Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Basket 0
(max 400 entries)x

Your basket is currently empty.

Select item(s) and click on "Add to basket" to create your own collection here
(400 entries max)

O08565

- CXCR4_RAT

UniProt

O08565 - CXCR4_RAT

Protein

C-X-C chemokine receptor type 4

Gene

Cxcr4

Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5- Experimental evidence at transcript leveli
    • BLAST
    • Align
    • Format
    • Add to basket
    • History
      Entry version 105 (01 Oct 2014)
      Sequence version 1 (01 Jul 1997)
      Previous versions | rss
    • Help video
    • Feedback
    • Comment

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

    Sites

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Binding sitei168 – 1681ChemokineBy similarity
    Binding sitei285 – 2851ChemokineBy similarity

    GO - Molecular functioni

    1. C-C chemokine receptor activity Source: RGD
    2. C-X-C chemokine receptor activity Source: RGD
    3. drug binding Source: RGD

    GO - Biological processi

    1. cardiac muscle contraction Source: RGD
    2. cell migration Source: RGD
    3. cellular response to cytokine stimulus Source: UniProtKB
    4. chemokine-mediated signaling pathway Source: GOC
    5. chemotaxis Source: InterPro
    6. epithelial cell development Source: RGD
    7. neuron migration Source: RGD
    8. neuron recognition Source: RGD
    9. neutrophil activation Source: InterPro
    10. regulation of calcium ion transport Source: RGD
    11. regulation of chemotaxis Source: RGD
    12. regulation of programmed cell death Source: RGD
    13. telencephalon cell migration Source: RGD

    Keywords - Molecular functioni

    G-protein coupled receptor, Receptor, Transducer

    Names & Taxonomyi

    Protein namesi
    Recommended name:
    C-X-C chemokine receptor type 4
    Short name:
    CXC-R4
    Short name:
    CXCR-4
    Alternative name(s):
    Fusin
    Leukocyte-derived seven transmembrane domain receptor
    Short name:
    LESTR
    Stromal cell-derived factor 1 receptor
    Short name:
    SDF-1 receptor
    CD_antigen: CD184
    Gene namesi
    Name:Cxcr4
    Synonyms:Cmkar4
    OrganismiRattus norvegicus (Rat)
    Taxonomic identifieri10116 [NCBI]
    Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus
    ProteomesiUP000002494: Unplaced

    Organism-specific databases

    RGDi620465. Cxcr4.

    Subcellular locationi

    Cell membrane By similarity; Multi-pass membrane protein By similarity. Cell junction By similarity. Early endosome By similarity. Late endosome By similarity. Lysosome By similarity
    Note: In unstimulated cells, diffuse pattern on plasma membrane. On agonist stimulation, colocalizes with ITCH at the plasma membrane where it becomes ubiquitinated By similarity. 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) By similarity.By similarity

    GO - Cellular componenti

    1. cell junction Source: UniProtKB-SubCell
    2. early endosome Source: UniProtKB
    3. endosome Source: RGD
    4. integral component of membrane Source: RGD
    5. late endosome Source: UniProtKB
    6. lysosome Source: UniProtKB
    7. plasma membrane Source: RGD

    Keywords - Cellular componenti

    Cell junction, Cell membrane, Endosome, Lysosome, Membrane

    PTM / Processingi

    Molecule processing

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Chaini1 – 349349C-X-C chemokine receptor type 4PRO_0000069358Add
    BLAST

    Amino acid modifications

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Modified residuei4 – 41SulfotyrosineBy similarity
    Glycosylationi8 – 81N-linked (GlcNAc...)By similarity
    Modified residuei9 – 91SulfotyrosineBy similarity
    Glycosylationi15 – 151O-linked (Xyl...) (chondroitin sulfate)By similarity
    Modified residuei18 – 181SulfotyrosineBy similarity
    Disulfide bondi25 ↔ 271PROSITE-ProRule annotation
    Disulfide bondi106 ↔ 183PROSITE-ProRule annotation
    Modified residuei316 – 3161PhosphoserineBy similarity
    Modified residuei318 – 3181PhosphoserineBy similarity
    Modified residuei321 – 3211Phosphoserine; by PKC and GRK6By similarity
    Modified residuei322 – 3221Phosphoserine; by PKC and GRK6By similarity
    Modified residuei327 – 3271Phosphoserine; by GRK6By similarity
    Modified residuei336 – 3361Phosphoserine; by GRK6By similarity
    Modified residuei345 – 3451PhosphoserineBy similarity
    Modified residuei348 – 3481PhosphoserineBy similarity

    Post-translational modificationi

    Phosphorylated on agonist stimulation. Rapidly phosphorylated on serine and threonine residues in the C-terminal. Phosphorylation at Ser-321 and Ser-322 leads to recruitment of ITCH, ubiquitination and protein degradation By similarity.By similarity
    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 By similarity.By similarity
    Sulfation is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization.By similarity
    O- and N-glycosylated. N-glycosylation can mask coreceptor function. The O-glycosylation chondroitin sulfate attachment does not affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity By similarity.By similarity

    Keywords - PTMi

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

    PTM databases

    PhosphoSiteiO08565.

    Expressioni

    Gene expression databases

    GenevestigatoriO08565.

    Interactioni

    Subunit structurei

    Monomer By similarity. Can form dimers By similarity. Interacts with CD164. 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; the interaction enhances intracellular calcium ions and reduces cellular cAMP levels By similarity. Interacts with DBN1; this interaction is enhanced by antigenic stimulation By similarity. Following LPS binding, may form a complex with GDF5, HSP90AA1 and HSPA8 By similarity.By similarity

    Structurei

    3D structure databases

    ProteinModelPortaliO08565.
    ModBaseiSearch...
    MobiDBiSearch...

