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    CXCL12 C-X-C motif chemokine ligand 12 [ Homo sapiens (human) ]

    Gene ID: 6387, updated on 1-May-2016
    Official Symbol
    CXCL12provided by HGNC
    Official Full Name
    C-X-C motif chemokine ligand 12provided by HGNC
    Primary source
    HGNC:HGNC:10672
    See related
    Ensembl:ENSG00000107562 HPRD:02904; MIM:600835; Vega:OTTHUMG00000018054
    Gene type
    protein coding
    RefSeq status
    REVIEWED
    Organism
    Homo sapiens
    Lineage
    Eukaryota; Metazoa; Chordata; Craniata; Vertebrata; Euteleostomi; Mammalia; Eutheria; Euarchontoglires; Primates; Haplorrhini; Catarrhini; Hominidae; Homo
    Also known as
    IRH; PBSF; SDF1; TLSF; TPAR1; SCYB12
    Summary
    This antimicrobial gene encodes a stromal cell-derived alpha chemokine member of the intercrine family. The encoded protein functions as the ligand for the G-protein coupled receptor, chemokine (C-X-C motif) receptor 4, and plays a role in many diverse cellular functions, including embryogenesis, immune surveillance, inflammation response, tissue homeostasis, and tumor growth and metastasis. Mutations in this gene are associated with resistance to human immunodeficiency virus type 1 infections. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2014]
    Orthologs
    Location:
    10q11.1
    Exon count:
    6
    Annotation release Status Assembly Chr Location
    107 current GRCh38.p2 (GCF_000001405.28) 10 NC_000010.11 (44370153..44385097, complement)
    105 previous assembly GRCh37.p13 (GCF_000001405.25) 10 NC_000010.10 (44865601..44880545, complement)

    Chromosome 10 - NC_000010.11Genomic Context describing neighboring genes Neighboring gene uncharacterized LOC101929465 Neighboring gene uncharacterized LOC105378278 Neighboring gene chromosome 10 open reading frame 142 Neighboring gene uncharacterized LOC105378279 Neighboring gene ribosomal protein L9 pseudogene 21 Neighboring gene eukaryotic translation initiation factor 2A pseudogene 4

    GeneRIFs: Gene References Into FunctionsWhat's a GeneRIF?

    Associated conditions

    Description Tests
    Human immunodeficiency virus type 1, susceptibility to
    MedGen: C1836230 OMIM: 609423 GeneReviews: Not available
    Compare labs

    NHGRI GWAS Catalog

    Description
    Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants.
    NHGRI GWA Catalog
    Genome-wide association study of clinical dimensions of schizophrenia: polygenic effect on disorganized symptoms.
    NHGRI GWA Catalog
    Genome-wide association study of peripheral neuropathy with D-drug-containing regimens in AIDS Clinical Trials Group protocol 384.
    NHGRI GWA Catalog
    Genomewide association analysis of coronary artery disease.
    NHGRI GWA Catalog
    Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease.
    NHGRI GWA Catalog
    Shared genetic susceptibility to ischemic stroke and coronary artery disease: a genome-wide analysis of common variants.
    NHGRI GWA Catalog

