Stromal Cell Derived Factor 1alpha (SDF1 alpha, SDF1a, SDF-1a, Chemokine (C-X-C Motif) Ligand 12, CXCL12, hIRH, Pre-B cell Growth-stimulating Factor, PBSF, SCYB12, TLSF-a, TPAR1)

This gene encodes a stromal cell-derived alpha chemokine member of the intercrine family. This gene product and its receptor CXCR4 can activate lymphocytes and have been implicated in the metastasis of some cancers such as breast cancer. Mutations in this gene are associated with resistance to human immunodeficiency virus type 1 infections. Multiple transcript variants encoding different isoforms have been found for this gene.

CXCL12: 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 another C-X-C chemokine receptor CXCR7, 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 CXCR7, 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 CXCR7 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. Monomer or homodimer; in equilibrium. Dimer formation is induced by non acidic pH and the presence of multivalent anions, and by binding to CXCR4 or heparin. Monomeric form is required for full chemotactic activity and resistance to ischemia/reperfusion injury, whereas the dimeric form acts as a partial agonist of CXCR4, stimulating Ca2+ mobilization but with no chemotactic activity and instead acts as a selective antagonist that blocks chemotaxis induced by the monomeric form. Interacts with the N- terminus of CXCR7. 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. Belongs to the intercrine alpha (chemokine CxC) family. 6 isoforms of the human protein are produced by alternative splicing.

Protein type: Chemokine; Motility/polarity/chemotaxis; Secreted; Cell development/differentiation; Secreted, signal peptide

Chromosomal Location of Human Ortholog: 10q11.1

Cellular Component: extracellular space; extracellular region; external side of plasma membrane

Molecular Function: growth factor activity; chemokine receptor binding; chemokine activity; CXCR chemokine receptor binding; receptor binding

Biological Process: response to peptide hormone stimulus; positive regulation of dopamine secretion; positive regulation of cell adhesion; blood circulation; adult locomotory behavior; neuron migration; motor axon guidance; signal transduction; chemotaxis; germ cell development; induction of positive chemotaxis; T cell proliferation; response to radiation; germ cell migration; cell adhesion; organ regeneration; regulation of actin polymerization and/or depolymerization; response to virus; cellular calcium ion homeostasis; patterning of blood vessels; G-protein coupled receptor protein signaling pathway; response to mechanical stimulus; response to heat; ameboidal cell migration; positive regulation of axon extension involved in axon guidance; response to hypoxia; immune response; positive regulation of endothelial cell proliferation; telencephalon cell migration

Disease: Human Immunodeficiency Virus Type 1, Susceptibility To