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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)DescriptionActionsGraphical viewLength
Sitei171ChemokineBy similarity1
Sitei288ChemokineBy similarity1

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)DescriptionActionsGraphical viewLength
Topological domaini1 – 38ExtracellularBy similarityAdd BLAST38
Transmembranei39 – 63Helical; Name=1By similarityAdd BLAST25
Topological domaini64 – 77CytoplasmicBy similarityAdd BLAST14
Transmembranei78 – 99Helical; Name=2By similarityAdd BLAST22
Topological domaini100 – 110ExtracellularBy similarityAdd BLAST11
Transmembranei111 – 130Helical; Name=3By similarityAdd BLAST20
Topological domaini131 – 154CytoplasmicBy similarityAdd BLAST24
Transmembranei155 – 174Helical; Name=4By similarityAdd BLAST20
Topological domaini175 – 195ExtracellularBy similarityAdd BLAST21
Transmembranei196 – 216Helical; Name=5By similarityAdd BLAST21
Topological domaini217 – 241CytoplasmicBy similarityAdd BLAST25
Transmembranei242 – 261Helical; Name=6By similarityAdd BLAST20
Topological domaini262 – 282ExtracellularBy similarityAdd BLAST21
Transmembranei283 – 302Helical; Name=7By similarityAdd BLAST20
Topological domaini303 – 352CytoplasmicBy similarityAdd BLAST50

GO - Cellular componenti

Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Chemistry databases

ChEMBLiCHEMBL1250366.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000693541 – 352C-X-C chemokine receptor type 4Add BLAST352

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei7SulfotyrosineBy similarity1
Glycosylationi11N-linked (GlcNAc...)By similarity1
Modified residuei12SulfotyrosineBy similarity1
Glycosylationi18O-linked (Xyl...) (chondroitin sulfate)By similarity1
Modified residuei21SulfotyrosineBy similarity1
Disulfide bondi28 ↔ 274PROSITE-ProRule annotation
Disulfide bondi109 ↔ 186PROSITE-ProRule annotation
Modified residuei319PhosphoserineBy similarity1
Modified residuei321PhosphoserineBy similarity1
Modified residuei324Phosphoserine; by PKC and GRK6By similarity1
Modified residuei325Phosphoserine; by PKC and GRK6By similarity1
Modified residuei330Phosphoserine; by GRK6By similarity1
Modified residuei339Phosphoserine; by GRK6By similarity1
Modified residuei348PhosphoserineBy similarity1
Modified residuei351PhosphoserineBy similarity1

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 databases

BindingDBiP79394.

Structurei

3D structure databases

ProteinModelPortaliP79394.
ModBaseiSearch...
MobiDBiSearch...

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 21Important for chemokine binding and signalingBy similarityAdd BLAST21
Regioni94 – 97Chemokine bindingBy similarity4
Regioni113 – 117Chemokine bindingBy similarity5
Regioni135 – 147Involved in dimerization; when bound to chemokineBy similarityAdd BLAST13
Regioni186 – 190Chemokine binding, important for signalingBy similarity5
Regioni191 – 210Involved in dimerizationBy similarityAdd BLAST20
Regioni266 – 268Involved in dimerizationBy similarity3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi133 – 135Important 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.
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)DescriptionActionsGraphical viewLength
Sequence conflicti67K → E in AAB54116 (PubMed:9108095).Curated1
Sequence conflicti214D → V in AAB54116 (PubMed:9108095).Curated1
Sequence conflicti214D → V in AAC39641 (PubMed:9591719).Curated1
Sequence conflicti348S → N in AAB54116 (PubMed:9108095).Curated1

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 databases

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...

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.