Skip Header

You are using a version of browser that may not display all the features of this website. Please consider upgrading your browser.
Protein

C-X-C chemokine receptor type 4

Gene

CXCR4

Organism
Homo sapiens (Human)
Status
Reviewed-Annotation score: Annotation score: 5 out of 5-Experimental evidence at protein 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.10 Publications
(Microbial infection) Acts as a coreceptor (CD4 being the primary receptor) for human immunodeficiency virus-1/HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus (PubMed:9427609, PubMed:10074122, PubMed:10756055). Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (PubMed:11276205).4 Publications

Sites

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Binding sitei171 – 1711Chemokine
Binding sitei288 – 2881Chemokine

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • coreceptor activity Source: ProtInc
  • C-X-C chemokine receptor activity Source: UniProtKB
  • drug binding Source: Ensembl
  • G-protein coupled receptor activity Source: ProtInc
  • myosin light chain binding Source: UniProtKB
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB
  • virus receptor activity Source: UniProtKB-KW

GO - Biological processi

  • activation of MAPK activity Source: ProtInc
  • apoptotic process Source: ProtInc
  • calcium-mediated signaling Source: MGI
  • cardiac muscle contraction Source: Ensembl
  • cellular response to cytokine stimulus Source: UniProtKB
  • dendritic cell chemotaxis Source: BHF-UCL
  • entry into host cell Source: Reactome
  • epithelial cell development Source: Ensembl
  • fusion of virus membrane with host plasma membrane Source: Reactome
  • G-protein coupled receptor signaling pathway Source: UniProtKB
  • inflammatory response Source: ProtInc
  • myelin maintenance Source: BHF-UCL
  • neuron migration Source: Ensembl
  • neuron recognition Source: Ensembl
  • positive regulation of cytosolic calcium ion concentration Source: ProtInc
  • positive regulation of oligodendrocyte differentiation Source: BHF-UCL
  • regulation of calcium ion transport Source: Ensembl
  • regulation of cell migration Source: InterPro
  • regulation of chemotaxis Source: UniProtKB
  • regulation of programmed cell death Source: Ensembl
  • response to hypoxia Source: UniProtKB
  • response to virus Source: ProtInc
  • telencephalon cell migration Source: Ensembl
Complete GO annotation...

Keywords - Molecular functioni

G-protein coupled receptor, Host cell receptor for virus entry, Receptor, Transducer

Keywords - Biological processi

Host-virus interaction

Enzyme and pathway databases

ReactomeiR-HSA-173107. Binding and entry of HIV virion.
R-HSA-380108. Chemokine receptors bind chemokines.
R-HSA-418594. G alpha (i) signalling events.
SignaLinkiP61073.
SIGNORiP61073.

Names & Taxonomyi

Protein namesi
Recommended name:
C-X-C chemokine receptor type 4
Short name:
CXC-R4
Short name:
CXCR-4
Alternative name(s):
FB22
Fusin
HM89
LCR1
Leukocyte-derived seven transmembrane domain receptor
Short name:
LESTR
Lipopolysaccharide-associated protein 3
Short name:
LAP-3
Short name:
LPS-associated protein 3
NPYRL
Stromal cell-derived factor 1 receptor
Short name:
SDF-1 receptor
CD_antigen: CD184
Gene namesi
Name:CXCR4
OrganismiHomo sapiens (Human)
Taxonomic identifieri9606 [NCBI]
Taxonomic lineageiEukaryotaMetazoaChordataCraniataVertebrataEuteleostomiMammaliaEutheriaEuarchontogliresPrimatesHaplorrhiniCatarrhiniHominidaeHomo
Proteomesi
  • UP000005640 Componenti: Chromosome 2

Organism-specific databases

HGNCiHGNC:2561. CXCR4.

Subcellular locationi

  • Cell membrane; Multi-pass membrane protein
  • Cell junction
  • Early endosome
  • Late endosome
  • Lysosome

  • Note: In unstimulated cells, diffuse pattern on plasma membrane. On agonist stimulation, colocalizes with ITCH at the plasma membrane where it becomes ubiquitinated. 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).

