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Category   Symbol Source: HGNC EntrezGene Ensembl GeneCards RNA genes CroW21
GIFtS

CXCR4 Gene

protein-coding   GIFtS: 77
GCID: GC02M136871

chemokine (C-X-C motif) receptor 4

(Previous names: chemokine (C-X-C motif), receptor 4 (fusin) )
 Explore 193 diseases affiliated with
CXCR4 via
MalaCards
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 Human Malady Compendium 
Biological research products
for CXCR4    

Aliases
for CXCR4 gene

(According to 1HGNC, 2Entrez Gene,
3UniProtKB/Swiss-Prot, 4UniProtKB/TrEMBL, 5OMIM, 6GeneLoc, 7Ensembl, 8DME, 9miRBase, and/or 10fRNAdb)
About This Section
Aliases
Chemokine (C-X-C Motif) Receptor 41 2     LCR12 3
HM891 2 3     NPYRL2 3
LESTR1 2 3     CD184 Antigen2 3
D2S201E1 2 5     SDF-1 Receptor2 3
NPY3R1 2 5     WHIM2 5
CD1841 2     Chemokine (C-X-C Motif), Receptor 4 (Fusin)1
HSY3RR1 2     LAP32
NPYR1 2     C-X-C Chemokine Receptor Type 42
NPYY3R1 2     Leukocyte-Derived Seven-Transmembrane-Domain Receptor2
Fusin3     Lipopolysaccharide-Associated Protein 32
Leukocyte-Derived Seven Transmembrane Domain Receptor2 3     Neuropeptide Y Receptor Y32
Stromal Cell-Derived Factor 1 Receptor2 3     Seven Transmembrane Helix Receptor2
CXC-R42 3     Seven-Transmembrane-Segment Receptor, Spleen2
CXCR-42 3     Fusin3
FB222 3     

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


Summaries
for CXCR4 gene

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

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:
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


Genomic Views
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 69), Regulatory elements and Epigenetics data according to QIAGEN, SABiosciences, and/or SwitchGear Genomics)
About This Section
RefSeq DNA sequence:
NC_000002.11  NC_018913.1  NT_022135.16  
Regulatory elements:
   SABiosciences 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 SABiosciences Chromatin IP Primers for CXCR4

Epigenetics:
QIAGEN PyroMark CpG Assay predesigned Pyrosequencing DNA Methylation assays 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

Proteins
for CXCR4 gene

(According to 1UniProtKB, HORDE, neXtProt, Ensembl, and/or Reactome, Modification sites according to 2PhosphoSitePlus, Specific Peptides from DME, Protein expression images according to data from SPIRE MOPED and PaxDb, 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, and/or Uscn,
Biochemical Assays by EMD Millipore, R&D Systems, OriGene, GenScript, Cell Signaling Technology, Enzo Life Sciences, and/or Uscn, Ontologies according to Gene Ontology Consortium 01 Mar 2013 and Entrez Gene, Antibodies by EMD Millipore, R&D Systems, GenScript, Cell Signaling Technology, OriGene, Novus Biologicals, Thermo Fisher Scientific, Abcam, and/or Uscn)
About This Section
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
Subcellular location: Cell membrane; Multi-pass membrane protein. Note=In unstimulated cells, diffuse pattern on plasma
membrane. On agonist stimulation, colocalizes with ITCH at the plasma membrane where it becomes ubiquitinated
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;
6/8 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

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
  • View modification sites using PhosphoSitePlus2
  • View neXtProt modification sites for NX_P61073

    • CXCR4 Protein expression data from MOPED and PaxDb:    About this image 
    Estimated protein expression log10 (pmol).

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

    ENSEMBL proteins: 
     ENSP00000386884   ENSP00000241393  
    Reactome Protein details: P61073
    Human Recombinant Protein Products: 
    EMD Millipore Purified and/or Recombinant CXCR4 Protein
    Browse R&D Systems for human recombinant proteins
    Browse recombinant and purified proteins available from Enzo Life Sciences
    Browse OriGene full length recombinant human proteins expressed in human HEK293 cells
    OriGene Protein Over-expression Lysate: CXCR4
    OriGene Custom Protein Services for CXCR4 
    GenScript Custom Purified and Recombinant Proteins Services for CXCR4
    Novus Biologicals CXCR4 Proteins
    Novus Biologicals CXCR4 Lysates
    Browse Sino Biological Recombinant Proteins
    Browse ProSpec Recombinant Proteins
    Uscn Proteins for CXCR4

