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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)DescriptionActionsGraphical viewLength
Binding sitei171Chemokine1
Binding sitei288Chemokine1

GO - Molecular functioni

  • actin binding Source: UniProtKB
  • coreceptor activity Source: ProtInc
  • C-X-C chemokine receptor activity Source: UniProtKB
  • 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
  • cellular response to cytokine stimulus Source: UniProtKB
  • dendritic cell chemotaxis Source: BHF-UCL
  • entry into host cell Source: Reactome
  • 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
  • positive regulation of cytosolic calcium ion concentration Source: ProtInc
  • positive regulation of oligodendrocyte differentiation Source: BHF-UCL
  • regulation of cell migration Source: InterPro
  • regulation of chemotaxis Source: UniProtKB
  • response to hypoxia Source: UniProtKB
  • response to virus Source: ProtInc
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.

Protein family/group databases

TCDBi9.A.14.13.17. the g-protein-coupled receptor (gpcr) family.

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

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)DescriptionActionsGraphical viewLength
Mutagenesisi2 – 9Missing : Reduced CXCL12 binding. Abolishes signaling. 1 Publication8
Mutagenesisi4 – 20Missing : Reduced CXCL12 binding. Impaired signaling. Reduced coreceptor activity for HIV-1 isolates LAI and NDK. 1 PublicationAdd BLAST17
Mutagenesisi7Y → 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 Publications1
Mutagenesisi7Y → 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 Publications1
Mutagenesisi8T → A: No effect on sulfate incorporation; when associated with A-9 and A-13. 1 Publication1
Mutagenesisi9S → A: No effect on sulfate incorporation; when associated with A-8 and A-13. 1 Publication1
Mutagenesisi10 – 20Missing : Reduced CXCL12 binding. No effect on signaling. 1 PublicationAdd BLAST11
Mutagenesisi11N → 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 Publication1
Mutagenesisi12Y → A: Greatly reduced coreceptor activity for HIV-1 isolates LAI and NDK; when associated with A-7. 2 Publications1
Mutagenesisi12Y → 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 Publications1
Mutagenesisi13T → A: Enhanced coreceptor activity on R5 HIV-1 isolate Envs. No effect on sulfate incorporation; when associated with A-8 and A-9. 1 Publication1
Mutagenesisi14 – 15EE → AA: Reduced CXCL12 binding. Reduced coreceptor activity for HIV-1 isolate NDK. 1 Publication2
Mutagenesisi18S → 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 Publication1
Mutagenesisi21Y → A: Reduced CXCL12 binding. Reduced coreceptor activity for HIV-1 isolates LAI and NDk. 2 Publications1
Mutagenesisi21Y → 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 Publications1
Mutagenesisi97D → N: Reduced CXCL12 binding. Abolishes signaling. Markedly reduced coreceptor activity for HIV-1 isolate LAI. 1 Publication1
Mutagenesisi119N → D: No reduction of agonist-induced G-protein activation. 1 Publication1
Mutagenesisi119N → K: Loss of agonist-induced G-protein activation. 1 Publication1
Mutagenesisi119N → S: Constitutive G-protein activation, with further activation induced by agonist. 1 Publication1
Mutagenesisi125L → W: Increased thermostability. 1
Mutagenesisi133D → N: No reduction of agonist-induced G-protein activation. 1 Publication1
Mutagenesisi134R → A: Loss of agonist-induced G-protein activation. 1 Publication1
Mutagenesisi135Y → A: No reduction of agonist-induced G-protein activation. 1 Publication1
Mutagenesisi171D → N: Reduced coreceptor activity for HIV-1 isolate NDK. 1 Publication1
Mutagenesisi176N → A: Enhanced coreceptor activity on R5 HIV-1 isolate Envs; when associated with A-11. 1 Publication1
Mutagenesisi183R → A: Reduced coreceptor activity for several HIV-1 isolates. 1 Publication1
Mutagenesisi187D → A: Reduced CXCL12 binding. Abolishes signaling. 1 Publication1
Mutagenesisi188R → A: Reduced coreceptor activity for several HIV-1 isolates. 1 Publication1
Mutagenesisi193D → A, S or N: Greatly reduced coreceptor activity for HIV-1 isolate NDK. Reduced coreceptor activity for several other HIV-1 isolates. 2 Publications1
Mutagenesisi193D → R: Abolishes coreceptor activity for HIV-1 isolate NDK. Reduced coreceptor activity for several other HIV-1 isolates. 2 Publications1
Mutagenesisi240T → P: Retains ligand-binding affinity but abolishes signaling. 1
Mutagenesisi262D → A: Markedly reduced coreceptor activity for HIV-1 isolate LAI. 1 Publication1
Mutagenesisi268E → A: Markedly reduced coreceptor activity for HIV-1 isolate NDK. Less effect for HIV-1 isolate LAI. 1 Publication1
Mutagenesisi288E → Q: Reduced CXCL12 binding. Impaired signaling. Reduced coreceptor activity for HIV-1 isolate LAI. Enhanced coreceptor activity for HIV-1 isolate NDK. 1 Publication1
Mutagenesisi324S → A: Moderate degradation. About 60% reduction in binding ITCH and no ubiquitination nor protein degradation; when associated with A-325. 1 Publication1
Mutagenesisi324S → D: Enhanced binding to ITCH. Enhanced binding to ITCH and greatly increased protein degradation; when associated with D-324. 1 Publication1
Mutagenesisi324S → D: Enhanced binding to ITCH. Enhanced binding to ITCH and greatly increased protein degradation; when associated with D-325. 1 Publication1
Mutagenesisi325S → A: Moderate degradation. About 60% reduction in binding ITCH and no ubiquitination nor protein degradation; when associated with A-324. 1 Publication1
Mutagenesisi330S → A: No effect on binding to ITCH. 1 Publication1

Organism-specific databases

DisGeNETi7852.
MalaCardsiCXCR4.
MIMi193670. phenotype.
OpenTargetsiENSG00000121966.
Orphaneti51636. WHIM syndrome.
PharmGKBiPA27058.