Topology

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Topological domaini1 – 3838ExtracellularAdd
BLAST
Transmembranei39 – 6325Helical; Name=1Add
BLAST
Topological domaini64 – 7714CytoplasmicAdd
BLAST
Transmembranei78 – 9922Helical; Name=2Add
BLAST
Topological domaini100 – 11011ExtracellularAdd
BLAST
Transmembranei111 – 13020Helical; Name=3Add
BLAST
Topological domaini131 – 15424CytoplasmicAdd
BLAST
Transmembranei155 – 17420Helical; Name=4Add
BLAST
Topological domaini175 – 19521ExtracellularAdd
BLAST
Transmembranei196 – 21621Helical; Name=5Add
BLAST
Topological domaini217 – 24125CytoplasmicAdd
BLAST
Transmembranei242 – 26120Helical; Name=6Add
BLAST
Topological domaini262 – 28221ExtracellularAdd
BLAST
Transmembranei283 – 30220Helical; Name=7Add
BLAST
Topological domaini303 – 35250CytoplasmicAdd
BLAST

GO - Cellular componenti

  • cell junction Source: UniProtKB-SubCell
  • cell leading edge Source: UniProtKB
  • cell surface Source: UniProtKB
  • cytoplasm Source: ProtInc
  • cytoplasmic, membrane-bounded vesicle Source: UniProtKB
  • cytoplasmic vesicle Source: UniProtKB
  • early endosome Source: UniProtKB
  • extracellular exosome Source: UniProtKB
  • integral component of membrane Source: UniProtKB-KW
  • late endosome Source: UniProtKB
  • lysosome Source: UniProtKB
  • plasma membrane Source: UniProtKB
Complete GO annotation...

Keywords - Cellular componenti

Cell junction, Cell membrane, Endosome, Lysosome, Membrane

Pathology & Biotechi

Involvement in diseasei

WHIM syndrome (WHIMS)1 Publication
The disease is caused by mutations affecting the gene represented in this entry.
Disease descriptionImmunodeficiency disease characterized by neutropenia, hypogammaglobulinemia and extensive human papillomavirus (HPV) infection. Despite the peripheral neutropenia, bone marrow aspirates from affected individuals contain abundant mature myeloid cells, a condition termed myelokathexis.
See also OMIM:193670

