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CXCR4

Family: Chemokine receptors

Contents:
Gene and Protein Information
Previous and Unofficial Names
Database Links
Selected 3D Structures
Agonists
Antagonists
Transduction Mechanisms
Tissue Distribution
Expression Datasets
Functional Assays
Physiological Functions
Physiological Consequences of Altering Gene Expression
Phenotypes, Alleles and Disease Models
Clinically-Relevant Mutations and Pathophysiology
Biologically Significant Variants
References
Gene and Protein Information
class A G protein-coupled receptor
Species TM AA Chromosomal Location Gene Symbol Gene Name Reference
Human 7 352 2q21 CXCR4 chemokine (C-X-C motif) receptor 4 10,29
Mouse 7 359 1 E3 Cxcr4 chemokine (C-X-C motif) receptor 4 15,33
Rat 7 349 13q12 Cxcr4 chemokine (C-X-C motif) receptor 4 23,42
Previous and Unofficial Names
Names References
HUMSTSR
HM89
fusin 6,10,15
LCR1 42
LESTR 29,33
NPY3R
NPYY3R
D2S201E
HSY3RR
NPYR
CD184
chemokine (C-X-C motif), receptor 4 (fusin)
MGC108696
C-X-C chemokine receptor type 4
CXC chemokine receptor
CXC-R4
CXCR-4
Chemokine receptor (LCR1)
SDF-1 receptor
leukocyte-derived seven transmembrane domain receptor
stromal cell-derived factor 1 receptor
PB-CKR
Cmkar4
Sdf1r
Database Links
ChEMBL Target 10473 (Hs), 101235 (Rn)
DrugBank Target 1162 (Hs)
Ensembl ENSG00000121966 (Hs), ENSMUSG00000045382 (Mm), ENSRNOG00000003866 (Rn)
Entrez Gene 7852 (Hs), 12767 (Mm), 60628 (Rn)
GeneCards CXCR4 (Hs)
GenitoUrinary Development Molecular Anatomy Project Cxcr4 (Mm)
HomoloGene 20739 (Hs)
Human Protein Reference Database 01217 (Hs)
InterPro P61073 (Hs), P70658 (Mm), O08565 (Rn)
KEGG Gene hsa:7852 (Hs), mmu:12767 (Mm), rno:60628 (Rn)
OMIM 162643 (Hs)
Orphanet Gene ORPHA120914 (Hs)
PharmGKB Gene PA27058 (Hs)
PhosphoSitePlus P61073 (Hs), P70658 (Mm), O08565 (Rn)
Protein Ontology (PRO) PRO:000001208 (Hs)
RefSeq Nucleotide NM_003467 (Hs), NM_009911 (Mm), NM_022205 (Rn)
RefSeq Protein NP_003458 (Hs), NP_034041 (Mm), NP_071541 (Rn)
TreeFam ENSG00000121966 (Hs), ENSMUSG00000045382 (Mm), ENSRNOG00000003866 (Rn)
UniGene Hs. 421986 (Hs)
UniProt P61073 (Hs), P70658 (Mm), O08565 (Rn)
Wikipedia CXCR4
Chemokine receptors
Selected 3D Structures
Image of receptor 3D structure from RCSB PDB
Description:  CXCR4 chemokine receptor in complex with small molecule antagonist
PDB Id:  3ODU
Ligand:  isothiourea-1t
Resolution:  2.5Å
Species:  Human
References:  43
Image of receptor 3D structure from RCSB PDB
Description:  Crystal structure of the CXCR4 chemokine receptor in complex with a cyclic peptide antagonist CVX15
PDB Id:  3OE0
Resolution:  2.9Å
Species:  Human
References:  43
Search for other structures on the PDB
Search by keyword: Chemokine receptors CXCR4 Search by accession number: O08565, P61073, P70658
Natural/Endogenous Ligand(s)
SDF-1α {Sp: Human}
SDF-1β {Sp: Human}
Comments: SDF1α and SDF1β are the active isomers of CXCL12
Agonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
[125I]SDF-1α (human) Hs Full agonist 8.1 – 8.4 pKd 9,18
SDF-1α {Sp: Human} Hs Full agonist 7.7 – 8.2 pKd 18,30
[125I]SDF-1β (human) Hs Full agonist 7.9 pKd 18
SDF-1β {Sp: Human} Hs Full agonist 7.86 pKd 18
CXCL12-(1-17) Hs Full agonist 6.1 pKi 30
CXCL12-(1-9) dimer Hs Full agonist 6.1 pKi 30
CXCL12-(1-9) Hs Full agonist 4.9 pKi 30
isothiourea-1t Hs Agonist 9.0 pEC50 41
isothiourea-1a Hs Agonist 7.96 pEC50 41
isothiourea-1t Hs Agonist 8.1 pIC50 41
isothiourea-1t Rn Agonist 7.96 pIC50 41
isothiourea-1a Hs Agonist 7.32 pIC50 41
isothiourea-1a Rn Agonist 7.26 pIC50 41
plerixafor Hs Partial agonist 7.0 pIC50 45
ALX40-4C Hs Partial agonist 6.1 pIC50 45
View species-specific agonist tables
Agonist Comments
SDF-1α and SDF-1β are both referred to as CXCL12 and they have equivalent binding affinity and potency [18].
Antagonists
Key to terms and symbols View all chemical structures Click column headers to sort
Ligand Sp. Action Affinity Units Reference
plerixafor Hs Antagonist 7.0 pKi 45
SDF-1, 1-9[P2G] dimer Hs Antagonist 5.6 pKi 30
T134 Hs Antagonist 8.4 pIC50 40
T140 Hs Inverse agonist 7.8 – 8.6 pIC50 40,45
vMIP-II Hs Antagonist 8.2 pIC50 26
T22 Hs Antagonist 7.3 pIC50 40
Antagonist Comments
AMD3100 is in clinical trials for hematopoietic progenitor cell mobilisation [28].