Chemistry databases

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

Polymorphism and mutation databases

BioMutaiCXCR4.
DMDMi46577576.

PTM / Processingi

Molecule processing

Feature keyPosition(s)DescriptionActionsGraphical viewLength
ChainiPRO_00000693521 – 352C-X-C chemokine receptor type 4Add BLAST352

Amino acid modifications

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Modified residuei7Sulfotyrosine; partial1 Publication1
Glycosylationi11N-linked (GlcNAc...)1 Publication1
Modified residuei12Sulfotyrosine; partial1 Publication1
Glycosylationi18O-linked (Xyl...) (chondroitin sulfate)1 Publication1
Modified residuei21Sulfotyrosine3 Publications1
Disulfide bondi28 ↔ 274PROSITE-ProRule annotation1 Publication
Disulfide bondi109 ↔ 186PROSITE-ProRule annotation1 Publication
Glycosylationi176N-linked (GlcNAc...)Sequence analysis1
Modified residuei319PhosphoserineCombined sources1
Modified residuei321PhosphoserineCombined sources1 Publication1
Modified residuei324Phosphoserine; by PKC and GRK6Combined sources2 Publications1
Modified residuei325Phosphoserine; by PKC and GRK6Combined sources2 Publications1
Modified residuei330Phosphoserine; by GRK61 Publication1
Modified residuei339Phosphoserine; by GRK61 Publication1
Modified residuei348PhosphoserineCombined sources1
Modified residuei351Phosphoserine1 Publication1

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.
PhosphoSitePlusiP61073.
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 interactors.
DIPiDIP-34773N.
DIP-46290N.
IntActiP61073. 20 interactors.
MINTiMINT-6630550.
STRINGi9606.ENSP00000386884.

Chemistry databases

BindingDBiP61073.

Structurei

Secondary structure

1352
Legend: HelixTurnBeta strandPDB Structure known for this area
Show more details
Feature keyPosition(s)DescriptionActionsGraphical viewLength
Beta strandi9 – 11Combined sources3
Beta strandi21 – 23Combined sources3
Beta strandi32 – 35Combined sources4
Helixi37 – 62Combined sources26
Turni63 – 66Combined sources4
Beta strandi67 – 69Combined sources3
Helixi72 – 88Combined sources17
Helixi91 – 99Combined sources9
Helixi105 – 139Combined sources35
Helixi141 – 143Combined sources3
Helixi145 – 153Combined sources9
Helixi155 – 159Combined sources5
Helixi161 – 166Combined sources6
Helixi169 – 174Combined sources6
Beta strandi175 – 179Combined sources5
Beta strandi181 – 188Combined sources8
Helixi193 – 207Combined sources15
Helixi209 – 225Combined sources17
Helixi226 – 228Combined sources3
Helixi231 – 266Combined sources36
Helixi274 – 291Combined sources18
Helixi294 – 301Combined sources8
Turni302 – 306Combined sources5
Helixi313 – 317Combined sources5

3D structure databases

Select the link destinations:
PDBei
RCSB PDBi
PDBji
Links Updated
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Miscellaneous databases

EvolutionaryTraceiP61073.

Family & Domainsi

Region

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Regioni1 – 21Important for chemokine binding, signaling and HIV-1 coreceptor activityAdd BLAST21
Regioni94 – 97Chemokine binding4
Regioni113 – 117Chemokine binding5
Regioni135 – 147Involved in dimerization; when bound to chemokineAdd BLAST13
Regioni186 – 190Chemokine binding, important for signaling and HIV-1 coreceptor activity5
Regioni191 – 210Involved in dimerizationAdd BLAST20
Regioni266 – 268Involved in dimerization3

Motif

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Motifi133 – 135Important for signaling3

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)DescriptionActionsGraphical viewLength
Sequence conflicti242 – 244VIL → IIP in AAK29630 (Ref. 12) Curated3
Sequence conflicti278N → S in BAG35177 (PubMed:14702039).Curated1

Alternative sequence

Feature keyPosition(s)DescriptionActionsGraphical viewLength
Alternative sequenceiVSP_0018901 – 5MEGIS → MSIPLPLLQ in isoform 2. 1 Publication5

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
PDB 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.
ModBaseiSearch...
MobiDBiSearch...

Protein-protein interaction databases

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

Chemistry databases

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

Protein family/group databases

TCDBi9.A.14.13.17. the g-protein-coupled receptor (gpcr) family.
GPCRDBiSearch...

PTM databases

iPTMnetiP61073.
PhosphoSitePlusiP61073.
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.
DisGeNETi7852.
GeneCardsiCXCR4.
HGNCiHGNC:2561. CXCR4.
MalaCardsiCXCR4.
MIMi162643. gene.
193670. phenotype.
neXtProtiNX_P61073.
OpenTargetsiENSG00000121966.
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: November 30, 2016
This is version 148 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.