SDF-1

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.

SDF-1 Related Areas

Cancer>>Angiogenesis>>Cytokines/Chemokines in Angiogenesis>>Fractalkine/CX3CL1

Immunology>>Cytokine & Receptor>>Chemokine & Receptor>>Fractalkine/CX3CL1

SDF-1 Alternative Names

Fractalkine, CX3CL1, CXC3, CXC3C, ABCD-3, SCYD1, C3Xkine, NTN, NTT, neurotactin [Homo sapiens]
Fractalkine, Cx3cl1, Cxc3, CX3C, ABCD-3, Scyd1, AI848747, D8Bwg0439e, AB030188 [Mus musculus]

Summaries for SDF-1

Entrez Gene summary for SDF-1:

SDF-1 is a chemoattractant molecule; involved in cell migratio

OMIM - description for SDF-1:

For background information on chemokines, see CXCL1 (155730). Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the intercrine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF (see 191160), or IL1 (see 147760). The intercrines are characterized by the presence of 4 conserved cysteines which form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, which includes beta chemokine, the cysteine residues are adjacent to each other. In the CXC subfamily, which includes alpha chemokine, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group.

Wikipedia summary for SDF-1:

SDF-1 (stromal cell-derived factor-1) is small cytokine belonging to the chemokine family that is officially designated Chemokine (C-X-C motif) ligand 12 (CXCL12). Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the intercrine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF, or IL1. The intercrines are characterized by the presence of 4 conserved cysteines that form 2 disulfide bonds. They can be classified into 2 subfamilies. In the CC subfamily, which includes beta chemokine, the cysteine residues are adjacent to each other. In the CXC subfamily, which includes alpha chemokine, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group.[1]

Human SDF-1 Protein General Information

 

• Protein names: Stromal cell-derived factor 1, Short name=SDF-1
• Sequence length: 93 AA.
• Domain: Signal
• Sequence similarities: Belongs to the intercrine alpha (chemokine CxC) family.
• Post-translational modification: 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 processsed at the N-terminus. The C-terminal processing of isoform Alpha is reduced by binding to heparin and, probably, cell surface proteoglycans.
• Subunit structure: 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.
• Subcellular location: Secreted.
• 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.

General information above from UniProt

Function for SDF-1 Protein

UniProtKB:

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.

Genatlas:

• SDF-1 is involved in the migration of primordial germ cells
• SDF-1 stimulating tumor growth directly, acting through the cognate receptor, CXCR4, which is expressed by carcinoma cells
• SDF-1 playing a major role in proliferative retinopathy in diabetes
• SDF-1 controls many aspects of stem cell function including trafficking and proliferation
• SDF-1 promotes the migration of osteoclast progenitors and enhances the cell fusion of osteoclast progenitors
• SDF-1 has crucial roles in the formation of multiple organ systems during embryogenesis and in the regulation of bone marrow haematopoiesis and immune function in the postnatal organism
• SDF-1 having a role in the processes of physiological and pathological bone remodelling
• SDF-1 possible chemotactic role in guiding the migratory neural crest cells to their destination
• SDF-1can enhance proliferation of neural progenitor cells through CXCR4 signaling
• CXCL12-increased IL6 production in synovial fibroblasts via the CXCR4 receptor, PI3K, Akt, c-Jun, and AP1 signaling pathways

Homology for human SDF-1

• ortholog to murine Cxcl12
• ortholog to rattus Cxcl12

Phenotype Information for SDF-1

• Gene/Locus: CXCL12, SDF1
• Phenotype: {AIDS, resistance to}

Phenotype Information for SDF-1 from OMIM (Online Mendelian Inheritance in Man)

Drugs for SDF-1

Target	Drug Name	Disease	Drug Status
SDF-1	AMD-070 DCL000040	HIV Infection	Discontinued in Phase I
SDF-1	AMD-3100	Chronic Lymphocytic Leukemia	Phase I/II
SDF-1	AMD-3100	HIV Infection	Discontinued
SDF-1	MSX-122	Late-stage Solid Tumors	Phase

Drugs for SDF-1 from TTD (Therapeutic Targets Database)