    Gene Ontology (GO): 5/9 cellular component terms (GO ID links to tree view) (see all 9):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0005737cytoplasm TAS10415069
    GO:0005886plasma membrane TAS--
    GO:0009897external side of plasma membrane IEA--
    GO:0009986cell surface IDA19106094
    GO:0016021integral to membrane IEA--


    CXCR4 for ontologies           About GeneDecksing



    CXCR4 Antibody Products: 
    EMD Millipore Mono- and Polyclonal Antibodies for the study of CXCR4
    R&D Systems Antibodies for CXCR4
    OriGene Antibodies (see all 3): CXCR4
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    Abcam antibodies for CXCR4 
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    ThermoFisher Antibody for CXCR4

    Assay Products for CXCR4: 
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    Uscn ELISAs and CLIAs for CXCR4

    Protein Domains /
    Families
    for CXCR4 gene

    (According to InterPro, ProtoNet, UniProtKB, and/or BLOCKS, Sets of similar genes according to GeneDecks)
    About This Section
    CXCR4 for domains           About GeneDecksing

    5 InterPro domains/families:
     IPR022726 Chemokine_CXCR4_N
     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 families:
    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


    Function
    for CXCR4 gene

    (According to 1UniProtKB, Genatlas, LifeMap Discovery™, IUBMB, and/or 2DME, Human phenotypes from GenomeRNAi, Animal models from MGI Mar 06 2013,
    bound targets from SABiosciences, miRNA Gene Targets from miRTarBase shRNA from OriGene, RNAi from EMD Millipore, siRNAs from OriGene, QIAGEN, microRNA from QIAGEN, Gene Editing from DNA2.0, Clones from EMD Millipore, OriGene, SwitchGear Genomics, GenScript, Sino Biological, DNA2.0, and Vector BioLabs, Cell Lines from GenScript, LifeMap BioReagents, In Situ Hybridization Assays from Advanced Cell Diagnostics, Ontologies according to Gene Ontology Consortium 01 Mar 2013 via Entrez Gene.)
    About This Section
    Function Summary:

         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

         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

    miRNA
    Products:            		miRTarBase miRNAs that target CXCR4:
    hsa-mir-146a (MIRT000006), hsa-mir-224 (MIRT000635)

    OriGene 3'-UTR Clone (see all 2): CXCR4
    Browse MicroRNA Expression Plasmids
    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CXCR4
    4 QIAGEN miScript miRNA Assays for microRNAs that regulate CXCR4:
    hsa-miR-9 hsa-miR-588 hsa-miR-3135 hsa-miR-622
    SwitchGear 3'UTR luciferase reporter plasmid: CXCR4 3' UTR sequence
    Inhib. RNA
    Products:            		Browse for Gene Knock-down Tools from EMD Millipore
    OriGene 29mer shRNA kits in GFP-retroviral vector in human, mouse, rat for CXCR4 (see all 7)
    OriGene shRNA RFP: CXCR4
    OriGene siRNA: CXCR4
    QIAGEN FlexiTube/FlexiPlate siRNA for gene silencing in human, mouse, rat CXCR4

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

    Clone
    Products:             		EMD Millipore Clones for the Expression of CXCR4
    OriGene Myc/DDK tagged cDNA clones in CMV expression vector in human, mouse, rat for CXCR4 (see all 4)
    OriGene untagged cDNA clones in CMV expression vector in human, mouse, rat for CXCR4 (see all 2)
    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 

    Cell Line
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    Search LifeMap BioReagents cell lines for CXCR4

    In Situ Assay
    Products:       
         		Advanced Cell Diagnostics RNAscope RNA in situ hybridization assays for CXCR4

    Gene Ontology (GO): 5/8 molecular function terms (GO ID links to tree view) (see all 8):    About this table

    GO IDQualified GO termEvidencePubMed IDs
    GO:0003779actin binding IDA12421915
    GO:0004930G-protein coupled receptor activity TAS8276799
    GO:0005515protein binding IPI12421915
    GO:0015026coreceptor activity TAS10754293
    GO:0016494C-X-C chemokine receptor activity NAS9468539


    CXCR4 for ontologies           About GeneDecksing


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

    Animal Models:
         Mouse knock-outs for CXCR4: Cxcr4tm1Qma Cxcr4tm1Yzo Cxcr4tm3.1Yzo Cxcr4tm1Tng
         15/16 MGI mutant phenotypes (inferred from 8 alleles) (MGI details for Cxcr4) (see all 16):
     cardiovascular system  cellular  craniofacial  digestive/alimentary  embryogenesis 
     growth/size  hematopoietic system  homeostasis/metabolism  immune system  mortality/aging 
     muscle  nervous system  renal/urinary system  reproductive system  respiratory system 