    Protein interactions

    Protein Gene Interaction Pubs
    Envelope surface glycoprotein gp120 env HIV-1 gp120 from a T-cell-tropic virus causes CD4-dependent antagonism of CXCR4 response to SDF-1alpha, whereas gp120 from macrophage-tropic viruses causes CD4-dependent antagonism of CCR5 response to MIP-1alpha PubMed
    env HIV-1 gp120-induced dephosphorylation of KV2.1 and re-localization of KV2.1 on the soma and proximal dendrites results in disruption of the clustered KV2.1 via activation of CCR5/CXCR4 co-receptors or SDF-1 alpha treatment PubMed
    env CXCL12 and HIV-1 gp120 modulate the excitability of Cajal-Retzius cells in opposite directions PubMed
    env The ability of HIV-1 gp120 to inhibit SDF-1alpha-induced chemotaxis is mediated by the CD4 receptor and Lck signaling PubMed
    env The entry of T cell-tropic HIV-1 isolates into cells is blocked by SDF-1, which interacts with the HIV-1 gp120 coreceptor CXCR4 PubMed
    env HIV-1 gp120 abnormally interferes with SDF-1-mediated T cell chemotaxis and cell migration in resting CD4+ T Cells PubMed
    env CXCL12 variant proteins exhibits the various levels of inhibition of HIV-1 X4 Env-mediated fusion. The strongest and weakest inhibition activities among the variant proteins in the X4 Env fusion assay are CXCL12gamma and CXCL12delta, respectively PubMed
    env RANTES, stromal derived factor-1alpha (SDF-1alpha), macrophage-derived chemokine (MDC), and their combination attenuate HIV-1 gp120-induced food and water intake decrease in rats PubMed
    env Apoptosis of CD8+ T cells is mediated by the interaction between TNF-alpha bound to the membrane of macrophages (mbTNF) and a receptor on CD8+ T cells (TNF-receptor II, or TNFRII), which is upregulated by treatment with recombinant HIV-1 gp120 or SDF-1 PubMed
    env The death rate of CD8+ T cells by apoptosis, which is induced by HIV-1 gp120 from CXCR4-tropic HIV strains or by the ligand of the chemokine receptor CXCR4 (SDF-1), increased markedly during HIV infection of peripheral blood mononuclear cells PubMed
    env A synthetic peptide domain of the V3 region of HIV-1 gp120 activates the FPRL1 receptor in monocytes and neutrophils and causes reduced response to several chemokines that use multiple cell receptors, including SDF-1alpha and RANTES PubMed
    env Chemokines such as fractalkine, macrophage-derived chemokine (MDC), RANTES, and SDF-1alpha are able to block gp120-induced apoptosis of hippocampal neurons; both fractalkine and MDC activate ERK-1/2, while SDF-1alpha activates CREB PubMed
    env SDF-1alpha reverses gp120-induced downregulation of CD79b in CD40- and IL-4-activated purified HIV-1 seronegative human peripheral blood B cells PubMed
    env CXCR4-tropic and CXCR4/CCR5 dual-tropic HIV-1 gp120 proteins inhibit B cell chemotaxis toward CXCL12, CCL20, and CCL21, and gp120-induced p38 MAPK activation is triggered by CCL21 and CCL20 PubMed
    env The fusion of insulin-like growth factor I (IGF I) with stromal cell-derived factor I or alpha1 proteinase inhibitor has the capacity to compete with the binding of HIV-1 gp120 to CD4 receptor PubMed
    Nef nef HIV-1 Nef inhibits CXCL12 induced chemotaxis in Jurkat cells, monocytes, and PBMCs, which leads to marked downregulation of F-actin accumulation in cells PubMed
    nef Disruption of the proline-rich region of HIV-1 Nef inhibits T-cell migration to SDF-1 alpha, suggesting Nef occupies a position in the CXCR4-mediated signaling pathway that is upstream of an SH3-dependent pathway PubMed
    nef An intracellular signaling pathway mediated by the binding of SDF-1alpha and CXCR4 is inhibited by Nef in both Jurkat T cells and primary peripheral CD4+ T lymphocytes PubMed
    Pr55(Gag) gag Expression of HIV-1 Gag attenuates SDF-1-mediated downregulation of CXCR4. The effect of Gag is dependent on a TSG101 interacting motif within the C-terminal p6 region of Gag PubMed
    Tat tat Microarray analysis indicates HIV-1 Tat-induced upregulation of chemokine (C-X-C motif) ligand 12 (CXCL12; SDF-1: stromal cell-derived factor 1) in primary human brain microvascular endothelial cells PubMed
    tat HIV-1 Tat tethered to the surface of syndecan-1 expression B-lymphoid cells or of peripheral blood monocytes promotes their transendothelial migration in vitro in response to CXCL12 or CCL5, respectively PubMed
    tat HIV-1 Tat increases CXCL12-induced internalization of CXCR4, and the Tat-mediated CXCR4 internalization requires activity of protein kinase C (zeta) PubMed
    tat HIV-1 Tat interacts with SDF-1alpha to induce apoptosis in Tat-treated erythroid cells PubMed
    tat HIV-1 Tat can inhibit CXCR4-mediated functions by interfering with the chemotactic activity of SDF-1/CXCL12, an effect mediated by Tat amino acids 25-31 PubMed
    tat HIV-1 Tat induces SDF-1alpha expression in neurons and Tat-mediated neurite outgrowth is blocked by anti-SDF-1alpha antibody, suggesting a role for SDF-1alpha in the neuronal response to HIV in brains of AIDS patients PubMed
    tat SDF-1 is upregulated by HIV-1 Tat treatment in human epithelial cells PubMed
    tat SDF-1alpha stimulates the ability of HIV-1 Tat to transactivate the HIV-1 LTR promoter PubMed
    tat HIV-1 Tat competes with SDF-1alpha for binding to CXCR4 PubMed

