stromal cell-derived factor 1 selections

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

Interactions

molecular events

General

CXC chemokine; alpha chemokine stromal cell derived factor

Properties

SIZE: entity length = 93 aa MW = 11 kD COMPARTMENT: extracellular compartment MOTIF: signal sequence {1-21} Receptor activation {22-23} domain {29-33} MOTIF: cysteine residue {C30} MODIFICATION: cysteine residue {C55} cysteine residue {C32} MODIFICATION: cysteine residue {C71} Receptor binding {39-41} Heparin binding {41-51} MOTIF: histidine residue {46} Receptor binding {48-50} cysteine residue {C55} MODIFICATION: cysteine residue {C30} Receptor binding {60-70} MOTIF: binding site SITE: 62-62 FOR-BINDING-OF: Heparin binding site SITE: 69-69 FOR-BINDING-OF: Heparin cysteine residue {C71} MODIFICATION: cysteine residue {C32} binding site SITE: 85-85 FOR-BINDING-OF: Heparin

References

UniProt :accession P48061
Wikipedia; Note: SDF-1 entry http://en.wikipedia.org/wiki/SDF-1_%28biology%29
SeattleSNPs http://pga.gs.washington.edu/data/cxcl12/

Databases & Figures

OMIM 600835 UniProt P48061 Pfam PF00048 Entrez Gene 6387 Kegg hsa:6387 CXC ligand and receptor binding