    CXCR4 for phenotypes           About GeneDecksing


    Pathways & Interactions
    for CXCR4 gene

    (Pathways according to EMD Millipore, R&D Systems, Cell Signaling Technology, KEGG, PharmGKB, BioSystems, Reactome, Tocris Bioscience, GeneGo (Thomson Reuters), QIAGEN, and/or UniProtKB, Sets of similar genes according to GeneDecks, Interaction Networks according to SABiosciences, 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 Mar 2013 via Entrez Gene).
    About This Section

    Unified GeneCards pathways - 5/33 super-pathways (see all 33) About this table 
    See pathways by source

    Super-pathwaycontained gene-specific pathways
    1Class A/1 (Rhodopsin-like receptors)
    		Class A/1 (Rhodopsin-like receptors)1.00
    		G alpha (i) signalling events0.44
    		GPCR ligand binding0.75
    		GPCRs, Class A Rhodopsin-like0.41
    		Peptide ligand-binding receptors0.61
    2Signaling by GPCR
    		Signaling by GPCR1.00
    		Signal Transduction0.56
    		GPCR downstream signaling0.89
    3Akt Signaling
    		Akt Signaling1.00
    		Tec Kinases Signaling0.55
    		p38 Signaling0.60
    4Cell adhesion_Integrin inside-out signaling
    		Cell adhesion_Integrin inside-out signaling1.00
    		Cell adhesion Integrin inside-out signaling0.99
    5Cytoskeleton remodeling_Reverse signaling by ephrin B
    		Cytoskeleton remodeling_Reverse signaling by ephrin B1.00
    		Cytoskeleton remodeling Reverse signaling by ephrin B0.94

    Pathway sources
    See GeneCards unified pathways
    Show all pathways

    4 EMD Millipore Pathways for CXCR4
        Chemotaxis CXCR4 signaling pathway
    Neuropeptides signaling through G-protein alpha-i & G-protein alpha-q
    Cell adhesion Integrin inside-out signaling
    Cytoskeleton remodeling Reverse signaling by ephrin B

    5/15 Downloadable PowerPoint Slides of QIAGEN 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

    5/8 BioSystems Pathways for CXCR4 (see all 8) 
        IL-4 signaling Pathway
    GPCRs, Class A Rhodopsin-like
    Syndecan-4-mediated signaling events
    Peptide GPCRs
    CXCR4-mediated signaling events

    5/13        Reactome Pathways for CXCR4 (see all 13)
        GPCR downstream signaling
    Peptide ligand-binding receptors
    Signaling by GPCR
    Early Phase of HIV Life Cycle
    GPCR ligand binding


    5/6         Kegg Pathways  (Kegg details for CXCR4) (see all 6):
        Cytokine-cytokine receptor interaction
    Chemokine signaling pathway
    Endocytosis
    Axon guidance
    Leukocyte transendothelial migration


    CXCR4 for pathways           About GeneDecksing

    Interactions:

        SABiosciences Gene Network CentralTM Interacting Genes and Proteins Network for CXCR4

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

    5/128 Interacting proteins for CXCR4 (P610731, 2, 3 ENSP000003868844) via UniProtKB, MINT, STRING, and/or I2D (see all 128)
    InteractantInteraction Details
    GeneCardExternal ID(s)
    CD74P042332, 3, ENSP000000095304MINT-7234512 MINT-7234528 MINT-7234542 MINT-7234499 I2D: score=1 STRING: ENSP00000009530
    MYH9P355791, 3, ENSP000002161814EBI-489411,EBI-1054343 I2D: score=3 STRING: ENSP00000216181
    CXCL12P480613, ENSP000003635484I2D: score=4 STRING: ENSP00000363548
    PTPN11Q061243, ENSP000003409444I2D: score=2 STRING: ENSP00000340944
    STAT1P422243, ENSP000003543944I2D: score=2 STRING: ENSP00000354394
    About this table

    Gene Ontology (GO): 5/27 biological process terms (GO ID links to tree view) (see all 27):    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--


