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O08565 (CXCR4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified April 16, 2014. Version 104. Feed History...

Clusters with 100%, 90%, 50% identity | Documents (1) | Third-party data text xml rdf/xml gff fasta
to top of pageNames·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·DocumentsCustomize order

Names and origin

Protein namesRecommended 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 names
Name:Cxcr4
Synonyms:Cmkar4
OrganismRattus norvegicus (Rat) [Reference proteome]
Taxonomic identifier10116 [NCBI]
Taxonomic lineageEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresGliresRodentiaSciurognathiMuroideaMuridaeMurinaeRattus

Protein attributes

Sequence length349 AA.
Sequence statusComplete.
Protein existenceEvidence at transcript level

General annotation (Comments)

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

Subunit structure

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.

Subcellular location

Cell membrane; 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.

Post-translational modification

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.

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.

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.

Sequence similarities

Belongs to the G-protein coupled receptor 1 family.

Ontologies

Keywords
   Cellular componentCell junction
Cell membrane
Endosome
Lysosome
Membrane
   DomainTransmembrane
Transmembrane helix
   Molecular functionG-protein coupled receptor
Receptor
Transducer
   PTMDisulfide bond
Glycoprotein
Phosphoprotein
Proteoglycan
Sulfation
Ubl conjugation
   Technical termComplete proteome
Reference proteome
Gene Ontology (GO)
   Biological_processcardiac muscle contraction

Inferred from mutant phenotype PubMed 17010372. Source: RGD

cell migration

Inferred from mutant phenotype PubMed 15358596. Source: RGD

cellular response to cytokine stimulus

Inferred from sequence or structural similarity. Source: UniProtKB

chemokine-mediated signaling pathway

Inferred from mutant phenotype PubMed 21294880. Source: GOC

chemotaxis

Inferred from electronic annotation. Source: InterPro

epithelial cell development

Inferred from mutant phenotype PubMed 15358596. Source: RGD

neuron migration

Inferred from direct assay PubMed 12401342. Source: RGD

neuron recognition

Inferred from expression pattern PubMed 12431218. Source: RGD

neutrophil activation

Inferred from electronic annotation. Source: InterPro

regulation of calcium ion transport

Inferred from mutant phenotype PubMed 12864967. Source: RGD

regulation of chemotaxis

Inferred from mutant phenotype PubMed 15358596. Source: RGD

regulation of programmed cell death

Inferred from mutant phenotype PubMed 14550764. Source: RGD

telencephalon cell migration

Inferred from mutant phenotype PubMed 16971524. Source: RGD

   Cellular_componentcell junction

Inferred from electronic annotation. Source: UniProtKB-SubCell

early endosome

Inferred from sequence or structural similarity. Source: UniProtKB

endosome

Inferred from direct assay PubMed 16952464. Source: RGD

integral component of membrane

Traceable author statement PubMed 12431218. Source: RGD

late endosome

Inferred from sequence or structural similarity. Source: UniProtKB

lysosome

Inferred from sequence or structural similarity. Source: UniProtKB

plasma membrane

Inferred from direct assay PubMed 17046839. Source: RGD

   Molecular_functionC-C chemokine receptor activity

Traceable author statement PubMed 12431218. Source: RGD

C-X-C chemokine receptor activity

Inferred from mutant phenotype PubMed 21294880. Source: RGD

drug binding

Inferred from direct assay PubMed 21294880. Source: RGD

Complete GO annotation...

Sequence annotation (Features)

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifier

Molecule processing

Chain1 – 349349C-X-C chemokine receptor type 4
PRO_0000069358

Regions

Topological domain1 – 3535Extracellular By similarity
Transmembrane36 – 6025Helical; Name=1; By similarity
Topological domain61 – 7414Cytoplasmic By similarity
Transmembrane75 – 9622Helical; Name=2; By similarity
Topological domain97 – 10711Extracellular By similarity
Transmembrane108 – 12720Helical; Name=3; By similarity
Topological domain128 – 15124Cytoplasmic By similarity
Transmembrane152 – 17120Helical; Name=4; By similarity
Topological domain172 – 19221Extracellular By similarity
Transmembrane193 – 21321Helical; Name=5; By similarity
Topological domain214 – 23825Cytoplasmic By similarity
Transmembrane239 – 25820Helical; Name=6; By similarity
Topological domain259 – 27921Extracellular By similarity
Transmembrane280 – 29920Helical; Name=7; By similarity
Topological domain300 – 34950Cytoplasmic By similarity
Region1 – 1818Important for chemokine binding and signaling By similarity
Region91 – 944Chemokine binding By similarity
Region110 – 1145Chemokine binding By similarity
Region132 – 14413Involved in dimerization; when bound to chemokine By similarity
Region183 – 1875Chemokine binding, important for signaling By similarity
Region188 – 20720Involved in dimerization By similarity
Region263 – 2653Involved in dimerization By similarity
Motif130 – 1323Important for signaling By similarity