Explore drug-target interactions for this set of compounds using iPHACE

Primary Transduction Mechanisms
Transducer Effector/Response
Gi/Go family Calcium channel
References:  33,35
Tissue Distribution
CD4 lymphocytes in normal intestinal mucosa.
Species:  Human
Technique:  Flow cytometry.
References:  2
CNS: Frontal lobe, temporal lobe, spinal cord.
Species:  Human
Technique:  Northern blotting.
References:  37
Basophils.
Species:  Human
Technique:  RT-PCR and flow cytometry.
References:  21
Glomerular podocytes.
Species:  Human
Technique:  RT-PCR.
References:  20
Bone marrow stromal cells (BMSCs).
Species:  Human
Technique:  Flow cytometry and RT-PCR.
References:  19
Testes.
Species:  Human
Technique:  RT-PCR.
References:  14
Blood dendritic cells.
Species:  Human
Technique:  RT-PCR.
References:  3
Microglia.
Species:  Human
Technique:  Flow cytometry.
References:  1,11
Colon.
Species:  Human
Technique:  RT-PCR and Immunohistochemistry.
References:  24
Natural killer (NK) cells.
Species:  Human
Technique:  Flow cytometric and RNase protection assay.
References:  22
Precursor and mature megakaryocyte cells, and platelets.
Species:  Human
Technique:  RT-PCR and flow cytometry.
References:  27
CD34+ hematopoietic progenitor cells.
Species:  Human
Technique:  RT-PCR and Southern blotting.
References:  7
Fetal thymocytes.
Species:  Human
Technique:  Flow cytometry.
References:  25
Developing CNS: retina, olfactory epithelium, olfactory bulb, hippocampus, cerebellum, spinal cord.
Species:  Human
Technique:  in situ hybridisation.
References:  46
Thymus > spleen.
Species:  Mouse
Technique:  Northern blotting.
References:  15
Primordial germ cells.
Species:  Mouse
Technique:  RT-PCR
References:  34
Developing neocortex and hippocampus.
Species:  Mouse
Technique:  in situ hybridisation.
References:  31
Testicular macrophages.
Species:  Rat
Technique:  Northern blotting.
References:  14
Hippocampal neurons.
Species:  Rat
Technique:  RT-PCR.
References:  32
Brain: choroid plexus > olfactory nucleus, cortex, pituitary.
Species:  Rat
Technique:  Radioligand binding.
References:  4
Primary cultures of rat astrocytes and microglia.
Species:  Rat
Technique:  Northern blotting.
References:  23
Expression Datasets

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Log average relative transcript abundance in mouse tissues measured by qPCR from Regard, J.B., Sato, I.T., and Coughlin, S.R. (2008). Anatomical profiling of G protein-coupled receptor expression. Cell, 135(3): 561-71. [PMID:18984166] [Raw data: website]