    Go to the HIV-1, Human Interaction Database

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    • Intestinal immune network for IgA production, organism-specific biosystem (from KEGG)
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    Products Interactant Other Gene Complex Source Pubs Description

    Markers

    Homology

    Gene Ontology Provided by GOA

    Function Evidence Code Pubs
    CXCR chemokine receptor binding IDA
    Inferred from Direct Assay
    more info
    PubMed 
    chemoattractant activity IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    chemokine activity IDA
    Inferred from Direct Assay
    more info
    PubMed 
    chemokine activity TAS
    Traceable Author Statement
    more info
    PubMed 
    chemokine receptor binding IMP
    Inferred from Mutant Phenotype
    more info
    PubMed 
    growth factor activity IEA
    Inferred from Electronic Annotation
    more info
     
    receptor binding TAS
    Traceable Author Statement
    more info
    PubMed 
    Process Evidence Code Pubs
    G-protein coupled receptor signaling pathway TAS
    Traceable Author Statement
    more info
    PubMed 
    adult locomotory behavior IEA
    Inferred from Electronic Annotation
    more info
     
    axon guidance IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    blood circulation TAS
    Traceable Author Statement
    more info
    PubMed 
    cell adhesion TAS
    Traceable Author Statement
    more info
    PubMed 
    cell chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    cellular calcium ion homeostasis TAS
    Traceable Author Statement
    more info
    PubMed 
    chemokine-mediated signaling pathway IDA
    Inferred from Direct Assay
    more info
    PubMed 
    chemotaxis TAS
    Traceable Author Statement
    more info
    PubMed 
    immune response IEA
    Inferred from Electronic Annotation
    more info
     
    induction of positive chemotaxis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    negative regulation of intrinsic apoptotic signaling pathway in response to DNA damage IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of leukocyte apoptotic process IDA
    Inferred from Direct Assay
    more info
    PubMed 
    negative regulation of leukocyte tethering or rolling IDA
    Inferred from Direct Assay
    more info
    PubMed 
    neuron migration IEA
    Inferred from Electronic Annotation
    more info
     
    organ regeneration IEA
    Inferred from Electronic Annotation
    more info
     
    positive chemotaxis IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    positive regulation of T cell migration IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of axon extension involved in axon guidance IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of calcium ion import TAS
    Traceable Author Statement
    more info
    PubMed 
    positive regulation of cell adhesion IDA
    Inferred from Direct Assay
    more info
    PubMed 
    positive regulation of dopamine secretion IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of endothelial cell proliferation IEA
    Inferred from Electronic Annotation
    more info
     
    positive regulation of monocyte chemotaxis IDA
    Inferred from Direct Assay
    more info
    PubMed 
    regulation of actin polymerization or depolymerization TAS
    Traceable Author Statement
    more info
    PubMed 
    response to heat IEA
    Inferred from Electronic Annotation
    more info
     
    response to hypoxia IEA
    Inferred from Electronic Annotation
    more info
     
    response to mechanical stimulus IEA
    Inferred from Electronic Annotation
    more info
     
    response to peptide hormone IEA
    Inferred from Electronic Annotation
    more info
     
    response to radiation IEA
    Inferred from Electronic Annotation
    more info
     
    response to virus TAS
    Traceable Author Statement
    more info
    PubMed 
    signal transduction TAS
    Traceable Author Statement
    more info
    PubMed 
    telencephalon cell migration IEA
    Inferred from Electronic Annotation
    more info
     
    Component Evidence Code Pubs
    external side of plasma membrane IBA
    Inferred from Biological aspect of Ancestor
    more info
     
    extracellular exosome IDA
    Inferred from Direct Assay
    more info
    PubMed 
    extracellular region TAS
    Traceable Author Statement
    more info
     
    extracellular space IEA
    Inferred from Electronic Annotation
    more info
     
    Preferred Names
    stromal cell-derived factor 1
    Names
    chemokine (C-X-C motif) ligand 12
    intercrine reduced in hepatomas
    pre-B cell growth-stimulating factor

    RefSeqs maintained independently of Annotated Genomes

    These reference sequences exist independently of genome builds. Explain

    These reference sequences are curated independently of the genome annotation cycle, so their versions may not match the RefSeq versions in the current genome build. Identify version mismatches by comparing the version of the RefSeq in this section to the one reported in Genomic regions, transcripts, and products above.

