,
    Tagged/untagged cDNA clones from OriGene, GenScript, DNA2.0, Vector BioLabs, and/or Addgene, Primers from OriGene, and/or QIAGEN, Flow cytometry from eBioscience )
    About This Section

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    REFSEQ mRNAs for CXCR4 gene (2 alternative transcripts): 
    NM_001008540.1  NM_003467.2  

    Unigene Cluster for CXCR4:

    Chemokine (C-X-C motif) receptor 4
    Hs.593413  [show with all ESTs]
    Unigene Representative Sequence: AF147204
    3 Ensembl transcripts including schematic representations, and UCSC links where relevant:
    ENST00000409817(uc002tuy.3) ENST00000241393(uc010fnk.3 uc002tuz.3)
    ENST00000466288
    miRNA
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    4 qRT-PCR Assays for microRNAs that regulate CXCR4:
    hsa-miR-9 hsa-miR-588 hsa-miR-3135 hsa-miR-622
    SwitchGear 3'UTR luciferase reporter plasmidCXCR4 3' UTR sequence
    Inhib. RNA
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    GenScript: all cDNA clones in your preferred vector (see all 2): CXCR4 (NM_001008540)
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    eBioscience FlowRNA Probe Sets ( VA1-10263) for CXCR4 

    Additional mRNA sequence: 

    AF025375.1 AF147204.1 AF348491.1 AK129916.1 AK296674.1 AK309641.1 AK309885.1 AK312244.1 
    AY242129.1 AY826773.1 BC020968.2 BT006660.1 D10924.1 L01639.1 L06797.1 M99293.1 
    X71635.1 

    10 DOTS entries:

    DT.99966073  DT.317915  DT.100879775  DT.95300550  DT.100758882  DT.121009420  DT.91841237  DT.92435681 
    DT.100804810  DT.86667426 

    Selected AceView cDNA sequences (see all 263):

    BX421287 AA490436 AV708227 CB215245 CD251331 BX397685 AA354267 BM920800 
    BM698707 CA389284 BX439223 BP338386 AA386000 AW418550 CR596547 AW594595 
    AI920946 AA356857 CR614663 CR598681 CR614594 BT006660 BI762229 AY242129 

    GeneLoc Exon Structure


    (RNA expression data according to H-InvDB, NONCODE, miRBase, and RNAdb, Expression images according to data from BioGPS, Illumina Human BodyMap, and CGAP SAGE, Sets of similar genes according to GeneDecks, in vivo and in vitro expression data from LifeMap Discovery™, Protein expression images according to data from SPIRE 1MOPED, 2PaxDb, and 3MaxQB, plus additional links to SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from QIAGEN, Primers from OriGene, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
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    CXCR4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS <intensity>2/3
    CGAP TAG: TTAAACTTAA
    CXCR4 Expression
    About this image


    CXCR4 expression in embryonic tissues and stem cells    About this table
    Data from LifeMap, the Embryonic Development and Stem Cells Database
     selected tissues (see all 42) fully expand
     
     Endoderm (Gastrulation Derivatives)    fully expand to see all 11 entries
             Definitive Endoderm Cells Definitive Endoderm
             Endoderm-like cell
     
     Skeletal Muscle (Muscoskeletal System)    fully expand to see all 25 entries
             Muscle Progenitor Cells Hypobranchial Muscles
     
     Blood (Cardiovascular System)    fully expand to see all 12 entries
             Large Pre B-Cells Hematopoietic Bone Marrow
             Peripheral blood-derived hematopoietic stem cells
             Enriched erythrocyte-like cells
     
     Pancreas (Endocrine System)    fully expand to see all 5 entries
             Pancreatic Progenitor Cells Ventral Pancreatic Bud
             Pancreatic endoderm-like cells
     
     Somite (Muscoskeletal System)    fully expand to see all 16 entries
             Mononuclear Myocytes Cervical Primary Hypaxial Myotome
    CXCR4 Protein expression data from MOPED1, PaxDb2 and MaxQB3    About this image

    CXCR4 Protein Expression

    SOURCE GeneReport for Unigene cluster: Hs.593413

    UniProtKB/Swiss-Prot: CXCR4_HUMAN, P61073
    Tissue specificity: Expressed in numerous tissues, such as peripheral blood leukocytes, spleen, thymus, spinal
    cord, heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, cerebellum, cerebral cortex and medulla
    (in microglia as well as in astrocytes), brain microvascular, coronary artery and umbilical cord endothelial
    cells. Isoform 1 is predominant in all tissues tested

