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Protein

C-X-C chemokine receptor type 4

Gene

Cxcr4

Organism
Rattus norvegicus (Rat)
Status
Reviewed-Annotation score: 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).By similarity

Sites

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Binding sitei168ChemokineBy similarity1
Binding sitei285ChemokineBy similarity1

GO - Molecular functioni

  • C-C chemokine receptor activity Source: RGD
  • C-X-C chemokine receptor activity Source: RGD
  • drug binding Source: RGD

GO - Biological processi

  • cardiac muscle contraction Source: RGD
  • cell migration Source: RGD
  • cellular response to cytokine stimulus Source: UniProtKB
  • cellular response to drug Source: RGD
  • chemotaxis Source: InterPro
  • endothelial cell differentiation Source: RGD
  • endothelial tube morphogenesis Source: RGD
  • epithelial cell development Source: RGD
  • neurogenesis Source: RGD
  • neuron migration Source: RGD
  • neuron recognition Source: RGD
  • positive regulation of cell migration Source: RGD
  • positive regulation of mesenchymal stem cell migration Source: RGD
  • positive regulation of vascular wound healing Source: RGD
  • regulation of calcium ion transport Source: RGD
  • regulation of chemotaxis Source: RGD
  • regulation of programmed cell death Source: RGD
  • regulation of viral process Source: RGD
  • response to activity Source: RGD
  • response to ultrasound Source: RGD
  • 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
Proteomesi
  • UP000002494 Componenti: 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

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 35ExtracellularBy similarityAdd BLAST35
Transmembranei36 – 60Helical; Name=1By similarityAdd BLAST25
Topological domaini61 – 74CytoplasmicBy similarityAdd BLAST14
Transmembranei75 – 96Helical; Name=2By similarityAdd BLAST22
Topological domaini97 – 107ExtracellularBy similarityAdd BLAST11
Transmembranei108 – 127Helical; Name=3By similarityAdd BLAST20
Topological domaini128 – 151CytoplasmicBy similarityAdd BLAST24
Transmembranei152 – 171Helical; Name=4By similarityAdd BLAST20
Topological domaini172 – 192ExtracellularBy similarityAdd BLAST21
Transmembranei193 – 213Helical; Name=5By similarityAdd BLAST21
Topological domaini214 – 238CytoplasmicBy similarityAdd BLAST25
Transmembranei239 – 258Helical; Name=6By similarityAdd BLAST20
Topological domaini259 – 279ExtracellularBy similarityAdd BLAST21
Transmembranei280 – 299Helical; Name=7By similarityAdd BLAST20
Topological domaini300 – 349CytoplasmicBy similarityAdd BLAST50

GO - Cellular componenti

  • cell junction Source: UniProtKB-SubCell
  • cytoplasm Source: RGD
  • early endosome Source: UniProtKB
  • endosome Source: RGD
  • integral component of membrane Source: RGD
  • late endosome Source: UniProtKB
  • lysosome Source: UniProtKB
  • plasma membrane Source: RGD
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL5556.
GuidetoPHARMACOLOGYi71.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000693581 – 349C-X-C chemokine receptor type 4Add BLAST349

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei4SulfotyrosineBy similarity1
Glycosylationi8N-linked (GlcNAc...)By similarity1
Modified residuei9SulfotyrosineBy similarity1
Glycosylationi15O-linked (Xyl...) (chondroitin sulfate)By similarity1
Modified residuei18SulfotyrosineBy similarity1
Disulfide bondi25 ↔ 271PROSITE-ProRule annotation
Disulfide bondi106 ↔ 183PROSITE-ProRule annotation
Modified residuei316PhosphoserineBy similarity1
Modified residuei318PhosphoserineBy similarity1
Modified residuei321Phosphoserine; by PKC and GRK6By similarity1
Modified residuei322Phosphoserine; by PKC and GRK6By similarity1
Modified residuei327Phosphoserine; by GRK6By similarity1
Modified residuei336Phosphoserine; by GRK6By similarity1
Modified residuei345PhosphoserineBy similarity1
Modified residuei348PhosphoserineBy similarity1

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

Proteomic databases

PaxDbiO08565.
PRIDEiO08565.

PTM databases

PhosphoSitePlusiO08565.

