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P61073

- CXCR4_HUMAN

UniProt

P61073 - CXCR4_HUMAN

Protein

C-X-C chemokine receptor type 4

Gene

CXCR4

Organism
Homo sapiens (Human)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at protein leveli
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    • History
      Entry version 126 (01 Oct 2014)
      Sequence version 1 (26 Apr 2004)
      Previous versions | rss
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    Functioni

    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. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes.10 Publications

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei171 – 1711Chemokine
    Binding sitei288 – 2881Chemokine

    GO - Molecular functioni

    1. actin binding Source: UniProtKB
    2. coreceptor activity Source: ProtInc
    3. C-X-C chemokine receptor activity Source: UniProtKB
    4. G-protein coupled receptor activity Source: ProtInc
    5. myosin light chain binding Source: UniProtKB
    6. protein binding Source: UniProtKB
    7. ubiquitin binding Source: UniProtKB
    8. ubiquitin protein ligase binding Source: UniProtKB
    9. virus receptor activity Source: UniProtKB-KW

    GO - Biological processi

    1. activation of MAPK activity Source: ProtInc
    2. ameboidal cell migration Source: Ensembl
    3. apoptotic process Source: ProtInc
    4. brain development Source: Ensembl
    5. calcium-mediated signaling Source: MGI
    6. cellular response to cytokine stimulus Source: UniProtKB
    7. chemokine-mediated signaling pathway Source: GOC
    8. dendritic cell chemotaxis Source: BHF-UCL
    9. entry into host cell Source: Reactome
    10. germ cell development Source: Ensembl
    11. germ cell migration Source: Ensembl
    12. G-protein coupled receptor signaling pathway Source: UniProtKB
    13. inflammatory response Source: ProtInc
    14. motor neuron axon guidance Source: Ensembl
    15. myelin maintenance Source: BHF-UCL
    16. neural precursor cell proliferation Source: Ensembl
    17. neuron migration Source: Ensembl
    18. neutrophil activation Source: InterPro
    19. patterning of blood vessels Source: Ensembl
    20. positive regulation of cytosolic calcium ion concentration Source: ProtInc
    21. positive regulation of oligodendrocyte differentiation Source: BHF-UCL
    22. regulation of cell migration Source: Ensembl
    23. regulation of chemotaxis Source: UniProtKB
    24. response to hypoxia Source: UniProtKB
    25. response to virus Source: ProtInc
    26. T cell proliferation Source: Ensembl
    27. viral process Source: Reactome

    Keywords - Molecular functioni

    G-protein coupled receptor, Host cell receptor for virus entry, Receptor, Transducer

    Keywords - Biological processi

    Host-virus interaction

    Enzyme and pathway databases

    ReactomeiREACT_15344. Chemokine receptors bind chemokines.
    REACT_19231. G alpha (i) signalling events.
    REACT_6903. Binding and entry of HIV virion.
    SignaLinkiP61073.

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    C-X-C chemokine receptor type 4
    Short name:
    CXC-R4
    Short name:
    CXCR-4
    Alternative name(s):
    FB22
    Fusin
    HM89
    LCR1
    Leukocyte-derived seven transmembrane domain receptor
    Short name:
    LESTR
    Lipopolysaccharide-associated protein 3
    Short name:
    LAP-3
    Short name:
    LPS-associated protein 3
    NPYRL
    Stromal cell-derived factor 1 receptor
    Short name:
    SDF-1 receptor
    CD_antigen: CD184
    Gene namesi
    Name:CXCR4
    OrganismiHomo sapiens (Human)
    Taxonomic identifieri9606 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
    ProteomesiUP000005640: Chromosome 2

    Organism-specific databases

    HGNCiHGNC:2561. CXCR4.

    Subcellular locationi

    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).

    GO - Cellular componenti

    1. cell junction Source: UniProtKB-SubCell
    2. cell leading edge Source: UniProtKB
    3. cell surface Source: UniProtKB
    4. cytoplasm Source: ProtInc
    5. cytoplasmic membrane-bounded vesicle Source: UniProtKB
    6. cytoplasmic vesicle Source: UniProtKB
    7. early endosome Source: UniProtKB
    8. external side of plasma membrane Source: Ensembl
    9. extracellular vesicular exosome Source: UniProt
    10. growth cone Source: Ensembl
    11. integral component of membrane Source: UniProtKB-KW
    12. late endosome Source: UniProtKB
    13. lysosome Source: UniProtKB
    14. plasma membrane Source: UniProtKB

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Endosome, Lysosome, Membrane

    Pathology & Biotechi

    Involvement in diseasei

    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.