        Pathway & Disease-focused RT2 Profiler PCR Arrays including CXCR4 (see all 15): 
              HIV Host Response in human mouse rat
              Fibrosis in human mouse rat
              Terminal Differentiation Markers in human mouse rat
              Lymphoma in human mouse rat
              Autophagy in human mouse rat

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    QuantiFast Probe-based Assays in human, mouse, rat CXCR4
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    Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CXCR4

    (Orthologs according to 1,2HomoloGene (2older version, for species not in 1newer version), 3euGenes, 4SGD , 5MGI Mar 06 2013, with possible further links to Flybase and/or WormBase, and/or 6Ensembl pan taxonomic compara , Gene Trees according to Ensembl and TreeFam)
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    This gene was present in the common ancestor of chordates.

    Orthologs for CXCR4 gene from Selected species (see all 13)    About this table
    Organism Taxonomic
    classification
    Gene Description Human
    Similarity
    Orthology
    Type
    Details
    mouse
    (Mus musculus)
    Mammalia Cxcr41 , 5 chemokine (C-X-C motif) receptor 41, 5 86.89(n)1
    90.69(a)1
      1 (56.43 cM)5
    127671  NM_009911.31  NP_034041.21 
     1285881995 
    chicken
    (Gallus gallus)
    Aves CXCR41 chemokine (C-X-C motif) receptor 4 74.03(n)
    81.49(a)
      395324  NM_204617.2  NP_989948.2 
    lizard
    (Anolis carolinensis)
    Reptilia CXCR46
    chemokine (C-X-C motif) receptor 4
    80(a)
    1 ↔ 1
    1(96948392-96955260)
    African clawed frog
    (Xenopus laevis)
    Amphibia cxcr4-prov2 chemokine (C-X-C motif) receptor 4 77.39(n)    BC044963.1 
    zebrafish
    (Danio rerio)
    Actinopterygii cxcr4a2 chemokine (C-X-C motif) receptor 4a 73.58(n)   140747  BC050172.1 


    ENSEMBL Gene Tree for CXCR4 (if available)
    TreeFam Gene Tree for CXCR4 (if available)

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
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    Paralogs for CXCR4 gene
    CCR52  CCR62  CXCR62  ACKR42  CXCR32  XCR12  CCR92  CCRL22  
    CCR72  ACKR22  CX3CR12  CCR82  CXCR22  CCR12  CCR42  CXCR12  
    CCR22  CXCR52  CCR102  CCR32  
    Selected SIMAP similar genes for CXCR4 using alignment to 2 protein entries:     CXCR4_HUMAN (see all proteins) (see all similar genes):
    BLR1    CXCR5    CCR7    CCR5    ACKR4    CCRL1
    CXCR1    CXCR6    CCR2    CCR9    CXCR2    CXCR3
    IL8RB    CCR4    CCR6    XCR1    CX3CR1    ACKR2

    Find genes that share paralogs with CXCR4           About GenesLikeMe



    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, 4UniProtKB, and DNA2.0, Linkage Disequilibrium by HapMap, Structural Variations(CNVs/InDels/Inversions) from the Database of Genomic Variants, Mutations from the Human Gene Mutation Database (HGMD), the Human Cytochrome P450 Allele Nomenclature Database, and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers, Cancer Mutation PCR Arrays and Assays, and Copy Number PCR Arrays from QIAGEN)
    About This Section

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    Selected SNPs for CXCR4 (see all 136)    About this table                                 

    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance
    Chr 2 posSequence#AA
    Chg
    TypeMore#Allele
    freq
    PopTotal
    sample
    More
    ----------
    rs1048936251,2
    Cpathogenic1136372726(-) CCACTG/TAGTCT 4 E * stg10--------
    rs1048936261,2
    Cpathogenic1136372740(-) ACATTC/GATCTG 4 S * stg10--------
    rs1048936241,2
    Cpathogenic1136372753(-) GAAAGC/TGAGGT 4 R * stg10--------
    rs1461870431,2
    C--136371706(+) GATACC/TGGATG 2 -- ds50010--------
    rs1878644291,2
    --136371721(+) AAGCAA/CACACC 2 -- ds50010--------
    rs133831391,2
    C--136371730(+) CCGTCT/GGGCAT 2 -- ds50011Minor allele frequency- G:0.00NA 2
    rs1922066441,2
    --136371740(+) TTGCAC/TAGACC 2 -- ds50010--------
    rs1385847761,2
    --136371811(+) TATACA/GTGCTT 2 -- ds50010--------
    rs1842747221,2
    --136371898(+) TGAAGC/GCTTCA 2 -- ds50010--------
    rs1403132041,2
    --136371914(+) GTTAAC/GTCATG 2 -- ds50010--------