    Genomic

    1. NG_016861.1 RefSeqGene

      Range
      5001..19945
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    mRNA and Protein(s)

    1. NM_000609.6NP_000600.1  stromal cell-derived factor 1 isoform beta precursor

      See identical proteins and their annotated locations for NP_000600.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (2) contains an alternate exon, and differs in the 3' coding region and UTR compared to variant 1. The resulting protein (isoform beta) is longer and has a distinct C-terminus compared to isoform alpha.
      Source sequence(s)
      AK292628, AL137026, L36033
      Consensus CDS
      CCDS44373.1
      UniProtKB/Swiss-Prot
      P48061
      Related
      ENSP00000363551, OTTHUMP00000019492, ENST00000374429, OTTHUMT00000047738
      Conserved Domains (1) summary
      cd00273
      Location:2788
      Chemokine_CXC; Chemokine_CXC: 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; many members ...
    2. NM_001033886.2NP_001029058.1  stromal cell-derived factor 1 isoform gamma precursor

      See identical proteins and their annotated locations for NP_001029058.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (3) contains an alternate exon, and differs in the 3' coding region and UTR compared to variant 1. The resulting protein (isoform gamma) is longer and has a distinct C-terminus compared to isoform alpha.
      Source sequence(s)
      AL137026, AY644456, BC031072, DQ345518
      Consensus CDS
      CCDS31186.1
      UniProtKB/Swiss-Prot
      P48061
      Related
      ENSP00000363548, OTTHUMP00000216979, ENST00000374426, OTTHUMT00000358150
      Conserved Domains (1) summary
      cd00273
      Location:2788
      Chemokine_CXC; Chemokine_CXC: 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; many members ...
    3. NM_001178134.1NP_001171605.1  stromal cell-derived factor 1 isoform delta precursor

      See identical proteins and their annotated locations for NP_001171605.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (4) lacks an alternate segment, which results in a frameshift, compared to variant 1. The resulting protein (isoform delta) is longer and has a distinct C-terminus compared to isoform alpha.
      Source sequence(s)
      AI092156, DA266752, DQ345517
      Consensus CDS
      CCDS53527.1
      UniProtKB/Swiss-Prot
      P48061
      Related
      ENSP00000379140, OTTHUMP00000216980, ENST00000395794, OTTHUMT00000358151
      Conserved Domains (1) summary
      cd00273
      Location:2788
      Chemokine_CXC; Chemokine_CXC: 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; many members ...
    4. NM_001277990.1NP_001264919.1  stromal cell-derived factor 1 isoform 5 precursor

      See identical proteins and their annotated locations for NP_001264919.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (5) uses an alternate splice site and an alternate 3'-terminal exon, compared to variant 1. The resulting protein (isoform 5) is longer and has a distinct C-terminus compared to isoform alpha.
      Source sequence(s)
      AK292628, AL137026, AU120056, L36033
      Consensus CDS
      CCDS60518.1
      UniProtKB/Swiss-Prot
      P48061
      Related
      ENSP00000379139, OTTHUMP00000216981, ENST00000395793, OTTHUMT00000047739
    5. NM_199168.3NP_954637.1  stromal cell-derived factor 1 isoform alpha precursor

      See identical proteins and their annotated locations for NP_954637.1

      Status: REVIEWED

      Description
      Transcript Variant: This variant (1) encodes the shortest protein (isoform alpha).
      Source sequence(s)
      AI092156, AL137026, BC031072, BC039893
      Consensus CDS
      CCDS7207.1
      UniProtKB/Swiss-Prot
      P48061
      Related
      ENSP00000339913, OTTHUMP00000019491, ENST00000343575, OTTHUMT00000047737
      Conserved Domains (1) summary
      cd00273
      Location:2788
      Chemokine_CXC; Chemokine_CXC: 1 of 4 subgroup designations based on the arrangement of the two N-terminal cysteine residues; includes a number of secreted growth factors and interferons involved in mitogenic, chemotactic, and inflammatory activity; many members ...

    RefSeqs of Annotated Genomes: Homo sapiens Annotation Release 107 details...

    The following sections contain reference sequences that belong to a specific genome build. Explain

    Reference GRCh38.p2 Primary Assembly

    Genomic

    1. NC_000010.11 Reference GRCh38.p2 Primary Assembly

      Range
      44370153..44385097 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)

    Alternate CHM1_1.1

    Genomic

    1. NC_018921.2 Alternate CHM1_1.1

      Range
      44904782..44919728 complement
      Download
      GenBank, FASTA, Sequence Viewer (Graphics)