    Mutagenesis

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Mutagenesisi2 – 98Missing: Reduced CXCL12 binding. Abolishes signaling.
    Mutagenesisi4 – 2017Missing: Reduced CXCL12 binding. Impaired signaling. Reduced coreceptor activity for HIV-1 isolates LAI and NDK. Add
    BLAST
    Mutagenesisi7 – 71Y → A: Reduced coreceptor activity for HIV-1 isolates LAI and NDK. Greatly reduced coreceptor activity for HIV-1 isolates LAI and NDK; when associated with A-12. 2 Publications
    Mutagenesisi7 – 71Y → F: Sulfate incorporation greatly reduced; when associated with F-12 and F-21. Moderate reduction in sulfate incorporation; when associated with F-12 and A-18. No sulfate incorporation and binding SDF-1alpha greatly reduced; when associated with F-12; A-18 and F-21. 2 Publications
    Mutagenesisi8 – 81T → A: No effect on sulfate incorporation; when associated with A-9 and A-13. 1 Publication
    Mutagenesisi9 – 91S → A: No effect on sulfate incorporation; when associated with A-8 and A-13. 1 Publication
    Mutagenesisi10 – 2011Missing: Reduced CXCL12 binding. No effect on signaling. Add
    BLAST
    Mutagenesisi11 – 111N → A: Reduced molecular weight. Enhanced coreceptor activity on R5 HIV-1 isolate Envs. Slight further enhancement of coreceptor activity; when associated with A-13. 1 Publication
    Mutagenesisi12 – 121Y → A: Greatly reduced coreceptor activity for HIV-1 isolates LAI and NDK; when associated with A-7. 2 Publications
    Mutagenesisi12 – 121Y → F: Sulfate incorporation greatly reduced; when associated with F-7 and F-21. Moderate reduction in sulfate incorporation; when associated with F-7 and A-18. No sulfate incorporation and binding SDF-1alpha greatly reduced; when associated with F-7; A-18 and F-21. 2 Publications
    Mutagenesisi13 – 131T → A: Enhanced coreceptor activity on R5 HIV-1 isolate Envs. No effect on sulfate incorporation; when associated with A-8 and A-9. 1 Publication
    Mutagenesisi14 – 152EE → AA: Reduced CXCL12 binding. Reduced coreceptor activity for HIV-1 isolate NDK.
    Mutagenesisi18 – 181S → A: Sulfate incorporation greatly reduced; when associated with F-21. Moderate reduction in sulfate incorporation; when associated with F-7 and F-12. No sulfate incorporation and binding SDF-1alpha greatly reduced; when associated with F-7; F-12; and F-21. 1 Publication
    Mutagenesisi21 – 211Y → A: Reduced CXCL12 binding. Reduced coreceptor activity for HIV-1 isolates LAI and NDk. 2 Publications
    Mutagenesisi21 – 211Y → F: Sulfate incorporation greatly reduced; when associated with F-7 and F-12. Sulfate incorporation greatly reduced; when associated with A-18. No sulfate incorporation and binding SDF-1alpha greatly reduced; when associated with F-7; F-12 and A-18. 2 Publications
    Mutagenesisi97 – 971D → N: Reduced CXCL12 binding. Abolishes signaling. Markedly reduced coreceptor activity for HIV-1 isolate LAI. 1 Publication
    Mutagenesisi119 – 1191N → D: No reduction of agonist-induced G-protein activation. 1 Publication
    Mutagenesisi119 – 1191N → K: Loss of agonist-induced G-protein activation. 1 Publication
    Mutagenesisi119 – 1191N → S: Constitutive G-protein activation, with further activation induced by agonist. 1 Publication
    Mutagenesisi125 – 1251L → W: Increased thermostability.
    Mutagenesisi133 – 1331D → N: No reduction of agonist-induced G-protein activation. 1 Publication
    Mutagenesisi134 – 1341R → A: Loss of agonist-induced G-protein activation. 1 Publication
    Mutagenesisi135 – 1351Y → A: No reduction of agonist-induced G-protein activation. 1 Publication
    Mutagenesisi171 – 1711D → N: Reduced coreceptor activity for HIV-1 isolate NDK. 1 Publication
    Mutagenesisi176 – 1761N → A: Enhanced coreceptor activity on R5 HIV-1 isolate Envs; when associated with A-11. 1 Publication
    Mutagenesisi183 – 1831R → A: Reduced coreceptor activity for several HIV-1 isolates. 1 Publication
    Mutagenesisi187 – 1871D → A: Reduced CXCL12 binding. Abolishes signaling. 1 Publication
    Mutagenesisi188 – 1881R → A: Reduced coreceptor activity for several HIV-1 isolates. 1 Publication
    Mutagenesisi193 – 1931D → A, S or N: Greatly reduced coreceptor activity for HIV-1 isolate NDK. Reduced coreceptor activity for several other HIV-1 isolates. 2 Publications
    Mutagenesisi193 – 1931D → R: Abolishes coreceptor activity for HIV-1 isolate NDK. Reduced coreceptor activity for several other HIV-1 isolates. 2 Publications
    Mutagenesisi240 – 2401T → P: Retains ligand-binding affinity but abolishes signaling.
    Mutagenesisi262 – 2621D → A: Markedly reduced coreceptor activity for HIV-1 isolate LAI. 1 Publication
    Mutagenesisi268 – 2681E → A: Markedly reduced coreceptor activity for HIV-1 isolate NDK. Less effect for HIV-1 isolate LAI. 1 Publication
    Mutagenesisi288 – 2881E → Q: Reduced CXCL12 binding. Impaired signaling. Reduced coreceptor activity for HIV-1 isolate LAI. Enhanced coreceptor activity for HIV-1 isolate NDK. 1 Publication
    Mutagenesisi324 – 3241S → A: Moderate degradation. About 60% reduction in binding ITCH and no ubiquitination nor protein degradation; when associated with A-325. 1 Publication
    Mutagenesisi324 – 3241S → D: Enhanced binding to ITCH. Enhanced binding to ITCH and greatly increased protein degradation; when associated with D-324. 1 Publication
    Mutagenesisi324 – 3241S → D: Enhanced binding to ITCH. Enhanced binding to ITCH and greatly increased protein degradation; when associated with D-325. 1 Publication
    Mutagenesisi325 – 3251S → A: Moderate degradation. About 60% reduction in binding ITCH and no ubiquitination nor protein degradation; when associated with A-324. 1 Publication
    Mutagenesisi330 – 3301S → A: No effect on binding to ITCH. 1 Publication

    Organism-specific databases

    MIMi193670. phenotype.
    Orphaneti51636. WHIM syndrome.
    PharmGKBiPA27058.

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 352352C-X-C chemokine receptor type 4PRO_0000069352Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei7 – 71Sulfotyrosine; partial2 Publications
    Glycosylationi11 – 111N-linked (GlcNAc...)1 Publication
    Modified residuei12 – 121Sulfotyrosine; partial2 Publications
    Glycosylationi18 – 181O-linked (Xyl...) (chondroitin sulfate)1 Publication
    Modified residuei21 – 211Sulfotyrosine4 Publications
    Disulfide bondi28 ↔ 2741 PublicationPROSITE-ProRule annotation
    Disulfide bondi109 ↔ 1861 PublicationPROSITE-ProRule annotation
    Glycosylationi176 – 1761N-linked (GlcNAc...)Sequence Analysis
    Modified residuei319 – 3191Phosphoserine1 Publication
    Modified residuei321 – 3211Phosphoserine1 Publication
    Modified residuei324 – 3241Phosphoserine; by PKC and GRK62 Publications
    Modified residuei325 – 3251Phosphoserine; by PKC and GRK62 Publications
    Modified residuei330 – 3301Phosphoserine; by GRK61 Publication
    Modified residuei339 – 3391Phosphoserine; by GRK61 Publication
    Modified residuei348 – 3481Phosphoserine1 Publication
    Modified residuei351 – 3511Phosphoserine1 Publication

    Post-translational modificationi

    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 degradation.3 Publications
    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 SFR5S.1 Publication
    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 dimerization.4 Publications
    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 activity.2 Publications

    Keywords - PTMi

    Disulfide bond, Glycoprotein, Phosphoprotein, Proteoglycan, Sulfation, Ubl conjugation

    Proteomic databases

    MaxQBiP61073.
    PaxDbiP61073.
    PRIDEiP61073.