    HapMap Linkage Disequilibrium report for CXCR4 (136871919 - 136875735 bp)

    Structural Variations
         Database of Genomic Variants (DGV) 1 variation for CXCR4:    About this table    
    Variant IDTypeSubtypePubMed ID
    nsv523997CNV Gain19592680

    Human Gene Mutation Database (HGMD): CXCR4
    Locus Specific Mutation Databases (LSDB): CXCR4

    Site Specific Mutation Identification with PCR Assays
    Search QIAGEN SeqTarget long-range PCR primers for resequencing CXCR4
    DNA2.0 Custom Variant and Variant Library Synthesis for CXCR4

    (in which this Gene is Involved, According to MalaCards, OMIM, UniProtKB, the University of Copenhagen DISEASES database, Novoseek, Genatlas, GeneTests, GAD, HuGE Navigator, and/or TGDB.)
    About This Section

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    OMIM gene information: 162643   
    OMIM disorders: 193670  
    UniProtKB/Swiss-Prot: CXCR4_HUMAN, P61073
  • WHIM syndrome (WHIM) [MIM:193670]: Immunodeficiency disease characterized by neutropenia,
    hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia,
    bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed
    myelokathexis. Note=The disease is caused by mutations affecting the gene represented in this entry

  • 13 diseases for CXCR4:    
    About MalaCards
    myelokathexis, isolated    whim syndrome    retinal hemangioblastoma    intraocular lymphoma
    mitral valve disease    chronic lymphocytic leukemia    usual interstitial pneumonia    enchondroma
    familial chronic lymphocytic leukemia    oligoastrocytoma    vipoma    breast cancer
    pancreatic cancer

    3 diseases from the University of Copenhagen DISEASES database for CXCR4:
    Agammaglobulinemia     Human immunodeficiency virus infectious disease     Breast cancer

    Find genes that share disorders with CXCR4           About GenesLikeMe

    Selected Novoseek inferred disease relationships for CXCR4 gene (see all 93)    About this table

    Disease   -log (P-Val)   Hits   PubMed IDs for Articles with Shared Sentences (# sentences)
    whim syndrome 87.5 29 15026312 (2), 15781337 (2), 16154852 (2), 16899028 (2) (see all 17)
    immunodeficiency 84.1 357 9343175 (3), 10074102 (3), 9108384 (2), 9160656 (2) (see all 99)
    metastasis 71 540 16230077 (6), 12499276 (6), 15240098 (6), 17355795 (6) (see all 99)
    hiv infections 69.4 78 9108384 (2), 14741421 (2), 10779364 (2), 9050881 (2) (see all 61)
    aids 56.6 73 16138573 (5), 10499817 (2), 11305873 (2), 17199940 (2) (see all 50)
    hypogammaglobulinemia 56.3 5 15026312 (1), 18436740 (1), 15604887 (1)
    aids dementia complex 55.6 3 11115360 (1), 9327737 (1), 11218674 (1)
    tumors 54.1 549 16269611 (6), 18593989 (6), 18701133 (5), 15472715 (5) (see all 99)
    cancer 53 232 20032431 (5), 18987663 (4), 16357147 (4), 16823836 (4) (see all 99)
    virus infection 46.8 39 8709256 (1), 11287575 (1), 11448156 (1), 15306840 (1) (see all 34)

    Genetic Association Database (GAD): CXCR4
    Human Genome Epidemiology (HuGE) Navigator: CXCR4 (63 documents)

    Export disorders for CXCR4 gene to outside databases

    (in PubMed. Associations of this gene to articles via 1Entrez Gene, 2UniProtKB/Swiss-Prot, 3HGNC, 4GAD, 5PharmGKB, 6HMDB, 7DrugBank, 8UniProtKB/TrEMBL, 9 Novoseek, and/or 10fRNAdb)
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    PubMed articles for CXCR4 gene, integrated from 10 sources (see all 2264):
    (articles sorted by number of sources associating them with CXCR4)
        Utopia: connect your pdf to the dynamic
    world of online information