Mutagenesis

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Mutagenesisi2 – 98Missing : Reduced CXCL12 binding. Abolishes signaling. 1 Publication
Mutagenesisi4 – 2017Missing : Reduced CXCL12 binding. Impaired signaling. Reduced coreceptor activity for HIV-1 isolates LAI and NDK. 1 PublicationAdd
BLAST
Mutagenesisi7 – 71Y → A: Reduced coreceptor activity for HIV-1 isolates LAI and NDK. Greatly reduced coreceptor activity for HIV-1 isolates LAI and NDK; when associated with A-12. 2 Publications
Mutagenesisi7 – 71Y → F: Sulfate incorporation greatly reduced; when associated with F-12 and F-21. Moderate reduction in sulfate incorporation; when associated with F-12 and A-18. No sulfate incorporation and binding SDF-1alpha greatly reduced; when associated with F-12; A-18 and F-21. 2 Publications
Mutagenesisi8 – 81T → A: No effect on sulfate incorporation; when associated with A-9 and A-13. 1 Publication
Mutagenesisi9 – 91S → A: No effect on sulfate incorporation; when associated with A-8 and A-13. 1 Publication
Mutagenesisi10 – 2011Missing : Reduced CXCL12 binding. No effect on signaling. 1 PublicationAdd
BLAST
Mutagenesisi11 – 111N → A: Reduced molecular weight. Enhanced coreceptor activity on R5 HIV-1 isolate Envs. Slight further enhancement of coreceptor activity; when associated with A-13. 1 Publication
Mutagenesisi12 – 121Y → A: Greatly reduced coreceptor activity for HIV-1 isolates LAI and NDK; when associated with A-7. 2 Publications
Mutagenesisi12 – 121Y → F: Sulfate incorporation greatly reduced; when associated with F-7 and F-21. Moderate reduction in sulfate incorporation; when associated with F-7 and A-18. No sulfate incorporation and binding SDF-1alpha greatly reduced; when associated with F-7; A-18 and F-21. 2 Publications
Mutagenesisi13 – 131T → A: Enhanced coreceptor activity on R5 HIV-1 isolate Envs. No effect on sulfate incorporation; when associated with A-8 and A-9. 1 Publication
Mutagenesisi14 – 152EE → AA: Reduced CXCL12 binding. Reduced coreceptor activity for HIV-1 isolate NDK. 1 Publication
Mutagenesisi18 – 181S → A: Sulfate incorporation greatly reduced; when associated with F-21. Moderate reduction in sulfate incorporation; when associated with F-7 and F-12. No sulfate incorporation and binding SDF-1alpha greatly reduced; when associated with F-7; F-12; and F-21. 1 Publication
Mutagenesisi21 – 211Y → A: Reduced CXCL12 binding. Reduced coreceptor activity for HIV-1 isolates LAI and NDk. 2 Publications
Mutagenesisi21 – 211Y → F: Sulfate incorporation greatly reduced; when associated with F-7 and F-12. Sulfate incorporation greatly reduced; when associated with A-18. No sulfate incorporation and binding SDF-1alpha greatly reduced; when associated with F-7; F-12 and A-18. 2 Publications
Mutagenesisi97 – 971D → N: Reduced CXCL12 binding. Abolishes signaling. Markedly reduced coreceptor activity for HIV-1 isolate LAI. 1 Publication
Mutagenesisi119 – 1191N → D: No reduction of agonist-induced G-protein activation. 1 Publication
Mutagenesisi119 – 1191N → K: Loss of agonist-induced G-protein activation. 1 Publication
Mutagenesisi119 – 1191N → S: Constitutive G-protein activation, with further activation induced by agonist. 1 Publication
Mutagenesisi125 – 1251L → W: Increased thermostability.
Mutagenesisi133 – 1331D → N: No reduction of agonist-induced G-protein activation. 1 Publication
Mutagenesisi134 – 1341R → A: Loss of agonist-induced G-protein activation. 1 Publication
Mutagenesisi135 – 1351Y → A: No reduction of agonist-induced G-protein activation. 1 Publication
Mutagenesisi171 – 1711D → N: Reduced coreceptor activity for HIV-1 isolate NDK. 1 Publication
Mutagenesisi176 – 1761N → A: Enhanced coreceptor activity on R5 HIV-1 isolate Envs; when associated with A-11. 1 Publication
Mutagenesisi183 – 1831R → A: Reduced coreceptor activity for several HIV-1 isolates. 1 Publication
Mutagenesisi187 – 1871D → A: Reduced CXCL12 binding. Abolishes signaling. 1 Publication
Mutagenesisi188 – 1881R → A: Reduced coreceptor activity for several HIV-1 isolates. 1 Publication
Mutagenesisi193 – 1931D → A, S or N: Greatly reduced coreceptor activity for HIV-1 isolate NDK. Reduced coreceptor activity for several other HIV-1 isolates. 2 Publications
Mutagenesisi193 – 1931D → R: Abolishes coreceptor activity for HIV-1 isolate NDK. Reduced coreceptor activity for several other HIV-1 isolates. 2 Publications
Mutagenesisi240 – 2401T → P: Retains ligand-binding affinity but abolishes signaling.
Mutagenesisi262 – 2621D → A: Markedly reduced coreceptor activity for HIV-1 isolate LAI. 1 Publication
Mutagenesisi268 – 2681E → A: Markedly reduced coreceptor activity for HIV-1 isolate NDK. Less effect for HIV-1 isolate LAI. 1 Publication
Mutagenesisi288 – 2881E → Q: Reduced CXCL12 binding. Impaired signaling. Reduced coreceptor activity for HIV-1 isolate LAI. Enhanced coreceptor activity for HIV-1 isolate NDK. 1 Publication
Mutagenesisi324 – 3241S → A: Moderate degradation. About 60% reduction in binding ITCH and no ubiquitination nor protein degradation; when associated with A-325. 1 Publication
Mutagenesisi324 – 3241S → D: Enhanced binding to ITCH. Enhanced binding to ITCH and greatly increased protein degradation; when associated with D-324. 1 Publication
Mutagenesisi324 – 3241S → D: Enhanced binding to ITCH. Enhanced binding to ITCH and greatly increased protein degradation; when associated with D-325. 1 Publication
Mutagenesisi325 – 3251S → A: Moderate degradation. About 60% reduction in binding ITCH and no ubiquitination nor protein degradation; when associated with A-324. 1 Publication
Mutagenesisi330 – 3301S → A: No effect on binding to ITCH. 1 Publication

