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FLASH GENE
Symbol CXCL12 contributors: mct/pgu - updated : 07-04-2016
HGNC name chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1)
HGNC id 10672
Location 10q11.21      Physical location : 44.865.606 - 44.880.545
Synonym name
  • growth stimulating factor pre-B
  • stromal cell-derived factor 1
  • C-X-C motif chemokine 12
  • pre-B cell growth-stimulating factor
  • SDF-1-beta(3-72)
  • Synonym symbol(s) SDF1, PBSF, SCYB12, TLSF, TPAR1, SDF1A, SDF1B, SDF-1a, SDF-1b, TLSF-a, TLSF-b, IRH
    DNA
    TYPE functioning gene
    STRUCTURE 14.94 kb     4 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    Binding site   transcription factor
    text structure proximal promoter was occupied by six putative Sp1-binding motifs
    MAPPING cloned Y linked N status confirmed
    Physical map
    LOC283029 10q11.21 similar to Ras suppressor protein 1 BMS1L 10q11.21 BMS1-like, ribosome assembly protein (yeast) RET 10q11.2 ret proto-oncogene (multiple endocrine neoplasia and medullary thyroid carcinoma 1, Hirschsprung disease) GALNACT-2 10q11.21 chondroitin sulfate GalNAcT-2 LOC221002 FXYD4 10q11.21 FXYD domain containing ion transport regulator 4 HNRPF 10q11.21-q11.22 heterogeneous nuclear ribonucleoprotein F LOC283031 10q11.21 hypothetical protein LOC283031 ZNF239 10q11.22-q11.23 zinc finger protein 239 LOC387660 10 hypothetical gene supported by M98474 LOC220992 10q11.21 Zinc finger protein 93 (Zinc finger protein HTF34) ZNF32 10q23-q24 zinc finger protein 32 (KOX 30) HNRPA3 10p11.1 heterogeneous nuclear ribonucleoprotein A3 LOC283034 10q11.21 hypothetical LOC283034 CXCL12 10q11.2 chemokine (C-X-C motif) ligand 12 (stromal cell-derived factor 1) LOC387661 10 similar to ribosomal protein L9; 60S ribosomal protein L9 LOC387662 10 hypothetical gene supported by BX538120 RASSF4 10q11.21 Ras association (RalGDS/AF-6) domain family 4 C10orf10 10q11.21 chromosome 10 open reading frame 10 C10orf25 10q11.21 chromosome 10 open reading frame 25 ZNF22 10q11.2 zinc finger protein 22 (KOX 15) LOC340765 10q11.21 similar to double homeobox, 4; double homeobox protein 4 LOC387663 10 similar to cubilin; intrinsic factor-cobalamin receptor; intrinsic factor B12-receptor LOC389957 10 similar to breast cancer antigen NY-BR-1.1 LOC389958 10 similar to cubilin; intrinsic factor-cobalamin receptor; intrinsic factor B12-receptor LOC220974 10q11.21 similar to olfactory receptor GA_x54KRFPKN04-58149882-58150865 OR13A1 10q22.2 olfactory receptor, family 13, subfamily A, member 1 ALOX5 10q11.2 arachidonate 5-lipoxygenase MIR 10q11.22 c-mir, cellular modulator of immune recognition LOC387664 10 LOC387664 ANUBL1 10q11.22 AN1, ubiquitin-like, homolog (Xenopus laevis) LOC143158 10q11.22 similar to ARF GTPase-activating protein LOC389959 10 similar to KIAA0592 protein KIAA0592 10q11.1 KIAA0592 protein MRIP2 10q11.22 ARF GTPase-activating protein LOC389960 10 hypothetical gene supported by AY258587; NM_003631
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    3 splicing 1940 10.1 89 highly in liver, pancreas, spleen 2008 18648536
    variant 1/isoform alpha
    4 splicing 3545 10.7 93 highly in liver, pancreas, spleen 2008 18648536
    variant 2/isoform beta
    4 splicing 524 13.6 119 adulthood nerve tissues (neurons, Schwann cells), heart 2008 18648536
  • variant 3/isoform gamma
  • regulate essential homeostatic functions by promoting directional migration and selective tissue homing of cells (Rueda 2008)
  • strongly interacted with cell membrane GAG, thus remaining mostly adsorbed on the plasmatic membrane upon secretion
  • - splicing 1209 15.4 140 fetal liver, several adult tissues 2006 16626895
    variant 4/isoform delta
    - splicing - - 90 fetal liver, several adult tissues 2006 16626895
    isoform epsilon
    - splicing - - 100 fetal liver, several adult tissues 2006 16626895
    isoform phi
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Cardiovascularheart   highly