    Topological domain

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Topological domaini1 – 3535ExtracellularBy similarityAdd
    BLAST
    Topological domaini61 – 7414CytoplasmicBy similarityAdd
    BLAST
    Topological domaini97 – 10711ExtracellularBy similarityAdd
    BLAST
    Topological domaini128 – 15124CytoplasmicBy similarityAdd
    BLAST
    Topological domaini172 – 19221ExtracellularBy similarityAdd
    BLAST
    Topological domaini214 – 23825CytoplasmicBy similarityAdd
    BLAST
    Topological domaini259 – 27921ExtracellularBy similarityAdd
    BLAST
    Topological domaini300 – 34950CytoplasmicBy similarityAdd
    BLAST

    Transmembrane

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Transmembranei36 – 6025Helical; Name=1By similarityAdd
    BLAST
    Transmembranei75 – 9622Helical; Name=2By similarityAdd
    BLAST
    Transmembranei108 – 12720Helical; Name=3By similarityAdd
    BLAST
    Transmembranei152 – 17120Helical; Name=4By similarityAdd
    BLAST
    Transmembranei193 – 21321Helical; Name=5By similarityAdd
    BLAST
    Transmembranei239 – 25820Helical; Name=6By similarityAdd
    BLAST
    Transmembranei280 – 29920Helical; Name=7By similarityAdd
    BLAST

    Family & Domainsi

    Region

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Regioni1 – 1818Important for chemokine binding and signalingBy similarityAdd
    BLAST
    Regioni91 – 944Chemokine bindingBy similarity
    Regioni110 – 1145Chemokine bindingBy similarity
    Regioni132 – 14413Involved in dimerization; when bound to chemokineBy similarityAdd
    BLAST
    Regioni183 – 1875Chemokine binding, important for signalingBy similarity
    Regioni188 – 20720Involved in dimerizationBy similarityAdd
    BLAST
    Regioni263 – 2653Involved in dimerizationBy similarity

    Motif

    Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
    Motifi130 – 1323Important for signalingBy similarity

    Sequence similaritiesi

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

    Keywords - Domaini

    Transmembrane, Transmembrane helix

    Phylogenomic databases

    eggNOGiNOG328039.
    HOGENOMiHOG000234122.
    HOVERGENiHBG106917.
    PhylomeDBiO08565.

    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]

    Sequencei

    Sequence statusi: Complete.

    O08565-1 [UniParc]FASTAAdd to Basket

    « Hide

    MEIYTSDNYS EEVGSGDYDS NKEPCFRDEN ENFNRIFLPT IYFIIFLTGI    50
    VGNGLVILVM GYQKKLRSMT DKYRLHLSVA DLLFVITLPF WAVDAMADWY 100
    FGKFLCKAVH IIYTVNLYSS VLILAFISLD RYLAIVHATN SQSARKLLAE 150
    KAVYVGVWIP ALLLTIPDII FADVSQGDGR YICDRLYPDS LWMVVFQFQH 200
    IMVGLILPGI VILSCYCIII SKLSHSKGHQ KRKALKTTVI LILAFFACWL 250
    PYYVGISIDS FILLEVIKQG CEFESVVHKW ISITEALAFF HCCLNPILYA 300
    FLGAKFKSSA QHALNSMSRG SSLKILSKGK RGGHSSVSTE SESSSFHSS 349
    Length:349
    Mass (Da):39,334
    Last modified:July 1, 1997 - v1
    Checksum:i7E0789A605C60C09
    GO

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U90610 mRNA. Translation: AAB50408.1.
    UniGeneiRn.44431.

    Genome annotation databases

    UCSCiRGD:620465. rat.

    Cross-referencesi

    Sequence databases

    Select the link destinations:
    EMBL
    GenBank
    DDBJ
    Links Updated
    U90610 mRNA. Translation: AAB50408.1 .
    UniGenei Rn.44431.

    3D structure databases

    ProteinModelPortali O08565.
    ModBasei Search...
    MobiDBi Search...

    Chemistry

    BindingDBi O08565.
    ChEMBLi CHEMBL5556.
    GuidetoPHARMACOLOGYi 71.

    Protein family/group databases

    GPCRDBi Search...

    PTM databases

    PhosphoSitei O08565.

    Protocols and materials databases

    Structural Biology Knowledgebase Search...

    Genome annotation databases

    UCSCi RGD:620465. rat.

    Organism-specific databases

    RGDi 620465. Cxcr4.

    Phylogenomic databases

    eggNOGi NOG328039.
    HOGENOMi HOG000234122.
    HOVERGENi HBG106917.
    PhylomeDBi O08565.

    Miscellaneous databases

    PROi O08565.

    Gene expression databases

    Genevestigatori O08565.

    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 of rat CXCR4."
      Harrison J.K., Salafranca M.N.
      Submitted (MAR-1997) to the EMBL/GenBank/DDBJ databases
      Cited for: NUCLEOTIDE SEQUENCE [MRNA].
      Strain: Wistar.
      Tissue: Spleen.

    Entry informationi

    Entry nameiCXCR4_RAT
    AccessioniPrimary (citable) accession number: O08565
    Entry historyi
    Integrated into UniProtKB/Swiss-Prot: November 1, 1997
    Last sequence update: July 1, 1997
    Last modified: October 1, 2014
    This is version 105 of the entry and version 1 of the sequence. [Complete history]
    Entry statusiReviewed (UniProtKB/Swiss-Prot)
    Annotation programChordata Protein Annotation Program

    Miscellaneousi

    Keywords - Technical termi

    Complete proteome, Reference proteome

    Documents

    1. SIMILARITY comments
      Index of protein domains and families

    External Data

    Dasty 3