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Functional Assays
Measurement of chemotaxis of thymocyte cells endogenously expressing the CXCR4 receptor.
Species:  Human
Tissue:  Thymocytes.
Response measured:  Chemotaxis.
References:  44
Measurement of Ca2+ levels in thymocytes endogenously expressing the CXCR4 receptor.
Species:  Human
Tissue:  Thymocytes.
Response measured:  Stimulation of Ca2+ influx.
References:  44
Detection of HIV-1 entry into human U87MG cells transfected with human HA-tagged CXCR4 receptors and human CD4.
Species:  Human
Tissue:  Human astroglioma cell line U87MG.
Response measured:  HIV-1 entry.
References:  6
Measurement of Ca2+ levels in the human colonic epithelial cell line HT-29 endogenously expressing the CXCR4 receptor.
Species:  Human
Tissue:  HT-29 cells.
Response measured:  Increase in intracellular Ca2+ concentration.
References:  24
Detection of neutrophil morphological change (activation) by light microscopy.
Species:  Human
Tissue:  Neutrophils.
Response measured:  Activation.
References:  12
Measurement of ERK and p38 MAPK activity in HEK 293 cells transfected with the human CXCR4 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Activation of ERK and p38 MAPK via β-arrestin2
References:  39
Measurement of chemotaxis of HEK 293 cells transfected with the human CXCR4 receptor.
Species:  Human
Tissue:  HEK 293 cells.
Response measured:  Chemotaxis involving β-arrstin2 and p38 MAPK activation.
References:  39
Measurement of Ca2+ currents in HEK 293 cells stably expressing N-type calcium channels and the rat CXCR4 receptor, using Ba2+ as the charge carrier (IBa).
Species:  Rat
Tissue:  HEK 293 cells.
Response measured:  IBa inhibition.
References:  35
Physiological Functions
HIV coreceptor.
Species:  Human
Tissue:  Intestinal cell line HT-29.
References:  8
Chemotaxis.
Species:  Human
Tissue:  Neutrophils.
References:  12
Lymphopoiesis.
Species:  Human
Tissue:  Thymocytes.
References:  25
Haematopoiesis.
Species:  Mouse
Tissue:  In vivo.
References:  46
Cell migration and survival.
Species:  Mouse
Tissue:  Primordial germ cells.
References:  34
Interneuron migration.
Species:  Mouse
Tissue:  Neocortex.
References:  38
Neovascularisation (angiogenesis).
Species:  Rat
Tissue:  Aorta.
References:  36
Physiological Consequences of Altering Gene Expression
CXCR4 receptor knockout mice exhibit defective haematopoiesis and cardiac development.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  46
CXCR4 receptor knockout mice exhibit small and malformed dorsal root ganglia as well as delayed migration of sensory neuron progenitors to the dorsal root ganglion.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  5
CXCR4 receptor knockout mice embryos exhibit defects in primordial germ cell migration and survival.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  34
CXCR4 receptor knockout mice exhibit fewer interneurons in the superficial layers of the neocortex, these interneurons instead being located in the deep layers of the neocortex.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  38
CXCR4 receptor knockout mice exhibit abnormal development of the dorsal root ganglia with major defects in cell migration in the developing cerebellar cortex.
Species:  Mouse
Tissue: 
Technique:  Gene targeting in embryonic stem cells.
References:  31
Phenotypes, Alleles and Disease Models Mouse data from MGI

