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O08565

- CXCR4_RAT

UniProt

O08565 - CXCR4_RAT

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Protein
C-X-C chemokine receptor type 4
Gene
Cxcr4, Cmkar4
Organism
Rattus norvegicus (Rat)
Status
Reviewed - Annotation score: 5 out of 5 - Experimental evidence at transcript leveli

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.

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei168 – 1681Chemokine By similarity
Binding sitei285 – 2851Chemokine By 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
Complete GO annotation...

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; 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.

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3535Extracellular By similarity
Add
BLAST
Transmembranei36 – 6025Helical; Name=1; By similarity
Add
BLAST
Topological domaini61 – 7414Cytoplasmic By similarity
Add
BLAST
Transmembranei75 – 9622Helical; Name=2; By similarity
Add
BLAST
Topological domaini97 – 10711Extracellular By similarity
Add
BLAST
Transmembranei108 – 12720Helical; Name=3; By similarity
Add
BLAST
Topological domaini128 – 15124Cytoplasmic By similarity
Add
BLAST
Transmembranei152 – 17120Helical; Name=4; By similarity
Add
BLAST
Topological domaini172 – 19221Extracellular By similarity
Add
BLAST
Transmembranei193 – 21321Helical; Name=5; By similarity
Add
BLAST
Topological domaini214 – 23825Cytoplasmic By similarity
Add
BLAST
Transmembranei239 – 25820Helical; Name=6; By similarity
Add
BLAST
Topological domaini259 – 27921Extracellular By similarity
Add
BLAST
Transmembranei280 – 29920Helical; Name=7; By similarity
Add
BLAST
Topological domaini300 – 34950Cytoplasmic By similarity
Add
BLAST

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
Complete GO annotation...

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 4
PRO_0000069358Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei4 – 41Sulfotyrosine By similarity
Glycosylationi8 – 81N-linked (GlcNAc...) By similarity
Modified residuei9 – 91Sulfotyrosine By similarity
Glycosylationi15 – 151O-linked (Xyl...) (chondroitin sulfate) By similarity
Modified residuei18 – 181Sulfotyrosine By similarity
Disulfide bondi25 ↔ 271 By similarity
Disulfide bondi106 ↔ 183 By similarity
Modified residuei316 – 3161Phosphoserine By similarity
Modified residuei318 – 3181Phosphoserine By similarity
Modified residuei321 – 3211Phosphoserine; by PKC and GRK6 By similarity
Modified residuei322 – 3221Phosphoserine; by PKC and GRK6 By similarity
Modified residuei327 – 3271Phosphoserine; by GRK6 By similarity
Modified residuei336 – 3361Phosphoserine; by GRK6 By similarity
Modified residuei345 – 3451Phosphoserine By similarity
Modified residuei348 – 3481Phosphoserine By 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.
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.

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.

Structurei

3D structure databases

ProteinModelPortaliO08565.

Family & Domainsi

Region

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

Motif

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

Sequence similaritiesi

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

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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: April 16, 2014
This is version 104 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

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