    Digestiveintestinelarge intestine  highly Homo sapiens
    Lymphoid/Immunespleen   highly
    Nervousbrain   highly
     gangliasensory gangliadorsal root  
    Urinarykidney   highly
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Connectivebonesubchondral  
    Epithelialsecretoryglandular  
    Epithelialsensory   
    Muscularstriatumskeletal  
    Nervouscentral   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Blood/Hematopoieticmonocyte Homo sapiens
    Lymphoid/Immunelymphocyte
    Nervousastrocyte
    Nervousglia
    cell lineage
    cell lines carcinoma-associated fibroblasts (CAFs) extracted from human breast carcinomas
    fluid/secretion
    at STAGE
    physiological period embryo, perinatal
    Text early postnatal nerve tissues
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
    HOMOLOGY
    interspecies ortholog to murine Cxcl12
    ortholog to rattus Cxcl12
    Homologene
    FAMILY
  • intercrine alpha (chemokine CxC) family
  • CATEGORY signaling cytokine growth factor
    SUBCELLULAR LOCALIZATION extracellular
    basic FUNCTION
  • involved in the migration of primordial germ cells
  • stimulating tumor growth directly, acting through the cognate receptor, CXCR4, which is expressed by carcinoma cells
  • playing a major role in proliferative retinopathy in diabetes
  • controls many aspects of stem cell function including trafficking and proliferation
  • with CXCR4, were shown to provide the critical signals that govern hematopoietic cell homing to the bone marrow
  • promotes the migration of osteoclast progenitors and enhances the cell fusion of osteoclast progenitors
  • 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
  • having a role in the processes of physiological and pathological bone remodelling
  • possible chemotactic role in guiding the migratory neural crest cells to their destination
  • can enhance proliferation of neural progenitor cells through CXCR4 signaling
  • CCL18 and CXCL12 are homeostatic chemokines with high constitutive concentrations in serum
  • autocrine CXCL12 production modulates differentiation of monocytes toward a distinct program with proangiogenic and immunosuppressive functions
  • regulates leading process branching and speed of migrating interneurons
  • CXCL12-increased IL6 production in synovial fibroblasts via the CXCR4 receptor, PI3K, Akt, c-Jun, and AP1 signaling pathways
  • functions to attract the angioblasts that express its receptor CXCR4
  • essential for the proper functioning of human neural progenitor cells
  • CXCL12/CXCR4 signal axis plays an important role in mediating BMP9-induced osteogenic differentiation of mesenchymal stem cells
  • CELLULAR PROCESS cell life, proliferation/growth
    PHYSIOLOGICAL PROCESS
    text calcium ion homeostasis
    PATHWAY
    metabolism
    signaling signal transduction
  • sensory perception
  • CXCL12 signaling through G protein-coupled CXCR4 regulates cell migration during ontogenesis and disease states including cancer and inflammation
  • melanocytes may have a unique mechanism of migration via CXCL12/ACKR3 signaling that is different from that of other cell types
  • CXCL12/CXCR4 signaling pathway is involved in the development of numerous neuronal and non-neuronal structures
  • a component
  • complexing with CXCR4 as expected and also with a proteoglycan, syndecan-4 (SDC4)
  • CXCL12/CXCR4 signaling playing a role in the development of migrating muscle progenitors and a threshold number of progenitor cells is required to generate muscle of appropriate size
  • INTERACTION
    DNA
    RNA
    small molecule
    protein
  • ligand for fusin/LESTR (leukocyte-expressed CXCR4)
  • interacting with SDC4
  • interacting with IGF2 (has the ability to strongly stimulate osteoclastogenesis by regulating PPBP expression in stromal cells and CXCL12 expression in osteoblastic cells)
  • with PPBP may promote the formation of giant osteoclasts
  • ligand for CXCR7
