InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CXCL12

Summary

InnateDB Protein

IDBP-238826.7

Last Modified

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

Gene Symbol

CXCL12

Protein Name

chemokine (C-X-C motif) ligand 12

Synonyms

IRH; PBSF; SCYB12; SDF1; TLSF; TPAR1;

Species

Homo sapiens

Ensembl Protein

ENSP00000379140

InnateDB Gene

IDBG-71595 (CXCL12)

Protein Structure

UniProt Annotation

Function

Chemoattractant active on T-lymphocytes, monocytes, but not neutrophils. Activates the C-X-C chemokine receptor CXCR4 to induce a rapid and transient rise in the level of intracellular calcium ions and chemotaxis. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. SDF-1-beta(3-72) and SDF-1- alpha(3-67) show a reduced chemotactic activity. Binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3- 67) and thus to preserve activity on local sites. Acts as a positive regulator of monocyte migration and a negative regulator of monocyte adhesion via the LYN kinase. Stimulates migration of monocytes and T-lymphocytes through its receptors, CXCR4 and ACKR3, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for beta-2 integrins. SDF1A/CXCR4 signaling axis inhibits beta-2 integrin LFA-1 mediated adhesion of monocytes to ICAM-1 through LYN kinase. Inhibits CXCR4-mediated infection by T- cell line-adapted HIV-1. Plays a protective role after myocardial infarction. Induces down-regulation and internalization of ACKR3 expressed in various cells. Has several critical functions during embryonic development; required for B-cell lymphopoiesis, myelopoiesis in bone marrow and heart ventricular septum formation. {ECO:0000269PubMed:11069075, ECO:0000269PubMed:11859124, ECO:0000269PubMed:16107333, ECO:0000269PubMed:18802065, ECO:0000269PubMed:19255243, ECO:0000269PubMed:8752281}.

Subcellular Localization

Secreted.

Disease Associations

Tissue Specificity

Isoform Alpha and isoform Beta are ubiquitously expressed, with highest levels detected in liver, pancreas and spleen. Isoform Gamma is mainly expressed in heart, with weak expression detected in several other tissues. Isoform Delta, isoform Epsilon and isoform Theta have highest expression levels in pancreas, with lower levels detected in heart, kidney, liver and spleen. {ECO:0000269PubMed:16626895}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 15 experimentally validated interaction(s) in this database.
They are also associated with 2 interaction(s) predicted by orthology.

Experimentally validated
Total	15 [view]
Protein-Protein	15 [view]
Protein-DNA	0
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	2 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0005102	receptor binding
GO:0008009	chemokine activity
GO:0008083	growth factor activity
GO:0042379	chemokine receptor binding
GO:0045236	CXCR chemokine receptor binding

Biological Process

GO:0001569	patterning of blood vessels
GO:0001666	response to hypoxia
GO:0001667	ameboidal cell migration
GO:0001764	neuron migration
GO:0001938	positive regulation of endothelial cell proliferation
GO:0006874	cellular calcium ion homeostasis
GO:0006935	chemotaxis
GO:0006955	immune response
GO:0007155	cell adhesion
GO:0007165	signal transduction
GO:0007186	G-protein coupled receptor signaling pathway
GO:0007281	germ cell development
GO:0007420	brain development
GO:0008015	blood circulation
GO:0008045	motor neuron axon guidance
GO:0008064	regulation of actin polymerization or depolymerization
GO:0008284	positive regulation of cell proliferation
GO:0008344	adult locomotory behavior
GO:0008354	germ cell migration
GO:0009314	response to radiation
GO:0009408	response to heat
GO:0009612	response to mechanical stimulus
GO:0009615	response to virus
GO:0022029	telencephalon cell migration
GO:0030334	regulation of cell migration
GO:0030335	positive regulation of cell migration
GO:0031100	organ regeneration
GO:0033603	positive regulation of dopamine secretion
GO:0042098	T cell proliferation
GO:0043434	response to peptide hormone
GO:0045666	positive regulation of neuron differentiation
GO:0045785	positive regulation of cell adhesion
GO:0048842	positive regulation of axon extension involved in axon guidance
GO:0050930	induction of positive chemotaxis
GO:0051924	regulation of calcium ion transport
GO:0060326	cell chemotaxis
GO:0070098	chemokine-mediated signaling pathway
GO:0090026	positive regulation of monocyte chemotaxis
GO:0090280	positive regulation of calcium ion import
GO:1902230	negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage
GO:2000107	negative regulation of leukocyte apoptotic process
GO:2000406	positive regulation of T cell migration

Cellular Component

GO:0005576	extracellular region
GO:0005615	extracellular space
GO:0005886	plasma membrane
GO:0009897	external side of plasma membrane
GO:0070062	extracellular vesicular exosome