    CXCR4 for ontologies           About GeneDecksing



    Drugs & Compounds
    for CXCR4 gene

    (Chemical Compounds according to UniProtKB, Enzo Life Sciences, EMD Millipore, Tocris Bioscience HMDB, BitterDB, and/or Novoseek, and Drugs according to DrugBank, Enzo Life Sciences, and/or PharmGKB, with drugs/clinical trials/news search links to CenterWatch)
    About This Section

    CXCR4 for compounds           About GeneDecksing

    Browse Small Molecules at EMD Millipore
    Browse drugs & compounds from Enzo Life Sciences

    Compounds for CXCR4 available from Tocris Bioscience    About this table
    CompoundAction CAS #
    AMD 3465 Potent, selective CXCR4 antagonist [185991-07-5]
    TC 14012CXCR4 antagonist; CXCR7 agonist[368874-34-4]
    AMD 3100 octahydrochlorideHighly selective CXCR4 antagonist[155148-31-5]

    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
    Plerixafor-- 110078-46-1targetantagonist18847313

    10/86 Novoseek 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)

    Search CenterWatch for drugs/clinical trials and news about CXCR4 

    Transcripts
    for CXCR4 gene

    (Secondary structures according to fRNAdb,
    GenBank/EMBL/DDBJ Accessions according to
    Unigene (Build 235 Homo sapiens; Mar 10 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,
    RNAi Products from EMD Millipore,
    siRNAs from OriGene, QIAGEN, shRNA from OriGene, microRNA from QIAGEN,
    Tagged/untagged cDNA clones from OriGene, SwitchGear Genomics, GenScript, DNA2.0, Vector BioLabs, Primers from OriGene, SABiosciences, and/or QIAGEN )
    About This Section
    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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    QIAGEN Custom miScript Target Protector blocks miRNA-binding site of human, mouse, rat CXCR4
    4 QIAGEN miScript miRNA Assays for microRNAs that regulate CXCR4:
    hsa-miR-9 hsa-miR-588 hsa-miR-3135 hsa-miR-622
    SwitchGear 3'UTR luciferase reporter plasmid: CXCR4 3' UTR sequence
    Inhib. RNA
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    Clone
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    GenScript: all cDNA clones in your preferred vector (see all 2): CXCR4 (NM_001008540)
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      QIAGEN QuantiFast Probe-based Assays in human, mouse, rat CXCR4

    Additional cDNA 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 

    24/263 AceView cDNA sequences (see all 263):

    CR594428 AI866909 BX089192 AA299445 D10924 AW594595 CB122606 L01639 
    AA386000 BP366593 CR596547 AA353051 BQ446320 BP338386 AA501992 CR598681 
    BX443334 BI916212 CR598713 CD251331 CA436903 AA354267 BX418530 BQ718617 

    GeneLoc Exon Structure


    Expression
    for CXCR4 gene

    (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™, plus additional links to Genevestigator, and/or SOURCE, and/or BioGPS, and/or UniProtKB,
    PCR Arrays from SABiosciences, Primers from OriGene, SABiosciences, and/or QIAGEN, In Situ Hybridization Assays from Advanced Cell Diagnostics)
    About This Section

    CXCR4 expression in normal human tissues (normalized intensities)
    See probesets specificity/sensitivity at GeneAnnot
    About this imageBioGPS
    CGAP TAG: TTAAACTTAA

    Microarray
    RNAseq (Illumina Body Map)
    (100×FPKM)½
    SAGE (Serial Analysis of Gene Expression)
    About this image

