InnateDB: Systems Biology of the Innate Immune Response

Mus musculus Protein: Cxcr4

Summary

InnateDB Protein

IDBP-190001.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

Cxcr4

Protein Name

chemokine (C-X-C motif) receptor 4

Synonyms

b2b220Clo; CD184; Cmkar4; LESTR; PB-CKR; PBSF/SDF-1; Sdf1r;

Species

Mus musculus

Ensembl Protein

ENSMUSP00000053489

InnateDB Gene

IDBG-189999 (Cxcr4)

Protein Structure

UniProt Annotation

Function

Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes (By similarity). 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. {ECO:0000250, ECO:0000269PubMed:9634237, ECO:0000269PubMed:9634238, ECO:0000269PubMed:9689100}.

Subcellular Localization

Cell membrane {ECO:0000250}; Multi-pass membrane protein {ECO:0000250}. Cell junction {ECO:0000250}. Early endosome {ECO:0000250}. Late endosome {ECO:0000250}. Lysosome {ECO:0000250}. Note=In unstimulated cells, diffuse pattern on plasma membrane. On agonist stimulation, colocalizes with ITCH at the plasma membrane where it becomes ubiquitinated (By similarity). In the presence of antigen, distributes to the immunological synapse forming at the T-cell-APC contact area, where it localizes at the peripheral and distal supramolecular activation cluster (SMAC) (By similarity). {ECO:0000250}.

Disease Associations

Tissue Specificity

Lymphocytes, macrophages, neutrophils, microglial cells and astrocytes. Found in spleen, thymus, bone marrow, lymph nodes and, at lower levels in brain, small intestine, stomach and kidney. CXCR4-A is predominant in all tissues tested. During embryonic development, high levels are detected in the endothelium of developing blood vessels and in many regions of the developing brain including the olfactory epithelium, olfactory bulb, hippocampus, cerebellum and spinal cord. {ECO:0000269PubMed:9634237, ECO:0000269PubMed:9634238}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 6 experimentally validated interaction(s) in this database.
They are also associated with 54 interaction(s) predicted by orthology.

Experimentally validated
Total	6 [view]
Protein-Protein	1 [view]
Protein-DNA	4 [view]
Protein-RNA	1 [view]
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	54 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0003779	actin binding
GO:0004930	G-protein coupled receptor activity
GO:0005515	protein binding
GO:0016494	C-X-C chemokine receptor activity
GO:0019955	cytokine binding
GO:0031625	ubiquitin protein ligase binding
GO:0032027	myosin light chain binding
GO:0043130	ubiquitin binding

Biological Process

GO:0001569	patterning of blood vessels
GO:0001666	response to hypoxia
GO:0001667	ameboidal cell migration
GO:0001764	neuron migration
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007281	germ cell development
GO:0007399	nervous system development
GO:0007420	brain development
GO:0008045	motor neuron axon guidance
GO:0008354	germ cell migration
GO:0009887	organ morphogenesis
GO:0019722	calcium-mediated signaling
GO:0030334	regulation of cell migration
GO:0042098	T cell proliferation
GO:0042119	neutrophil activation
GO:0043217	myelin maintenance
GO:0045087	innate immune response (InnateDB)
GO:0048699	generation of neurons
GO:0048714	positive regulation of oligodendrocyte differentiation
GO:0050920	regulation of chemotaxis
GO:0061351	neural precursor cell proliferation
GO:0070098	chemokine-mediated signaling pathway
GO:0071345	cellular response to cytokine stimulus

Cellular Component

GO:0005764	lysosome
GO:0005769	early endosome
GO:0005770	late endosome
GO:0005886	plasma membrane
GO:0005911	cell-cell junction
GO:0009897	external side of plasma membrane
GO:0009986	cell surface
GO:0016021	integral component of membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0030426	growth cone
GO:0031252	cell leading edge
GO:0031410	cytoplasmic vesicle
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

MGI:109563

InterPro

IPR000276 G protein-coupled receptor, rhodopsin-like
IPR000355 Chemokine receptor family
IPR001277 CXC chemokine receptor 4
IPR017452 GPCR, rhodopsin-like, 7TM
IPR019424 7TM GPCR, olfactory receptor/chemoreceptor Srsx
IPR022726 CXC chemokine receptor 4 N-terminal domain

PFAM

PF00001
PF10320
PF12109

PRINTS

PR00237
PR00657
PR00645

PIRSF

SMART

TIGRFAMs

Post-translational Modifications

Modification

Cross-References

SwissProt

P70658