    PTM databases

    PhosphoSiteiP61073.

    Miscellaneous databases

    PMAP-CutDBP61073.

    Expressioni

    Tissue specificityi

    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.1 Publication

    Gene expression databases

    ArrayExpressiP61073.
    BgeeiP61073.
    CleanExiHS_CXCR4.
    GenevestigatoriP61073.

    Organism-specific databases

    HPAiCAB011447.

    Interactioni

    Subunit structurei

    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. Following LPS binding, may form a complex with GDF5, HSP90AA1 and HSPA8.19 Publications

    Binary interactionsi

    WithEntry#Exp.IntActNotes
    CD164Q049002EBI-489411,EBI-2115896
    CD74P042334EBI-489411,EBI-2622890
    CXCR5P323023EBI-489411,EBI-2835269
    DBN1Q166435EBI-489411,EBI-351394
    Dbn1Q07266-13EBI-489411,EBI-8786792From a different organism.
    MYH9P355795EBI-489411,EBI-350338

    Protein-protein interaction databases

    BioGridi113607. 23 interactions.
    DIPiDIP-34773N.
    DIP-46290N.
    IntActiP61073. 14 interactions.
    MINTiMINT-6630550.
    STRINGi9606.ENSP00000386884.

    Structurei

    Secondary structure

    1
    352
    Legend: HelixTurnBeta strand
    Show more details
    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Beta strandi9 – 113
    Beta strandi21 – 233
    Beta strandi32 – 354
    Helixi37 – 6226
    Turni63 – 664
    Beta strandi67 – 693
    Helixi72 – 8817
    Helixi91 – 999
    Helixi105 – 13935
    Helixi141 – 1433
    Helixi145 – 1539
    Helixi155 – 1595
    Helixi161 – 1666
    Helixi169 – 1746
    Beta strandi175 – 1795
    Beta strandi181 – 1888
    Helixi193 – 20715
    Helixi209 – 22517
    Helixi226 – 2283
    Helixi231 – 26636
    Helixi274 – 29118
    Helixi294 – 3018
    Turni302 – 3065
    Helixi313 – 3175

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    EntryMethodResolution (Å)ChainPositionsPDBsum
    2K03NMR-B/D1-38[»]
    2K04NMR-B/D1-38[»]
    2K05NMR-B/D1-38[»]
    3ODUX-ray2.50A/B2-319[»]
    3OE0X-ray2.90A2-319[»]
    3OE6X-ray3.20A2-325[»]
    3OE8X-ray3.10A/B/C2-319[»]
    3OE9X-ray3.10A/B2-319[»]
    ProteinModelPortaliP61073.
    SMRiP61073. Positions 1-318.
    ModBaseiSearch...
    MobiDBiSearch...

    Miscellaneous databases

    EvolutionaryTraceiP61073.

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3838ExtracellularAdd
    BLAST
    Topological domaini64 – 7714CytoplasmicAdd
    BLAST
    Topological domaini100 – 11011ExtracellularAdd
    BLAST
    Topological domaini131 – 15424CytoplasmicAdd
    BLAST
    Topological domaini175 – 19521ExtracellularAdd
    BLAST
    Topological domaini217 – 24125CytoplasmicAdd
    BLAST
    Topological domaini262 – 28221ExtracellularAdd
    BLAST
    Topological domaini303 – 35250CytoplasmicAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei39 – 6325Helical; Name=1Add
    BLAST
    Transmembranei78 – 9922Helical; Name=2Add
    BLAST
    Transmembranei111 – 13020Helical; Name=3Add
    BLAST
    Transmembranei155 – 17420Helical; Name=4Add
    BLAST
    Transmembranei196 – 21621Helical; Name=5Add
    BLAST
    Transmembranei242 – 26120Helical; Name=6Add
    BLAST
    Transmembranei283 – 30220Helical; Name=7Add
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 2121Important for chemokine binding, signaling and HIV-1 coreceptor activityAdd
    BLAST
    Regioni94 – 974Chemokine binding
    Regioni113 – 1175Chemokine binding
    Regioni135 – 14713Involved in dimerization; when bound to chemokineAdd
    BLAST
    Regioni186 – 1905Chemokine binding, important for signaling and HIV-1 coreceptor activity
    Regioni191 – 21020Involved in dimerizationAdd
    BLAST
    Regioni266 – 2683Involved in dimerization

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi133 – 1353Important for signaling

    Domaini

    The amino-terminus is critical for ligand binding. Residues in all four extracellular regions contribute to HIV-1 coreceptor activity.1 Publication

    Sequence similaritiesi

    Belongs to the G-protein coupled receptor 1 family.PROSITE-ProRule annotation

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG328039.
    HOVERGENiHBG106917.
    KOiK04189.
    OMAiSHSKGYQ.
    OrthoDBiEOG73Z2TB.
    PhylomeDBiP61073.
    TreeFamiTF330966.

    Family and domain databases

    Gene3Di1.20.1070.10. 1 hit.
    InterProiIPR001277. Chemokine_CXCR4.
    IPR022726. Chemokine_CXCR4_N_dom.
    IPR000355. Chemokine_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view]
    PANTHERiPTHR24227. PTHR24227. 1 hit.
    PTHR24227:SF7. PTHR24227:SF7. 1 hit.
    PfamiPF00001. 7tm_1. 1 hit.
    PF12109. CXCR4_N. 1 hit.
    [Graphical view]
    PRINTSiPR00657. CCCHEMOKINER.
    PR00645. CXCCHMKINER4.
    PR00237. GPCRRHODOPSN.
    PROSITEiPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view]

    Sequences (2)i

    Sequence statusi: Complete.

    This entry describes 2 isoformsi produced by alternative splicing. Align

    Note: Additional isoforms seem to exist.