  • interacting with SOCS3 (SOCS3-regulated CXCL12-induced FAK phosphorylation through the ubiquitin-proteasome pathway)
  • interacting with RUNX3 (CXCL12 autocrine/paracrine signaling down-regulates the expression of the transcription factor RUNX3 and contributes to maintain the long-term CD4 and CD14 expression in monocytes/macrophages)
  • positive correlation between CXCL12 signaling and SNAI2 activity, thus corroborating the role of these two proteins in bone cellular context
  • both ACKR3 and CXCR4 are important for endothelial progenitor cells (EPCs) in response to CXCL12
  • GNAI2 and ZAP70 mediate RASGRP1 membrane localization and activation of CXCL12-induced T cell functions
  • ACKR3 plays an important role in human cord blood derived endothelial progenitor cells (EPCs) in response to CXCL12
  • HMGB1 promotes recruitment of inflammatory cells to damaged tissues by forming a complex with CXCL12 and signaling via CXCR4
  • regulatory pathways targeting ACKR3 C-terminal serine/threonine sites may control the CXCL12 scavenger activity of ACKR3
  • CXCL12 protects neural progenitor cells (hNPCs) from apoptotic challenges through CXCR7- and CXCR4-mediated endocytotic signaling
  • ACKR3 can relay CXCL12 signaling in the cell
  • ACKR3 plays an important role on cell repair processing induced by CXCL12, and ACKR3 silencing attenuates cell adaptive response to acute CXCL12 stimulation after hypoxia
  • CXCL12-dependent migration of human malignant B cells requires both PI3K signaling and PLEKHA2
  • CXCL14 represents, along with CXCR7, molecules that co-evolved with the CXCL12-CXCR4 axis to modulate important physiological processes in development, stem cell maintenance, and immune responses
  • ACKR3 binds the chemokines CXCL12 and CXCL11
  • interfering with the CXCL12-scavenging activity of CXCR7 causes loss of CXCR4 function as a consequence of excessive CXCL12-mediated CXCR4 activation and degradation
  • RGS3 bridges ephrin-B reverse signaling and CXCL12 induced G protein signaling
  • addition of CXCL12 leads to the dissociation of EIF2S2 from CXCR4 suggesting that stimulation of the receptor may trigger the local protein synthesis required for efficient cell movement
  • NR4A1 binds directly to the CXCL12 promoter, resulting in inhibition of CXCL12 expression
  • GNG4 is an inhibitor of CXCL12/CXCR4-dependent signaling
  • PTK2B/STAP2 interaction is a novel mechanism to regulate CXCL12-dependent T-cell chemotaxis
  • cell & other
    REGULATION
    induced by VEGF in activated perivascular myofibroblasts
    Other regulation of its production by osteoblasts (a possible mechanism for stem cell homing
    cleavage of the N-terminal two residues by DPP8
    ASSOCIATED DISORDERS
    corresponding disease(s)
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    synergistically with VEGF in ascites of ovarian carcinoma
    constitutional     --over  
    with CXCR4 in patients with heart failure
    tumoral     --over  
    in insulinomas versus human pancreatic islet
    constitutional     --over  
    within injured white matter leads to the differentiation of CXCR4-expressing oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes that produce myelin
    constitutional     --over  
    significantly up-regulated within activated astrocytes and microglia in the corpus callosum during demyelination
    constitutional     --over  
    in synovial fluid of patients with osteoarthritis (OA)
    Susceptibility to HIV-1 infection
    Variant & Polymorphism other AIDS symptoms onset with a recessive protective effect of the mutation SDF1-3'A
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    cancerangiogenesis 
    interrupting synergistic axis VEGF/CXCL12, rather than VEGF alone, will be a novel efficient antiangiogenesis strategy to treat ovarian cancer
    neurosensorialvisualdegenerative
    ideal target for the prevention of proliferative retinopathy (in diabetes)
    ANIMAL & CELL MODELS