Stromal cell-derived factor 1

Chemokine (C-X-C motif) ligand 12
PDB rendering based on 1a15.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1A15, 1QG7, 1SDF, 1VMC, 2J7Z, 2K01, 2K03, 2K04, 2K05, 2KEC, 2KED, 2KEE, 2KOL, 2NWG, 2SDF, 3GV3, 3HP3, 4LMQ, 4UAI
Identifiers
Symbols	CXCL12 ; IRH; PBSF; SCYB12; SDF1; TLSF; TPAR1
External IDs	OMIM: 600835 MGI: 103556 HomoloGene: 128606 GeneCards: CXCL12 Gene
Gene ontology Molecular function • receptor binding • chemokine activity • growth factor activity • chemokine receptor binding • CXCR chemokine receptor binding Cellular component • extracellular region • extracellular space • external side of plasma membrane • extracellular exosome Biological process • patterning of blood vessels • response to hypoxia • ameboidal-type cell migration • neuron migration • positive regulation of endothelial cell proliferation • cellular calcium ion homeostasis • chemotaxis • immune response • cell adhesion • signal transduction • G-protein coupled receptor signaling pathway • germ cell development • blood circulation • motor neuron axon guidance • regulation of actin polymerization or depolymerization • adult locomotory behavior • germ cell migration • response to radiation • response to heat • response to mechanical stimulus • response to virus • telencephalon cell migration • organ regeneration • positive regulation of dopamine secretion • T cell proliferation • response to peptide hormone • positive regulation of cell adhesion • positive regulation of axon extension involved in axon guidance • induction of positive chemotaxis • cell chemotaxis • chemokine-mediated signaling pathway • positive regulation of monocyte chemotaxis • positive regulation of calcium ion import • positive regulation of myoblast fusion • negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage • negative regulation of leukocyte tethering or rolling • negative regulation of leukocyte apoptotic process • positive regulation of T cell migration Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	6387	20315
Ensembl	ENSG00000107562	ENSMUSG00000061353
UniProt	P48061	P40224
RefSeq (mRNA)	NM_000609	NM_001012477
RefSeq (protein)	NP_000600	NP_001012495
Location (UCSC)	Chr 10: 44.37 – 44.39 Mb	Chr 6: 117.17 – 117.18 Mb
PubMed search	[1]	[2]

The stromal cell-derived factor 1 (SDF-1) also known as C-X-C motif chemokine 12 (CXCL12) is a chemokine protein that in humans is encoded by the CXCL12 gene.

Stromal cell-derived factors 1-alpha and 1-beta are small cytokines that belong to the chemokine family, members of which activate leukocytes and are often induced by proinflammatory stimuli such as lipopolysaccharide, TNF, or IL1. The chemokines 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, the cysteine residues are adjacent to each other. In the CXC subfamily, they are separated by an intervening amino acid. The SDF1 proteins belong to the latter group.

Structure

SDF-1 is produced in two forms, SDF-1α/CXCL12a and SDF-1β/CXCL12b, by alternate splicing of the same gene. Chemokines are characterized by the presence of four conserved cysteines, which form two disulfide bonds. The CXCL12 proteins belong to the group of CXC chemokines, whose initial pair of cysteines are separated by one intervening amino acid.

Function

Chemotaxis

CXCL12 is strongly chemotactic for lymphocytes. During embryogenesis it directs the migration of hematopoietic cells from foetal liver to bone marrow and the formation of large blood vessels. Mice that were knocked-out for CXCL12 gene were lethal before the birth or within just 1 hour of life.

In adulthood, CXCL12 plays an important role in angiogenesis by recruiting endothelial progenitor cells (EPCs) from the bone marrow through a CXCR4 dependent mechanism. It is this function of CXCL12 that makes it a very important factor in carcinogenesis and the neovascularisation linked to tumour progression. CXCL12 also has a role in tumor metastasis where cancer cells that express the receptor CXCR4 are attracted to metastasis target tissues that release the ligand, CXCL12. In breast cancer, however, increased expression of CXCL12 determines a reduced risk of distant metastasis.

In 2011, CXCL12 was shown to be responsible for recruiting macrophages to breast tumours in mice in response to the experimental anti-cancer drug combretastatin A-4 phosphate, which damages tumour blood vessels. This macrophage recruitment is believed to stimulate tumour blood vessel growth, counteracting the effects of the drug.

Blocking CXCR4, the receptor for CXCL12, with Plerixafor (AMD-3100) increased the effectiveness of combretastatin in a mouse model of breast cancer, it is presumed by preventing macrophages from being recruited to tumours.

CXCL12 is expressed in the area of inflammatory bone destruction. It is chemotactic for mesenchymal stem cells and mediates their suppressive effect on osteoclastogenesis.

Other

By blocking CXCR4, a major coreceptor for HIV-1 entry, CXCL12 acts as an endogenous inhibitor of CXCR4-tropic HIV-1 strains. CXCL12 was shown to be expressed in many tissues in mice (including brain, thymus, heart, lung, liver, kidney, spleen and bone marrow).

Receptor

The receptor for this chemokine is CXCR4, which was previously called LESTR or fusin. This CXCL12-CXCR4 interaction used to be considered exclusive (unlike for other chemokines and their receptors), but recently it was suggested that CXCL12 may also bind the CXCR7 receptor.

Gene

The gene for CXCL12 is located on human chromosome 10. In human and mouse both CXCL12 and CXCR4 show high identity of sequence: 99% and 90%, respectively.