    Isoform 1 (identifier: P61073-1) [UniParc]FASTAAdd to Basket

    This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

    « Hide

    MEGISIYTSD NYTEEMGSGD YDSMKEPCFR EENANFNKIF LPTIYSIIFL    50
    TGIVGNGLVI LVMGYQKKLR SMTDKYRLHL SVADLLFVIT LPFWAVDAVA 100
    NWYFGNFLCK AVHVIYTVNL YSSVLILAFI SLDRYLAIVH ATNSQRPRKL 150
    LAEKVVYVGV WIPALLLTIP DFIFANVSEA DDRYICDRFY PNDLWVVVFQ 200
    FQHIMVGLIL PGIVILSCYC IIISKLSHSK GHQKRKALKT TVILILAFFA 250
    CWLPYYIGIS IDSFILLEII KQGCEFENTV HKWISITEAL AFFHCCLNPI 300
    LYAFLGAKFK TSAQHALTSV SRGSSLKILS KGKRGGHSSV STESESSSFH 350
    SS 352
    Length:352
    Mass (Da):39,746
    Last modified:April 26, 2004 - v1
    Checksum:i8C8476A186786B83
    GO
    Isoform 2 (identifier: P61073-2) [UniParc] [UniParc]FASTAAdd to Basket

    Also known as: CXCR4-LO

    The sequence of this isoform differs from the canonical sequence as follows:
         1-5: MEGIS → MSIPLPLLQ

    Show »
    Length:356
    Mass (Da):40,221
    Checksum:i83F9E099F41FAB9B
    GO

    Sequence cautioni

    The sequence CAA12166.1 differs from that shown. Reason: Intron retention.

    Experimental Info

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Sequence conflicti242 – 2443VIL → IIP in AAK29630. 1 PublicationCurated
    Sequence conflicti278 – 2781N → S in BAG35177. (PubMed:14702039)Curated

    Alternative sequence

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Alternative sequencei1 – 55MEGIS → MSIPLPLLQ in isoform 2. 1 PublicationVSP_001890

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L01639 mRNA. Translation: AAA16594.1.
    M99293 mRNA. Translation: AAA16617.1.
    X71635 mRNA. Translation: CAA50641.1.
    L06797 mRNA. Translation: AAA03209.1.
    D10924 mRNA. Translation: BAA01722.1.
    AF005058 Genomic DNA. Translation: AAB93982.1.
    AF052572 Genomic DNA. Translation: AAC34581.1.
    AJ224869 Genomic DNA. Translation: CAA12166.1. Sequence problems.
    AF025375 mRNA. Translation: AAB81970.1.
    Y14739 Genomic DNA. Translation: CAA75034.1.
    AF147204 mRNA. Translation: AAF00130.1.
    AF348491 mRNA. Translation: AAK29630.1.
    AK312244 mRNA. Translation: BAG35177.1.
    AY242129 mRNA. Translation: AAO92296.1.
    BT006660 mRNA. Translation: AAP35306.1.
    AY728138 Genomic DNA. Translation: AAU05775.1.
    AC068492 Genomic DNA. Translation: AAY24044.1.
    CH471058 Genomic DNA. Translation: EAX11616.1.
    BC020968 mRNA. Translation: AAH20968.1.
    CCDSiCCDS33295.1. [P61073-2]
    CCDS46420.1.
    PIRiA45747.
    RefSeqiNP_001008540.1. NM_001008540.1. [P61073-2]
    NP_003458.1. NM_003467.2. [P61073-1]
    UniGeneiHs.593413.

    Genome annotation databases

    EnsembliENST00000241393; ENSP00000241393; ENSG00000121966. [P61073-1]
    ENST00000409817; ENSP00000386884; ENSG00000121966. [P61073-2]
    GeneIDi7852.
    KEGGihsa:7852.
    UCSCiuc002tuy.3. human. [P61073-2]
    uc002tuz.3. human.

    Polymorphism databases

    DMDMi46577576.

    Keywords - Coding sequence diversityi

    Alternative splicing

    Cross-referencesi

    Web resourcesi

    CXCR4base

    CXCR4 mutation db

    Wikipedia

    CXC chemokine receptors entry

    Wikipedia

    CXCR4 entry

    SeattleSNPs

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    L01639 mRNA. Translation: AAA16594.1 .
    M99293 mRNA. Translation: AAA16617.1 .
    X71635 mRNA. Translation: CAA50641.1 .
    L06797 mRNA. Translation: AAA03209.1 .
    D10924 mRNA. Translation: BAA01722.1 .
    AF005058 Genomic DNA. Translation: AAB93982.1 .
    AF052572 Genomic DNA. Translation: AAC34581.1 .
    AJ224869 Genomic DNA. Translation: CAA12166.1 . Sequence problems.
    AF025375 mRNA. Translation: AAB81970.1 .
    Y14739 Genomic DNA. Translation: CAA75034.1 .
    AF147204 mRNA. Translation: AAF00130.1 .
    AF348491 mRNA. Translation: AAK29630.1 .
    AK312244 mRNA. Translation: BAG35177.1 .
    AY242129 mRNA. Translation: AAO92296.1 .
    BT006660 mRNA. Translation: AAP35306.1 .
    AY728138 Genomic DNA. Translation: AAU05775.1 .
    AC068492 Genomic DNA. Translation: AAY24044.1 .
    CH471058 Genomic DNA. Translation: EAX11616.1 .
    BC020968 mRNA. Translation: AAH20968.1 .
    CCDSi CCDS33295.1. [P61073-2 ]
    CCDS46420.1.
    PIRi A45747.
    RefSeqi NP_001008540.1. NM_001008540.1. [P61073-2 ]
    NP_003458.1. NM_003467.2. [P61073-1 ]
    UniGenei Hs.593413.

    3D structure databases

    Select the link destinations:
    PDBe
    RCSB PDB
    PDBj
    Links Updated
    Entry Method Resolution (Å) Chain Positions PDBsum
    2K03 NMR - B/D 1-38 [» ]
    2K04 NMR - B/D 1-38 [» ]
    2K05 NMR - B/D 1-38 [» ]
    3ODU X-ray 2.50 A/B 2-319 [» ]
    3OE0 X-ray 2.90 A 2-319 [» ]
    3OE6 X-ray 3.20 A 2-325 [» ]
    3OE8 X-ray 3.10 A/B/C 2-319 [» ]
    3OE9 X-ray 3.10 A/B 2-319 [» ]
    ProteinModelPortali P61073.
    SMRi P61073. Positions 1-318.
    ModBasei Search...
    MobiDBi Search...

    Protein-protein interaction databases

    BioGridi 113607. 23 interactions.
    DIPi DIP-34773N.
    DIP-46290N.
    IntActi P61073. 14 interactions.
    MINTi MINT-6630550.
    STRINGi 9606.ENSP00000386884.

    Chemistry

    BindingDBi P61073.
    ChEMBLi CHEMBL2107.
    DrugBanki DB00452. Framycetin.
    GuidetoPHARMACOLOGYi 71.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei P61073.

