C-X-C chemokine receptor type 4 - Rattus norvegicus (Rat)

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O08565 (CXCR4_RAT) Reviewed, UniProtKB/Swiss-Prot

Last modified May 1, 2013. Version 95. History...

Clusters with 100%, 90%, 50% identity |

Documents (1) |

Third-party data

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Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents Customize order

Names and origin

Protein names

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 names

Name:	Cxcr4
Synonyms:	Cmkar4

Organism

Rattus norvegicus (Rat) [Reference proteome]

Taxonomic identifier

10116 [NCBI]

Taxonomic lineage

Eukaryota › Metazoa › Chordata › Craniata › Vertebrata › Euteleostomi › Mammalia › Eutheria › Euarchontoglires › Glires › Rodentia › Sciurognathi › Muroidea › Muridae › Murinae › Rattus

Protein attributes

Sequence length	349 AA.
Sequence status	Complete.
Protein existence	Evidence 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.
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.
Subcellular location	Cell membrane; Multi-pass membrane protein 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.
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 component	Cell membrane Membrane
Domain	Transmembrane Transmembrane helix
Molecular function	G-protein coupled receptor Receptor Transducer
PTM	Disulfide bond Glycoprotein Phosphoprotein Proteoglycan Sulfation Ubl conjugation
Technical term	Complete proteome Reference proteome
Gene Ontology (GO)
Biological_process	cardiac muscle contraction Inferred from mutant phenotype PubMed 17010372. Source: RGD chemotaxis Inferred from electronic annotation. Source: InterPro elevation of cytosolic calcium ion concentration 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_component	endosome Inferred from direct assay PubMed 16952464. Source: RGD integral to membrane Traceable author statement PubMed 12431218. Source: RGD plasma membrane Inferred from direct assay PubMed 17046839. Source: RGD
Molecular_function	C-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 key

Position(s)

Length

Description

Graphical view

Feature identifier

Molecule processing

Chain

1 – 349

349

C-X-C chemokine receptor type 4

PRO_0000069358

Regions

Topological domain

1 – 35

Extracellular By similarity

Transmembrane

36 – 60

Helical; Name=1; By similarity

Topological domain

61 – 74

Cytoplasmic By similarity

Transmembrane

75 – 96

Helical; Name=2; By similarity

Topological domain

97 – 107

Extracellular By similarity

Transmembrane

108 – 127

Helical; Name=3; By similarity

Topological domain

128 – 151

Cytoplasmic By similarity

Transmembrane

152 – 171

Helical; Name=4; By similarity

Topological domain

172 – 192

Extracellular By similarity

Transmembrane

193 – 213

Helical; Name=5; By similarity

Topological domain

214 – 238

Cytoplasmic By similarity

Transmembrane

239 – 258

Helical; Name=6; By similarity

Topological domain

259 – 279

Extracellular By similarity

Transmembrane

280 – 299

Helical; Name=7; By similarity

Topological domain

300 – 349

Cytoplasmic By similarity

Region

1 – 18

Important for chemokine binding and signaling By similarity

Region

91 – 94

Chemokine binding By similarity

Region

110 – 114

Chemokine binding By similarity

Region

132 – 144

Involved in dimerization; when bound to chemokine By similarity

Region

183 – 187

Chemokine binding, important for signaling By similarity

Region

188 – 207

Involved in dimerization By similarity

Region

263 – 265

Involved in dimerization By similarity

Motif

130 – 132

Important for signaling By similarity

Sites

Binding site

168

Chemokine By similarity

Binding site

285

Chemokine By similarity

Amino acid modifications

Modified residue

Sulfotyrosine By similarity

Modified residue

Sulfotyrosine By similarity

Modified residue

Sulfotyrosine By similarity

Modified residue

316

Phosphoserine By similarity

Modified residue

318

Phosphoserine By similarity

Modified residue

321

Phosphoserine; by PKC and GRK6 By similarity

Modified residue

322

Phosphoserine; by PKC and GRK6 By similarity

Modified residue

327

Phosphoserine; by GRK6 By similarity

Modified residue

336

Phosphoserine; by GRK6 By similarity

Modified residue

345

Phosphoserine By similarity

Modified residue

348

Phosphoserine By similarity

Glycosylation

N-linked (GlcNAc...) By similarity

Glycosylation

O-linked (Xyl...) (chondroitin sulfate) By similarity

Disulfide bond

25 ↔ 271

By similarity

Disulfide bond

106 ↔ 183

By similarity

Sequences

Sequence

Length

Mass (Da)

Tools

O08565 [UniParc].

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

349

39,334

        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

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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.
IPI	IPI00554141.
UniGene	Rn.44431.
3D structure databases
ProteinModelPortal	O08565.
ModBase	Search...
Protein family/group databases
GPCRDB	Search...
PTM databases
PhosphoSite	O08565.
Protocols and materials databases
StructuralBiologyKnowledgebase	Search...
Genome annotation databases
UCSC	RGD:620465. rat.
Organism-specific databases
RGD	620465. Cxcr4.
Phylogenomic databases
eggNOG	NOG328039.
HOGENOM	HOG000234122.
HOVERGEN	HBG106917.
OrthoDB	EOG46MBKB.
Gene expression databases
ArrayExpress	O08565.
Genevestigator	O08565.
GermOnline	ENSRNOG00000003866. Rattus norvegicus.
Family and domain databases
InterPro	IPR001277. Chemokine_CXCR4. IPR022726. Chemokine_CXCR4_N. IPR000355. Chemokine_rcpt. IPR000276. GPCR_Rhodpsn. IPR017452. GPCR_Rhodpsn_7TM. [Graphical view]
Pfam	PF00001. 7tm_1. 1 hit. PF12109. CXCR4_N. 1 hit. [Graphical view]
PRINTS	PR00657. CCCHEMOKINER. PR00645. CXCCHMKINER4. PR00237. GPCRRHODOPSN.
PROSITE	PS00237. G_PROTEIN_RECEP_F1_1. 1 hit. PS50262. G_PROTEIN_RECEP_F1_2. 1 hit. [Graphical view]
ProtoNet	Search...
Other
BindingDB	O08565.
ChEMBL	CHEMBL5556.

Entry information

Entry name

CXCR4_RAT

Accession

Primary (citable) accession number: O08565

Entry history

Integrated into UniProtKB/Swiss-Prot:	November 1, 1997
Last sequence update:	July 1, 1997
Last modified:	May 1, 2013
This is version 95 of the entry and version 1 of the sequence. [Complete history]

Entry status

Reviewed (UniProtKB/Swiss-Prot)

Annotation program

Chordata Protein Annotation Program

Relevant documents

SIMILARITY comments

Index of protein domains and families

Names·Attributes·General annotation·Ontologies·Sequence annotation·Sequences·References·Cross-refs·Entry info·Documents

Preferred order of sections

Names and origin

Protein attributes

General annotation (Comments)

Ontologies

Sequence annotation (Features)

Molecule processing

Regions

Sites

Amino acid modifications

Sequences

References

Cross-references

Sequence databases

3D structure databases

Protein family/group databases

PTM databases

Protocols and materials databases

Genome annotation databases

Organism-specific databases

Phylogenomic databases

Gene expression databases

Family and domain databases

Other

Entry information

Relevant documents