InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CXCR4

Summary

InnateDB Protein

IDBP-71034.6

Last Modified

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

Gene Symbol

CXCR4

Protein Name

chemokine (C-X-C motif) receptor 4

Synonyms

CD184; D2S201E; FB22; HM89; HSY3RR; LAP-3; LAP3; LCR1; LESTR; NPY3R; NPYR; NPYRL; NPYY3R; WHIM;

Species

Homo sapiens

Ensembl Protein

ENSP00000241393

InnateDB Gene

IDBG-71032 (CXCR4)

Protein Structure

UniProt Annotation

Function

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. Acts as a coreceptor (CD4 being the primary receptor) for HIV-1 X4 isolates and as a primary receptor for some HIV-2 isolates. Promotes Env-mediated fusion of the virus. Binds bacterial lipopolysaccharide (LPS) et mediates LPS-induced inflammatory response, including TNF secretion by monocytes. {ECO:0000269PubMed:10074102, ECO:0000269PubMed:10644702, ECO:0000269PubMed:10825158, ECO:0000269PubMed:11276205, ECO:0000269PubMed:17197449, ECO:0000269PubMed:20048153, ECO:0000269PubMed:20228059, ECO:0000269PubMed:20505072, ECO:0000269PubMed:8752280, ECO:0000269PubMed:8752281}.

Subcellular Localization

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).

Disease Associations

WHIM syndrome (WHIM) [MIM:193670]: Immunodeficiency 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. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

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. {ECO:0000269PubMed:11276205}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 83 experimentally validated interaction(s) in this database.
They are also associated with 4 interaction(s) predicted by orthology.

Experimentally validated
Total	83 [view]
Protein-Protein	61 [view]
Protein-DNA	22 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	4 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0001618	virus receptor activity
GO:0003779	actin binding
GO:0004930	G-protein coupled receptor activity
GO:0005515	protein binding
GO:0015026	coreceptor activity
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:0000187	activation of MAPK activity
GO:0001666	response to hypoxia
GO:0002407	dendritic cell chemotaxis
GO:0006915	apoptotic process
GO:0006954	inflammatory response
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007204	positive regulation of cytosolic calcium ion concentration
GO:0009615	response to virus
GO:0016032	viral process
GO:0019722	calcium-mediated signaling
GO:0030260	entry into host cell
GO:0042119	neutrophil activation
GO:0043217	myelin maintenance
GO:0045087	innate immune response (InnateDB)
GO:0048714	positive regulation of oligodendrocyte differentiation
GO:0050920	regulation of chemotaxis
GO:0070098	chemokine-mediated signaling pathway
GO:0071345	cellular response to cytokine stimulus

Cellular Component

GO:0005737	cytoplasm
GO:0005764	lysosome
GO:0005769	early endosome
GO:0005770	late endosome
GO:0005886	plasma membrane
GO:0009986	cell surface
GO:0016021	integral component of membrane
GO:0016023	cytoplasmic membrane-bounded vesicle
GO:0030054	cell junction
GO:0031252	cell leading edge
GO:0031410	cytoplasmic vesicle
GO:0070062	extracellular vesicular exosome

Protein Structure and Domains

PDB ID

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

P61073