Organism-specific databases

MalaCardsiCXCR4.
MIMi193670. phenotype.
Orphaneti51636. WHIM syndrome.
PharmGKBiPA27058.

Chemistry

ChEMBLiCHEMBL2107.
DrugBankiDB00452. Framycetin.
DB06809. Plerixafor.
GuidetoPHARMACOLOGYi71.

Polymorphism and mutation databases

BioMutaiCXCR4.
DMDMi46577576.

PTM / Processingi

Molecule processing

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Chaini1 – 352352C-X-C chemokine receptor type 4PRO_0000069352Add
BLAST

Amino acid modifications

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Modified residuei7 – 71Sulfotyrosine; partial1 Publication
Glycosylationi11 – 111N-linked (GlcNAc...)1 Publication
Modified residuei12 – 121Sulfotyrosine; partial1 Publication
Glycosylationi18 – 181O-linked (Xyl...) (chondroitin sulfate)1 Publication
Modified residuei21 – 211Sulfotyrosine3 Publications
Disulfide bondi28 ↔ 274PROSITE-ProRule annotation1 Publication
Disulfide bondi109 ↔ 186PROSITE-ProRule annotation1 Publication
Glycosylationi176 – 1761N-linked (GlcNAc...)Sequence analysis
Modified residuei319 – 3191PhosphoserineCombined sources
Modified residuei321 – 3211PhosphoserineCombined sources1 Publication
Modified residuei324 – 3241Phosphoserine; by PKC and GRK6Combined sources2 Publications
Modified residuei325 – 3251Phosphoserine; by PKC and GRK6Combined sources2 Publications
Modified residuei330 – 3301Phosphoserine; by GRK61 Publication
Modified residuei339 – 3391Phosphoserine; by GRK61 Publication
Modified residuei348 – 3481PhosphoserineCombined sources
Modified residuei351 – 3511Phosphoserine1 Publication

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.3 Publications
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.1 Publication
Sulfation on Tyr-21 is required for efficient binding of CXCL12/SDF-1alpha and promotes its dimerization. Tyr-7 and Tyr-12 are sulfated in a sequential manner after Tyr-21 is almost fully sulfated, with the binding affinity for CXCL12/SDF-1alpha increasing with the number of sulfotyrosines present. Sulfotyrosines Tyr-7 and Tyr-12 occupy clefts on opposing CXCL12 subunits, thus bridging the CXCL12 dimer interface and promoting CXCL12 dimerization.4 Publications
O- and N-glycosylated. Asn-11 is the principal site of N-glycosylation. There appears to be very little or no glycosylation on Asn-176. N-glycosylation masks coreceptor function in both X4 and R5 laboratory-adapted and primary HIV-1 strains through inhibiting interaction with their Env glycoproteins. The O-glycosylation chondroitin sulfate attachment does not affect interaction with CXCL12/SDF-1alpha nor its coreceptor activity.2 Publications

Keywords - PTMi

Disulfide bond, Glycoprotein, Phosphoprotein, Proteoglycan, Sulfation, Ubl conjugation

Proteomic databases

MaxQBiP61073.
PaxDbiP61073.
PeptideAtlasiP61073.
PRIDEiP61073.