Sites

Binding site1681Chemokine By similarity
Binding site2851Chemokine By similarity

Amino acid modifications

Modified residue41Sulfotyrosine By similarity
Modified residue91Sulfotyrosine By similarity
Modified residue181Sulfotyrosine By similarity
Modified residue3161Phosphoserine By similarity
Modified residue3181Phosphoserine By similarity
Modified residue3211Phosphoserine; by PKC and GRK6 By similarity
Modified residue3221Phosphoserine; by PKC and GRK6 By similarity
Modified residue3271Phosphoserine; by GRK6 By similarity
Modified residue3361Phosphoserine; by GRK6 By similarity
Modified residue3451Phosphoserine By similarity
Modified residue3481Phosphoserine By similarity
Glycosylation81N-linked (GlcNAc...) By similarity
Glycosylation151O-linked (Xyl...) (chondroitin sulfate) By similarity
Disulfide bond25 ↔ 271 By similarity
Disulfide bond106 ↔ 183 By similarity

Sequences

Sequence LengthMass (Da)Tools
O08565 [UniParc].

Last modified July 1, 1997. Version 1.
Checksum: 7E0789A605C60C09

FASTA34939,334
        10         20         30         40         50         60 
MEIYTSDNYS EEVGSGDYDS NKEPCFRDEN ENFNRIFLPT IYFIIFLTGI VGNGLVILVM 

        70         80         90        100        110        120 
GYQKKLRSMT DKYRLHLSVA DLLFVITLPF WAVDAMADWY FGKFLCKAVH IIYTVNLYSS 

       130        140        150        160        170        180 
VLILAFISLD RYLAIVHATN SQSARKLLAE KAVYVGVWIP ALLLTIPDII FADVSQGDGR 

       190        200        210        220        230        240 
YICDRLYPDS LWMVVFQFQH IMVGLILPGI VILSCYCIII SKLSHSKGHQ KRKALKTTVI 

       250        260        270        280        290        300 
LILAFFACWL PYYVGISIDS FILLEVIKQG CEFESVVHKW ISITEALAFF HCCLNPILYA 

       310        320        330        340 
FLGAKFKSSA QHALNSMSRG SSLKILSKGK RGGHSSVSTE SESSSFHSS 

« Hide

References

[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.
+Additional computationally mapped references.

Cross-references

Sequence databases

EMBL
GenBank
DDBJ
U90610 mRNA. Translation: AAB50408.1.
UniGeneRn.44431.

3D structure databases

ProteinModelPortalO08565.
ModBaseSearch...
MobiDBSearch...

Chemistry

BindingDBO08565.
ChEMBLCHEMBL5556.
GuidetoPHARMACOLOGY71.

Protein family/group databases

GPCRDBSearch...

PTM databases

PhosphoSiteO08565.

Protocols and materials databases

StructuralBiologyKnowledgebaseSearch...

Genome annotation databases

UCSCRGD:620465. rat.

Organism-specific databases

RGD620465. Cxcr4.

Phylogenomic databases

eggNOGNOG328039.
HOGENOMHOG000234122.
HOVERGENHBG106917.
PhylomeDBO08565.

Gene expression databases

GenevestigatorO08565.

Family and domain databases

Gene3D1.20.1070.10. 1 hit.
InterProIPR001277. Chemokine_CXCR4.
IPR022726. Chemokine_CXCR4_N_dom.
IPR000355. Chemokine_rcpt.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERPTHR24227. PTHR24227. 1 hit.
PTHR24227:SF7. PTHR24227:SF7. 1 hit.
PfamPF00001. 7tm_1. 1 hit.
PF12109. CXCR4_N. 1 hit.
[Graphical view]
PRINTSPR00657. CCCHEMOKINER.
PR00645. CXCCHMKINER4.
PR00237. GPCRRHODOPSN.
PROSITEPS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.
[Graphical view]
ProtoNetSearch...

Other

PROO08565.

Entry information

Entry nameCXCR4_RAT
AccessionPrimary (citable) accession number: O08565
Entry history
Integrated into UniProtKB/Swiss-Prot: November 1, 1997
Last sequence update: July 1, 1997
Last modified: April 16, 2014
This is version 104 of the entry and version 1 of the sequence. [Complete history]
Entry statusReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families