    Polymorphism databases

    DMDMi 46577576.

    Proteomic databases

    MaxQBi P61073.
    PaxDbi P61073.
    PRIDEi P61073.

    Protocols and materials databases

    DNASUi 7852.
    Structural Biology Knowledgebase Search...

    Genome annotation databases

    Ensembli ENST00000241393 ; ENSP00000241393 ; ENSG00000121966 . [P61073-1 ]
    ENST00000409817 ; ENSP00000386884 ; ENSG00000121966 . [P61073-2 ]
    GeneIDi 7852.
    KEGGi hsa:7852.
    UCSCi uc002tuy.3. human. [P61073-2 ]
    uc002tuz.3. human.

    Organism-specific databases

    CTDi 7852.
    GeneCardsi GC02M136871.
    HGNCi HGNC:2561. CXCR4.
    HPAi CAB011447.
    MIMi 162643. gene.
    193670. phenotype.
    neXtProti NX_P61073.
    Orphaneti 51636. WHIM syndrome.
    PharmGKBi PA27058.
    GenAtlasi Search...

    Phylogenomic databases

    eggNOGi NOG328039.
    HOVERGENi HBG106917.
    KOi K04189.
    OMAi SHSKGYQ.
    OrthoDBi EOG73Z2TB.
    PhylomeDBi P61073.
    TreeFami TF330966.

    Enzyme and pathway databases

    Reactomei REACT_15344. Chemokine receptors bind chemokines.
    REACT_19231. G alpha (i) signalling events.
    REACT_6903. Binding and entry of HIV virion.
    SignaLinki P61073.

    Miscellaneous databases

    ChiTaRSi CXCR4. human.
    EvolutionaryTracei P61073.
    GeneWikii CXCR4.
    GenomeRNAii 7852.
    NextBioi 30286.
    PMAP-CutDB P61073.
    PROi P61073.
    SOURCEi Search...

    Gene expression databases

    ArrayExpressi P61073.
    Bgeei P61073.
    CleanExi HS_CXCR4.
    Genevestigatori P61073.

    Family and domain databases

    Gene3Di 1.20.1070.10. 1 hit.
    InterProi IPR001277. Chemokine_CXCR4.
    IPR022726. Chemokine_CXCR4_N_dom.
    IPR000355. Chemokine_rcpt.
    IPR000276. GPCR_Rhodpsn.
    IPR017452. GPCR_Rhodpsn_7TM.
    [Graphical view ]
    PANTHERi PTHR24227. PTHR24227. 1 hit.
    PTHR24227:SF7. PTHR24227:SF7. 1 hit.
    Pfami PF00001. 7tm_1. 1 hit.
    PF12109. CXCR4_N. 1 hit.
    [Graphical view ]
    PRINTSi PR00657. CCCHEMOKINER.
    PR00645. CXCCHMKINER4.
    PR00237. GPCRRHODOPSN.
    PROSITEi PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
    PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
    [Graphical view ]
    ProtoNeti Search...