    CXCR4 expression in embryonic tissues and stem cells
    Expression by the Database of Embryonic development, Stem cell research, and Regenerative medicine    About this table
    10/49 LifeMap In Vivo Development Anatomical Compartments/Cells (see all 49) 
    Tissue Anatomical Compartment CellCategory (developmental path)
    Head MesenchymeHypobranchial MusclesMuscle Progenitor CellsSkeletal Muscle
    PancreasDorsal Pancreatic BudPancreatic Progenitor CellsPancreas
    PancreasPrepancreatic Dorsal Foregut EndodermPre-Pancreatic Foregut Endoderm CellsPancreas
    PancreasPrepancreatic Ventral Foregut EndodermPre-Pancreatic Foregut Endoderm CellsPancreas
    PancreasVentral Pancreatic BudPancreatic Progenitor CellsPancreas
    BloodPeripheral BloodImmature B CellsBlood
    BloodPeripheral BloodPre-B CellsBlood
    Head MesenchymeHypobranchial MusclesMyoblastsSkeletal Muscle
    KidneyUreteric BudUreteric Bud Tip CellsKidney
    LimbForelimb Dorsal MusclesMononuclear MyocytesSkeletal Muscle
    Expression: Positive    Negative     Selective marker
    Experimental details: Curated     Microarrays     In-situ hybridization
    Stem Cell Differentiation: 10/32 LifeMap Cells (see all 32) 
    NameCategory
    Neural stem cells (Fetal Stem / Progenitor Cell)Spinal Cord
    Bone marrow-derived mesenchymal stem cells (Stempeucel) (Adult Stem / Progenitor Cell)Bone
    HSF-1 (UC01) (Embryonic Stem Cell)Early Embryo, Inner Cell Mass
    Line H9 (WA09) (Embryonic Stem Cell)Early Embryo, Inner Cell Mass
    PureStem™ endothelial progenitor 30-MV2-12 (Embryonic Progenitor Cell)Blood, Endothelium
    PureStem™ endothelial Progenitor 30-SM2-3 (Embryonic Progenitor Cell)Blood, Endothelium
    PureStem™ endothelial progenitor 30-SM2-1 (Embryonic Progenitor Cell)Endothelium
    Blast colony cells (Generation and expan...)
    Embryoid bodies (Generation and expan...)
    Mesoderm-like cells (Direct differentiati...)Mesoderm

    See CXCR4 Protein Expression from SPIRE MOPED and PaxDB
    Genevestigator expression for CXCR4

    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

        SABiosciences Expression via Pathway-Focused 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

    Primer
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    In Situ
    Assay Products:     
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    Orthologs
    for CXCR4 gene

    (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)
    About This Section
    This gene was present in the common ancestor of chordates.

    Orthologs for CXCR4 gene from 4/13 species (see all 13)    About this table
    Organism Taxonomic
    classification    		 Gene Description Human
    Similarity    		 Orthology
    Type    		 Details
    chicken
    (Gallus gallus)    		 Aves CXCR41 chemokine (C-X-C motif) receptor 4 74.86(n)
    82.57(a)    		   395324  NM_204617.2  NP_989948.2 
    lizard
    (Anolis carolinensis)    		 Reptilia CXCR46
    		 --
    		 80(a)
    		 1 ↔ 1
    		 1(96949460-96950527)
    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
    for CXCR4 gene

    (Paralogs according to 1HomoloGene,
    2Ensembl, and 3SIMAP, Pseudogenes according to 4Pseudogene.org Build 68)
    About This Section
    Paralogs for CXCR4 gene
    CCR62  CCR52  CXCR62  CXCR32  XCR12  CCR92  CCBP22  CCRL22  
    CCR72  CX3CR12  CCR82  CXCR22  CCRL12  CCR42  CXCR12  CCR12  
    CCR22  CXCR52  CCR102  CCR32  
    18/46 SIMAP similar genes for CXCR4 using alignment to 2 protein entries:     CXCR4_HUMAN (see all proteins) (see all similar genes):
    BLR1    CXCR5    CCR7    CCR5    CCRL1    CXCR1
    CXCR6    CCR9    CXCR2    CXCR3    IL8RB    CCR2
    CCR4    CCR6    XCR1    CX3CR1    CCBP2    CCR1

    CXCR4 for paralogs           About GeneDecksing



    Genomic Variants
    for CXCR4 gene

    (SNPs/Variants according to the 1NCBI SNP Database, 2Ensembl, 3PupaSUITE, UniProtKB, 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) and the Locus Specific Mutation Databases (LSDB), Blood group antigen gene mutations by BGMUT, Resequencing Primers from QIAGEN, Cancer Mutation PCR Arrays and Assays and Copy Number PCR Arrays from SABiosciences)
    About This Section