Click here to show/hide data

Allele Composition & genetic background Accession Phenotype Id Phenotype Reference
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
involves: 129P2/OlaHsd		 MGI:109563  MP:0000260 abnormal angiogenesis PMID: 9634237 
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
involves: 129P2/OlaHsd		 MGI:109563  MP:0002144 abnormal B cell differentiation PMID: 9634237 
Cd19+|Cd19tm1(cre)Cgn|Cxcr4tm2Yzo Cd19tm1(cre)Cgn/Cd19+,Cxcr4tm2Yzo/Cxcr4tm2Yzo
involves: 129P2/OlaHsd		 MGI:109563  MGI:88319  MP:0002144 abnormal B cell differentiation PMID: 15520246 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0000872 abnormal cerebellum external granule cell layer morphology PMID: 9634238 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0000849 abnormal cerebellum morphology PMID: 9689100 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0000849 abnormal cerebellum morphology PMID: 9634238 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0000788 abnormal cerebral cortex morphology PMID: 11983855 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0000812 abnormal dentate gyrus morphology PMID: 11983855  12183377 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0000281 abnormal interventricular septum morphology PMID: 9634238 
Cxcr4tm1Yiw|Tg(Lck-cre)1Jtak Cxcr4tm1Yiw/Cxcr4tm1Yiw,Tg(Lck-cre)1Jtak/0
Not Specified		 MGI:109563  MGI:3655253  MP:0003156 abnormal leukocyte migration PMID: 20939892 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0005460 abnormal leukopoiesis PMID: 9634238 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0002401 abnormal lymphopoiesis PMID: 9634238 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
B6.129X-Cxcr4/J		 MGI:109563  MP:0003090 abnormal muscle progenitor cell migration PMID: 16166380 
Cxcr4tm1Qma|Gab1tm1Wbm Cxcr4tm1Qma/Cxcr4tm1Qma,Gab1tm1Wbm/Gab1tm1Wbm
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6		 MGI:108088  MGI:109563  MP:0003090 abnormal muscle progenitor cell migration PMID: 16166380 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
B6.129X-Cxcr4/J		 MGI:109563  MP:0000729 abnormal myogenesis PMID: 16166380 
Cxcr4tm1Qma|Gab1tm1Wbm Cxcr4tm1Qma/Cxcr4tm1Qma,Gab1tm1Wbm/Gab1tm1Wbm
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6		 MGI:108088  MGI:109563  MP:0000729 abnormal myogenesis PMID: 16166380 
Cd19+|Cd19tm1(cre)Cgn|Cxcr4tm2Yzo Cd19tm1(cre)Cgn/Cd19+,Cxcr4tm2Yzo/Cxcr4tm2Yzo
involves: 129P2/OlaHsd		 MGI:109563  MGI:88319  MP:0002389 abnormal Peyer's patch follicle morphology PMID: 15520246 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0002982 abnormal primordial germ cell migration PMID: 12900445 
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
B6.Cg-Cxcr4		 MGI:109563  MP:0002982 abnormal primordial germ cell migration PMID: 12684531 
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
B6.Cg-Cxcr4		 MGI:109563  MP:0002145 abnormal T cell differentiation PMID: 12707343 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0000853 absent cerebellar foliation PMID: 9689100 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0001177 atelectasis PMID: 9689100 
Cd19+|Cd19tm1(cre)Cgn|Cxcr4tm2Yzo Cd19tm1(cre)Cgn/Cd19+,Cxcr4tm2Yzo/Cxcr4tm2Yzo
involves: 129P2/OlaHsd		 MGI:109563  MGI:88319  MP:0004978 decreased B-1 B cell number PMID: 15520246 
Cd19+|Cd19tm1(cre)Cgn|Cxcr4tm2Yzo Cd19tm1(cre)Cgn/Cd19+,Cxcr4tm2Yzo/Cxcr4tm2Yzo
involves: 129P2/OlaHsd		 MGI:109563  MGI:88319  MP:0008207 decreased B-2 B cell number PMID: 15520246 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0001265 decreased body size PMID: 9689100 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0000333 decreased bone marrow cell number PMID: 9689100 
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
B6.Cg-Cxcr4		 MGI:109563  MP:0005092 decreased double-positive T cell number PMID: 12707343 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0004200 decreased fetal size PMID: 9634238 
Cd19+|Cd19tm1(cre)Cgn|Cxcr4tm2Yzo Cd19tm1(cre)Cgn/Cd19+,Cxcr4tm2Yzo/Cxcr4tm2Yzo
involves: 129P2/OlaHsd		 MGI:109563  MGI:88319  MP:0002460 decreased immunoglobulin level PMID: 15520246 
Cd19+|Cd19tm1(cre)Cgn|Cxcr4tm2Yzo Cd19tm1(cre)Cgn/Cd19+,Cxcr4tm2Yzo/Cxcr4tm2Yzo
involves: 129P2/OlaHsd		 MGI:109563  MGI:88319  MP:0008211 decreased mature B cell number PMID: 15520246 
Cd19+|Cd19tm1(cre)Cgn|Cxcr4tm2Yzo Cd19tm1(cre)Cgn/Cd19+,Cxcr4tm2Yzo/Cxcr4tm2Yzo
involves: 129P2/OlaHsd		 MGI:109563  MGI:88319  MP:0008098 decreased plasma cell number PMID: 15520246 
Cd19+|Cd19tm1(cre)Cgn|Cxcr4tm1Tng|Cxcr4tm2Tng Cd19tm1(cre)Cgn/Cd19+,Cxcr4tm1Tng/Cxcr4tm2Tng
involves: 129P2/OlaHsd * C57BL/6		 MGI:109563  MGI:88319  MP:0008098 decreased plasma cell number PMID: 15189736 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0008392 decreased primordial germ cell number PMID: 12900445 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0008208 decreased pro-B cell number PMID: 9689100 
Cxcr4tm1Yiw|Tg(Lck-cre)1Jtak Cxcr4tm1Yiw/Cxcr4tm1Yiw,Tg(Lck-cre)1Jtak/0
Not Specified		 MGI:109563  MGI:3655253  MP:0003436 decreased susceptibility to induced arthritis PMID: 20939892 
Cxcr4tm1Yiw|Tg(Lck-cre)1Jtak Cxcr4tm1Yiw/Cxcr4tm1Yiw,Tg(Lck-cre)1Jtak/0
Not Specified		 MGI:109563  MGI:3655253  MP:0000715 decreased thymocyte number PMID: 20939892 
Cxcr4tm1Qma|Gab1tm1Wbm Cxcr4tm1Qma/Cxcr4tm1Qma,Gab1tm1Wbm/Gab1tm1Wbm
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6		 MGI:108088  MGI:109563  MP:0009907 decreased tongue size PMID: 16166380 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0000885 ectopic Purkinje cell PMID: 9689100 
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
involves: 129P2/OlaHsd		 MGI:109563  MP:0001603 failure of myelopoiesis PMID: 9634237 
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
involves: 129P2/OlaHsd		 MGI:109563  MP:0000465 gastrointestinal hemorrhage PMID: 9634237 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0002192 hydrops fetalis PMID: 9634238 
Cxcr4tm1Qma|Gab1tm1Wbm Cxcr4tm1Qma/Cxcr4tm1Qma,Gab1tm1Wbm/Gab1tm1Wbm
involves: 129P2/OlaHsd * 129X1/SvJ * C57BL/6		 MGI:108088  MGI:109563  MP:0003359 hypaxial muscle hypoplasia PMID: 16166380 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0001602 impaired myelopoiesis PMID: 9689100 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0001602 impaired myelopoiesis PMID: 9634238 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0000533 kidney hemorrhage PMID: 9689100 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0000532 kidney vascular congestion PMID: 9689100 
Cxcr4tm1Yzo Cxcr4tm1Yzo/Cxcr4tm1Yzo
Not Specified		 MGI:109563  MP:0006208 lethality throughout fetal growth and development PMID: 9634238 
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
involves: 129P2/OlaHsd		 MGI:109563  MP:0002058 neonatal lethality PMID: 9634237 
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
involves: 129P2/OlaHsd		 MGI:109563  MP:0010418 perimembraneous ventricular septal defect PMID: 9634237 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0002081 perinatal lethality PMID: 9689100 
Cxcr4tm1Tng Cxcr4tm1Tng/Cxcr4tm1Tng
involves: 129P2/OlaHsd		 MGI:109563  MP:0002081 perinatal lethality PMID: 9634237 
Cxcr4tm1Qma Cxcr4tm1Qma/Cxcr4tm1Qma
involves: 129X1/SvJ		 MGI:109563  MP:0000873 thin external granule cell layer PMID: 9689100 
Clinically-Relevant Mutations and Pathophysiology
Disease:  WHIM syndrome
OMIM:  193670
Orphanet:  51636
Comments:  Truncating mutations in the cytoplasmic tail domain of the CXCR4 gene have been identified in many cases of WHIM (warts, hypogammaglobulinemia, immunodeficiency, and myelokathexi) syndrome. The mutations result in gain of function: prolonged agonist-dependent signalling.
References:  17
Mutations not determined
Biologically Significant Variants
An unspliced version of the human CXCR4 receptor, called CXCR4-Lo, has been found, with a 9 amino acid extension at the N-terminus. This receptor may be a functional backup to CXCR4 during embryogenesis.
Type:  Splice variant.
Species:  Human
References:  13
A fully functioning splice variant of the mouse CXCR4 receptor, CXCR4-B, has been found with a different expression pattern from CXCR4.
Type:  Splice variant.
Species:  Mouse
References:  16,33