    Publicationsi

    1. "Molecular cloning, characterization, and localization of the human homolog to the reported bovine NPY Y3 receptor: lack of NPY binding and activation."
      Herzog H., Hort Y.J., Shine J., Selbie L.A.
      DNA Cell Biol. 12:465-471(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PRELIMINARY FUNCTION.
      Tissue: Lung.
    2. "A proposed bovine neuropeptide Y (NPY) receptor cDNA clone, or its human homologue, confers neither NPY binding sites nor NPY responsiveness on transfected cells."
      Jazin E.E., Yoo H., Blomqvist A.G., Yee F., Weng G., Walker M.W., Salon J., Larhammar D., Wahlestedt C.R.
      Regul. Pept. 47:247-258(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), PRELIMINARY FUNCTION.
      Tissue: Fetal brain.
    3. "Molecular cloning of the cDNA and chromosomal localization of the gene for a putative seven-transmembrane segment (7-TMS) receptor isolated from human spleen."
      Federsppiel B., Melhado I.G., Duncan A.M.V., Delaney A.D., Schappert K., Clark-Lewis I., Jirik F.R.
      Genomics 16:707-712(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Fetal spleen.
    4. "Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes."
      Loetscher M., Geiser T., O'Reilly T., Zwahlen R., Baggiolini M., Moser B.
      J. Biol. Chem. 269:232-237(1994) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
      Tissue: Monocyte.
    5. "Molecular cloning of cDNAs encoding a LD78 receptor and putative leukocyte chemotactic peptide receptors."
      Nomura H., Nielsen B.W., Matsushima K.
      Int. Immunol. 5:1239-1249(1993) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    6. "HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor."
      Feng Y., Broder C.C., Kennedy P.E., Berger E.A.
      Science 272:872-877(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1), CHARACTERIZATION OF ITS HIV-1 CORECEPTOR FUNCTION.
    7. "Genomic organization and functional characterization of the chemokine receptor CXCR4, a major entry co-receptor for human immunodeficiency virus type 1."
      Wegner S.A., Ehrenberg P.K., Chang G., Dayhoff D.E., Sleeker A.L., Michael N.L.
      J. Biol. Chem. 273:4754-4760(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Peripheral blood leukocyte.
    8. Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    9. "Partial resistance to infection by R5X4 primary HIV type 1 isolates in an exposed-uninfected individual homozygous for CCR5 32-base pair deletion."
      Xiao L., Weiss S.H., Qari S.H., Rudolph D., Zhao C., Denny T.N., Hodge T., Lal R.B.
      AIDS Res. Hum. Retroviruses 15:1201-1208(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    10. "Genomic organization and expression of the CXCR4 gene in mouse and man: absence of a splice variant corresponding to mouse CXCR4-B in human tissues."
      Frodl R., Gierschik P., Moepps B.
      J. Recept. Signal Transduct. 18:321-344(1998) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
      Tissue: Peripheral blood lymphocyte.
    11. "CXCR4-Lo: molecular cloning and functional expression of a novel human CXCR4 splice variant."
      Gupta S.K., Pillarisetti K.
      J. Immunol. 163:2368-2372(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 2).
      Tissue: Neutrophil.
    12. Fan Z., Li T., Li J., Luo B.
      Submitted (FEB-2001) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA] (ISOFORM 1).
    13. "Complete sequencing and characterization of 21,243 full-length human cDNAs."
      Ota T., Suzuki Y., Nishikawa T., Otsuki T., Sugiyama T., Irie R., Wakamatsu A., Hayashi K., Sato H., Nagai K., Kimura K., Makita H., Sekine M., Obayashi M., Nishi T., Shibahara T., Tanaka T., Ishii S.
      , Yamamoto J., Saito K., Kawai Y., Isono Y., Nakamura Y., Nagahari K., Murakami K., Yasuda T., Iwayanagi T., Wagatsuma M., Shiratori A., Sudo H., Hosoiri T., Kaku Y., Kodaira H., Kondo H., Sugawara M., Takahashi M., Kanda K., Yokoi T., Furuya T., Kikkawa E., Omura Y., Abe K., Kamihara K., Katsuta N., Sato K., Tanikawa M., Yamazaki M., Ninomiya K., Ishibashi T., Yamashita H., Murakawa K., Fujimori K., Tanai H., Kimata M., Watanabe M., Hiraoka S., Chiba Y., Ishida S., Ono Y., Takiguchi S., Watanabe S., Yosida M., Hotuta T., Kusano J., Kanehori K., Takahashi-Fujii A., Hara H., Tanase T.-O., Nomura Y., Togiya S., Komai F., Hara R., Takeuchi K., Arita M., Imose N., Musashino K., Yuuki H., Oshima A., Sasaki N., Aotsuka S., Yoshikawa Y., Matsunawa H., Ichihara T., Shiohata N., Sano S., Moriya S., Momiyama H., Satoh N., Takami S., Terashima Y., Suzuki O., Nakagawa S., Senoh A., Mizoguchi H., Goto Y., Shimizu F., Wakebe H., Hishigaki H., Watanabe T., Sugiyama A., Takemoto M., Kawakami B., Yamazaki M., Watanabe K., Kumagai A., Itakura S., Fukuzumi Y., Fujimori Y., Komiyama M., Tashiro H., Tanigami A., Fujiwara T., Ono T., Yamada K., Fujii Y., Ozaki K., Hirao M., Ohmori Y., Kawabata A., Hikiji T., Kobatake N., Inagaki H., Ikema Y., Okamoto S., Okitani R., Kawakami T., Noguchi S., Itoh T., Shigeta K., Senba T., Matsumura K., Nakajima Y., Mizuno T., Morinaga M., Sasaki M., Togashi T., Oyama M., Hata H., Watanabe M., Komatsu T., Mizushima-Sugano J., Satoh T., Shirai Y., Takahashi Y., Nakagawa K., Okumura K., Nagase T., Nomura N., Kikuchi H., Masuho Y., Yamashita R., Nakai K., Yada T., Nakamura Y., Ohara O., Isogai T., Sugano S.
      Nat. Genet. 36:40-45(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Adrenal gland.
    14. "cDNA clones of human proteins involved in signal transduction sequenced by the Guthrie cDNA resource center (www.cdna.org)."
      Warren C.N., Aronstam R.S., Sharma S.V.
      Submitted (FEB-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Lung.
    15. "Cloning of human full-length CDSs in BD Creator(TM) system donor vector."
      Kalnine N., Chen X., Rolfs A., Halleck A., Hines L., Eisenstein S., Koundinya M., Raphael J., Moreira D., Kelley T., LaBaer J., Lin Y., Phelan M., Farmer A.
      Submitted (MAY-2003) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
    16. SeattleSNPs variation discovery resource
      Submitted (AUG-2004) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [GENOMIC DNA].
    17. "Generation and annotation of the DNA sequences of human chromosomes 2 and 4."
      Hillier L.W., Graves T.A., Fulton R.S., Fulton L.A., Pepin K.H., Minx P., Wagner-McPherson C., Layman D., Wylie K., Sekhon M., Becker M.C., Fewell G.A., Delehaunty K.D., Miner T.L., Nash W.E., Kremitzki C., Oddy L., Du H.