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

Protein-protein interaction databases

IntActiO08565. 1 interactor.
STRINGi10116.ENSRNOP00000005143.

Chemistry databases

BindingDBiO08565.

Structurei

3D structure databases

ProteinModelPortaliO08565.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 18Important for chemokine binding and signalingBy similarityAdd BLAST18
Regioni91 – 94Chemokine bindingBy similarity4
Regioni110 – 114Chemokine bindingBy similarity5
Regioni132 – 144Involved in dimerization; when bound to chemokineBy similarityAdd BLAST13
Regioni183 – 187Chemokine binding, important for signalingBy similarity5
Regioni188 – 207Involved in dimerizationBy similarityAdd BLAST20
Regioni263 – 265Involved in dimerizationBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi130 – 132Important for signalingBy similarity3

Sequence similaritiesi

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

Keywords - Domaini

Transmembrane, Transmembrane helix

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiO08565.
PhylomeDBiO08565.

Family and domain databases

InterProiIPR022726. Chemokine_CXCR4_N_dom.
IPR000355. Chemokine_rcpt.
IPR033039. CXCR4.
IPR001277. CXCR4/ACKR2.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR10489:SF594. PTHR10489:SF594. 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

        10         20         30         40         50
MEIYTSDNYS EEVGSGDYDS NKEPCFRDEN ENFNRIFLPT IYFIIFLTGI
60 70 80 90 100
VGNGLVILVM GYQKKLRSMT DKYRLHLSVA DLLFVITLPF WAVDAMADWY
110 120 130 140 150
FGKFLCKAVH IIYTVNLYSS VLILAFISLD RYLAIVHATN SQSARKLLAE
160 170 180 190 200
KAVYVGVWIP ALLLTIPDII FADVSQGDGR YICDRLYPDS LWMVVFQFQH
210 220 230 240 250
IMVGLILPGI VILSCYCIII SKLSHSKGHQ KRKALKTTVI LILAFFACWL
260 270 280 290 300
PYYVGISIDS FILLEVIKQG CEFESVVHKW ISITEALAFF HCCLNPILYA
310 320 330 340
FLGAKFKSSA QHALNSMSRG SSLKILSKGK RGGHSSVSTE SESSSFHSS
Length:349
Mass (Da):39,334
Last modified:July 1, 1997 - v1
Checksum:i7E0789A605C60C09
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U90610 mRNA. Translation: AAB50408.1.
UniGeneiRn.44431.

Genome annotation databases

UCSCiRGD:620465. rat.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U90610 mRNA. Translation: AAB50408.1.
UniGeneiRn.44431.

3D structure databases

ProteinModelPortaliO08565.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

IntActiO08565. 1 interactor.
STRINGi10116.ENSRNOP00000005143.

Chemistry databases

BindingDBiO08565.
ChEMBLiCHEMBL5556.
GuidetoPHARMACOLOGYi71.

Protein family/group databases

GPCRDBiSearch...

PTM databases

PhosphoSitePlusiO08565.

Proteomic databases

PaxDbiO08565.
PRIDEiO08565.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

UCSCiRGD:620465. rat.

Organism-specific databases

RGDi620465. Cxcr4.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiO08565.
PhylomeDBiO08565.

Miscellaneous databases

PROiO08565.

Family and domain databases

InterProiIPR022726. Chemokine_CXCR4_N_dom.
IPR000355. Chemokine_rcpt.
IPR033039. CXCR4.
IPR001277. CXCR4/ACKR2.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
[Graphical view]
PANTHERiPTHR10489:SF594. PTHR10489:SF594. 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]
ProtoNetiSearch...

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: November 2, 2016
This is version 117 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

Similar proteinsi

Links to similar proteins from the UniProt Reference Clusters (UniRef) at 100%, 90% and 50% sequence identity:
100%UniRef100 combines identical sequences and sub-fragments with 11 or more residues from any organism into one UniRef entry.
90%UniRef90 is built by clustering UniRef100 sequences that have at least 90% sequence identity to, and 80% overlap with, the longest sequence (a.k.a seed sequence).
50%UniRef50 is built by clustering UniRef90 seed sequences that have at least 50% sequence identity to, and 80% overlap with, the longest sequence in the cluster.