REFERENCES

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1. Albright, A. V., Shieh, J. T., Itoh, T., Lee, B., Pleasure, D., O'Connor, M. J., Doms, R. W. and González-Scarano, F. (1999) Microglia express CCR5, CXCR4, and CCR3, but of these, CCR5 is the principal coreceptor for human immunodeficiency virus type 1 dementia isolates. J Virol, 73: 205-213. [PMID:9847323]

2. Anton, P. A., Elliott, J., Poles, M. A., McGowan, I. M., Matud, J., Hultin, L. E., Grovit-Ferbas, K., Mackay, C. R., Chen, I. S. Y. and Giorgi, J. V. (2000) Enhanced levels of functional HIV-1 co-receptors on human mucosal T cells demonstrated using intestinal biopsy tissue. AIDS, 14: 1761-1765. [PMID:10985313]

3. Ayehunie, S., Garcia-Zepeda, E. A., Hoxie, J. A., Horuk, R., Kupper, T. S., Luster, A. D. and Ruprecht, R. M. (1997) Human immunodeficiency virus-1 entry into purified blood dendritic cells through CC and CXC chemokine coreceptors. Blood, 90: 1379-1386. [PMID:9269754]

4. Banisadr, G., Dicou, E., Berbar, T., Rostene, W., Lombet, A. and Haour, F. (2000) Characterization and visualization of [125I] stromal cell-derived factor-1alpha binding to CXCR4 receptors in rat brain and human neuroblastoma cells. J Neuroimmunol, 110: 151-160. [PMID:11024545]

