stromal cell-derived factor 1; SDF-1; hSDF-1; C-X-C motif chemokine 12; intercrine reduced in hepatomas; IRH; hIRH; pre-B cell growth-stimulating factor; PBSF (CXCL12, SDF1, SDF1A, SDF1B)

Function

• chemoattractant active on T-lymphocytes, monocytes
• not chemoattractant for neutrophils
• principal ligand for CXCR4
  • activates the C-X-C chemokine receptor CXCR4 to induce a rapid & transient rise in the level of intracellular Ca+2 & chemotaxis
• also binds to another C-X-C chemokine receptor CXCR7, which activates the beta-arrestin pathway & acts as a scavenger receptor for SDF-1
• SDF-1-beta(3-72) & SDF-1-alpha(3-67) show a reduced c hemotactic activity
• binding to cell surface proteoglycans seems to inhibit formation of SDF-1-alpha(3-67) & thus to preserve activity on local sites
• acts as a positive regulator of monocyte migration & a negative regulator of monocyte adhesion via the LYN kinase
• stimulates migration of monocytes & T-lymphocytes through its receptors, CXCR4 & CXCR7, & 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
• potent inhibitor in vitro of infection by lymphocyte tropic HIV1
• inhibits CXCR4-mediated infection by T-cell line-adapted HIV1
• protective role after myocardial infarction
• induces down-regulation & internalization of CXCR7 expressed in various cells
• several functions during embryonic development
  • B-cell lymphopoiesis
  • myelopoiesis in bone marrow
  • cardiac ventricular septum formation
• processed forms SDF-1-beta(3-72) & SDF-1-alpha(3-67) are produced after secretion by proteolytic cleavage of isoforms beta & alpha, respectively
• 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
• C-terminal processing of isoform alpha is reduced by binding to heparin an&, probably, cell surface proteoglycans
• monomer or homodimer; in equilibrium
  • dimer formation is induced by non acidic pH & the presence of multivalent anions, & by binding to CXCR4 or heparin
• monomer has chemotactic activity & resistance to ischemia/ reperfusion injury
• dimer acts as a partial agonist of CXCR4,
  • stimulates Ca2+ mobilization
  • no chemotactic activity
  • instead acts as a selective antagonist that blocks chemotaxis induced by the monomer
• interacts with the N-terminus of CXCR7

Structure

• belongs to the intercrine alpha (chemokine CxC) family

Compartment

secreted

Alternative splicing

• named isoforms=6
• alpha, beta, gamma, delta, epsilon, theta

Expression

• isoform alpha & isoform beta are ubiquitously expressed
  • highest levels detected in liver, pancreas & spleen
• isoform gamma is mainly expressed in heart
  • weak expression detected in several other tissues
• isoform delta, isoform epsilon & isoform theta have highest expression in pancreas
  • lower levels detected in heart, kidney, liver & spleen
• isoform alpha is ubiquitously expressed in fetal tissues
• isoform beta & isoform delta have more limited expression patterns in the fetus
  • highest levels detected in fetal spleen & fetal liver, respectively
• isoform gamma & isoform theta are weakly detected in fetal kidney

More general terms

• CXC chemokine; alpha chemokine
• stromal cell derived factor

Database

• Entrez gene: http://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Retrieve&dopt=Graphics&list_uids=6387
• Kegg: http://www.genome.jp/dbget-bin/www_bget?hsa:6387
• OMIM: https://mirror.omim.org/entry/600835
• UniProt: http://www.uniprot.org/uniprot/P48061.html