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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)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei172 – 1721ChemokineBy similarity
Binding sitei289 – 2891ChemokineBy similarity

GO - Molecular functioni

GO - Biological processi

Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Receptor, Transducer

Enzyme and pathway databases

ReactomeiR-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

  • 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)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3939ExtracellularBy similarityAdd
BLAST
Transmembranei40 – 6425Helical; Name=1By similarityAdd
BLAST
Topological domaini65 – 7814CytoplasmicBy similarityAdd
BLAST
Transmembranei79 – 10022Helical; Name=2By similarityAdd
BLAST
Topological domaini101 – 11111ExtracellularBy similarityAdd
BLAST
Transmembranei112 – 13120Helical; Name=3By similarityAdd
BLAST
Topological domaini132 – 15524CytoplasmicBy similarityAdd
BLAST
Transmembranei156 – 17520Helical; Name=4By similarityAdd
BLAST
Topological domaini176 – 19621ExtracellularBy similarityAdd
BLAST
Transmembranei197 – 21721Helical; Name=5By similarityAdd
BLAST
Topological domaini218 – 24225CytoplasmicBy similarityAdd
BLAST
Transmembranei243 – 26220Helical; Name=6By similarityAdd
BLAST
Topological domaini263 – 28321ExtracellularBy similarityAdd
BLAST
Transmembranei284 – 30320Helical; Name=7By similarityAdd
BLAST
Topological domaini304 – 35350CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Endosome, Lysosome, Membrane

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 353353C-X-C chemokine receptor type 4PRO_0000247979Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei7 – 71SulfotyrosineBy similarity
Glycosylationi11 – 111N-linked (GlcNAc...)By similarity
Modified residuei12 – 121SulfotyrosineBy similarity
Glycosylationi19 – 191O-linked (Xyl...) (chondroitin sulfate)By similarity
Modified residuei22 – 221SulfotyrosineBy similarity
Disulfide bondi29 ↔ 275PROSITE-ProRule annotation
Disulfide bondi110 ↔ 187PROSITE-ProRule annotation
Modified residuei320 – 3201PhosphoserineBy similarity
Modified residuei322 – 3221PhosphoserineBy similarity
Modified residuei325 – 3251Phosphoserine; by PKC and GRK6By similarity
Modified residuei326 – 3261Phosphoserine; by PKC and GRK6By similarity
Modified residuei331 – 3311Phosphoserine; by GRK6By similarity
Modified residuei340 – 3401Phosphoserine; by GRK6By similarity
Modified residuei349 – 3491PhosphoserineBy similarity
Modified residuei352 – 3521PhosphoserineBy similarity

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.

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

STRINGi9615.ENSCAFP00000007600.

Structurei

3D structure databases

ProteinModelPortaliQ3LSL6.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2222Important for chemokine binding and signalingBy similarityAdd
BLAST
Regioni95 – 984Chemokine bindingBy similarity
Regioni114 – 1185Chemokine bindingBy similarity
Regioni136 – 14813Involved in dimerization; when bound to chemokineBy similarityAdd
BLAST
Regioni187 – 1915Chemokine binding, important for signalingBy similarity
Regioni192 – 21120Involved in dimerizationBy similarityAdd
BLAST
Regioni267 – 2693Involved in dimerizationBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi134 – 1363Important for signalingBy similarity

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.
OMAiILVMGYQ.
OrthoDBiEOG73Z2TB.
TreeFamiTF330966.

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.

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.

Cross-referencesi

Sequence databases

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

3D structure databases

ProteinModelPortaliQ3LSL6.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9615.ENSCAFP00000007600.

Protein family/group databases

GPCRDBiSearch...

Proteomic databases

PaxDbiQ3LSL6.

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

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

Organism-specific databases

CTDi7852.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118785.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiQ3LSL6.
KOiK04189.
OMAiILVMGYQ.
OrthoDBiEOG73Z2TB.
TreeFamiTF330966.

Enzyme and pathway databases

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

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...

Publicationsi

  1. "Evaluation of the canine CXCR4 and CXCL12 genes as a candidate for chronic neutropenia with myelokathexis in a border collie dog."
    Tsuchida S., Kagi A., Takahashi T.
    Submitted (AUG-2005) to the EMBL/GenBank/DDBJ databases
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].

Entry informationi

Entry nameiCXCR4_CANLF
AccessioniPrimary (citable) accession number: Q3LSL6
Entry historyi
Integrated into UniProtKB/Swiss-Prot: September 5, 2006
Last sequence update: October 25, 2005
Last modified: June 8, 2016
This is version 86 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. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. 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.