5. Belmadani, A., Tran, P. B., Ren, D., Assimacopoulos, S., Grove, E. A. and Miller, R. J. (2005) The chemokine stromal cell-derived factor-1 regulates the migration of sensory neuron progenitors. J Neurosci, 25: 3995-4003. [PMID:15843601]

6. Berson, J. F., Long, D., Doranz, B. J., Rucker, J., Jirik, F. R. and Doms, R. W. (1996) A seven-transmembrane domain receptor involved in fusion and entry of T-cell-tropic human immunodeficiency virus type 1 strains. J Virol, 70: 6288-6295. [PMID:8709256]

7. Deichmann, M., Kronenwett, R. and Haas, R. (1997) Expression of the human immunodeficiency virus type-1 coreceptors CXCR-4 (fusin, LESTR) and CKR-5 in CD34+ hematopoietic progenitor cells. Blood, 89: 3522-3528. [PMID:9160656]

8. Delézay, O., Koch, N., Yahi, N., Hammache, D., Tourres, C., Tamalet, C. and Fantini, J. (1997) Co-expression of CXCR4/fusin and galactosylceramide in the human intestinal epithelial cell line HT-29. AIDS, 11: 1311-1318. [PMID:9302439]

9. Di Salvo, J., Koch, G. E., Johnson, K. E., Blake, A. D., Daugherty, B. L., DeMartino, J. A., Sirotina-Meisher, A., Liu, Y., Springer, M. S., Cascieri, M. A. and Sullivan, K. A. (2000) The CXCR4 agonist ligand stromal derived factor-1 maintains high affinity for receptors in both Galpha(i)-coupled and uncoupled states. Eur J Pharmacol, 409: 143-154. [PMID:11104827]

10. Feng, Y., Broder, C. C., Kennedy, P. E. and Berger, E. A. (1996) HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor. Science, 272: 872-877. [PMID:8629022]

11. Flynn, G., Maru, S., Loughlin, J., Romero, I. A. and Male, D. (2003) Regulation of chemokine receptor expression in human microglia and astrocytes. J Neuroimmunol, 136: 84-93. [PMID:12620646]

12. Gouwy, M., Struyf, S., Catusse, J., Proost, P. and Van Damme, J. (2004) Synergy between proinflammatory ligands of G protein-coupled receptors in neutrophil activation and migration. J Leukoc Biol, 76: 185-194. [PMID:15075362]

13. Gupta, S. K. and Pillarisetti, K. (1999) Cutting edge: CXCR4-Lo: molecular cloning and functional expression of a novel human CXCR4 splice variant. J Immunol, 163: 2368-2372. [PMID:10452968]

14. Habasque, C., Aubry, F., Jégou, B. and Samson, M. (2002) Study of the HIV-1 receptors CD4, CXCR4, CCR5 and CCR3 in the human and rat testis. Mol Hum Reprod, 8: 419-425. [PMID:11994538]

15. Heesen, M., Berman, M. A., Benson, J. D., Gerard, C. and Dorf, M. E. (1996) Cloning of the mouse fusin gene, homologue to a human HIV-1 co-factor. J Immunol, 157: 5455-5460. [PMID:8955194]

16. Heesen, M., Berman, M. A., Höpken, U. E., Gerard, N. P. and Dorf, M. E. (1997) Alternate splicing of mouse fusin/CXC chemokine receptor-4: stromal cell-derived factor-1alpha is a ligand for both CXC chemokine receptor-4 isoforms. J Immunol, 158: 3561-3564. [PMID:9103415]

17. Hernandez, P. A., Gorlin, R. J., Lukens, J. N., Taniuchi, S., Bohinjec, J., Francois, F., Klotman, M. E. and Diaz, G. A. (2003) Mutations in the chemokine receptor gene CXCR4 are associated with WHIM syndrome, a combined immunodeficiency disease. Nat Genet, 34: 70-74. [PMID:12692554]

18. Hesselgesser, J., Liang, M., Hoxie, J., Greenberg, M., Brass, L. F., Orsini, M. J., Taub, D. and Horuk, R. (1998) Identification and characterization of the CXCR4 chemokine receptor in human T cell lines: ligand binding, biological activity, and HIV-1 infectivity. J Immunol, 160: 877-883. [PMID:9551924]

19. Honczarenko, M., Le, Y., Swierkowski, M., Ghiran, I., Glodek, A. and Silberstein, L. E. (2005) HUMAN BONE MARROW STROMAL CELLS EXPRESS A DISTINCT SET OF BIOLOGICALLY FUNCTIONAL CHEMOKINE RECEPTORS. Stem Cells, : -. [PMID:16253981]

