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Protein

C-X-C chemokine receptor type 4

Gene

CXCR4

Organism
Macaca mulatta (Rhesus macaque)
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
Sitei171 – 1711ChemokineBy similarity
Sitei288 – 2881ChemokineBy similarity

GO - Molecular functioni

GO - Biological processi

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
OrganismiMacaca mulatta (Rhesus macaque)
Taxonomic identifieri9544 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniCercopithecidaeCercopithecinaeMacaca
Proteomesi
  • UP000006718 Componenti: Unplaced

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 – 3838ExtracellularBy similarityAdd
BLAST
Transmembranei39 – 6325Helical; Name=1By similarityAdd
BLAST
Topological domaini64 – 7714CytoplasmicBy similarityAdd
BLAST
Transmembranei78 – 9922Helical; Name=2By similarityAdd
BLAST
Topological domaini100 – 11011ExtracellularBy similarityAdd
BLAST
Transmembranei111 – 13020Helical; Name=3By similarityAdd
BLAST
Topological domaini131 – 15424CytoplasmicBy similarityAdd
BLAST
Transmembranei155 – 17420Helical; Name=4By similarityAdd
BLAST
Topological domaini175 – 19521ExtracellularBy similarityAdd
BLAST
Transmembranei196 – 21621Helical; Name=5By similarityAdd
BLAST
Topological domaini217 – 24125CytoplasmicBy similarityAdd
BLAST
Transmembranei242 – 26120Helical; Name=6By similarityAdd
BLAST
Topological domaini262 – 28221ExtracellularBy similarityAdd
BLAST
Transmembranei283 – 30220Helical; Name=7By similarityAdd
BLAST
Topological domaini303 – 35250CytoplasmicBy similarityAdd
BLAST

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Chemistry

ChEMBLiCHEMBL1250366.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 352352C-X-C chemokine receptor type 4PRO_0000069354Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei7 – 71SulfotyrosineBy similarity
Glycosylationi11 – 111N-linked (GlcNAc...)By similarity
Modified residuei12 – 121SulfotyrosineBy similarity
Glycosylationi18 – 181O-linked (Xyl...) (chondroitin sulfate)By similarity
Modified residuei21 – 211SulfotyrosineBy similarity
Disulfide bondi28 ↔ 274PROSITE-ProRule annotation
Disulfide bondi109 ↔ 186PROSITE-ProRule annotation
Modified residuei319 – 3191PhosphoserineBy similarity
Modified residuei321 – 3211PhosphoserineBy similarity
Modified residuei324 – 3241Phosphoserine; by PKC and GRK6By similarity
Modified residuei325 – 3251Phosphoserine; by PKC and GRK6By similarity
Modified residuei330 – 3301Phosphoserine; by GRK6By similarity
Modified residuei339 – 3391Phosphoserine; by GRK6By similarity
Modified residuei348 – 3481PhosphoserineBy similarity
Modified residuei351 – 3511PhosphoserineBy similarity

Post-translational modificationi

Phosphorylated on agonist stimulation. Rapidly phosphorylated on serine and threonine residues in the C-terminal. Phosphorylation at Ser-324 and Ser-325 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

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

STRINGi9544.ENSMMUP00000036080.

Chemistry

BindingDBiP79394.

Structurei

3D structure databases

ProteinModelPortaliP79394.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2121Important for chemokine binding and signalingBy similarityAdd
BLAST
Regioni94 – 974Chemokine bindingBy similarity
Regioni113 – 1175Chemokine bindingBy similarity
Regioni135 – 14713Involved in dimerization; when bound to chemokineBy similarityAdd
BLAST
Regioni186 – 1905Chemokine binding, important for signalingBy similarity
Regioni191 – 21020Involved in dimerizationBy similarityAdd
BLAST
Regioni266 – 2683Involved in dimerizationBy similarity

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi133 – 1353Important 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.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP79394.
KOiK04189.

