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Protein

C-X-C chemokine receptor type 4

Gene

CXCR4

Organism
Canis lupus familiaris (Dog) (Canis familiaris)
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 sitei172ChemokineBy similarity1
Binding sitei289ChemokineBy similarity1

GO - Molecular functioni

GO - Biological processi

Keywordsi

Molecular functionG-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-CFA-376176. Signaling by ROBO receptors.
R-CFA-380108. Chemokine receptors bind chemokines.
R-CFA-418594. G alpha (i) signalling events.

Names & Taxonomyi

Protein namesi
Recommended name:
C-X-C chemokine receptor type 4
Short name:
CXC-R4
Short name:
CXCR-4
Alternative name(s):
CD_antigen: CD184
Gene namesi
Name:CXCR4
OrganismiCanis lupus familiaris (Dog) (Canis familiaris)
Taxonomic identifieri9615 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaLaurasiatheriaCarnivoraCaniformiaCanidaeCanis
Proteomesi
  • UP000002254 Componenti: Chromosome 19

Subcellular locationi

Extracellular region or secreted Cytosol Plasma membrane Cytoskeleton Lysosome Endosome Peroxisome ER Golgi apparatus Nucleus Mitochondrion Manual annotation Automatic computational assertionGraphics by Christian Stolte; Source: COMPARTMENTS

Topology

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Topological domaini1 – 39ExtracellularBy similarityAdd BLAST39
Transmembranei40 – 64Helical; Name=1By similarityAdd BLAST25
Topological domaini65 – 78CytoplasmicBy similarityAdd BLAST14
Transmembranei79 – 100Helical; Name=2By similarityAdd BLAST22
Topological domaini101 – 111ExtracellularBy similarityAdd BLAST11
Transmembranei112 – 131Helical; Name=3By similarityAdd BLAST20
Topological domaini132 – 155CytoplasmicBy similarityAdd BLAST24
Transmembranei156 – 175Helical; Name=4By similarityAdd BLAST20
Topological domaini176 – 196ExtracellularBy similarityAdd BLAST21
Transmembranei197 – 217Helical; Name=5By similarityAdd BLAST21
Topological domaini218 – 242CytoplasmicBy similarityAdd BLAST25
Transmembranei243 – 262Helical; Name=6By similarityAdd BLAST20
Topological domaini263 – 283ExtracellularBy similarityAdd BLAST21
Transmembranei284 – 303Helical; Name=7By similarityAdd BLAST20
Topological domaini304 – 353CytoplasmicBy similarityAdd BLAST50

Keywords - Cellular componenti

Cell junction, Cell membrane, Endosome, Lysosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00002479791 – 353C-X-C chemokine receptor type 4Add BLAST353

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei7SulfotyrosineBy similarity1
Glycosylationi11N-linked (GlcNAc...) asparagineBy similarity1
Modified residuei12SulfotyrosineBy similarity1
Glycosylationi19O-linked (Xyl...) (chondroitin sulfate) serineBy similarity1
Modified residuei22SulfotyrosineBy similarity1
Disulfide bondi29 ↔ 275PROSITE-ProRule annotation
Disulfide bondi110 ↔ 187PROSITE-ProRule annotation
Modified residuei320PhosphoserineBy similarity1
Modified residuei322PhosphoserineBy similarity1
Modified residuei325Phosphoserine; by PKC and GRK6By similarity1
Modified residuei326Phosphoserine; by PKC and GRK6By similarity1
Modified residuei331Phosphoserine; by GRK6By similarity1
Modified residuei340Phosphoserine; by GRK6By similarity1
Modified residuei349PhosphoserineBy similarity1
Modified residuei352PhosphoserineBy similarity1

Post-translational modificationi

Phosphorylated on agonist stimulation. Rapidly phosphorylated on serine and threonine residues in the C-terminal. Phosphorylation at Ser-325 and Ser-326 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

PaxDbiQ3LSL6.

Expressioni

Gene expression databases

BgeeiENSCAFG00000005109.

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

GO - Molecular functioni

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000007600.

Structurei

3D structure databases

ProteinModelPortaliQ3LSL6.
SMRiQ3LSL6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 22Important for chemokine binding and signalingBy similarityAdd BLAST22
Regioni95 – 98Chemokine bindingBy similarity4
Regioni114 – 118Chemokine bindingBy similarity5
Regioni136 – 148Involved in dimerization; when bound to chemokineBy similarityAdd BLAST13
Regioni187 – 191Chemokine binding, important for signalingBy similarity5
Regioni192 – 211Involved in dimerizationBy similarityAdd BLAST20
Regioni267 – 269Involved in dimerizationBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi134 – 136Important 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.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiQ3LSL6.
KOiK04189.
OMAiVHKWISI.
OrthoDBiEOG091G0HEN.
TreeFamiTF330966.

Family and domain databases

InterProiView protein in InterPro
IPR022726. Chemokine_CXCR4_N_dom.
IPR000355. Chemokine_rcpt.
IPR001277. CXCR4/ACKR2.
IPR000276. GPCR_Rhodpsn.
IPR017452. GPCR_Rhodpsn_7TM.
PfamiView protein in Pfam
PF00001. 7tm_1. 1 hit.
PF12109. CXCR4_N. 1 hit.
PRINTSiPR00657. CCCHEMOKINER.
PR00645. CXCCHMKINER4.
PR00237. GPCRRHODOPSN.
PROSITEiView protein in PROSITE
PS00237. G_PROTEIN_RECEP_F1_1. 1 hit.
PS50262. G_PROTEIN_RECEP_F1_2. 1 hit.

Sequencei

Sequence statusi: Complete.

Q3LSL6-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEELHIYPSD NYTEEDLGSG DYDSMKEPCF REENAHFNRI FLPTVYSIIF
60 70 80 90 100
LTGIVGNGLV ILVMGYQKKL RSMTDKYRLH LSVADLLFVL TLPFWAVEAV
110 120 130 140 150
ANWYFGNFLC KAVHVIYTVN LYSSVLILAF ISLDRYLAIV HATNSQRPRK
160 170 180 190 200
LLAEKVVYVG VWIPALLLTI PDFIFANVRE ADDRYICDRF YPNDSWLVVF
210 220 230 240 250
QFQHIMVGLI LPGIVILSCY CIIISKLSHS KGYQKRKALK TTVILILAFF
260 270 280 290 300
ACWLPYYIGI SIDSFILLEI IKQGCEFEKT VHKWISITEA LAFFHCCLNP
310 320 330 340 350
ILYAFLGAKF KTSAQHALTS VSRGSSLKIL SKGKRGGHSS VSTESESSSF

HSS
Length:353
Mass (Da):40,109
Last modified:October 25, 2005 - v1
Checksum:i56F9A02CEECE9161
GO

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
DQ182699 mRNA. Translation: ABA28309.1.
RefSeqiNP_001041491.1. NM_001048026.1.
UniGeneiCfa.16645.

Genome annotation databases

EnsembliENSCAFT00000008205; ENSCAFP00000007600; ENSCAFG00000005109.
GeneIDi483900.
KEGGicfa:483900.

Similar proteinsi

Entry informationi

Entry nameiCXCR4_CANLF
AccessioniPrimary (citable) accession number: Q3LSL6
Entry historyiIntegrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: October 25, 2005
Last modified: November 22, 2017
This is version 94 of the entry and version 1 of the sequence. See complete history.
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program

Miscellaneousi

Keywords - Technical termi

Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. SIMILARITY comments
    Index of protein domains and families