PTM databases

iPTMnetiP61073.
PhosphoSiteiP61073.
SwissPalmiP61073.

Miscellaneous databases

PMAP-CutDBP61073.

Expressioni

Tissue specificityi

Expressed in numerous tissues, such as peripheral blood leukocytes, spleen, thymus, spinal cord, heart, placenta, lung, liver, skeletal muscle, kidney, pancreas, cerebellum, cerebral cortex and medulla (in microglia as well as in astrocytes), brain microvascular, coronary artery and umbilical cord endothelial cells. Isoform 1 is predominant in all tissues tested.1 Publication

Inductioni

(Microbial infection) May be down-regulated by human cytomegalovirus/HHV-5 (PubMed:22496149). May be down-regulated by HIV-1 tat (PubMed:11027346).2 Publications

Gene expression databases

BgeeiENSG00000121966.
CleanExiHS_CXCR4.
GenevisibleiP61073. HS.

Interactioni

Subunit structurei

Monomer. Can form dimers. 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. Interacts with DBN1; this interaction is enhanced by antigenic stimulation. Following LPS binding, may form a complex with GDF5, HSP90AA1 and HSPA8.14 Publications
(Microbial infection) Interacts with HIV-1 surface protein gp120 and Tat (PubMed:9427609, PubMed:10074122, PubMed:10756055, PubMed:11027346).4 Publications
(Microbial infection) May interact with human cytomegalovirus/HHV-5 protein UL78.1 Publication

Binary interactionsi

WithEntry#Exp.IntActNotes
CD164Q049002EBI-489411,EBI-2115896
CD74P042334EBI-489411,EBI-2622890
CXCR5P323023EBI-489411,EBI-2835269
DBN1Q166435EBI-489411,EBI-351394
Dbn1Q07266-13EBI-489411,EBI-8786792From a different organism.
MYH9P355795EBI-489411,EBI-350338

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • myosin light chain binding Source: UniProtKB
  • ubiquitin binding Source: UniProtKB
  • ubiquitin protein ligase binding Source: UniProtKB

Protein-protein interaction databases

BioGridi113607. 37 interactions.
DIPiDIP-34773N.
DIP-46290N.
IntActiP61073. 20 interactions.
MINTiMINT-6630550.
STRINGi9606.ENSP00000386884.

Chemistry

BindingDBiP61073.

Structurei

Secondary structure

1
352
Legend: HelixTurnBeta strand
Show more details
Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Beta strandi9 – 113Combined sources
Beta strandi21 – 233Combined sources
Beta strandi32 – 354Combined sources
Helixi37 – 6226Combined sources
Turni63 – 664Combined sources
Beta strandi67 – 693Combined sources
Helixi72 – 8817Combined sources
Helixi91 – 999Combined sources
Helixi105 – 13935Combined sources
Helixi141 – 1433Combined sources
Helixi145 – 1539Combined sources
Helixi155 – 1595Combined sources
Helixi161 – 1666Combined sources
Helixi169 – 1746Combined sources
Beta strandi175 – 1795Combined sources
Beta strandi181 – 1888Combined sources
Helixi193 – 20715Combined sources
Helixi209 – 22517Combined sources
Helixi226 – 2283Combined sources
Helixi231 – 26636Combined sources
Helixi274 – 29118Combined sources
Helixi294 – 3018Combined sources
Turni302 – 3065Combined sources
Helixi313 – 3175Combined sources

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2K03NMR-B/D1-38[»]
2K04NMR-B/D1-38[»]
2K05NMR-B/D1-38[»]
2N55NMR-B1-38[»]
3ODUX-ray2.50A/B2-319[»]
3OE0X-ray2.90A2-319[»]
3OE6X-ray3.20A2-325[»]
3OE8X-ray3.10A/B/C2-319[»]
3OE9X-ray3.10A/B2-319[»]
4RWSX-ray3.10A2-228[»]
A231-319[»]
ProteinModelPortaliP61073.
SMRiP61073. Positions 1-318.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61073.