    10/117 NCBI SNPs in CXCR4 are shown (see all 117)     About this table
    Genomic DataTranscription Related DataAllele Frequencies
    SNP IDValidClinical
    significance    		Chr 2 posSequence#AA
    Chg    		TypeMore#Allele
    freq    		PopTotal
    sample    		More
    ----------
    rs1048936241,2
    		Cpathogenic154513708(-) GAAAGC/TGAGGT 4 R * stg10--------
    rs1048936261,2
    		Cpathogenic154513721(-) ACATTC/GATCTG 4 S * stg10--------
    rs133831391,2
    		C--128863979(+) CCGTCT/GGGCAT 2 -- ds50011Minor allele frequency- G:0.00NA 2
    rs789917281,2
    		--128864411(+) CAGAAC/TATAAC 2 -- ds50010--------
    rs178480601,2
    		C,--128864513(-) AATGCT/AGGTTT 2 -- ut312Minor allele frequency- A:0.01NS 92
    rs24718591,2
    		C,F,--128866508(-) TGCGCT/CTTAGG 2 -- us2k1 int117Minor allele frequency- C:0.31NS NA WA CSA EA 1112
    rs178480561,2
    		C,F,--128866622(-) ATACCC/TCAAGC 2 -- us2k1 int19Minor allele frequency- T:0.09NS WA 840
    rs1127842691,2
    		--128866850(+) TACCCG/CGCCAC 2 -- us2k1 int11Minor allele frequency- C:0.50CSA 2
    rs2010142811,2
    		C--128867247(+) TCTTAA/CCCGCC 2 -- us2k1 int10--------
    rs67122641,2
    		C,F,--128867393(+) CTCGCG/AGCCGT 2 -- us2k1 int11Minor allele frequency- A:0.02WA 118

    HapMap Linkage Disequilibrium report for CXCR4 (136871919 - 136875735 bp)
    Structural Variations (Copy Number Variations, Insertions/Deletions, Inversions)
          Database of Genomic Variants (DGV) variations for CXCR4: --
    Human Gene Mutation Database (HGMD): CXCR4

    Locus Specific Mutation Databases (LSDB): CXCR4

    SABiosciences Cancer Mutation PCR Assays
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    Disorders / Diseases
    for CXCR4 gene

    (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
    CXCR4 for disorders           About GeneDecksing

    OMIM gene information: 162643   
    OMIM disorders: 193670  
    UniProtKB/Swiss-Prot: CXCR4_HUMAN, P61073
  • Defects in CXCR4 are a cause of WHIM syndrome (WHIM) [MIM:193670]; also known as warts, hypogammaglobulinemia,
    • infections and myelokathexis. WHIM syndrome is an 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

    20/193 diseases for CXCR4 (see all 193):    About MalaCards
    myelokathexis    von hippel-lindau disease    myelokathexis, isolated    breast cancer
    toxic epidermal necrolysis    stevens-johnson syndrome    aids dementia complex    human t-cell leukemia virus type 1
    hematopoiesis    age related macular degeneration    human immunodeficiency virus infectious disease    severe combined immunodeficiency
    west nile virus    usual interstitial pneumonia    intraocular lymphoma    whim syndrome
    abdominal aortic aneurysm    waldenstrom macroglobulinemia    mitral valve disease    severe congenital neutropenia

    10 diseases from the University of Copenhagen DISEASES database for CXCR4:
    Human immunodeficiency virus infectious disease     Breast cancer     Leukemia     Multiple myeloma
    Lymphoma     Agammaglobulinemia     Myocardial infarction     Vascular disease
    Malignant glioma     Carcinoma

    10/93 Novoseek 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

    Publications
    for CXCR4 gene

    (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)
    About This Section

    PubMed articles for CXCR4 gene, integrated from 9 sources (see all 2141):
    (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. (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. (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. (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. (2010)
    5. Sequential tyrosine sulfation of CXCR4 by tyrosylprotein sulfotransferases. (PubMed id 18834145)1, 2, 9 Seibert C....Sakmar T.P. (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. (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. (1996)
    8. 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. (2009)
    9. Risk for HIV-1 infection associated with a common CXCL12 (SDF1) polymorphism and CXCR4 variation in an African population. (PubMed id 16284526)1, 4, 9 Petersen D.C....Hayes V.M. (2005)
    10. Genomic organization and functional characterization of the chemokine receptor CXCR4, a major entry co-receptor for human immunodeficiency virus type 1. (PubMed id 9468539)1, 2, 9 Wegner S.A....Michael N.L. (1998)

    External Searches for CXCR4 gene

    (in PubMed, OMIM, and NCBI Bookshelf)
    About This Section
     ANDOR
    Aliases
    Disorders
    Free Text  
      Query String
    		PubMed
    OMIM
    NCBI Bookshelf
      (Note: In FireFox, select the above section and copy using Ctrl-C)

    Genome Databases showing CXCR4 gene

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

    Other Databases showing CXCR4 gene

    (According to HUGE)
    About This Section
    		   --

    Specialized Databases showing CXCR4 gene

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

    Intellectual Property
    for CXCR4 gene

    (Patent information from GeneIP,
    Licensable technologies from WIS Yeda, Salk, Tufts,
    IP news from LifeMap Sciences, Inc.)
    About This Section
    		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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    About This Section

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