20. Huber, T. B., Reinhardt, H. C., Exner, M., Burger, J. A., Kerjaschki, D., Saleem, M. A. and Pavenstädt, H. (2002) Expression of functional CCR and CXCR chemokine receptors in podocytes. J Immunol, 168: 6244-6252. [PMID:12055238]

21. Iikura, M., Miyamasu, M., Yamaguchi, M., Kawasaki, H., Matsushima, K., Kitaura, M., Morita, Y., Yoshie, O., Yamamoto, K. and Hirai, K. (2001) Chemokine receptors in human basophils: inducible expression of functional CXCR4. J Leukoc Biol, 70: 113-120. [PMID:11435493]

22. Inngjerdingen, M., Damaj, B. and Maghazachi, A. A. (2001) Expression and regulation of chemokine receptors in human natural killer cells. Blood, 97: 367-375. [PMID:11154210]

23. Jiang, Y., Salafranca, M. N., Adhikari, S., Xia, Y., Feng, L., Sonntag, M. K., deFiebre, C. M., Pennell, N. A., Streit, W. J. and Harrison, J. K. (1998) Chemokine receptor expression in cultured glia and rat experimental allergic encephalomyelitis. J Neuroimmunol, 86: 1-12. [PMID:9655467]

24. Jordan, N. J., Kolios, G., Abbot, S. E., Sinai, M. A., Thompson, D. A., Petraki, K. and Westwick, J. (1999) Expression of functional CXCR4 chemokine receptors on human colonic epithelial cells. J Clin Invest, 104: 1061-1069. [PMID:10525044]

25. Kitchen, S. G. and Zack, J. A. (1997) CXCR4 expression during lymphopoiesis: implications for human immunodeficiency virus type 1 infection of the thymus. J Virol, 71: 6928-6934. [PMID:9261420]

26. Kledal, T. N., Rosenkilde, M. M., Coulin, F., Simmons, G., Johnsen, A. H., Alouani, S., Power, C. A., Luttichau, H. R., Gerstoft, J., Clapham, P. R., Clark-Lewis, I., Wells, T. N. and Schwartz, T. W. (1997) A broad-spectrum chemokine antagonist encoded by Kaposi's sarcoma-associated herpesvirus. Science, 277: 1656-1659. [PMID:9287217]

27. Kowalska, M. A., Ratajczak, J., Hoxie, J., Brass, L. F., Gewirtz, A., Poncz, M. and Ratajczak, M. Z. (1999) Megakaryocyte precursors, megakaryocytes and platelets express the HIV co-receptor CXCR4 on their surface: determination of response to stromal-derived factor-1 by megakaryocytes and platelets. Br J Haematol, 104: 220-229. [PMID:10050701]

28. Larochelle, A., Krouse, A., Metzger, M., Orlic, D., Donahue, R. E., Fricker, S., Bridger, G., Dunbar, C. E. and Hematti, P. (2006) AMD3100 mobilizes hematopoietic stem cells with long-term repopulating capacity in nonhuman primates. Blood, 107: 3772-3778. [PMID:16439684]

29. Loetscher, M., Geiser, T., O'Reilly, T., Zwahlen, R., Baggiolini, M. and Moser, B. (1994) Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem, 269: 232-237. [PMID:8276799]

30. Loetscher, P., Gong, J. H., Dewald, B., Baggiolini, M. and Clark-Lewis, I. (1998) N-terminal peptides of stromal cell-derived factor-1 with CXC chemokine receptor 4 agonist and antagonist activities. J Biol Chem, 273: 22279-22283. [PMID:9712844]

31. Lu, M., Grove, E. A. and Miller, R. J. (2002) Abnormal development of the hippocampal dentate gyrus in mice lacking the CXCR4 chemokine receptor. Proc Natl Acad Sci U S A, 99: 7090-7095. [PMID:11983855]

32. Meucci, O., Fatatis, A., Simen, A. A., Bushell, T. J., Gray, P. W. and Miller, R. J. (1998) Chemokines regulate hippocampal neuronal signaling and gp120 neurotoxicity. Proc Natl Acad Sci U S A, 95: 14500-14505. [PMID:9826729]

33. Moepps, B., Frodl, R., Rodewald, H. R., Baggiolini, M. and Gierschik, P. (1997) Two murine homologues of the human chemokine receptor CXCR4 mediating stromal cell-derived factor 1alpha activation of Gi2 are differentially expressed in vivo. Eur J Immunol, 27: 2102-2112. [PMID:9295051]