Family & Domainsi

Region

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Regioni1 – 2121Important for chemokine binding, signaling and HIV-1 coreceptor activityAdd
BLAST
Regioni94 – 974Chemokine binding
Regioni113 – 1175Chemokine binding
Regioni135 – 14713Involved in dimerization; when bound to chemokineAdd
BLAST
Regioni186 – 1905Chemokine binding, important for signaling and HIV-1 coreceptor activity
Regioni191 – 21020Involved in dimerizationAdd
BLAST
Regioni266 – 2683Involved in dimerization

Motif

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Motifi133 – 1353Important for signaling

Domaini

The amino-terminus is critical for ligand binding. Residues in all four extracellular regions contribute to HIV-1 coreceptor activity.1 Publication

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.
HOVERGENiHBG106917.
InParanoidiP61073.
KOiK04189.
OMAiILVMGYQ.
OrthoDBiEOG091G0HEN.
PhylomeDBiP61073.
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]

Sequences (2)i

Sequence statusi: Complete.

This entry describes 2 isoformsi produced by alternative splicing. AlignAdd to basket

Note: Additional isoforms seem to exist.
Isoform 1 (identifier: P61073-1) [UniParc]FASTAAdd to basket

This isoform has been chosen as the 'canonical' sequence. All positional information in this entry refers to it. This is also the sequence that appears in the downloadable versions of the entry.

« Hide

        10         20         30         40         50
MEGISIYTSD NYTEEMGSGD YDSMKEPCFR EENANFNKIF LPTIYSIIFL
60 70 80 90 100
TGIVGNGLVI LVMGYQKKLR SMTDKYRLHL SVADLLFVIT LPFWAVDAVA
110 120 130 140 150
NWYFGNFLCK AVHVIYTVNL YSSVLILAFI SLDRYLAIVH ATNSQRPRKL
160 170 180 190 200
LAEKVVYVGV WIPALLLTIP DFIFANVSEA DDRYICDRFY PNDLWVVVFQ
210 220 230 240 250
FQHIMVGLIL PGIVILSCYC 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):39,746
Last modified:April 26, 2004 - v1
Checksum:i8C8476A186786B83
GO
Isoform 2 (identifier: P61073-2) [UniParc] [UniParc]FASTAAdd to basket
Also known as: CXCR4-LO

The sequence of this isoform differs from the canonical sequence as follows:
     1-5: MEGIS → MSIPLPLLQ

Show »
Length:356
Mass (Da):40,221
Checksum:i83F9E099F41FAB9B
GO

Sequence cautioni

The sequence CAA12166 differs from that shown.Intron retention.Curated

Experimental Info

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Sequence conflicti242 – 2443VIL → IIP in AAK29630 (Ref. 12) Curated
Sequence conflicti278 – 2781N → S in BAG35177 (PubMed:14702039).Curated

Alternative sequence

Feature keyPosition(s)LengthDescriptionGraphical viewFeature identifierActions
Alternative sequencei1 – 55MEGIS → MSIPLPLLQ in isoform 2. 1 PublicationVSP_001890