    1. Genomic organization and promoter characterization of human CXCR4 gene. (PubMed id 9599023)1, 2, 3, 9 Caruz A.... Arenzana-Seisdedos F. (FEBS Lett. 1998)
    2. Identification of CXCR4 domains that support coreceptor and chemokine receptor functions. (PubMed id 10074122)1, 2, 9 Doranz B.J.... Doms R.W. (J. Virol. 1999)
    3. Cloning and analysis of the promoter region of CXCR4, a coreceptor for HIV-1 entry. (PubMed id 9379028)1, 3, 9 Moriuchi M....Fauci A.S. (J. Immunol. 1997)
    4. Site-specific phosphorylation of CXCR4 is dynamically regulated by multiple kinases and results in differential modulation of CXCR4 signaling. (PubMed id 20048153)1, 2, 9 Busillo J.M....Benovic J.L. (J. Biol. Chem. 2010)
    5. Sequential tyrosine sulfation of CXCR4 by tyrosylprotein sulfotransferases. (PubMed id 18834145)1, 2, 9 Seibert C....Sakmar T.P. (Biochemistry 2008)
    6. beta-arrestin differentially regulates the chemokine receptor CXCR4- mediated signaling and receptor internalization, and this implicates multiple interaction sites between beta-arrestin and CXCR4. (PubMed id 10644702)1, 2, 9 Cheng Z.J.... Pei G. (J. Biol. Chem. 2000)
    7. The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry. (PubMed id 8752280)1, 2, 9 Bleul C.C.... Springer T.A. (Nature 1996)
    8. Do human polyoma viruses and human immunodeficiency virus share common co-receptors? (PubMed id 19950235)1, 4, 9 Borissov K....Argirova R. (J. Med. Virol. 2010)
    9. The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction. (PubMed id 19116316)1, 2, 9 Bhandari D.... Marchese A. (Mol. Biol. Cell 2009)
    10. SDF1 gene variation is associated with circulating SDF1alpha level and endothelial progenitor cell number: the Bruneck Study. (PubMed id 19115008)1, 4, 9 Xiao Q....Xu Q. (PLoS ONE 2008)

    (in PubMed, OMIM, and NCBI Bookshelf)
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     ANDOR
    Aliases
    Disorders
    Free Text  

      Query String
    PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    (According to Entrez Gene, HGNC, AceView, euGenes, Ensembl, miRBase, ECgene, Kegg, and/or H-InvDB)
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    Entrez Gene: 7852 HGNC: 2561 AceView: CXCR4 Ensembl:ENSG00000121966 euGenes: HUgn7852
    ECgene: CXCR4 Kegg: 7852 H-InvDB: CXCR4

    (According to HUGE)
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      --

    (According to PharmGKB, ATLAS, HORDE, IMGT, LEIDEN, UniProtKB/Swiss-Prot, UniProtKB/TrEMBL, and/or others, e.g. Wikipedia and GeneReviews, via UniProtKB/Swiss-Prot)
    About This Section

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    NameDescription
    PharmGKB entry for CXCR4 Pharmacogenomics, SNPs, Pathways
    ATLAS Chromosomes in Cancer entry for CXCR4 Genetics and Cytogenetics in Oncology and Haematology
    CXCR4basehttp://bioinf.uta.fi/CXCR4base/
    Wikipedia http://en.wikipedia.org/wiki/CXC_chemokine_receptors
    Wikipedia http://en.wikipedia.org/wiki/CXCR4
    SeattleSNPshttp://pga.gs.washington.edu/data/cxcr4/

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
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    Patent Information for CXCR4 gene:
    Search GeneIP for patents involving CXCR4

    Licensable Technologies for CXCR4 gene:
    Weizmann Institute:Enrichment of Repopulating Stem Cells For Clinical Protocols
     Salk Institute: Alpha-Complementation Viral Fusion Assay
    GeneCards and IP:
    Japan Patent Office Licenses GeneCards     European Patent Office Licenses GeneCards     Improving the IP Search



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    Advanced Cell Diagnostics, Animal models from inGenious Targeting Laboratory, genOway)
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