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.

P79394-1 [UniParc]FASTAAdd to basket

« Hide

        10         20         30         40         50
MEGISIYTSD NYTEEMGSGD YDSIKEPCFR EENAHFNRIF LPTIYSIIFL
60 70 80 90 100
TGIVGNGLVI LVMGYQKKLR SMTDKYRLHL SVADLLFVIT LPFWAVDAVA
110 120 130 140 150
NWYFGNFLCK AVHVIYTVNL YSSVLILAFI SLDRYLAIVH ATNSQKPRKL
160 170 180 190 200
LAEKVVYVGV WIPALLLTIP DFIFASVSEA DDRYICDRFY PNDLWVVVFQ
210 220 230 240 250
FQHIMVGLIL PGIDILSCYC IIISKLSHSK GHQKRKALKT TVILILAFFA
260 270 280 290 300
CWLPYYIGIS IDSFILLEII KQGCEFENTV HKWISITEAL AFFHCCLNPI
310 320 330 340 350
LYAFLGAKFK TSAQHALTSV SRGSSLKILS KGKRGGHSSV STESESSSFH

SS
Length:352
Mass (Da):39,739
Last modified:May 1, 1997 - v1
Checksum:iEC415E4820699C3F
GO

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti67 – 671K → E in AAB54116 (PubMed:9108095).Curated
Sequence conflicti214 – 2141D → V in AAB54116 (PubMed:9108095).Curated
Sequence conflicti214 – 2141D → V in AAC39641 (PubMed:9591719).Curated
Sequence conflicti348 – 3481S → N in AAB54116 (PubMed:9108095).Curated

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73740 mRNA. Translation: AAC51159.1.
U93311 mRNA. Translation: AAB54116.1.
AF001928 mRNA. Translation: AAC39641.1.
RefSeqiNP_001036110.1. NM_001042645.1.
UniGeneiMmu.2390.

Genome annotation databases

GeneIDi707329.
KEGGimcc:707329.

Cross-referencesi

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
U73740 mRNA. Translation: AAC51159.1.
U93311 mRNA. Translation: AAB54116.1.
AF001928 mRNA. Translation: AAC39641.1.
RefSeqiNP_001036110.1. NM_001042645.1.
UniGeneiMmu.2390.

3D structure databases

ProteinModelPortaliP79394.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

STRINGi9544.ENSMMUP00000036080.

Chemistry

BindingDBiP79394.
ChEMBLiCHEMBL1250366.

Protein family/group databases

GPCRDBiSearch...

Protocols and materials databases

Structural Biology KnowledgebaseSearch...

Genome annotation databases

GeneIDi707329.
KEGGimcc:707329.

Organism-specific databases

CTDi7852.

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
HOGENOMiHOG000234122.
HOVERGENiHBG106917.
InParanoidiP79394.
KOiK04189.

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. "Genetically divergent strains of simian immunodeficiency virus use CCR5 as a coreceptor for entry."
    Chen Z., Zhou P., Ho D.D., Landau N.R., Marx P.A.
    J. Virol. 71:2705-2714(1997) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Indian macaque.
  2. Cited for: NUCLEOTIDE SEQUENCE [MRNA].
  3. "New widespread CXCR4 allele in rhesus macaques does not predict subspecies or clinical evolution."
    Pretet J.-L., Guillet J.-G., Butor C.
    AIDS Res. Hum. Retroviruses 14:639-641(1998) [PubMed] [Europe PMC] [Abstract]
    Cited for: NUCLEOTIDE SEQUENCE [MRNA].
    Strain: Chinese.

Entry informationi

Entry nameiCXCR4_MACMU
AccessioniPrimary (citable) accession number: P79394
Secondary accession number(s): O02745, O46428
Entry historyi
Integrated into UniProtKB/Swiss-Prot: July 15, 1998
Last sequence update: May 1, 1997
Last modified: June 8, 2016
This is version 106 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.