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L01639 mRNA. Translation: AAA16594.1.
M99293 mRNA. Translation: AAA16617.1.
X71635 mRNA. Translation: CAA50641.1.
L06797 mRNA. Translation: AAA03209.1.
D10924 mRNA. Translation: BAA01722.1.
AF005058 Genomic DNA. Translation: AAB93982.1.
AF052572 Genomic DNA. Translation: AAC34581.1.
AJ224869 Genomic DNA. Translation: CAA12166.1. Sequence problems.
AF025375 mRNA. Translation: AAB81970.1.
Y14739 Genomic DNA. Translation: CAA75034.1.
AF147204 mRNA. Translation: AAF00130.1.
AF348491 mRNA. Translation: AAK29630.1.
AK312244 mRNA. Translation: BAG35177.1.
AY242129 mRNA. Translation: AAO92296.1.
BT006660 mRNA. Translation: AAP35306.1.
AY728138 Genomic DNA. Translation: AAU05775.1.
AC068492 Genomic DNA. Translation: AAY24044.1.
CH471058 Genomic DNA. Translation: EAX11616.1.
BC020968 mRNA. Translation: AAH20968.1.
CCDSiCCDS33295.1. [P61073-2]
CCDS46420.1.
PIRiA45747.
RefSeqiNP_001008540.1. NM_001008540.1. [P61073-2]
NP_003458.1. NM_003467.2. [P61073-1]
UniGeneiHs.593413.

Genome annotation databases

EnsembliENST00000241393; ENSP00000241393; ENSG00000121966. [P61073-1]
ENST00000409817; ENSP00000386884; ENSG00000121966. [P61073-2]
GeneIDi7852.
KEGGihsa:7852.
UCSCiuc002tuy.3. human.

Keywords - Coding sequence diversityi

Alternative splicing

Cross-referencesi

Web resourcesi

CXCR4base

CXCR4 mutation db

Wikipedia

CXC chemokine receptors entry

Wikipedia

CXCR4 entry

SeattleSNPs

Sequence databases

Select the link destinations:
EMBLi
GenBanki
DDBJi
Links Updated
L01639 mRNA. Translation: AAA16594.1.
M99293 mRNA. Translation: AAA16617.1.
X71635 mRNA. Translation: CAA50641.1.
L06797 mRNA. Translation: AAA03209.1.
D10924 mRNA. Translation: BAA01722.1.
AF005058 Genomic DNA. Translation: AAB93982.1.
AF052572 Genomic DNA. Translation: AAC34581.1.
AJ224869 Genomic DNA. Translation: CAA12166.1. Sequence problems.
AF025375 mRNA. Translation: AAB81970.1.
Y14739 Genomic DNA. Translation: CAA75034.1.
AF147204 mRNA. Translation: AAF00130.1.
AF348491 mRNA. Translation: AAK29630.1.
AK312244 mRNA. Translation: BAG35177.1.
AY242129 mRNA. Translation: AAO92296.1.
BT006660 mRNA. Translation: AAP35306.1.
AY728138 Genomic DNA. Translation: AAU05775.1.
AC068492 Genomic DNA. Translation: AAY24044.1.
CH471058 Genomic DNA. Translation: EAX11616.1.
BC020968 mRNA. Translation: AAH20968.1.
CCDSiCCDS33295.1. [P61073-2]
CCDS46420.1.
PIRiA45747.
RefSeqiNP_001008540.1. NM_001008540.1. [P61073-2]
NP_003458.1. NM_003467.2. [P61073-1]
UniGeneiHs.593413.

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
EntryMethodResolution (Å)ChainPositionsPDBsum
2K03NMR-B/D1-38[»]
2K04NMR-B/D1-38[»]
2K05NMR-B/D1-38[»]
2N55NMR-B1-38[»]
3ODUX-ray2.50A/B2-319[»]
3OE0X-ray2.90A2-319[»]
3OE6X-ray3.20A2-325[»]
3OE8X-ray3.10A/B/C2-319[»]
3OE9X-ray3.10A/B2-319[»]
4RWSX-ray3.10A2-228[»]
A231-319[»]
ProteinModelPortaliP61073.
SMRiP61073. Positions 1-318.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

BioGridi113607. 37 interactions.
DIPiDIP-34773N.
DIP-46290N.
IntActiP61073. 20 interactions.
MINTiMINT-6630550.
STRINGi9606.ENSP00000386884.

Chemistry

BindingDBiP61073.
ChEMBLiCHEMBL2107.
DrugBankiDB00452. Framycetin.
DB06809. Plerixafor.
GuidetoPHARMACOLOGYi71.