      , Sun H., Bradshaw-Cordum H., Ali J., Carter J., Cordes M., Harris A., Isak A., van Brunt A., Nguyen C., Du F., Courtney L., Kalicki J., Ozersky P., Abbott S., Armstrong J., Belter E.A., Caruso L., Cedroni M., Cotton M., Davidson T., Desai A., Elliott G., Erb T., Fronick C., Gaige T., Haakenson W., Haglund K., Holmes A., Harkins R., Kim K., Kruchowski S.S., Strong C.M., Grewal N., Goyea E., Hou S., Levy A., Martinka S., Mead K., McLellan M.D., Meyer R., Randall-Maher J., Tomlinson C., Dauphin-Kohlberg S., Kozlowicz-Reilly A., Shah N., Swearengen-Shahid S., Snider J., Strong J.T., Thompson J., Yoakum M., Leonard S., Pearman C., Trani L., Radionenko M., Waligorski J.E., Wang C., Rock S.M., Tin-Wollam A.-M., Maupin R., Latreille P., Wendl M.C., Yang S.-P., Pohl C., Wallis J.W., Spieth J., Bieri T.A., Berkowicz N., Nelson J.O., Osborne J., Ding L., Meyer R., Sabo A., Shotland Y., Sinha P., Wohldmann P.E., Cook L.L., Hickenbotham M.T., Eldred J., Williams D., Jones T.A., She X., Ciccarelli F.D., Izaurralde E., Taylor J., Schmutz J., Myers R.M., Cox D.R., Huang X., McPherson J.D., Mardis E.R., Clifton S.W., Warren W.C., Chinwalla A.T., Eddy S.R., Marra M.A., Ovcharenko I., Furey T.S., Miller W., Eichler E.E., Bork P., Suyama M., Torrents D., Waterston R.H., Wilson R.K.
      Nature 434:724-731(2005) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    18. Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA].
    19. "The status, quality, and expansion of the NIH full-length cDNA project: the Mammalian Gene Collection (MGC)."
      The MGC Project Team
      Genome Res. 14:2121-2127(2004) [PubMed] [Europe PMC] [Abstract]
      Cited for: NUCLEOTIDE SEQUENCE [LARGE SCALE MRNA] (ISOFORM 1).
      Tissue: Colon.
    20. "The lymphocyte chemoattractant SDF-1 is a ligand for LESTR/fusin and blocks HIV-1 entry."
      Bleul C.C., Farzan M., Choe H., Parolin C., Clark-Lewis I., Sodroski J., Springer T.A.
      Nature 382:829-833(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    21. "The CXC chemokine SDF-1 is the ligand for LESTR/fusin and prevents infection by T-cell-line-adapted HIV-1."
      Oberlin E., Amara A., Bachelerie F., Bessia C., Virelizier J.-L., Arenzana-Seisdedos F., Schwartz O., Heard J.-M., Clark-Lewis I., Legler D.F., Loetscher M., Baggiolini M., Moser B.
      Nature 382:833-835(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION.
    22. "Evidence for cell-surface association between fusin and the CD4-gp120 complex in human cell lines."
      Lapham C.K., Ouyang J., Chandrasekhar B., Nguyen N.Y., Dimitrov D.S., Golding H.
      Science 274:602-605(1996) [PubMed] [Europe PMC] [Abstract]
      Cited for: CHARACTERIZATION AS HIV-1 CORECEPTOR.
    23. Cited for: CHARACTERIZATION AS HIV-2 PRIMARY RECEPTOR IN SOME ISOLATES.
    24. Cited for: ANTAGONIST, INTERACTION WITH CXCL12, CHARACTERIZATION AS HIV-1 CORECEPTOR.
    25. "Tyrosine sulfation of the amino terminus of CCR5 facilitates HIV-1 entry."
      Farzan M., Mirzabekov T., Kolchinsky P., Wyatt R., Cayabyab M., Gerard N.P., Gerard C., Sodroski J., Choe H.
      Cell 96:667-676(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: SULFATION.
    26. "Effect of mutations in the second extracellular loop of CXCR4 on its utilization by human and feline immunodeficiency viruses."
      Brelot A., Heveker N., Adema K., Hosie M.J., Willett B., Alizon M.
      J. Virol. 73:2576-2586(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ARG-183; ARG-188 AND ASP-193.
    27. "Identification of CXCR4 domains that support coreceptor and chemokine receptor functions."
      Doranz B.J., Orsini M.J., Turner J.D., Hoffman T.L., Berson J.F., Hoxie J.A., Peiper S.C., Brass L.F., Doms R.W.
      J. Virol. 73:2752-2761(1999) [PubMed] [Europe PMC] [Abstract]
      Cited for: DOMAINS, INTERACTION WITH HIV-1 SURFACE PROTEIN GP120.
    28. "beta-arrestin differentially regulates the chemokine receptor CXCR4-mediated signaling and receptor internalization, and this implicates multiple interaction sites between beta-arrestin and CXCR4."
      Cheng Z.J., Zhao J., Sun Y., Hu W., Wu Y.L., Cen B., Wu G.-X., Pei G.
      J. Biol. Chem. 275:2479-2485(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ARRB2, FUNCTION.
    29. "Identification of residues of CXCR4 critical for human immunodeficiency virus coreceptor and chemokine receptor activities."
      Brelot A., Heveker N., Montes M., Alizon M.
      J. Biol. Chem. 275:23736-23744(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH CXCL12, MUTAGENESIS OF 2-GLU--SER-9; 4-ILE--ASP-20; TYR-7; 10-ASP--ASP-20; TYR-12; 14-GLU-GLU-15; TYR-21; ASP-97; ASP-171; ASP-187; ASP-193; ASP-262; GLU-268 AND GLU-288.
    30. "N-linked glycosylation of CXCR4 masks coreceptor function for CCR5-dependent human immunodeficiency virus type 1 isolates."
      Chabot D.J., Chen H., Dimitrov D.S., Broder C.C.
      J. Virol. 74:4404-4413(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT ASN-11, INTERACTION WITH HIV-1 ENV, SUBUNIT, MUTAGENESIS OF ASN-11; THR-13 AND ASN-176.
    31. "Selective CXCR4 antagonism by Tat: implications for in vivo expansion of coreceptor use by HIV-1."
      Xiao H., Neuveut C., Tiffany H.L., Benkirane M., Rich E.A., Murphy P.M., Jeang K.-T.
      Proc. Natl. Acad. Sci. U.S.A. 97:11466-11471(2000) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HIV-1 TAT.
    32. Cited for: FUNCTION, IDENTIFICATION AS LPS RECEPTOR, INTERACTION WITH GDF5; HSP90AA1 AND HSPA8, TISSUE SPECIFICITY.
    33. "The role of post-translational modifications of the CXCR4 amino terminus in stromal-derived factor 1 alpha association and HIV-1 entry."
      Farzan M., Babcock G.J., Vasilieva N., Wright P.L., Kiprilov E., Mirzabekov T., Choe H.
      J. Biol. Chem. 277:29484-29489(2002) [PubMed] [Europe PMC] [Abstract]
      Cited for: GLYCOSYLATION AT SER-18, IDENTIFICATION OF PROTEOGLYCAN, INTERACTION WITH CXCL12, SULFATION AT TYR-21, MUTAGENESIS OF TYR-7; THR-8; SER-9; TYR-12; SER-18 AND TYR-21.
    34. "The E3 ubiquitin ligase AIP4 mediates ubiquitination and sorting of the G protein-coupled receptor CXCR4."
      Marchese A., Raiborg C., Santini F., Keen J.H., Stenmark H., Benovic J.L.
      Dev. Cell 5:709-722(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: UBIQUITINATION BY ITCH, SUBCELLULAR LOCATION.
    35. "Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease."
      Hernandez P.A., Gorlin R.J., Lukens J.N., Taniuchi S., Bohinjec J., Francois F., Klotman M.E., Diaz G.A.
      Nat. Genet. 34:70-74(2003) [PubMed] [Europe PMC] [Abstract]
      Cited for: DISEASE.
    36. "Global, in vivo, and site-specific phosphorylation dynamics in signaling networks."
