CXCL12

CXCL12 (C-X-C Motif Chemokine Ligand 12) is a Protein Coding gene. Diseases associated with CXCL12 include Human Immunodeficiency Virus Type 1 and Aids Dementia Complex. Among its related pathways are Apoptotic Pathways in Synovial Fibroblasts and PAK Pathway. Gene Ontology (GO) annotations related to this gene include receptor binding and chemokine activity.

C-X-C Motif Chemokine Ligand 12

Chemoattractant active on T-lymphocytes and 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. 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. Also binds to atypical chemokine receptor ACKR3, which activates the beta-arrestin pathway and acts as a scavenger receptor for SDF-1. Binds to the allosteric site (site 2) of integrins and activates integrins ITGAV:ITGB3, ITGA4:ITGB1 and ITGA5:ITGB1 in a CXCR4-independent manner (PubMed:29301984).

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. Stimulates the proliferation of bone marrow-derived B-cell progenitors in the presence of IL7 as well as growth of stromal cell-dependent pre-B-cells (By similarity).

Adult locomotory behavior Source: Ensembl
Animal organ regeneration Source: Ensembl
Antimicrobial humoral immune response mediated by antimicrobial peptide Source: UniProtKB
Axon guidance Source: GO_Central
Blood circulation Source: ProtInc
Cell adhesion Source: ProtInc
Cell chemotaxis Source: UniProtKB
Cellular calcium ion homeostasis Source: ProtInc
Cellular response to chemokine Source: BHF-UCL
Chemokine (C-X-C motif) ligand 12 signaling pathway Source: BHF-UCL
Chemokine-mediated signaling pathway Source: BHF-UCL
Chemotaxis Source: UniProtKB
Defense response Source: InterPro
Detection of mechanical stimulus involved in sensory perception of pain Source: Ensembl
Detection of temperature stimulus involved in sensory perception of pain Source: Ensembl
G protein-coupled receptor signaling pathway Source: Reactome
Immune response Source: ProtInc
Induction of positive chemotaxis Source: GO_Central
Integrin activation Source: UniProtKB
Killing of cells of other organism Source: UniProtKB
Negative regulation of dendritic cell apoptotic process Source: BHF-UCL
Negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage Source: BHF-UCL
Negative regulation of leukocyte tethering or rolling Source: UniProtKB
Neuron migration Source: Ensembl
Positive regulation of axon extension involved in axon guidance Source: Ensembl
Positive regulation of calcium ion import Source: BHF-UCL
Positive regulation of cell adhesion Source: MGI
Positive regulation of cell migration Source: GO_Central
Positive regulation of dopamine secretion Source: Ensembl
Positive regulation of endothelial cell proliferation Source: Ensembl
Positive regulation of monocyte chemotaxis Source: UniProtKB
Positive regulation of neuron differentiation Source: Ensembl
Positive regulation of T cell migration Source: MGI
Regulation of actin polymerization or depolymerization Source: ProtInc
Response to heat Source: Ensembl
Response to hypoxia Source: Ensembl
Response to peptide hormone Source: Ensembl
Response to radiation Source: Ensembl
Response to ultrasound Source: Ensembl
Response to virus Source: ProtInc
Signal transduction Source: ProtInc
T cell chemotaxis Source: UniProtKB
Telencephalon cell migration Source: Ensembl
Viral process Source: UniProtKB-KW

Secreted

Processed forms SDF-1-beta(3-72) and SDF-1-alpha(3-67) are produced after secretion by proteolytic cleavage of isoforms Beta and Alpha, respectively. The N-terminal processing is probably achieved by DPP4. Isoform Alpha is first cleaved at the C-terminus to yield a SDF-1-alpha(1-67) intermediate before being processed at the N-terminus. The C-terminal processing of isoform Alpha is reduced by binding to heparin and, probably, cell surface proteoglycans.