Protein family/group databases

GPCRDBiSearch...

PTM databases

iPTMnetiP61073.
PhosphoSiteiP61073.
SwissPalmiP61073.

Polymorphism and mutation databases

BioMutaiCXCR4.
DMDMi46577576.

Proteomic databases

MaxQBiP61073.
PaxDbiP61073.
PeptideAtlasiP61073.
PRIDEiP61073.

Protocols and materials databases

DNASUi7852.
Structural Biology KnowledgebaseSearch...

Genome annotation databases

EnsembliENST00000241393; ENSP00000241393; ENSG00000121966. [P61073-1]
ENST00000409817; ENSP00000386884; ENSG00000121966. [P61073-2]
GeneIDi7852.
KEGGihsa:7852.
UCSCiuc002tuy.3. human.

Organism-specific databases

CTDi7852.
GeneCardsiCXCR4.
HGNCiHGNC:2561. CXCR4.
MalaCardsiCXCR4.
MIMi162643. gene.
193670. phenotype.
neXtProtiNX_P61073.
Orphaneti51636. WHIM syndrome.
PharmGKBiPA27058.
GenAtlasiSearch...

Phylogenomic databases

eggNOGiKOG3656. Eukaryota.
ENOG410XRW9. LUCA.
GeneTreeiENSGT00760000118785.
HOVERGENiHBG106917.
InParanoidiP61073.
KOiK04189.
OMAiILVMGYQ.
OrthoDBiEOG091G0HEN.
PhylomeDBiP61073.
TreeFamiTF330966.

Enzyme and pathway databases

ReactomeiR-HSA-173107. Binding and entry of HIV virion.
R-HSA-380108. Chemokine receptors bind chemokines.
R-HSA-418594. G alpha (i) signalling events.
SignaLinkiP61073.
SIGNORiP61073.

Miscellaneous databases

ChiTaRSiCXCR4. human.
EvolutionaryTraceiP61073.
GeneWikiiCXCR4.
GenomeRNAii7852.
PMAP-CutDBP61073.
PROiP61073.
SOURCEiSearch...

Gene expression databases

BgeeiENSG00000121966.
CleanExiHS_CXCR4.
GenevisibleiP61073. HS.

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_HUMAN
AccessioniPrimary (citable) accession number: P61073
Secondary accession number(s): B2R5N0
, O60835, P30991, P56438, Q53S69, Q9BXA0, Q9UKN2
Entry historyi
Integrated into UniProtKB/Swiss-Prot: April 26, 2004
Last sequence update: April 26, 2004
Last modified: September 7, 2016
This is version 145 of the entry and version 1 of the sequence. [Complete history]
Entry statusiReviewed (UniProtKB/Swiss-Prot)
Annotation programChordata Protein Annotation Program
DisclaimerAny medical or genetic information present in this entry is provided for research, educational and informational purposes only. It is not in any way intended to be used as a substitute for professional medical advice, diagnosis, treatment or care.

Miscellaneousi

Miscellaneous

Plerixafor (AMD3100), an antagonist of CXCR4 activity, blocks HIV-1 entry, interaction with CXCL12 and subsequent CXCR4 signaling.

Caution

Was originally (PubMed:8329116 and PubMed:8234909) thought to be a receptor for neuropeptide Y type 3 (NPY3R) (NPY3-R).Curated

Keywords - Technical termi

3D-structure, Complete proteome, Reference proteome

Documents

  1. 7-transmembrane G-linked receptors
    List of 7-transmembrane G-linked receptor entries
  2. Human cell differentiation molecules
    CD nomenclature of surface proteins of human leucocytes and list of entries
  3. Human chromosome 2
    Human chromosome 2: entries, gene names and cross-references to MIM
  4. MIM cross-references
    Online Mendelian Inheritance in Man (MIM) cross-references in UniProtKB/Swiss-Prot
  5. PDB cross-references
    Index of Protein Data Bank (PDB) cross-references
  6. 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.