Chemokine (C-X-C motif) receptor 4
CXCR4 in complex with IT1t(PDB 3OE9)
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 2K03, 2K04, 2K05, 3ODU, 3OE0, 3OE6, 3OE8, 3OE9
Identifiers
Symbols	CXCR4; CD184; D2S201E; FB22; HM89; HSY3RR; LAP3; LCR1; LESTR; NPY3R; NPYR; NPYRL; NPYY3R; WHIM
External IDs	OMIM: 162643 MGI: 109563 HomoloGene: 20739 IUPHAR: CXCR4 ChEMBL: 2107 GeneCards: CXCR4 Gene
Gene Ontology Molecular function • actin binding • signal transducer activity • receptor activity • G-protein coupled receptor activity • protein binding • coreceptor activity • C-X-C chemokine receptor activity • ubiquitin protein ligase binding • myosin light chain binding • ubiquitin binding Cellular component • cytoplasm • plasma membrane • cell surface • integral to membrane • cytoplasmic membrane-bounded vesicle • cell leading edge • cytoplasmic vesicle Biological process • activation of MAPK activity • response to hypoxia • dendritic cell chemotaxis • apoptotic process • inflammatory response • G-protein coupled receptor signaling pathway • G-protein coupled receptor signaling pathway • elevation of cytosolic calcium ion concentration • response to virus • viral reproduction • initiation of viral infection • calcium-mediated signaling • entry into host cell • myelin maintenance • interspecies interaction between organisms • positive regulation of oligodendrocyte differentiation • regulation of chemotaxis Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	7852	12767
Ensembl	ENSG00000121966	ENSMUSG00000045382
UniProt	P61073	P70658
RefSeq (mRNA)	NM_001008540.1	NM_009911.3
RefSeq (protein)	NP_001008540.1	NP_034041.2
Location (UCSC)	Chr 2: 136.87 – 136.88 Mb	Chr 1: 130.48 – 130.49 Mb
PubMed search	[1]	[2]
This box: view talk edit

C-X-C chemokine receptor type 4 (CXCR-4) also known as fusin or CD184 (cluster of differentiation 184) is a protein that in humans is encoded by the CXCR4 gene.^[1][2]

Function[link]

CXCR-4 is an alpha-chemokine receptor specific for stromal-derived-factor-1 (SDF-1 also called CXCL12), a molecule endowed with potent chemotactic activity for lymphocytes. This receptor is one of several chemokine receptors that HIV can use to infect CD4+ T cells. HIV isolates that use CXCR4 are traditionally known as T-cell tropic isolates. Typically, these viruses are found late in infection. It is unclear as to whether the emergence of CXCR4-using HIV is a consequence or a cause of immunodeficiency.

CXCR4 is upregulated during the implantation window in natural and hormone replacement therapy cycles in the endometrium, producing, in presence of a human blastocyst, a surface polarization of the CXCR4 receptors suggesting that this receptor is implicated in the adhesion phase of human implantation.

CXCR4's ligand SDF-1 is known to be important in hematopoietic stem cell homing to the bone marrow and in hematopoietic stem cell quiescence. Until recently, SDF-1 and CXCR4 were believed to be a relatively "monogamous" ligand-receptor pair (other chemokines tend to use several different chemokine receptors in a fairly "promiscuous" manner). Recent evidence demonstrates ubiquitin is also a natural ligand of CXCR4.^[3] Ubiquitin is a small (76-amino acid) protein highly conserved among eukaryotic cells. It is best known for its intracellular role in targeting ubiquitylated proteins for degradation via the ubiquitin proteasome system. Evidence in numerous animal models suggests ubiquitin is anti-inflammatory immune modulator and endogenous opponent of proinflammatory damage associated molecular pattern molecules.^[4] It is speculated this interaction may be through CXCR4 mediated signalling pathways.

Clinical significance[link]

Drugs that block the CXCR4 receptor appear to be capable of "mobilizing" hematopoietic stem cells into the bloodstream as peripheral blood stem cells. Peripheral blood stem cell mobilization is very important in hematopoietic stem cell transplantation (as a recent alternative to transplantation of surgically-harvested bone marrow) and is currently performed using drugs such as G-CSF. G-CSF is a growth factor for neutrophils (a common type of white blood cells), and may act by increasing the activity of neutrophil-derived proteases such as neutrophil elastase in the bone marrow leading to proteolytic degradation of SDF-1. Plerixafor (AMD3100) is a drug, recently approved for routine clinical use^[5], which directly blocks the CXCR4 receptor. It is a very efficient inducer of hematopoietic stem cell mobilization in animal and human studies.

It has been associated with WHIM syndrome.^[6]

Drug response[link]

Chronic exposure to THC increased T lymphocyte CXCR4 expression on both CD4+ and CD8+ T lymphocytes. ^[7]

Interactions[link]

CXCR4 has been shown to interact with USP14.^[8]

See also[link]

• HIV tropism
• Entry inhibitor
• Discovery and development of CCR5 receptor antagonists

References[link]

Further reading[link]

External links[link]

• "Chemokine Receptors: CXCR4". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. http://www.iuphar-db.org/GPCR/ReceptorDisplayForward?receptorID=2216. 

This cell biology article is a stub. You can help Wikipedia by expanding it. v t e