      Olsen J.V., Blagoev B., Gnad F., Macek B., Kumar C., Mortensen P., Mann M.
      Cell 127:635-648(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    37. "Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells."
      Forde S., Tye B.J., Newey S.E., Roubelakis M., Smythe J., McGuckin C.P., Pettengell R., Watt S.M.
      Blood 109:1825-1833(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH CD164.
    38. "Direct assessment of CXCR4 mutant conformations reveals complex link between receptor structure and G(alpha)(i) activation."
      Berchiche Y.A., Chow K.Y., Lagane B., Leduc M., Percherancier Y., Fujii N., Tamamura H., Bachelerie F., Heveker N.
      J. Biol. Chem. 282:5111-5115(2007) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, MUTAGENESIS OF ASN-119; ASP-133; ARG-134 AND TYR-135.
    39. "Sequential tyrosine sulfation of CXCR4 by tyrosylprotein sulfotransferases."
      Seibert C., Veldkamp C.T., Peterson F.C., Chait B.T., Volkman B.F., Sakmar T.P.
      Biochemistry 47:11251-11262(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: SULFATION AT TYR-7; TYR-12 AND TYR-21, INTERACTION WITH CXCL12.
    40. "Combining protein-based IMAC, peptide-based IMAC, and MudPIT for efficient phosphoproteomic analysis."
      Cantin G.T., Yi W., Lu B., Park S.K., Xu T., Lee J.-D., Yates J.R. III
      J. Proteome Res. 7:1346-1351(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    41. Cited for: PHOSPHORYLATION [LARGE SCALE ANALYSIS] AT SER-319 AND SER-348, IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    42. "The E3 ubiquitin ligase atrophin interacting protein 4 binds directly to the chemokine receptor CXCR4 via a novel WW domain-mediated interaction."
      Bhandari D., Robia S.L., Marchese A.
      Mol. Biol. Cell 20:1324-1339(2009) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH ITCH, SUBCELLULAR LOCATION, PHOSPHORYLATION AT SER-324 AND SER-325, MUTAGENESIS OF SER-324; SER-325 AND SER-330.
    43. "Site-specific phosphorylation of CXCR4 is dynamically regulated by multiple kinases and results in differential modulation of CXCR4 signaling."
      Busillo J.M., Armando S., Sengupta R., Meucci O., Bouvier M., Benovic J.L.
      J. Biol. Chem. 285:7805-7817(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: PHOSPHORYLATION AT SER-321; SER-324; SER-325; SER-330; SER-339 AND SER-351, INTERACTION WITH ARRB2 AND ARRC, FUNCTION, IDENTIFICATION BY MASS SPECTROMETRY.
    44. "CXC chemokine receptor 4 is a cell surface receptor for extracellular ubiquitin."
      Saini V., Marchese A., Majetschak M.
      J. Biol. Chem. 285:15566-15576(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH UBIQUITIN.
    45. Cited for: INTERACTION WITH DBN1, SUBCELLULAR LOCATION.
    46. "Arrestin-2 interacts with the endosomal sorting complex required for transport machinery to modulate endosomal sorting of CXCR4."
      Malik R., Marchese A.
      Mol. Biol. Cell 21:2529-2541(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: FUNCTION, INTERACTION WITH UBIQUITIN.
    47. "Quantitative phosphoproteomics reveals widespread full phosphorylation site occupancy during mitosis."
      Olsen J.V., Vermeulen M., Santamaria A., Kumar C., Miller M.L., Jensen L.J., Gnad F., Cox J., Jensen T.S., Nigg E.A., Brunak S., Mann M.
      Sci. Signal. 3:RA3-RA3(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: IDENTIFICATION BY MASS SPECTROMETRY [LARGE SCALE ANALYSIS].
      Tissue: Cervix carcinoma.
    48. "Down-modulation of the G-protein-coupled estrogen receptor, GPER, from the cell surface occurs via a trans-Golgi-proteasome pathway."
      Cheng S.B., Quinn J.A., Graeber C.T., Filardo E.J.
      J. Biol. Chem. 286:22441-22455(2011) [PubMed] [Europe PMC] [Abstract]
      Cited for: SUBCELLULAR LOCATION.
    49. "Human cytomegalovirus-encoded UL33 and UL78 heteromerize with host CCR5 and CXCR4 impairing their HIV coreceptor activity."
      Tadagaki K., Tudor D., Gbahou F., Tschische P., Waldhoer M., Bomsel M., Jockers R., Kamal M.
      Blood 119:4908-4918(2012) [PubMed] [Europe PMC] [Abstract]
      Cited for: INTERACTION WITH HHV-5 PROTEIN UL78.
    50. "Recognition of a CXCR4 sulfotyrosine by the chemokine stromal cell-derived factor-1alpha (SDF-1alpha/CXCL12)."
      Veldkamp C.T., Seibert C., Peterson F.C., Sakmar T.P., Volkman B.F.
      J. Mol. Biol. 359:1400-1409(2006) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-38, SULFATION AT TYR-21, IDENTIFICATION BY MASS SPECTROMETRY, INTERACTION WITH CXCL12.
    51. "Structural basis of CXCR4 sulfotyrosine recognition by the chemokine SDF-1/CXCL12."
      Veldkamp C.T., Seibert C., Peterson F.C., De la Cruz N.B., Haugner J.C. III, Basnet H., Sakmar T.P., Volkman B.F.
      Sci. Signal. 1:RA4-RA4(2008) [PubMed] [Europe PMC] [Abstract]
      Cited for: STRUCTURE BY NMR OF 1-38 OF SULFATED MUTANT ALA-28 IN COMPLEX WITH CXCL12.
    52. "Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists."
      Wu B., Chien E.Y., Mol C.D., Fenalti G., Liu W., Katritch V., Abagyan R., Brooun A., Wells P., Bi F.C., Hamel D.J., Kuhn P., Handel T.M., Cherezov V., Stevens R.C.
      Science 330:1066-1071(2010) [PubMed] [Europe PMC] [Abstract]
      Cited for: X-RAY CRYSTALLOGRAPHY (2.5 ANGSTROMS) OF 2-325 OF MUTANTS LEU-125 AND THR-240 IN COMPLEX WITH ANTAGONISTS CVX15 AND IT1T, HOMODIMERIZATION, DISULFIDE BONDS.

    Entry informationi

    Entry nameiCXCR4_HUMAN
    AccessioniPrimary (citable) accession number: P61073
    Secondary accession number(s): B2R5N0
    , O60835, P30991, P56438, Q53S69, Q9BXA0, Q9UKN2
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: April 26, 2004
    Last sequence update: April 26, 2004
    Last modified: October 1, 2014
    This is version 126 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program
    DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

    Miscellaneousi

    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).Curated

    Keywords - Technical termi

    3D-structure, Complete proteome, Reference proteome

    Documents

    1. 7-transmembrane G-linked receptors
      List of 7-transmembrane G-linked receptor entries
    2. Human cell differentiation molecules
      CD nomenclature of surface proteins of human leucocytes and list of entries
    3. Human chromosome 2
      Human chromosome 2: entries, gene names and cross-references to MIM
    4. MIM cross-references
      Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
    5. PDB cross-references
      Index of Protein Data Bank (PDB) cross-references
    6. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3