34. Molyneaux, K. A., Zinszner, H., Kunwar, P. S., Schaible, K., Stebler, J., Sunshine, M. J., O'Brien, W., Raz, E., Littman, D., Wylie, C. and Lehmann, R. (2003) The chemokine SDF1/CXCL12 and its receptor CXCR4 regulate mouse germ cell migration and survival. Development, 130: 4279-4286. [PMID:12900445]

35. Oh, S. B., Endoh, T., Simen, A. A., Ren, D. and Miller, R. J. (2002) Regulation of calcium currents by chemokines and their receptors. J Neuroimmunol, 123: 66-75. [PMID:11880151]

36. Salcedo, R., Wasserman, K., Young, H. A., Grimm, M. C., Howard, O. M., Anver, M. R., Kleinman, H. K., Murphy, W. J. and Oppenheim, J. J. (1999) Vascular endothelial growth factor and basic fibroblast growth factor induce expression of CXCR4 on human endothelial cells: In vivo neovascularization induced by stromal-derived factor-1alpha. Am J Pathol, 154: 1125-1135. [PMID:10233851]

37. Sehgal, A., Ricks, S., Boynton, A. L., Warrick, J. and Murphy, G. P. (1998) Molecular characterization of CXCR-4: a potential brain tumor-associated gene. J Surg Oncol, 69: 239-248. [PMID:9881942]

38. Stumm, R. K., Zhou, C., Ara, T., Lazarini, F., Dubois-Dalcq, M., Nagasawa, T., Höllt, V. and Schulz, S. (2003) CXCR4 regulates interneuron migration in the developing neocortex. J Neurosci, 23: 5123-5130. [PMID:12832536]

39. Sun, Y., Cheng, Z., Ma, L. and Pei, G. (2002) Beta-arrestin2 is critically involved in CXCR4-mediated chemotaxis, and this is mediated by its enhancement of p38 MAPK activation. J Biol Chem, 277: 49212-49219. [PMID:12370187]

40. Tamamura, H., Xu, Y., Hattori, T., Zhang, X., Arakaki, R., Kanbara, K., Omagari, A., Otaka, A., Ibuka, T., Yamamoto, N., Nakashima, H. and Fujii, N. (1998) A low-molecular-weight inhibitor against the chemokine receptor CXCR4: a strong anti-HIV peptide T140. Biochem. Biophys. Res. Commun., 253: 877-882. [PMID:9918823]

41. Thoma, G; Streiff, MB; Kovarik, J; Glickman, F; Wagner, T; Beerli, C; Zerwes, HG. (2008) Orally bioavailable isothioureas block function of the chemokine receptor CXCR4 in vitro and in vivo. J. Med. Chem., 51 (24): 7915-20. [PMID:19053768]

42. Wong, M. L., Xin, W. W. and Duman, R. S. (1996) Rat LCR1: cloning and cellular distribution of a putative chemokine receptor in brain. Mol Psychiatry, 1: 133-140. [PMID:9118323]

43. Wu, B; , EY; , CD; , G; , W; , V; , R; , A; , P; , FC; , DJ; , P; , TM; , V; , RC. (2010) Structures of the CXCR4 Chemokine GPCR with Small-Molecule and Cyclic Peptide Antagonists. Science, . [PMID:20929726]

44. Zamarchi, R., Allavena, P., Borsetti, A., Stievano, L., Tosello, V., Marcato, N., Esposito, G., Roni, V., Paganin, C., Bianchi, G., Titti, F., Verani, P., Gerosa, G. and Amadori, A. (2002) Expression and functional activity of CXCR-4 and CCR-5 chemokine receptors in human thymocytes. Clin Exp Immunol, 127: 321-330. [PMID:11876757]

45. Zhang, W. B., Navenot, J. M., Haribabu, B., Tamamura, H., Hiramatu, K., Omagari, A., Pei, G., Manfredi, J. P., Fujii, N., Broach, J. R. and Peiper, S. C. (2002) A point mutation that confers constitutive activity to CXCR4 reveals that T140 is an inverse agonist and that AMD3100 and ALX40-4C are weak partial agonists. J Biol Chem, 277: 24515-24521. [PMID:11923301]

46. Zou, Y. R., Kottmann, A. H., Kuroda, M., Taniuchi, I. and Littman, D. R. (1998) Function of the chemokine receptor CXCR4 in haematopoiesis and in cerebellar development. Nature, 393: 595-599. [PMID:9634238]

To cite this database page, please use the following:

Israel F. Charo, Rebecca Hills, Richard Horuk, Kouji Matsushima, Philip M. Murphy, Joost J. Oppenheim.
Chemokine receptors: CXCR4. Last modified on 11/03/2013. Accessed on 18/05/2013. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=71.


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