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MGP002796

UniProt Annotations

Entry Information
Gene Namechemokine (C-X-C motif) ligand 12
Protein EntrySDF1_HUMAN
UniProt IDP48061
SpeciesHuman
Comments
Comment typeDescription
Alternative ProductsEvent=Alternative splicing; Named isoforms=7; Name=Beta; Synonyms=SDF-1-beta(1-72), hSDF-1beta; IsoId=P48061-1; Sequence=Displayed; Name=Alpha; Synonyms=SDF-1-alpha(1-68), hSDF-1alpha; IsoId=P48061-2; Sequence=VSP_001056; Name=Gamma; Synonyms=hSDF-1gamma, SDF-1g; IsoId=P48061-3; Sequence=VSP_041209; Name=Delta; Synonyms=hSDF-1delta; IsoId=P48061-4; Sequence=VSP_042118; Name=Epsilon; Synonyms=hSDFepsilon; IsoId=P48061-5; Sequence=VSP_042119; Name=Theta; Synonyms=hSDFphi, hSDFtheta, Phi; IsoId=P48061-6; Sequence=VSP_042120; Name=7; IsoId=P48061-7; Sequence=VSP_054781; Note=Gene prediction based on EST data.;
Developmental StageIsoform Alpha is ubiquitously expressed in fetal tissues. Isoform Beta and isoform Delta have more limited expression patterns, with highest levels detected in fetal spleen and fetal liver, respectively. Isoform Gamma and isoform Theta are weakly detected in fetal kidney. {ECO:0000269|PubMed:16626895}.
FunctionChemoattractant 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 atypical chemokine receptor ACKR3, 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 ACKR3, 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 ACKR3 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. {ECO:0000269|PubMed:11069075, ECO:0000269|PubMed:11859124, ECO:0000269|PubMed:16107333, ECO:0000269|PubMed:18802065, ECO:0000269|PubMed:19255243, ECO:0000269|PubMed:8752281}.
Mass SpectrometryMass=7606; Method=Electrospray; Range=24-88 (P48061-2); Evidence={ECO:0000269|PubMed:14525775};
Mass SpectrometryMass=7959; Method=Electrospray; Range=22-89 (P48061-2); Evidence={ECO:0000269|PubMed:14525775};
Mass SpectrometryMass=8297; Method=Electrospray; Range=24-93 (P48061-1); Evidence={ECO:0000269|PubMed:14525775};
Mass SpectrometryMass=8522; Method=Electrospray; Range=22-93 (P48061-1); Evidence={ECO:0000269|PubMed:14525775};
PtmProcessed 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 processed at the N-terminus. The C-terminal processing of isoform Alpha is reduced by binding to heparin and, probably, cell surface proteoglycans. {ECO:0000269|PubMed:14525775}.
Sequence CautionSequence=CAC10202.1; Type=Erroneous gene model prediction; Evidence={ECO:0000305};
SimilarityBelongs to the intercrine alpha (chemokine CxC) family. {ECO:0000305}.
Subcellular LocationSecreted.
SubunitMonomer 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 ACKR3. {ECO:0000269|PubMed:10446158, ECO:0000269|PubMed:16107333, ECO:0000269|PubMed:16725153, ECO:0000269|PubMed:17264079, ECO:0000269|PubMed:18799424, ECO:0000269|PubMed:19255243, ECO:0000269|PubMed:9427609}.
Tissue SpecificityIsoform 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. {ECO:0000269|PubMed:16626895}.
Web ResourceName=SeattleSNPs; URL="http://pga.gs.washington.edu/data/cxcl12/";
Web ResourceName=Wikipedia; Note=SDF-1 entry; URL="http://en.wikipedia.org/wiki/SDF-1_%28biology%29";
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